Injectable self-healing carboxymethyl chitosan-zinc supramolecular hydrogels and their antibacterial activity.

Science.gov (United States)

Wahid, Fazli; Zhou, Ya-Ning; Wang, Hai-Song; Wan, Tong; Zhong, Cheng; Chu, Li-Qiang

2018-04-07

Injectable and self-healing hydrogels have found numerous applications in drug delivery, tissue engineering and 3D cell culture. Herein, we report an injectable self-healing carboxymethyl chitosan (CMCh) supramolecular hydrogels cross-linked by zinc ions (Zn 2+ ). Supramolecular hydrogels were obtained by simple addition of metal ions solution to CMCh solution at an appropriate pH value. The mechanical properties of these hydrogels were adjustable by the concentration of Zn 2+ . For example, the hydrogel with the highest concentration of Zn 2+ (CMCh-Zn4) showed strongest mechanical properties (storage modulus~11,000Pa) while hydrogel with the lowest concentration of Zn 2+ (CMCh-Zn1) showed weakest mechanical properties (storage modulus~220Pa). As observed visually and confirmed rheologically, the CMCh-Zn1 hydrogel with the lowest Zn 2+ concentration showed thixotropic property. CMCh-Zn1 hydrogel also presented injectable property. Moreover, the antibacterial properties of the prepared supramolecular hydrogels were studied against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) by agar well diffusion method. The results revealed Zn 2+ dependent antibacterial properties against both kinds of strains. The inhibition zones were ranging from ~11-24mm and ~10-22mm against S. aureus and E. coli, respectively. We believe that the prepared supramolecular hydrogels could be used as a potential candidate in biomedical fields. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of Photocrosslinked Lutrol Hydrogel for Tissue Printing applications

NARCIS (Netherlands)

Fedorovich, Natalja E.; Swennen, Ives; Girones, Jordi; Moroni, Lorenzo; van Blitterswijk, Clemens; Schacht, Etienne; Alblas, Jacqueline; Dhert, Wouter J.A.

2009-01-01

Application of hydrogels in tissue engineering and innovative strategies such as organ printing, which is based on layered 3D deposition of cell-laden hydrogels, requires design of novel hydrogel matrices. Hydrogel demands for 3D printing include: 1) preservation of the printed shape after the

Hydrogel based cartilaginous tissue regeneration: recent insights and technologies.

Science.gov (United States)

Chuah, Yon Jin; Peck, Yvonne; Lau, Jia En Josias; Hee, Hwan Tak; Wang, Dong-An

2017-03-28

Hydrogels have been extensively employed as an attractive biomaterial to address numerous existing challenges in the fields of regenerative medicine and research because of their unique properties such as the capability to encapsulate cells, high water content, ease of modification, low toxicity, injectability, in situ spatial fit and biocompatibility. These inherent properties have created many opportunities for hydrogels as a scaffold or a cell/drug carrier in tissue regeneration, especially in the field of cartilaginous tissue such as articular cartilage and intervertebral discs. A concise overview of the anatomy/physiology of these cartilaginous tissues and their pathophysiology, epidemiology and existing clinical treatments will be briefly described. This review article will discuss the current state-of-the-art of various polymers and developing strategies that are explored in establishing different technologies for cartilaginous tissue regeneration. In particular, an innovative approach to generate scaffold-free cartilaginous tissue via a transient hydrogel scaffolding system for disease modeling to pre-clinical trials will be examined. Following that, the article reviews numerous hydrogel-based medical implants used in clinical treatment of osteoarthritis and degenerated discs. Last but not least, the challenges and future directions of hydrogel based medical implants in the regeneration of cartilaginous tissue are also discussed.

Tunable Collagen I Hydrogels for Engineered Physiological Tissue Micro-Environments

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Antoine, Elizabeth E.; Vlachos, Pavlos P.; Rylander, Marissa N.

2015-01-01

Collagen I hydrogels are commonly used to mimic the extracellular matrix (ECM) for tissue engineering applications. However, the ability to design collagen I hydrogels similar to the properties of physiological tissues has been elusive. This is primarily due to the lack of quantitative correlations between multiple fabrication parameters and resulting material properties. This study aims to enable informed design and fabrication of collagen hydrogels in order to reliably and reproducibly mimic a variety of soft tissues. We developed empirical predictive models relating fabrication parameters with material and transport properties. These models were obtained through extensive experimental characterization of these properties, which include compression modulus, pore and fiber diameter, and diffusivity. Fabrication parameters were varied within biologically relevant ranges and included collagen concentration, polymerization pH, and polymerization temperature. The data obtained from this study elucidates previously unknown fabrication-property relationships, while the resulting equations facilitate informed a priori design of collagen hydrogels with prescribed properties. By enabling hydrogel fabrication by design, this study has the potential to greatly enhance the utility and relevance of collagen hydrogels in order to develop physiological tissue microenvironments for a wide range of tissue engineering applications. PMID:25822731

Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.

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Seol, Young-Joon; Park, Ju Young; Jeong, Wonju; Kim, Tae-Ho; Kim, Shin-Yoon; Cho, Dong-Woo

2015-04-01

The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site. © 2014 Wiley Periodicals, Inc.

Recent advances in hydrogels for cartilage tissue engineering

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SL Vega

2017-01-01

Full Text Available Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks, new techniques to process hydrogels (e.g. 3D printing and better incorporation of biological signals (e.g. controlled release. This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

Recent advances in hydrogels for cartilage tissue engineering.

Science.gov (United States)

Vega, S L; Kwon, M Y; Burdick, J A

2017-01-30

Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

A Self-Folding Hydrogel In Vitro Model for Ductal Carcinoma.

Science.gov (United States)

Kwag, Hye Rin; Serbo, Janna V; Korangath, Preethi; Sukumar, Saraswati; Romer, Lewis H; Gracias, David H

2016-04-01

A significant challenge in oncology is the need to develop in vitro models that accurately mimic the complex microenvironment within and around normal and diseased tissues. Here, we describe a self-folding approach to create curved hydrogel microstructures that more accurately mimic the geometry of ducts and acini within the mammary glands, as compared to existing three-dimensional block-like models or flat dishes. The microstructures are composed of photopatterned bilayers of poly (ethylene glycol) diacrylate (PEGDA), a hydrogel widely used in tissue engineering. The PEGDA bilayers of dissimilar molecular weights spontaneously curve when released from the underlying substrate due to differential swelling ratios. The photopatterns can be altered via AutoCAD-designed photomasks so that a variety of ductal and acinar mimetic structures can be mass-produced. In addition, by co-polymerizing methacrylated gelatin (methagel) with PEGDA, microstructures with increased cell adherence are synthesized. Biocompatibility and versatility of our approach is highlighted by culturing either SUM159 cells, which were seeded postfabrication, or MDA-MB-231 cells, which were encapsulated in hydrogels; cell viability is verified over 9 and 15 days, respectively. We believe that self-folding processes and associated tubular, curved, and folded constructs like the ones demonstrated here can facilitate the design of more accurate in vitro models for investigating ductal carcinoma.

Short-peptide-based molecular hydrogels: novel gelation strategies and applications for tissue engineering and drug delivery

Science.gov (United States)

Wang, Huaimin; Yang, Zhimou

2012-08-01

Molecular hydrogels hold big potential for tissue engineering and controlled drug delivery. Our lab focuses on short-peptide-based molecular hydrogels formed by biocompatible methods and their applications in tissue engineering (especially, 3D cell culture) and controlled drug delivery. This feature article firstly describes our recent progresses of the development of novel methods to form hydrogels, including the strategy of disulfide bond reduction and assistance with specific protein-peptide interactions. We then introduce the applications of our hydrogels in fields of controlled stem cell differentiation, cell culture, surface modifications of polyester materials by molecular self-assembly, and anti-degradation of recombinant complex proteins. A novel molecular hydrogel system of hydrophobic compounds that are only formed by hydrolysis processes was also included in this article. The hydrogels of hydrophobic compounds, especially those of hydrophobic therapeutic agents, may be developed into a carrier-free delivery system for long term delivery of therapeutic agents. With the efforts in this field, we believe that molecular hydrogels formed by short peptides and hydrophobic therapeutic agents can be practically applied for 3D cell culture and long term drug delivery in near future, respectively.

Design, fabrication and characterization of oxidized alginate-gelatin hydrogels for muscle tissue engineering applications.

Science.gov (United States)

Baniasadi, Hossein; Mashayekhan, Shohreh; Fadaoddini, Samira; Haghirsharifzamini, Yasamin

2016-07-01

In this study, we reported the preparation of self cross-linked oxidized alginate-gelatin hydrogels for muscle tissue engineering. The effect of oxidation degree (OD) and oxidized alginate/gelatin (OA/GEL) weight ratio were examined and the results showed that in the constant OA/GEL weight ratio, both cross-linking density and Young's modulus enhanced by increasing OD due to increment of aldehyde groups. Furthermore, the degradation rate was increased with increasing OD probably due to decrement in alginate molecular weight during oxidation reaction facilitated degradation of alginate chains. MTT cytotoxicity assays performed on Wharton's Jelly-derived umbilical cord mesenchymal stem cells cultured on hydrogels with OD of 30% showed that the highest rate of cell proliferation belong to hydrogel with OA/GEL weight ratio of 30/70. Overall, it can be concluded from all obtained results that the prepared hydrogel with OA/GEL weight ratio and OD of 30/70 and 30%, respectively, could be proper candidate for use in muscle tissue engineering. © The Author(s) 2016.

Functional Self-Assembling Peptide Nanofiber Hydrogels Designed for Nerve Degeneration.

Science.gov (United States)

Sun, Yuqiao; Li, Wen; Wu, Xiaoli; Zhang, Na; Zhang, Yongnu; Ouyang, Songying; Song, Xiyong; Fang, Xinyu; Seeram, Ramakrishna; Xue, Wei; He, Liumin; Wu, Wutian

2016-01-27

Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G' than G″ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells (NPCs)/stem cells (NSCs) fully embedded in the 3D-IKVAV/-RGD nanofiber hydrogel survived, whereas those embedded within the RADA 16-I hydrogel hardly survived. Moreover, the -IKVAV/-RGD nanofiber hydrogel supported NPC/NSC neuron and astrocyte differentiation in a 3D environment without adding extra growth factors. Studies of three nerve injury models, including sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection, indicated that the designer -IKVAV/-RGD nanofiber hydrogel provided a more permissive environment for nerve regeneration than the RADA 16-I hydrogel. Therefore, we reported a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration.

When Parents’ Praise Inflates, Children's Self-Esteem Deflates

NARCIS (Netherlands)

Brummelman, Eddie; Nelemans, Stefanie A.; Thomaes, Sander; Orobio De Castro, Bram

2017-01-01

Western parents often give children overly positive, inflated praise. One perspective holds that inflated praise sets unattainable standards for children, eventually lowering children's self-esteem (self-deflation hypothesis). Another perspective holds that children internalize inflated praise to

Hydrogels for precision meniscus tissue engineering: a comprehensive review.

Science.gov (United States)

Rey-Rico, Ana; Cucchiarini, Magali; Madry, Henning

The meniscus plays a pivotal role to preserve the knee joint homeostasis. Lesions to the meniscus are frequent, have a reduced ability to heal, and may induce tibiofemoral osteoarthritis. Current reconstructive therapeutic options mainly focus on the treatment of lesions in the peripheral vascularized region. In contrast, few approaches are capable of stimulating repair of damaged meniscal tissue in the central, avascular portion. Tissue engineering approaches are of high interest to repair or replace damaged meniscus tissue in this area. Hydrogel-based biomaterials are of special interest for meniscus repair as its inner part contains relatively high proportions of proteoglycans which are responsible for the viscoelastic compressive properties and hydration grade. Hydrogels exhibiting high water content and providing a specific three-dimensional (3D) microenvironment may be engineered to precisely resemble this topographical composition of the meniscal tissue. Different polymers of both natural and synthetic origins have been manipulated to produce hydrogels hosting relevant cell populations for meniscus regeneration and provide platforms for meniscus tissue replacement. So far, these compounds have been employed to design controlled delivery systems of bioactive molecules involved in meniscal reparative processes or to host genetically modified cells as a means to enhance meniscus repair. This review describes the most recent advances on the use of hydrogels as platforms for precision meniscus tissue engineering.

Hydrogel microfabrication technology toward three dimensional tissue engineering

Directory of Open Access Journals (Sweden)

Fumiki Yanagawa

2016-03-01

Full Text Available The development of biologically relevant three-dimensional (3D tissue constructs is essential for the alternative methods of organ transplantation in regenerative medicine, as well as the development of improved drug discovery assays. Recent technological advances in hydrogel microfabrication, such as micromolding, 3D bioprinting, photolithography, and stereolithography, have led to the production of 3D tissue constructs that exhibit biological functions with precise 3D microstructures. Furthermore, microfluidics technology has enabled the development of the perfusion culture of 3D tissue constructs with vascular networks. In this review, we present these hydrogel microfabrication technologies for the in vitro reconstruction and cultivation of 3D tissues. Additionally, we discuss current challenges and future perspectives of 3D tissue engineering.

Prodrugs as self-assembled hydrogels: a new paradigm for biomaterials.

Science.gov (United States)

Vemula, Praveen Kumar; Wiradharma, Nikken; Ankrum, James A; Miranda, Oscar R; John, George; Karp, Jeffrey M

2013-12-01

Prodrug-based self-assembled hydrogels represent a new class of active biomaterials that can be harnessed for medical applications, in particular the design of stimuli responsive drug delivery devices. In this approach, a promoiety is chemically conjugated to a known-drug to generate an amphiphilic prodrug that is capable of forming self-assembled hydrogels. Prodrug-based self-assembled hydrogels are advantageous as they alter the solubility of the drug, enhance drug loading, and eliminate the use of harmful excipients. In addition, self-assembled prodrug hydrogels can be designed to undergo controlled drug release or tailored degradation in response to biological cues. Herein we review the development of prodrug-based self-assembled hydrogels as an emerging class of biomaterials that overcome several common limitations encountered in conventional drug delivery. Published by Elsevier Ltd.

Application of Extrusion-Based Hydrogel Bioprinting for Cartilage Tissue Engineering.

Science.gov (United States)

You, Fu; Eames, B Frank; Chen, Xiongbiao

2017-07-23

Extrusion-based bioprinting (EBB) is a rapidly developing technique that has made substantial progress in the fabrication of constructs for cartilage tissue engineering (CTE) over the past decade. With this technique, cell-laden hydrogels or bio-inks have been extruded onto printing stages, layer-by-layer, to form three-dimensional (3D) constructs with varying sizes, shapes, and resolutions. This paper reviews the cell sources and hydrogels that can be used for bio-ink formulations in CTE application. Additionally, this paper discusses the important properties of bio-inks to be applied in the EBB technique, including biocompatibility, printability, as well as mechanical properties. The printability of a bio-ink is associated with the formation of first layer, ink rheological properties, and crosslinking mechanisms. Further, this paper discusses two bioprinting approaches to build up cartilage constructs, i.e., self-supporting hydrogel bioprinting and hybrid bioprinting, along with their applications in fabricating chondral, osteochondral, and zonally organized cartilage regenerative constructs. Lastly, current limitations and future opportunities of EBB in printing cartilage regenerative constructs are reviewed.

Application of Extrusion-Based Hydrogel Bioprinting for Cartilage Tissue Engineering

Science.gov (United States)

You, Fu; Eames, B. Frank; Chen, Xiongbiao

2017-01-01

Extrusion-based bioprinting (EBB) is a rapidly developing technique that has made substantial progress in the fabrication of constructs for cartilage tissue engineering (CTE) over the past decade. With this technique, cell-laden hydrogels or bio-inks have been extruded onto printing stages, layer-by-layer, to form three-dimensional (3D) constructs with varying sizes, shapes, and resolutions. This paper reviews the cell sources and hydrogels that can be used for bio-ink formulations in CTE application. Additionally, this paper discusses the important properties of bio-inks to be applied in the EBB technique, including biocompatibility, printability, as well as mechanical properties. The printability of a bio-ink is associated with the formation of first layer, ink rheological properties, and crosslinking mechanisms. Further, this paper discusses two bioprinting approaches to build up cartilage constructs, i.e., self-supporting hydrogel bioprinting and hybrid bioprinting, along with their applications in fabricating chondral, osteochondral, and zonally organized cartilage regenerative constructs. Lastly, current limitations and future opportunities of EBB in printing cartilage regenerative constructs are reviewed. PMID:28737701

Application of Extrusion-Based Hydrogel Bioprinting for Cartilage Tissue Engineering

Directory of Open Access Journals (Sweden)

Fu You

2017-07-01

Full Text Available Extrusion-based bioprinting (EBB is a rapidly developing technique that has made substantial progress in the fabrication of constructs for cartilage tissue engineering (CTE over the past decade. With this technique, cell-laden hydrogels or bio-inks have been extruded onto printing stages, layer-by-layer, to form three-dimensional (3D constructs with varying sizes, shapes, and resolutions. This paper reviews the cell sources and hydrogels that can be used for bio-ink formulations in CTE application. Additionally, this paper discusses the important properties of bio-inks to be applied in the EBB technique, including biocompatibility, printability, as well as mechanical properties. The printability of a bio-ink is associated with the formation of first layer, ink rheological properties, and crosslinking mechanisms. Further, this paper discusses two bioprinting approaches to build up cartilage constructs, i.e., self-supporting hydrogel bioprinting and hybrid bioprinting, along with their applications in fabricating chondral, osteochondral, and zonally organized cartilage regenerative constructs. Lastly, current limitations and future opportunities of EBB in printing cartilage regenerative constructs are reviewed.

Integration of Self-Assembled Microvascular Networks with Microfabricated PEG-Based Hydrogels.

Science.gov (United States)

Cuchiara, Michael P; Gould, Daniel J; McHale, Melissa K; Dickinson, Mary E; West, Jennifer L

2012-11-07

Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co-culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self-assembly and employs an anastomotic interface for integration of self-assembled micro-vascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra-vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo.

Interfacial self-healing of nanocomposite hydrogels: Theory and experiment

Science.gov (United States)

Wang, Qiming; Gao, Zheming; Yu, Kunhao

2017-12-01

Polymers with dynamic bonds are able to self-heal their fractured interfaces and restore the mechanical strengths. It is largely elusive how to analytically model this self-healing behavior to construct the mechanistic relationship between the self-healing properties (e.g., healed interfacial strength and equilibrium healing time) and the material compositions and healing conditions. Here, we take a self-healable nanocomposite hydrogel as an example to illustrate an interfacial self-healing theory for hydrogels with dynamic bonds. In the theory, we consider the free polymer chains diffuse across the interface and reform crosslinks to bridge the interface. We analytically reveal that the healed strengths of nanocomposite hydrogels increase with the healing time in an error-function-like form. The equilibrium self-healing time of the full-strength recovery decreases with the temperature and increases with the nanoparticle concentration. We further analytically reveal that the healed interfacial strength decreases with increasing delaying time before the healing process. The theoretical results quantitatively match with our experiments on nanosilica hydrogels, and also agree well with other researchers' experiments on nanoclay hydrogels. We expect that this theory would open promising avenues for quantitative understanding of the self-healing mechanics of various polymers with dynamic bonds, and offer insights for designing high-performance self-healing polymers.

Hydrogel-laden paper scaffold system for origami-based tissue engineering.

Science.gov (United States)

Kim, Su-Hwan; Lee, Hak Rae; Yu, Seung Jung; Han, Min-Eui; Lee, Doh Young; Kim, Soo Yeon; Ahn, Hee-Jin; Han, Mi-Jung; Lee, Tae-Ik; Kim, Taek-Soo; Kwon, Seong Keun; Im, Sung Gap; Hwang, Nathaniel S

2015-12-15

In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca(2+). This procedure ensures the formation of alginate hydrogel on the paper due to Ca(2+) diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs.

Preparation and characterization of a novel sodium alginate incorporated self-assembled Fmoc-FF composite hydrogel

Energy Technology Data Exchange (ETDEWEB)

Gong, Xiao [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620 (China); Branford-White, Christopher [Institute for Health Research and Policy, London Metropolitan University, London N78 DB (United Kingdom); Tao, Lei [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Li, Shubai [Changzhou Institute of Engineering Technology, Changzhou 213164 (China); Quan, Jing [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Nie, Huali, E-mail: niehuali@dhu.edu.cn [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620 (China); Zhu, Limin, E-mail: lzhu@dhu.edu.cn [College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China)

2016-01-01

Dipeptides and their derivatives have attracted tremendous attention owning to their excellent abilities of self-assemble assembling into various structures which have great potentials for applications in biology and/or nanotechnology. In the present study, we dedicate to fabricate a rigid and structure controllable Fmoc-FF/SA composite hydrogel. We found that the modified dipeptide, fluorenyl-9-methoxycarbonyl (Fmoc)-diphenylalanine (Phe-Phe) can self-assemble into rigid hydrogels with structures of nanowires, layered thin films or honeycombs as the change of sodium alginate (SA) concentration. Meanwhile, CD-spectroscopy demonstrated that SA appeared to control the process, but it did not change the arrangement of the Fmoc-FF peptide. Our results demonstrated that the formed hydrogel showed physical and chemical stability as well as possessing good biocompatibility. Rheological measurements showed that the addition of SA could improve the stability of the hydrogel. Cell viability assay revealed that the Fmoc-FF and Fmoc-FF/SA hydrogels are both beneficial for cell proliferation in-vitro. Our results indicated that the fabricated Fmoc-FF/SA composite hydrogels could be used in tissue engineering and drug delivery in the future. - Highlights: • A facile, time-saving approach to assemble Fomc-FF composite hydrogels was designed. • Hydrogel structures including nanowires, layered films and honeycombs can be controlled. • The role of SA in the Fmoc-FF/SA composite hydrogel was further clarified.

Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs.

Science.gov (United States)

Navaei, Ali; Saini, Harpinder; Christenson, Wayne; Sullivan, Ryan Tanner; Ros, Robert; Nikkhah, Mehdi

2016-09-01

The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels. In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly

Photo-patterning of porous hydrogels for tissue engineering.

Science.gov (United States)

Bryant, Stephanie J; Cuy, Janet L; Hauch, Kip D; Ratner, Buddy D

2007-07-01

Since pore size and geometry strongly impact cell behavior and in vivo reaction, the ability to create scaffolds with a wide range of pore geometries that can be tailored to suit a particular cell type addresses a key need in tissue engineering. In this contribution, we describe a novel and simple technique to design porous, degradable poly(2-hydroxyethyl methacrylate) hydrogel scaffolds with well-defined architectures using a unique photolithography process and optimized polymer chemistry. A sphere-template was used to produce a highly uniform, monodisperse porous structure. To create a patterned and porous hydrogel scaffold, a photomask and initiating light were employed. Open, vertical channels ranging in size from 360+/-25 to 730+/-70 microm were patterned into approximately 700 microm thick hydrogels with pore diameters of 62+/-8 or 147+/-15 microm. Collagen type I was immobilized onto the scaffolds to facilitate cell adhesion. To assess the potential of these novel scaffolds for tissue engineering, a skeletal myoblast cell line (C2C12) was seeded onto scaffolds with 147 microm pores and 730 microm diameter channels, and analyzed by histology and digital volumetric imaging. Cell elongation, cell spreading and fibrillar formation were observed on these novel scaffolds. In summary, 3D architectures can be patterned into porous hydrogels in one step to create a wide range of tissue engineering scaffolds that may be tailored for specific applications.

Nanoreinforced Hydrogels for Tissue Engineering: Biomaterials that are Compatible with Load-Bearing and Electroactive Tissues

DEFF Research Database (Denmark)

Mehrali, Mehdi; Thakur, Ashish; Pennisi, Christian Pablo

2017-01-01

, mechanical, and electrical properties. Here, recent advances in the fabrication and application of nanocomposite hydrogels in tissue engineering applications are described, with specific attention toward skeletal and electroactive tissues, such as cardiac, nerve, bone, cartilage, and skeletal muscle......Given their highly porous nature and excellent water retention, hydrogel-based biomaterials can mimic critical properties of the native cellular environment. However, their potential to emulate the electromechanical milieu of native tissues or conform well with the curved topology of human organs...

Fibre-reinforced hydrogels for tissue engineering

Science.gov (United States)

Waters, Sarah; Byrne, Helen; Chen, Mike; Dias Castilho, Miguel; Kimpton, Laura; Please, Colin; Whiteley, Jonathan

2017-11-01

Tissue engineers aim to grow replacement tissues in vitro to replace those in the body that have been damaged through age, trauma or disease. One approach is to seed cells within a scaffold consisting of an interconnected 3D-printed lattice of polymer fibres, cast in a hydrogel, and subject the construct (cell-seeded scaffold) to an applied load in a bioreactor. A key question is to understand how this applied load is distributed throughout the construct to the mechanosensitive cells. To address this, we exploit the disparate length scales (small inter-fibre spacing compared with construct dimensions). The fibres are treated as a linear elastic material and the hydrogel as a poroelastic material. We employ homogenisation theory to derive equations governing the material properties of a periodic, elastic-poroelastic composite. To validate the mobel, model solutions are compared to experimental data describing the unconfined compression of the fibre-reinforced hydrogels. The model is used to derive the bulk mechanical properties of a cylindrical construct of the composite material for a range of fibre spacings, and the local mechanical environment experienced by cells embedded within the construct is determined. Funded by the European Union Seventh Framework Programme (FP7/2007-2013).

Self-assembling Fmoc dipeptide hydrogel for in situ 3D cell culturing

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Akpe Victor

2007-12-01

Full Text Available Abstract Background Conventional cell culture studies have been performed on 2D surfaces, resulting in flat, extended cell growth. More relevant studies are desired to better mimic 3D in vivo tissue growth. Such realistic environments should be the aim of any cell growth study, requiring new methods for culturing cells in vitro. Cell biology is also tending toward miniaturization for increased efficiency and specificity. This paper discusses the application of a self-assembling peptide-derived hydrogel for use as a 3D cell culture scaffold at the microscale. Results Phenylalanine derivative hydrogel formation was seen to occur in multiple dispersion media. Cells were immobilized in situ within microchambers designed for cell analysis. Use of the highly biocompatible hydrogel components and simplistic procedures significantly reduced the cytotoxic effects seen with alternate 3D culture materials and microstructure loading methods. Cells were easily immobilized, sustained and removed from microchambers. Differences in growth morphology were seen in the cultured cells, owing to the 3-dimentional character of the gel structure. Degradation improved the removal of hydrogel from the microstructures, permitting reuse of the analysis platforms. Conclusion Self-assembling diphenylalanine derivative hydrogel provided a method to dramatically reduce the typical difficulties of microculture formation. Effective generation of patterned 3D cultures will lead to improved cell study results by better modeling in vivo growth environments and increasing efficiency and specificity of cell studies. Use of simplified growth scaffolds such as peptide-derived hydrogel should be seen as highly advantageous and will likely become more commonplace in cell culture methodology.

Fabrication of three-dimensional porous cell-laden hydrogel for tissue engineering

International Nuclear Information System (INIS)

Hwang, Chang Mo; Sant, Shilpa; Masaeli, Mahdokht; Kachouie, Nezamoddin N; Zamanian, Behnam; Khademhosseini, Ali; Lee, Sang-Hoon

2010-01-01

For tissue engineering applications, scaffolds should be porous to enable rapid nutrient and oxygen transfer while providing a three-dimensional (3D) microenvironment for the encapsulated cells. This dual characteristic can be achieved by fabrication of porous hydrogels that contain encapsulated cells. In this work, we developed a simple method that allows cell encapsulation and pore generation inside alginate hydrogels simultaneously. Gelatin beads of 150-300 μm diameter were used as a sacrificial porogen for generating pores within cell-laden hydrogels. Gelation of gelatin at low temperature (4 0 C) was used to form beads without chemical crosslinking and their subsequent dissolution after cell encapsulation led to generation of pores within cell-laden hydrogels. The pore size and porosity of the scaffolds were controlled by the gelatin bead size and their volume ratio, respectively. Fabricated hydrogels were characterized for their internal microarchitecture, mechanical properties and permeability. Hydrogels exhibited a high degree of porosity with increasing gelatin bead content in contrast to nonporous alginate hydrogel. Furthermore, permeability increased by two to three orders while compressive modulus decreased with increasing porosity of the scaffolds. Application of these scaffolds for tissue engineering was tested by encapsulation of hepatocarcinoma cell line (HepG2). All the scaffolds showed similar cell viability; however, cell proliferation was enhanced under porous conditions. Furthermore, porous alginate hydrogels resulted in formation of larger spheroids and higher albumin secretion compared to nonporous conditions. These data suggest that porous alginate hydrogels may have provided a better environment for cell proliferation and albumin production. This may be due to the enhanced mass transfer of nutrients, oxygen and waste removal, which is potentially beneficial for tissue engineering and regenerative medicine applications.

Synthesis, characterization and in vitro biocompatibility assessment of a novel tripeptide hydrogelator, as a promising scaffold for tissue engineering applications.

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Pospišil, Tihomir; Ferhatović Hamzić, Lejla; Brkić Ahmed, Lada; Lovrić, Marija; Gajović, Srećko; Frkanec, Leo

2016-10-20

We have synthesized and characterized a self-assembling tripeptide hydrogelator Ac-l-Phe-l-Phe-l-Ala-NH2. A series of experiments showed that the hydrogel material could serve as a stabile and biocompatible physical support as it improves the survival of HEK293T cells in vitro, thus being a promising biomaterial for use in tissue engineering applications.

Hydrogel based tissue mimicking phantom for in-vitro ultrasound contrast agents studies.

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Demitri, Christian; Sannino, Alessandro; Conversano, Francesco; Casciaro, Sergio; Distante, Alessandro; Maffezzoli, Alfonso

2008-11-01

Ultrasound medical imaging (UMI) is the most widely used image analysis technique, and often requires advanced in-vitro set up to perform morphological and functional investigations. These studies are based on contrast properties both related to tissue structure and injectable contrast agents (CA). In this work, we present a three-dimensional structure composed of two different hydrogels reassembly the microvascular network of a human tissue. This phantom was particularly suitable for the echocontrastographic measurements in human microvascular system. This phantom has been characterized to present the acoustic properties of an animal liver, that is, acoustic impedance (Z) and attenuation coefficient (AC), in UMI signal analysis in particular; the two different hydrogels have been selected to simulate the target organ and the acoustic properties of the vascular system. The two hydrogels were prepared starting from cellulose derivatives to simulating the target organ parenchyma and using a PEG-diacrylate to reproduce the vascular system. Moreover, harmonic analysis was performed on the hydrogel mimicking the liver parenchyma hydrogel to evaluate the ultrasound (US) distortion during echographic measurement. The phantom was employed in the characterization of an experimental US CA. Perfect agreement was found when comparing the hydrogel acoustical properties materials with the corresponding living reference tissues (i.e., vascular and parenchimal tissue).

A comparison of self-assembly and hydrogel encapsulation as a means to engineer functional cartilaginous grafts using culture expanded chondrocytes.

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Mesallati, Tariq; Buckley, Conor T; Kelly, Daniel J

2014-01-01

Despite an increased interest in the use of hydrogel encapsulation and cellular self-assembly (often termed "self-aggregating" or "scaffold-free" approaches) for tissue-engineering applications, to the best of our knowledge, no study to date has been undertaken to directly compare both approaches for generating functional cartilaginous grafts. The objective of this study was to directly compare self-assembly (SA) and agarose hydrogel encapsulation (AE) as a means to engineer such grafts using passaged chondrocytes. Agarose hydrogels (5 mm diameter × 1.5 mm thick) were seeded with chondrocytes at two cell seeding densities (900,000 cells or 4 million cells in total per hydrogel), while SA constructs were generated by adding the same number of cells to custom-made molds. Constructs were either supplemented with transforming growth factor (TGF)-β3 for 6 weeks, or only supplemented with TGF-β3 for the first 2 weeks of the 6 week culture period. The SA method was only capable of generating geometrically uniform cartilaginous tissues at high seeding densities (4 million cells). At these high seeding densities, we observed that total sulphated glycosaminoglycan (sGAG) and collagen synthesis was greater with AE than SA, with higher sGAG retention also observed in AE constructs. When normalized to wet weight, however, SA constructs exhibited significantly higher levels of collagen accumulation compared with agarose hydrogels. Furthermore, it was possible to engineer such functionality into these tissues in a shorter timeframe using the SA approach compared with AE. Therefore, while large numbers of chondrocytes are required to engineer cartilaginous grafts using the SA approach, it would appear to lead to the faster generation of a more hyaline-like tissue, with a tissue architecture and a ratio of collagen to sGAG content more closely resembling native articular cartilage.

An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering

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Chen, Feng; Yu, Songrui; Liu, Bing; Ni, Yunzhou; Yu, Chunyang; Su, Yue; Zhu, Xinyuan; Yu, Xiaowei; Zhou, Yongfeng; Yan, Deyue

2016-01-01

In this study, an enzymatically cross-linked injectable and biodegradable hydrogel system comprising carboxymethyl pullulan-tyramine (CMP-TA) and chondroitin sulfate-tyramine (CS-TA) conjugates was successfully developed under physiological conditions in the presence of both horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) for cartilage tissue engineering (CTTE). The HRP crosslinking method makes this injectable system feasible, minimally invasive and easily translatable for regenerative medicine applications. The physicochemical properties of the mechanically stable hydrogel system can be modulated by varying the weight ratio and concentration of polymer as well as the concentrations of crosslinking reagents. Additionally, the cellular behaviour of porcine auricular chondrocytes encapsulated into CMP-TA/CS-TA hydrogels demonstrates that the hydrogel system has a good cyto-compatibility. Specifically, compared to the CMP-TA hydrogel, these CMP-TA/CS-TA composite hydrogels have enhanced cell proliferation and increased cartilaginous ECM deposition, which significantly facilitate chondrogenesis. Furthermore, histological analysis indicates that the hydrogel system exhibits acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable pullulan/chondroitin sulfate composite hydrogels presented here are expected to be useful biomaterial scaffold for regenerating cartilage tissue.

Stimuli-responsive hydrogels in drug delivery and tissue engineering.

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Sood, Nikhil; Bhardwaj, Ankur; Mehta, Shuchi; Mehta, Abhinav

2016-01-01

Hydrogels are the three-dimensional network structures obtained from a class of synthetic or natural polymers which can absorb and retain a significant amount of water. Hydrogels are one of the most studied classes of polymer-based controlled drug release. These have attracted considerable attention in biochemical and biomedical fields because of their characteristics, such as swelling in aqueous medium, biocompatibility, pH and temperature sensitivity or sensitivity towards other stimuli, which can be utilized for their controlled zero-order release. The hydrogels are expected to explore new generation of self-regulated delivery system having a wide array of desirable properties. This review highlights the exciting opportunities and challenges in the area of hydrogels. Here, we review different literatures on stimuli-sensitive hydrogels, such as role of temperature, electric potential, pH and ionic strength to control the release of drug from hydrogels.

Self-Supporting Nanoclay as Internal Scaffold Material for Direct Printing of Soft Hydrogel Composite Structures in Air.

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Jin, Yifei; Liu, Chengcheng; Chai, Wenxuan; Compaan, Ashley; Huang, Yong

2017-05-24

Three dimensional (3D) bioprinting technology enables the freeform fabrication of complex constructs from various hydrogels and is receiving increasing attention in tissue engineering. The objective of this study is to develop a novel self-supporting direct hydrogel printing approach to extrude complex 3D hydrogel composite structures in air without the help of a support bath. Laponite, a member of the smectite mineral family, is investigated to serve as an internal scaffold material for the direct printing of hydrogel composite structures in air. In the proposed printing approach, due to its yield-stress property, Laponite nanoclay can be easily extruded through a nozzle as a liquid and self-supported after extrusion as a solid. Its unique crystal structure with positive and negative charges enables it to be mixed with many chemically and physically cross-linked hydrogels, which makes it an ideal internal scaffold material for the fabrication of various hydrogel structures. By mixing Laponite nanoclay with various hydrogel precursors, the hydrogel composites retain their self-supporting capacity and can be printed into 3D structures directly in air and retain their shapes before cross-linking. Then, the whole structures are solidified in situ by applying suitable cross-linking stimuli. The addition of Laponite nanoclay can effectively improve the mechanical and biological properties of hydrogel composites. Specifically, the addition of Laponite nanoclay results in a significant increase in the Young's modulus of each hydrogel-Laponite composite: 1.9-fold increase for the poly(ethylene glycol) diacrylate (PEGDA)-Laponite composite, 7.4-fold increase for the alginate-Laponite composite, and 3.3-fold increase for the gelatin-Laponite composite.

Reusable self-healing hydrogels realized via in situ polymerization.

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Vivek, Balachandran; Prasad, Edamana

2015-04-09

In this work, a self-healing hydrogel has been prepared using in situ polymerization of acrylic acid and acrylamide in the presence of glycogen. The hydrogel was characterized using NMR, SEM, FT-IR, rheology, and dynamic light scattering (DLS) studies. The developed hydrogel exhibits self-healing properties at neutral pH, high swelling ability, high elasticity, and excellent mechanical strength. The hydrogel exhibits modulus values (G', G″) as high as 10(6) Pa and shows an exceptionally high degree of swelling ratio (∼3.5 × 10(3)). Further, the polymer based hydrogel adsorbs toxic metal ions (Cd(2+), Pb(2+), and Hg(2+)) and organic dyes (methylene blue and methyl orange) from contaminated water with remarkable efficiency (90-98%). The mechanistic analysis indicated the presence of pseudo-second-order reaction kinetics. The reusability of the hydrogel has been demonstrated by repeating the adsorption-desorption process over five cycles with identical results in the adsorption efficiency.

Nano-in-Micro Self-Reporting Hydrogel Constructs.

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Tirella, Annalisa; La Marca, Margherita; Brace, Leigh-Anne; Mattei, Giorgio; Aylott, Jonathan W; Ahluwalia, Arti

2015-08-01

Highly reproducible Nano-in-Micro constructs are fabricated to provide a well-defined and self-reporting biomimetic environment for hepatocytes. Based on a protein/hydrogel formulation with controlled shape, size and composition, the constructs enable efficient nutrient exchange and provide an adhesive 3D framework to cells. Co-encapsulation of hepatocytes and ratiometric optical nanosensors with pH sensitivity in the physiological range allows continuous monitoring of the microenvironment. The lobule-sized microbeads are fabricated using an automated droplet generator, Sphyga (Spherical Hydrogel Generator) combining alginate, collagen, decellularized hepatic tissue, pH-nanosensors and hepatocytes. The pH inside the Nano-in-Micro constructs is monitored during culture, while assaying media for hepatic function and vitality markers. Although the local pH changes by several units during bead fabrication, when encapsulated cells are most likely to undergo stress, it is stable and buffered by cell culture media thereafter. Albumin secretion and urea production are significantly higher in the microbeads compared with controls, indicating that the encapsulated Nano-in-Micro environment is conducive to enhanced hepatic function.

Macroporous Hydrogel Scaffolds for Three-Dimensional Cell Culture and Tissue Engineering.

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Fan, Changjiang; Wang, Dong-An

2017-10-01

Hydrogels have been promising candidate scaffolds for cell delivery and tissue engineering due to their tissue-like physical properties and capability for homogeneous cell loading. However, the encapsulated cells are generally entrapped and constrained in the submicron- or nanosized gel networks, seriously limiting cell growth and tissue formation. Meanwhile, the spatially confined settlement inhibits attachment and spreading of anchorage-dependent cells, leading to their apoptosis. In recent years, macroporous hydrogels have attracted increasing attention in use as cell delivery vehicles and tissue engineering scaffolds. The introduction of macropores within gel scaffolds not only improves their permeability for better nutrient transport but also creates space/interface for cell adhesion, proliferation, and extracellular matrix deposition. Herein, we will first review the development of macroporous gel scaffolds and outline the impact of macropores on cell behaviors. In the first part, the advantages and challenges of hydrogels as three-dimensional (3D) cell culture scaffolds will be described. In the second part, the fabrication of various macroporous hydrogels will be presented. Third, the enhancement of cell activities within macroporous gel scaffolds will be discussed. Finally, several crucial factors that are envisaged to propel the improvement of macroporous gel scaffolds are proposed for 3D cell culture and tissue engineering.

Drug-Loadable Calcium Alginate Hydrogel System for Use in Oral Bone Tissue Repair.

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Chen, Luyuan; Shen, Renze; Komasa, Satoshi; Xue, Yanxiang; Jin, Bingyu; Hou, Yepo; Okazaki, Joji; Gao, Jie

2017-05-06

This study developed a drug-loadable hydrogel system with high plasticity and favorable biological properties to enhance oral bone tissue regeneration. Hydrogels of different calcium alginate concentrations were prepared. Their swelling ratio, degradation time, and bovine serum albumin (BSA) release rate were measured. Human periodontal ligament cells (hPDLCs) and bone marrow stromal cells (BMSCs) were cultured with both calcium alginate hydrogels and polylactic acid (PLA), and then we examined the proliferation of cells. Inflammatory-related factor gene expressions of hPDLCs and osteogenesis-related gene expressions of BMSCs were observed. Materials were implanted into the subcutaneous tissue of rabbits to determine the biosecurity properties of the materials. The materials were also implanted in mandibular bone defects and then scanned using micro-CT. The calcium alginate hydrogels caused less inflammation than the PLA. The number of mineralized nodules and the expression of osteoblast-related genes were significantly higher in the hydrogel group compared with the control group. When the materials were implanted in subcutaneous tissue, materials showed favorable biocompatibility. The calcium alginate hydrogels had superior osteoinductive bone ability to the PLA. The drug-loadable calcium alginate hydrogel system is a potential bone defect reparation material for clinical dental application.

Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink

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Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D.; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

2016-01-01

Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types. PMID:27166839

Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink.

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Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

2016-04-21

Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types.

Extracellular Matrix Hydrogel Promotes Tissue Remodeling, Arteriogenesis, and Perfusion in a Rat Hindlimb Ischemia Model

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Jessica L. Ungerleider, BS

2016-01-01

Full Text Available Although surgical and endovascular revascularization can be performed in peripheral arterial disease (PAD, 40% of patients with critical limb ischemia do not have a revascularization option. This study examines the efficacy and mechanisms of action of acellular extracellular matrix-based hydrogels as a potential novel therapy for treating PAD. We tested the efficacy of using a tissue-specific injectable hydrogel derived from decellularized porcine skeletal muscle (SKM and compared this to a new human umbilical cord-derived matrix (hUC hydrogel, which could have greater potential for tissue regeneration because of the younger age of the tissue source. In a rodent hindlimb ischemia model, both hydrogels were injected 1-week post-surgery and perfusion was regularly monitored with laser speckle contrast analysis to 35 days post-injection. There were significant improvements in hindlimb tissue perfusion and perfusion kinetics with both biomaterials. Histologic analysis indicated that the injected hydrogels were biocompatible, and resulted in arteriogenesis, rather than angiogenesis, as well as improved recruitment of skeletal muscle progenitors. Skeletal muscle fiber morphology analysis indicated that the muscle treated with the tissue-specific SKM hydrogel more closely matched healthy tissue morphology. Whole transcriptome analysis indicated that the SKM hydrogel caused a shift in the inflammatory response, decreased cell death, and increased blood vessel and muscle development. These results show the efficacy of an injectable ECM hydrogel alone as a potential therapy for treating patients with PAD. Our results indicate that the SKM hydrogel improved functional outcomes through stimulation of arteriogenesis and muscle progenitor cell recruitment.

Rationally designed synthetic protein hydrogels with predictable mechanical properties.

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Wu, Junhua; Li, Pengfei; Dong, Chenling; Jiang, Heting; Bin Xue; Gao, Xiang; Qin, Meng; Wang, Wei; Bin Chen; Cao, Yi

2018-02-12

Designing synthetic protein hydrogels with tailored mechanical properties similar to naturally occurring tissues is an eternal pursuit in tissue engineering and stem cell and cancer research. However, it remains challenging to correlate the mechanical properties of protein hydrogels with the nanomechanics of individual building blocks. Here we use single-molecule force spectroscopy, protein engineering and theoretical modeling to prove that the mechanical properties of protein hydrogels are predictable based on the mechanical hierarchy of the cross-linkers and the load-bearing modules at the molecular level. These findings provide a framework for rationally designing protein hydrogels with independently tunable elasticity, extensibility, toughness and self-healing. Using this principle, we demonstrate the engineering of self-healable muscle-mimicking hydrogels that can significantly dissipate energy through protein unfolding. We expect that this principle can be generalized for the construction of protein hydrogels with customized mechanical properties for biomedical applications.

Ultrasensitive Wearable Soft Strain Sensors of Conductive, Self-healing, and Elastic Hydrogels with Synergistic "Soft and Hard" Hybrid Networks.

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Liu, Yan-Jun; Cao, Wen-Tao; Ma, Ming-Guo; Wan, Pengbo

2017-08-02

Robust, stretchable, and strain-sensitive hydrogels have recently attracted immense research interest because of their potential application in wearable strain sensors. The integration of the synergistic characteristics of decent mechanical properties, reliable self-healing capability, and high sensing sensitivity for fabricating conductive, elastic, self-healing, and strain-sensitive hydrogels is still a great challenge. Inspired by the mechanically excellent and self-healing biological soft tissues with hierarchical network structures, herein, functional network hydrogels are fabricated by the interconnection between a "soft" homogeneous polymer network and a "hard" dynamic ferric (Fe 3+ ) cross-linked cellulose nanocrystals (CNCs-Fe 3+ ) network. Under stress, the dynamic CNCs-Fe 3+ coordination bonds act as sacrificial bonds to efficiently dissipate energy, while the homogeneous polymer network leads to a smooth stress-transfer, which enables the hydrogels to achieve unusual mechanical properties, such as excellent mechanical strength, robust toughness, and stretchability, as well as good self-recovery property. The hydrogels demonstrate autonomously self-healing capability in only 5 min without the need of any stimuli or healing agents, ascribing to the reorganization of CNCs and Fe 3+ via ionic coordination. Furthermore, the resulted hydrogels display tunable electromechanical behavior with sensitive, stable, and repeatable variations in resistance upon mechanical deformations. Based on the tunable electromechanical behavior, the hydrogels can act as a wearable strain sensor to monitor finger joint motions, breathing, and even the slight blood pulse. This strategy of building synergistic "soft and hard" structures is successful to integrate the decent mechanical properties, reliable self-healing capability, and high sensing sensitivity together for assembling a high-performance, flexible, and wearable strain sensor.

Surface-Assisted Self-Assembly Strategies Leading to Supramolecular Hydrogels.

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Vigier-Carrière, Cécile; Boulmedais, Fouzia; Schaaf, Pierre; Jierry, Loïc

2018-02-05

Localized molecular self-assembly processes leading to the growth of nanostructures exclusively from the surface of a material is one of the great challenges in surface chemistry. In the last decade, several works have been reported on the ability of modified or unmodified surfaces to manage the self-assembly of low-molecular-weight hydrogelators (LMWH) resulting in localized supramolecular hydrogel coatings mainly based on nanofiber architectures. This Minireview highlights all strategies that have emerged recently to initiate and localize LMWH supramolecular hydrogel formation, their related fundamental issues and applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermal gelation and tissue adhesion of biomimetic hydrogels

International Nuclear Information System (INIS)

Burke, Sean A; Ritter-Jones, Marsha; Lee, Bruce P; Messersmith, Phillip B

2007-01-01

Marine and freshwater mussels are notorious foulers of natural and manmade surfaces, secreting specialized protein adhesives for rapid and durable attachment to wet substrates. Given the strong and water-resistant nature of mussel adhesive proteins, significant potential exists for mimicking their adhesive characteristics in bioinspired synthetic polymer materials. An important component of these proteins is L-3,4-dihydroxylphenylalanine (DOPA), an amino acid believed to contribute to mussel glue solidification through oxidation and crosslinking reactions. Synthetic polymers containing DOPA residues have previously been shown to crosslink into hydrogels upon the introduction of oxidizing reagents. Here we introduce a strategy for stimuli responsive gel formation of mussel adhesive protein mimetic polymers. Lipid vesicles with a bilayer melting transition of 37 0 C were designed from a mixture of dipalmitoyl and dimyristoyl phosphatidylcholines and exploited for the release of a sequestered oxidizing reagent upon heating from ambient to physiologic temperature. Colorimetric studies indicated that sodium-periodate-loaded liposomes released their cargo at the phase transition temperature, and when used in conjunction with a DOPA-functionalized poly(ethylene glycol) polymer gave rise to rapid solidification of a crosslinked polymer hydrogel. The tissue adhesive properties of this biomimetic system were determined by in situ thermal gelation of liposome/polymer hydrogel between two porcine dermal tissue surfaces. Bond strength measurements showed that the bond formed by the adhesive hydrogel (mean = 35.1 kPa, SD = 12.5 kPa, n = 11) was several times stronger than a fibrin glue control tested under the same conditions. The results suggest a possible use of this biomimetic strategy for repair of soft tissues

Alginate nanobeads interspersed fibrin network as in situ forming hydrogel for soft tissue engineering.

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Deepthi, S; Jayakumar, R

2018-06-01

Hydrogels are a class of materials that has the property of injectability and in situ gel formation. This property of hydrogels is manipulated in this study to develop a biomimetic bioresorbable injectable system of alginate nanobeads interspersed in fibrin network. Alginate nanobeads developed by calcium cross-linking yielded a size of 200-500 nm. The alginate nanobeads fibrin hydrogel was formed using dual syringe apparatus. Characterization of the in situ injectable hydrogel was done by SEM, FTIR and Rheometer. The developed hydrogel showed mechanical strength of 19 kPa which provides the suitable compliance for soft tissue engineering. Cytocompatibility studies using human umbilical cord blood derived mesenchymal stem cells showed good attachment, proliferation and infiltration within the hydrogel similar to fibrin gel. The developed in situ forming hydrogel could be a suitable delivery carrier of stem cells for soft tissue regeneration.

A bioprintable form of chitosan hydrogel for bone tissue engineering.

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Demirtaş, Tuğrul Tolga; Irmak, Gülseren; Gümüşderelioğlu, Menemşe

2017-07-13

Bioprinting can be defined as 3D patterning of living cells and other biologics by filling and assembling them using a computer-aided layer-by-layer deposition approach to fabricate living tissue and organ analogs for tissue engineering. The presence of cells within the ink to use a 'bio-ink' presents the potential to print 3D structures that can be implanted or printed into damaged/diseased bone tissue to promote highly controlled cell-based regeneration and remineralization of bone. In this study, it was shown for the first time that chitosan solution and its composite with nanostructured bone-like hydroxyapatite (HA) can be mixed with cells and printed successfully. MC3T3-E1 pre-osteoblast cell laden chitosan and chitosan-HA hydrogels, which were printed with the use of an extruder-based bioprinter, were characterized by comparing these hydrogels to alginate and alginate-HA hydrogels. Rheological analysis showed that all groups had viscoelastic properties. It was also shown that under simulated physiological conditions, chitosan and chitosan-HA hydrogels were stable. Also, the viscosity values of the bio-solutions were in an applicable range to be used in 3D bio-printers. Cell viability and proliferation analyses documented that after printing with bio-solutions, cells continued to be viable in all groups. It was observed that cells printed within chitosan-HA composite hydrogel had peak expression levels for early and late stages osteogenic markers. It was concluded that cells within chitosan and chitosan-HA hydrogels had mineralized and differentiated osteogenically after 21 days of culture. It was also discovered that chitosan is superior to alginate, which is the most widely used solution preferred in bioprinting systems, in terms of cell proliferation and differentiation. Thus, applicability and printability of chitosan as a bio-printing solution were clearly demonstrated. Furthermore, it was proven that the presence of bone-like nanostructured HA in

Alginate nanobeads interspersed fibrin network as in situ forming hydrogel for soft tissue engineering

Directory of Open Access Journals (Sweden)

S. Deepthi

2018-06-01

Full Text Available Hydrogels are a class of materials that has the property of injectability and in situ gel formation. This property of hydrogels is manipulated in this study to develop a biomimetic bioresorbable injectable system of alginate nanobeads interspersed in fibrin network. Alginate nanobeads developed by calcium cross-linking yielded a size of 200–500 nm. The alginate nanobeads fibrin hydrogel was formed using dual syringe apparatus. Characterization of the in situ injectable hydrogel was done by SEM, FTIR and Rheometer. The developed hydrogel showed mechanical strength of 19 kPa which provides the suitable compliance for soft tissue engineering. Cytocompatibility studies using human umbilical cord blood derived mesenchymal stem cells showed good attachment, proliferation and infiltration within the hydrogel similar to fibrin gel. The developed in situ forming hydrogel could be a suitable delivery carrier of stem cells for soft tissue regeneration.

Enzymetically regulating the self-healing of protein hydrogels with high healing efficiency.

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Gao, Yuzhou; Luo, Quan; Qiao, Shanpeng; Wang, Liang; Dong, Zeyuan; Xu, Jiayun; Liu, Junqiu

2014-08-25

Enzyme-mediated self-healing of dynamic covalent bond-driven protein hydrogels was realized by the synergy of two enzymes, glucose oxidase (GOX) and catalase (CAT). The reversible covalent attachment of glutaraldehyde to lysine residues of GOX, CAT, and bovine serum albumin (BSA) led to the formation and functionalization of the self-healing protein hydrogel system. The enzyme-mediated protein hydrogels exhibit excellent self-healing properties with 100% recovery. The self-healing process was reversible and effective with an external glucose stimulus at room temperature. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling programmable deformation of self-folding all-polymer structures with temperature-sensitive hydrogels

International Nuclear Information System (INIS)

Guo, Wei; Zhou, Jinxiong; Li, Meie

2013-01-01

Combination of soft active hydrogels with hard passive polymers gives rise to all-polymer composites. The hydrogel is sensitive to external stimuli while the passive polymer is inert. Utilizing the different behaviors of two materials subject to environmental variation, for example temperature, results in self-folding soft machines. We report our efforts to model the programmable deformation of self-folding structures with temperature-sensitive hydrogels. The self-folding structures are realized either by constructing a bilayer structure or by incorporating hydrogels as hinges. The methodology and the results may aid the design, control and fabrication of 3D complex structures from 2D simple configurations through self-assembly. (paper)

Nondestructive evaluation of a new hydrolytically degradable and photo-clickable PEG hydrogel for cartilage tissue engineering.

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Neumann, Alexander J; Quinn, Timothy; Bryant, Stephanie J

2016-07-15

Photopolymerizable and hydrolytically labile poly(ethylene glycol) (PEG) hydrogels formed from photo-clickable reactions were investigated as cell delivery platforms for cartilage tissue engineering (TE). PEG hydrogels were formed from thiol-norbornene PEG macromers whereby the crosslinks contained caprolactone segments with hydrolytically labile ester linkages. Juvenile bovine chondrocytes encapsulated in the hydrogels were cultured for up to four weeks and assessed biochemically and histologically, using standard destructive assays, and for mechanical and ultrasound properties, as nondestructive assays. Bulk degradation of acellular hydrogels was confirmed by a decrease in compressive modulus and an increase in mass swelling ratio over time. Chondrocytes deposited increasing amounts of sulfated glycosaminoglycans and collagens in the hydrogels with time. Spatially, collagen type II and aggrecan were present in the neotissue with formation of a territorial matrix beginning at day 21. Nondestructive measurements revealed an 8-fold increase in compressive modulus from days 7 to 28, which correlated with total collagen content. Ultrasound measurements revealed changes in the constructs over time, which differed from the mechanical properties, and appeared to correlate with ECM structure and organization shown by immunohistochemical analysis. Overall, non-destructive and destructive measurements show that this new hydrolytically degradable PEG hydrogel is promising for cartilage TE. Designing synthetic hydrogels whose degradation matches tissue growth is critical to maintaining mechanical integrity as the hydrogel degrades and new tissue forms, but is challenging due to the nature of the hydrogel crosslinks that inhibit diffusion of tissue matrix molecules. This study details a promising, new, photo-clickable and synthetic hydrogel whose degradation supports cartilaginous tissue matrix growth leading to the formation of a territorial matrix, concomitant with an

Injectable alginate-O-carboxymethyl chitosan/nano fibrin composite hydrogels for adipose tissue engineering.

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Jaikumar, Dhanya; Sajesh, K M; Soumya, S; Nimal, T R; Chennazhi, K P; Nair, Shantikumar V; Jayakumar, R

2015-03-01

Injectable, biodegradable scaffolds are required for soft tissue reconstruction owing to its minimally invasive approach. Such a scaffold can mimic the native extracellular matrix (ECM), provide uniform distribution of cells and overcome limitations like donor site morbidity, volume loss, etc. So, here we report two classes of biocompatible and biodegradable hydrogel blend systems namely, Alginate/O-carboxymethyl chitosan (O-CMC) and Alginate/poly (vinyl alcohol) (PVA) with the inclusion of fibrin nanoparticles in each. The hydrogels were prepared by ionic cross-linking method. The developed hydrogels were compared in terms of its swelling ratio, degradation profile, compressive strength and elastic moduli. From these preliminary findings, it was concluded that Alginate/O-CMC formed a better blend for tissue engineering applications. The potential of the formed hydrogel as an injectable scaffold was revealed by the survival of adipose derived stem cells (ADSCs) on the scaffold by its adhesion, proliferation and differentiation into adipocytes. Cell differentiation studies of fibrin incorporated hydrogel scaffolds showed better differentiation was confirmed by Oil Red O staining technique. These injectable gels have potential in soft tissue regeneration. Copyright © 2014 Elsevier B.V. All rights reserved.

Supramolecular Self-Assembly of a Model Hydrogelator: Characterization of Fiber Formation and Morphology

Directory of Open Access Journals (Sweden)

Yuan Gao

2016-10-01

Full Text Available Hydrogels are of intense recent interest in connection with biomedical applications ranging from 3-D cell cultures and stem cell differentiation to regenerative medicine, controlled drug delivery, and tissue engineering. This prototypical form of soft matter has many emerging material science applications outside the medical field. The physical processes underlying this type of solidification are incompletely understood, and this limits design efforts aimed at optimizing these materials for applications. We address this general problem by applying multiple techniques (e.g., NMR, dynamic light scattering, small angle neutron scattering, rheological measurements to the case of a peptide derivative hydrogelator (molecule 1, NapFFKYp over a broad range of concentration and temperature to characterize both the formation of individual nanofibers and the fiber network. We believe that a better understanding of the hierarchical self-assembly process and control over the final morphology of this kind of material should have broad significance for biological and medicinal applications utilizing hydrogels.

Smart Polymeric Hydrogels for Cartilage Tissue Engineering: A Review on the Chemistry and Biological Functions.

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Eslahi, Niloofar; Abdorahim, Marjan; Simchi, Abdolreza

2016-11-14

Stimuli responsive hydrogels (SRHs) are attractive bioscaffolds for tissue engineering. The structural similarity of SRHs to the extracellular matrix (ECM) of many tissues offers great advantages for a minimally invasive tissue repair. Among various potential applications of SRHs, cartilage regeneration has attracted significant attention. The repair of cartilage damage is challenging in orthopedics owing to its low repair capacity. Recent advances include development of injectable hydrogels to minimize invasive surgery with nanostructured features and rapid stimuli-responsive characteristics. Nanostructured SRHs with more structural similarity to natural ECM up-regulate cell-material interactions for faster tissue repair and more controlled stimuli-response to environmental changes. This review highlights most recent advances in the development of nanostructured or smart hydrogels for cartilage tissue engineering. Different types of stimuli-responsive hydrogels are introduced and their fabrication processes through physicochemical procedures are reported. The applications and characteristics of natural and synthetic polymers used in SRHs are also reviewed with an outline on clinical considerations and challenges.

Cartilaginous extracellular matrix-modified chitosan hydrogels for cartilage tissue engineering.

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Choi, Bogyu; Kim, Soyon; Lin, Brian; Wu, Benjamin M; Lee, Min

2014-11-26

Cartilaginous extracellular matrix (ECM) components such as type-II collagen (Col II) and chondroitin sulfate (CS) play a crucial role in chondrogenesis. However, direct clinical use of natural Col II or CS as scaffolds for cartilage tissue engineering is limited by their instability and rapid enzymatic degradation. Here, we investigate the incorporation of Col II and CS into injectable chitosan hydrogels designed to gel upon initiation by exposure to visible blue light (VBL) in the presence of riboflavin. Unmodified chitosan hydrogel supported proliferation and deposition of cartilaginous ECM by encapsulated chondrocytes and mesenchymal stem cells. The incorporation of native Col II or CS into chitosan hydrogels further increased chondrogenesis. The incorporation of Col II, in particular, was found to be responsible for the enhanced cellular condensation and chondrogenesis observed in modified hydrogels. This was mediated by integrin α10 binding to Col II, increasing cell-matrix adhesion. These findings demonstrate the potential of cartilage ECM-modified chitosan hydrogels as biomaterials to promote cartilage regeneration.

Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

Science.gov (United States)

Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

2013-10-01

Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

Fabrication and evaluation of thermosensitive chitosan/collagen/α, β-glycerophosphate hydrogels for tissue regeneration.

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Dang, Qifeng; Liu, Kai; Zhang, Zhenzhen; Liu, Chengsheng; Liu, Xi; Xin, Ying; Cheng, Xiaoyu; Xu, Tao; Cha, Dongsu; Fan, Bing

2017-07-01

Thermosensitive hydrogels whose physiological properties are similar to extracellular matrix have been extensively used for tissue regeneration. Polysaccharides and proteins, as biocompatible substrates similar to bio-macromolecules that could be recognized by human body, are two preferred polymers for fabrication of such hydrogels. A series of novel thermosensitive hydrogels (CS-ASC-HGs) containing chitosan (CS) and acid-soluble collagen (ASC) were thus prepared, in the presence of α, β-glycerophosphate, to mimic extracellular microenvironment for tissue regeneration. Rheological measurements demonstrated excellent thermosensitivity. FT-IR and SEM indicated CS-ASC-HGs possessed 3D porous architectures with fibrous ASC, and the molecular structure of ASC was well-maintained in hydrogels. Hemolysis, acute toxicity, and cytotoxicity tests suggested CS-ASC-HGs were of good biocompatibility. CS-ASC-HGs were able to support the survival and proliferation of L929 cells encapsulated in them. Moreover, CS-ASC-HGs had better pH stability and biocompatibility than pure CS hydrogel. These results suggested that CS-ASC-HGs could serve as promising scaffolds for tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

International Nuclear Information System (INIS)

Wei, Y T; Tian, W M; Yu, X; Cui, F Z; Hou, S P; Xu, Q Y; Lee, In-Seop

2007-01-01

A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue

Injectable dextran hydrogels fabricated by metal-free click chemistry for cartilage tissue engineering.

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Wang, Xiaoyu; Li, Zihan; Shi, Ting; Zhao, Peng; An, Kangkang; Lin, Chao; Liu, Hongwei

2017-04-01

Injectable dextran-based hydrogels were prepared for the first time by bioorthogonal click chemistry for cartilage tissue engineering. Click-crosslinked injectable hydrogels based on cyto-compatible dextran (Mw=10kDa) were successfully fabricated under physiological conditions by metal-free alkyne-azide cycloaddition (click) reaction between azadibenzocyclooctyne-modified dextran (Dex-ADIBO) and azide-modified dextran (Dex-N 3 ). Gelation time of these dextran hydrogels could be regulated in the range of approximately 1.1 to 10.2min, depending on the polymer concentrations (5% or 10%) and ADIBO substitution degree (DS, 5 or 10) of Dex-ADIBO. Rheological analysis indicated that the dextran hydrogels were elastic and had storage moduli from 2.1 to 6.0kPa with increasing DS of ADIBO from 5 to 10. The in vitro tests revealed that the dextran hydrogel crosslinked from Dex-ADIBO DS 10 and Dex-N 3 DS 10 at a polymer concentration of 10% could support high viability of individual rabbit chondrocytes and the chondrocyte spheroids encapsulated in the hydrogel over 21days. Individual chondrocytes and chondrocyte spheroids in the hydrogel could produce cartilage matrices such as collagen and glycosaminoglycans. However, the chondrocyte spheroids produced a higher content of matrices than individual chondrocytes. This study indicates that metal-free click chemistry is effective to produce injectable dextran hydrogels for cartilage tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Resilin-like polypeptide-poly(ethylene gylcol) hybrid hydrogels for mechanically-demanding tissue engineering applications

Science.gov (United States)

McGann, Christopher Leland

Technological progress in the life sciences and engineering has combined with important insights in the fields of biology and material science to make possible the development of biological substitutes which aim to restore function to damaged tissue. Numerous biomimetic hydrogels have been developed with the purpose of harnessing the regenerative capacity of cells and tissue through the rational deployment of biological signals. Aided by recombinant DNA technology and protein engineering methods, a new class of hydrogel precursor, the biosynthetic protein polymer, has demonstrated great promise towards the development of highly functional tissue engineering materials. In particular, protein polymers based upon resilin, a natural protein elastomer, have demonstrated outstanding mechanical properties that would have great value in soft tissue applications. This dissertation introduces hybrid hydrogels composed of recombinant resilin-like polypeptides (RLPs) cross-linked with multi-arm PEG macromers. Two different chemical strategies were employed to form RLP-PEG hydrogels: one utilized a Michael-type addition reaction between the thiols of cysteine residues present within the RLP and vinyl sulfone moieties functionalized on a multi-arm PEG macromer; the second system cross-links a norbornene-functionalized RLP with a thiol-functionalized multi-arm PEG macromer via a photoinitiated thiol-ene step polymerization. Oscillatory rheology and tensile testing confirmed the formation of elastic, resilient hydrogels in the RLP-PEG system cross-linked via Michael-type addition. These hydrogels supported the encapsulation and culture of both human aortic adventitial fibroblasts and human mesenchymal stem cells. Additionally, these RLP-PEG hydrogels exhibited phase separation behavior during cross-linking that led to the formation of a heterogeneous microstructure. Degradation could be triggered through incubation with matrix metalloproteinase. Photocross-linking was conferred to

Temporally controlled growth factor delivery from a self-assembling peptide hydrogel and electrospun nanofibre composite scaffold.

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Bruggeman, Kiara F; Wang, Yi; Maclean, Francesca L; Parish, Clare L; Williams, Richard J; Nisbet, David R

2017-09-21

Tissue-specific self-assembling peptide (SAP) hydrogels designed based on biologically relevant peptide sequences have great potential in regenerative medicine. These materials spontaneously form 3D networks of physically assembled nanofibres utilising non-covalent interactions. The nanofibrous structure of SAPs is often compared to that of electrospun scaffolds. These electrospun nanofibers are produced as sheets that can be engineered from a variety of polymers that can be chemically modified to incorporate many molecules including drugs and growth factors. However, their macroscale morphology limits them to wrapping and bandaging applications. Here, for the first time, we combine the benefits of these systems to describe a two-component composite scaffold from these biomaterials, with the design goal of providing a hydrogel scaffold that presents 3D structures, and also has temporal control over drug delivery. Short fibres, cut from electrospun scaffolds, were mixed with our tissue-specific SAP hydrogel to provide a range of nanofibre sizes found in the extracellular matrix (10-300 nm in diameter). The composite material maintained the shear-thinning and void-filling properties of SAP hydrogels that have previously been shown to be effective for minimally invasive material injection, cell delivery and subsequent in vivo integration. Both scaffold components were separately loaded with growth factors, important signaling molecules in tissue regeneration whose rapid degradation limits their clinical efficacy. The two biomaterials provided sequential growth factor delivery profiles: the SAP hydrogel provided a burst release, with the release rate decreasing over 12 hours, while the electrospun nanofibres provided a more constant, sustained delivery. Importantly, this second release commenced 6 days later. The design rules established here to provide temporally distinct release profiles can enable researchers to target specific stages in regeneration, such as the

Injectable self-gelling composites for bone tissue engineering based on gellan gum hydrogel enriched with different bioglasses

Czech Academy of Sciences Publication Activity Database

Douglas, T.E.L.; Piwowarczyk, W.; Pamula, E.; Lišková, Jana; Schaubroeck, D.; Leeuwenburgh, S. C. G.; Brackman, G.; Balcaen, L.; Detsch, R.; Declercq, H.; Cholewa-Kowalska, K.; Dokupil, A.; Cuijpers, V.M.J.I.; Vanhaecke, F.; Cornelissen, R.; Coenye, T.; Boccaccini, A. R.; Dubruel, P.

2014-01-01

Roč. 9, č. 4 (2014), 045014 ISSN 1748-6041 R&D Projects: GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : hydrogel * bone tissue engineering * gellan gum * bioglass Subject RIV: EI - Biotechnology ; Bionics Impact factor: 3.697, year: 2014

The self-crosslinking smart hyaluronic acid hydrogels as injectable three-dimensional scaffolds for cells culture.

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Bian, Shaoquan; He, Mengmeng; Sui, Junhui; Cai, Hanxu; Sun, Yong; Liang, Jie; Fan, Yujiang; Zhang, Xingdong

2016-04-01

Although the disulfide bond crosslinked hyaluronic acid hydrogels have been reported by many research groups, the major researches were focused on effectively forming hydrogels. However, few researchers paid attention to the potential significance of controlling the hydrogel formation and degradation, improving biocompatibility, reducing the toxicity of exogenous and providing convenience to the clinical operations later on. In this research, the novel controllable self-crosslinking smart hydrogels with in-situ gelation property was prepared by a single component, the thiolated hyaluronic acid derivative (HA-SH), and applied as a three-dimensional scaffold to mimic native extracellular matrix (ECM) for the culture of fibroblasts cells (L929) and chondrocytes. A series of HA-SH hydrogels were prepared depending on different degrees of thiol substitution (ranging from 10 to 60%) and molecule weights of HA (0.1, 0.3 and 1.0 MDa). The gelation time, swelling property and smart degradation behavior of HA-SH hydrogel were evaluated. The results showed that the gelation and degradation time of hydrogels could be controlled by adjusting the component of HA-SH polymers. The storage modulus of HA-SH hydrogels obtained by dynamic modulus analysis (DMA) could be up to 44.6 kPa. In addition, HA-SH hydrogels were investigated as a three-dimensional scaffold for the culture of fibroblasts cells (L929) and chondrocytes cells in vitro and as an injectable hydrogel for delivering chondrocytes cells in vivo. These results illustrated that HA-SH hydrogels with controllable gelation process, intelligent degradation behavior, excellent biocompatibility and convenient operational characteristics supplied potential clinical application capacity for tissue engineering and regenerative medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

Experimental investigation and theoretical modelling of the nonlinear acoustical behaviour of a liver tissue and comparison with a tissue mimicking hydrogel.

Science.gov (United States)

Casciaro, Sergio; Demitri, Christian; Conversano, Francesco; Casciaro, Ernesto; Distante, Alessandro

2008-02-01

Native harmonics generated by nonlinear distortion of ultrasound during propagation in a medium may cause misinterpretations in spectral analysis when studying contrast agents. The aim of this paper is to quantitatively evaluate nonlinear propagation effects of diagnostic ultrasound pulses in biological tissues and to assess whether a cellulose-based hydrogel can be a suitable material for tissue mimicking purposes. Hydrogel and pig liver tissue samples of various thicknesses were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values (range 0.06-0.60). Second harmonic and first harmonic amplitudes were extracted from spectra of received signals and their ratio was then used to compare hydrogel and liver behaviours. Resulting trends are very similar for sample thicknesses up to 8 cm and highlight a significant increase in nonlinearity for MI > 0.3, for both liver and hydrogel. A numerical procedure was also employed to calculate pressure distribution along the beam axis: these theoretical results showed a very good agreement with experimental data in the low pressure range, though failed in predicting the MI threshold. In conclusion, the hydrogel resulted to be a suitable material for manufacturing tissue mimicking phantoms, in particular to study contrast agent behaviour with a "low power approach".

Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering

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Baei, Payam [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Jalili-Firoozinezhad, Sasan [Department of Biomedicine and Surgery, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel (Switzerland); Department of Bioengineeringand IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa (Portugal); Rajabi-Zeleti, Sareh [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad [Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Baharvand, Hossein, E-mail: Baharvand@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Developmental Biology, University of Science and Culture, ACECR, Tehran (Iran, Islamic Republic of); Aghdami, Nasser, E-mail: Nasser.Aghdami@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of)

2016-06-01

Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m{sup −1} was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering

International Nuclear Information System (INIS)

Baei, Payam; Jalili-Firoozinezhad, Sasan; Rajabi-Zeleti, Sareh; Tafazzoli-Shadpour, Mohammad; Baharvand, Hossein; Aghdami, Nasser

2016-01-01

Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m"−"1 was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

Full experimental modelling of a liver tissue mimicking phantom for medical ultrasound studies employing different hydrogels.

Science.gov (United States)

Casciaro, Sergio; Conversano, Francesco; Musio, Stefano; Casciaro, Ernesto; Demitri, Christian; Sannino, Alessandro

2009-04-01

Tissue mimicking phantoms have been widely reported to be an important tool for development, optimisation and performance testing of ultrasound-based diagnostic techniques. In particular, modern applications of tissue mimicking phantoms often include characterisation of the nonlinear behaviour of experimental ultrasound contrast agents. In such cases, the tissue-mimicking materials should be chosen not only based on the values of their density, speed of sound and attenuation coefficient, but also considering their effect on the appearance of "native harmonics" due to nonlinear distortion of ultrasound signal during propagation. In a previous paper it was demonstrated that a cellulose-based hydrogel is suitable to simulate nonlinear acoustical behaviour of liver tissue for thicknesses up to 8 cm. In this paper we present the experimental characterisation of the nonlinear acoustical behaviour of a different polyethylene glycol diacrylate (PEGDA)-based hydrogel, in order to assess whether and how it can improve the performances and overcome some limitations of the cellulose-based hydrogel as liver tissue-mimicking material. Samples of pig liver tissue, cellulose-based hydrogel and PEGDA-based hydrogel were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values. Second harmonic and first harmonic amplitudes were extracted from the spectra of received signals and their difference was then used to compare sample behaviours. Obtained results show how a new more accurate and combined experimental model of linear and nonlinear acoustical behaviour of liver tissue is feasible. In fact, a further confirmation of the cellulose-based hydrogel effectiveness to precisely simulate the liver tissue for penetration depths up to 8 cm was provided, and it was also shown that the employment of the PEGDA-based hydrogel can extend the range of useful tissue-mimicking material thicknesses up to 11 cm, moreover allowing a

Biomimetic hydrogel loaded with silk and l-proline for tissue engineering and wound healing applications.

Science.gov (United States)

Thangavel, Ponrasu; Ramachandran, Balaji; Kannan, Ramya; Muthuvijayan, Vignesh

2017-08-01

The aim of this article was to develop silk protein (SF) and l-proline (LP) loaded chitosan-(CS) based hydrogels via physical cross linking for tissue engineering and wound healing applications. Silk fibroin, a biodegradable and biocompatible protein, and l-proline, an important imino acid that is required for collagen synthesis, were added to chitosan to improve the wound healing properties of the hydrogel. Characterization of these hydrogels revealed that CS/SF/LP hydrogels were blended properly and LP incorporated hydrogels showed excellent thermal stability and good surface morphology. Swelling study showed the water holding efficiency of the hydrogels to provide enough moisture at the wound surface. In vitro biodegradation results demonstrated that the hydrogels had good degradation rate in PBS with lysozyme. LP loaded hydrogels showed approximately a twofold increase in antioxidant activity. In vitro cytocompatibility studies using NIH 3T3 L1 cells showed increased cell viability (p Cell adhesion on SF and LP hydrogels were observed using SEM and compared to CS hydrogel. LP incorporation showed 74-78% of wound closure compared to 35% for CS/SF and 3% for CS hydrogels at 48 h. These results suggest that incorporation of LP can significantly accelerate wound healing process compared to pure CS and SF-loaded CS hydrogels. Hence, CS/LP hydrogels could be a potential wound dressing material for the enhanced wound tissue regeneration and repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1401-1408, 2017. © 2016 Wiley Periodicals, Inc.

Inflation without self-reproduction in F( R) gravity

Science.gov (United States)

Nojiri, Shin'ichi; Odintsov, Sergei D.

2015-05-01

We investigate inflation in frames of two classes of F( R) gravity and check its consistency with Planck data. It is shown that F( R) inflation without self-reproduction may be constructed in close analogy with the corresponding scalar example proposed by Mukhanov for the resolution of the problems of multiverse, predictability and initial conditions.

Composite hydrogel of chitosan-poly(hydroxybutyrate-co-valerate) with chondroitin sulfate nanoparticles for nucleus pulposus tissue engineering.

Science.gov (United States)

Nair, Manitha B; Baranwal, Gaurav; Vijayan, Prajuna; Keyan, Kripa S; Jayakumar, R

2015-12-01

Intervertebral disc degeneration, occurring mainly in nucleus pulposus (NP), is a leading cause of low back pain. In seeking to mitigate this condition, investigators in the field of NP tissue engineering have increasingly studied the use of hydrogels. However, these hydrogels should possess appropriate mechanical strength and swelling pressure, and concurrently support the proliferation of chondrocyte-like cells. The objective of this study was to develop and validate a composite hydrogel for NP tissue engineering, made of chitosan-poly(hydroxybutyrate-co-valerate) (CP) with chondroitin sulfate (CS) nanoparticles, without using a cross linker. The water uptake ability, as well as the viscoelastic properties of this composite hydrogel, was similar to native tissue, as reflected in the complex shear modulus and stress relaxation values. The hydrogel could withstand varying stress corresponding to daily activities like lying down (0.01 MPa), sitting (0.5 MPa) and standing (1.0 MPa) under dynamic conditions. The hydrogels were stable in PBS for 2 weeks and its stiffness, elastic and viscous modulus did not alter significantly during this period. Both CP and CP-CS hydrogels could assist the viability and adhesion of adipose derived rat mesenchymal stem cells (ADMSCs). The viability and chondrogenic differentiation of MSCs was significantly enhanced in presence of CS nanoparticles. Thus, CS nanoparticles-incorporated chitosan-PHBV hydrogels offer great potential for NP tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

Dynamic transformation of self-assembled structures using anisotropic magnetized hydrogel microparticles

Science.gov (United States)

Yoshida, Satoru; Takinoue, Masahiro; Iwase, Eiji; Onoe, Hiroaki

2016-08-01

This paper describes a system through which the self-assembly of anisotropic hydrogel microparticles is achieved, which also enables dynamic transformation of the assembled structures. Using a centrifuge-based microfluidic device, anisotropic hydrogel microparticles encapsulating superparamagnetic materials on one side are fabricated, which respond to a magnetic field. We successfully achieve dynamic assembly using these hydrogel microparticles and realize three different self-assembled structures (single and double pearl chain structures, and close-packed structures), which can be transformed to other structures dynamically via tuning of the precessional magnetic field. We believe that the developed system has potential application as an effective platform for a dynamic cell manipulation and cultivation system, in biomimetic autonomous microrobot organization, and that it can facilitate further understanding of the self-organization and complex systems observed in nature.

Enzymatically crosslinked silk-hyaluronic acid hydrogels.

Science.gov (United States)

Raia, Nicole R; Partlow, Benjamin P; McGill, Meghan; Kimmerling, Erica Palma; Ghezzi, Chiara E; Kaplan, David L

2017-07-01

In this study, silk fibroin and hyaluronic acid (HA) were enzymatically crosslinked to form biocompatible composite hydrogels with tunable mechanical properties similar to that of native tissues. The formation of di-tyrosine crosslinks between silk fibroin proteins via horseradish peroxidase has resulted in a highly elastic hydrogel but exhibits time-dependent stiffening related to silk self-assembly and crystallization. Utilizing the same method of crosslinking, tyramine-substituted HA forms hydrophilic and bioactive hydrogels that tend to have limited mechanics and degrade rapidly. To address the limitations of these singular component scaffolds, HA was covalently crosslinked with silk, forming a composite hydrogel that exhibited both mechanical integrity and hydrophilicity. The composite hydrogels were assessed using unconfined compression and infrared spectroscopy to reveal of the physical properties over time in relation to polymer concentration. In addition, the hydrogels were characterized by enzymatic degradation and for cytotoxicity. Results showed that increasing HA concentration, decreased gelation time, increased degradation rate, and reduced changes that were observed over time in mechanics, water retention, and crystallization. These hydrogel composites provide a biologically relevant system with controllable temporal stiffening and elasticity, thus offering enhanced tunable scaffolds for short or long term applications in tissue engineering. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biosynthetic hydrogels--studies on chemical and physical characteristics on long-term cellular response for tissue engineering.

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Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2014-07-01

Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate-poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering. © 2013 Wiley Periodicals, Inc.

Self-assembling electroactive hydrogels for flexible display technology

Energy Technology Data Exchange (ETDEWEB)

Jones, Scott L; Wong, Kok Hou; Ladouceur, Francois [School of Electrical Engineering and Telecommunications, University of NSW, Sydney, NSW, 2052 (Australia); Thordarson, Pall, E-mail: f.ladouceur@unsw.edu.a [School of Chemistry, University of NSW, Sydney, NSW, 2052 (Australia)

2010-12-15

We have assessed the potential of self-assembling hydrogels for use in conformal displays. The self-assembling process can be used to alter the transparency of the material to all visible light due to scattering by fibres. The reversible transition is shown to be of low energy by differential scanning calorimetry. For use in technology it is imperative that this transition is controlled electrically. We have thus synthesized novel self-assembling hydrogelator molecules which contain an electroactive group. The well-known redox couple of anthraquinone/anthrahydroquinone has been used as the hydrophobic component for a series of small molecule gelators. They are further functionalized with peptide combinations of L-phenylalanine and glycine to provide the hydrophilic group to complete 'head-tail' models of self-assembling gels. The gelation and electroactive characteristics of the series were assessed. Cyclic voltammetry shows the reversible redox cycle to be only superficially altered by functionalization. Additionally, spectroelectrochemical measurements show a reversible transparency and colour change induced by the redox process.

Self-assembling electroactive hydrogels for flexible display technology

International Nuclear Information System (INIS)

Jones, Scott L; Wong, Kok Hou; Ladouceur, Francois; Thordarson, Pall

2010-01-01

We have assessed the potential of self-assembling hydrogels for use in conformal displays. The self-assembling process can be used to alter the transparency of the material to all visible light due to scattering by fibres. The reversible transition is shown to be of low energy by differential scanning calorimetry. For use in technology it is imperative that this transition is controlled electrically. We have thus synthesized novel self-assembling hydrogelator molecules which contain an electroactive group. The well-known redox couple of anthraquinone/anthrahydroquinone has been used as the hydrophobic component for a series of small molecule gelators. They are further functionalized with peptide combinations of L-phenylalanine and glycine to provide the hydrophilic group to complete 'head-tail' models of self-assembling gels. The gelation and electroactive characteristics of the series were assessed. Cyclic voltammetry shows the reversible redox cycle to be only superficially altered by functionalization. Additionally, spectroelectrochemical measurements show a reversible transparency and colour change induced by the redox process.

Self-Healing Supramolecular Hydrogels Based on Reversible Physical Interactions

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Satu Strandman

2016-04-01

Full Text Available Dynamic and reversible polymer networks capable of self-healing, i.e., restoring their mechanical properties after deformation and failure, are gaining increasing research interest, as there is a continuous need towards extending the lifetime and improving the safety and performance of materials particularly in biomedical applications. Hydrogels are versatile materials that may allow self-healing through a variety of covalent and non-covalent bonding strategies. The structural recovery of physical gels has long been a topic of interest in soft materials physics and various supramolecular interactions can induce this kind of recovery. This review highlights the non-covalent strategies of building self-repairing hydrogels and the characterization of their mechanical properties. Potential applications and future prospects of these materials are also discussed.

UV-crosslinkable photoreactive self-adhesive hydrogels based on acrylics

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Czech Zbigniew

2016-06-01

Full Text Available Hydrogels are a unique class of macromolecular networks that can hold a large fraction of an aqueous solvent within their structure. They are suitable for biomedical area including controlled drug delivery and for technical applications as self-adhesive materials for bonding of wet surfaces. This paper describes photoreactive self-adhesive hydrogels based on acrylics crosslinked using UV radiation. They are prepared in ethyl acetate through radical polymerization of monomers mixture containing 2-ethylhexyl acrylate (2-EHA, butyl acrylate (BA, acrylic acid (AA and copolymerizable photoinitiator 4-acryloyloxy benzophenone (ABP at presence of radical starter 2.2’-azobis-diisobutyronitrile AIBN. The synthesized acrylic copolymers were determined by viscosity and GPC analysis and later modified using ethoxylated amines. 4-acryloyloxy benzophenone (ABP was used as crosslinking monomer. After UV crosslinking the properties of these novel synthesized hydrogels, such as tack, peel adhesion, shears strength, elongation and water adsorption were also studied.

pH-responsive self-healing injectable hydrogel based on N-carboxyethyl chitosan for hepatocellular carcinoma therapy.

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Qu, Jin; Zhao, Xin; Ma, Peter X; Guo, Baolin

2017-08-01

Injectable hydrogels with pH-responsiveness and self-healing ability have great potential for anti-cancer drug delivery. Herein, we developed a series of polysaccharide-based self-healing hydrogels with pH-sensitivity as drug delivery vehicles for hepatocellular carcinoma therapy. The hydrogels were prepared by using N-carboxyethyl chitosan (CEC) synthesized via Michael reaction in aqueous solution and dibenzaldehyde-terminated poly(ethylene glycol) (PEGDA). Doxorubicin (Dox), as a model of water-soluble small molecule anti-cancer drug was encapsulated into the hydrogel in situ. Self-healing behavior of the hydrogels was investigated at microscopic and macroscopic levels, and the hydrogels showed rapid self-healing performance without any external stimulus owing to the dynamic covalent Schiff-base linkage between amine groups from CEC and benzaldehyde groups from PEGDA. The chemical structures, rheological property, in vitro gel degradation, morphology, gelation time and in vitro Dox release behavior from the hydrogels were characterized. Injectability was verified by in vitro injection and in vivo subcutaneous injection in a rat. pH-responsive behavior was verified by in vitro Dox release from hydrogels in PBS solutions with different pH values. Furthermore, the activity of Dox released from hydrogel matrix was evaluated by employing human hepatocellular liver carcinoma (HepG2). Cytotoxicity test of the hydrogels using L929 cells confirmed their good cytocompatibility. Together, these pH-responsive self-healing injectable hydrogels are excellent candidates as drug delivery vehicles for liver cancer treatment. STATEMENT OF SIGNIFICANCE: pH-responsive drug delivery system could release drug efficiently in targeted acid environment and minimalize the amount of drug release in normal physiological environment. pH-sensitive injectable hydrogels as smart anti-cancer drug delivery carriers show great potential application for cancer therapy. The hydrogels with self

Recent Developments in Thiolated Polymeric Hydrogels for Tissue Engineering Applications.

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Gajendiran, Mani; Rhee, Jae-Sung; Kim, Kyobum

2018-02-01

This review focuses on the recent strategy in the preparation of thiolated polymers and fabrication of their hydrogel matrices. The mechanism involved in the synthesis of thiolated polymers and fabrication of thiolated polymer hydrogels is exemplified with suitable schematic representations reported in the recent literature. The 2-iminothiolane namely "Traut's reagent" has been widely used for effectively thiolating the natural polymers such as collagen and gelatin, which contain free amino group in their backbone. The free carboxylic acid group containing polymers such as hyaluronic acid and heparin have been thiolated by using the bifunctional molecules such as cysteamine and L-cysteine via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling reaction. The degree of thiolation in the polymer chain has been widely determined by using Ellman's assay method. The thiolated polymer hydrogels are prepared by disulfide bond formation (or) thiol-ene reaction (or) Michael-type addition reaction. The thiolated polymers such as thiolated gelatin are reacted with polyethylene glycol diacrylate for obtaining interpenetrating polymer network hydrogel scaffolds. Several in vitro cell culture experiments indicate that the developed thiolated polymer hydrogels exhibited biocompatibility and cellular mimicking properties. The developed hydrogel scaffolds efficiently support proliferation and differentiation of various cell types. In the present review article, the thiol-functionalized protein-based biopolymers, carbohydrate-based polymers, and some synthetic polymers have been covered with recently published research articles. In addition, the usage of new thiolated nanomaterials as a crosslinking agent for the preparation of three-dimensional tissue-engineered hydrogels is highlighted.

Preparation and characterization of self-assembly hydrogels with exfoliated montmorillonite nanosheets and chitosan

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Wang, Wei; Zhao, Yunliang; Yi, Hao; Chen, Tianxing; Kang, Shichang; Li, Hongqiang; Song, Shaoxian

2018-01-01

Novel montmorillonite-nanosheet/chitosan (MMTNS/CS) hydrogels fabricated via the self-assembly of exfoliated MMTNS and CS chains were investigated. The exfoliation of MMTNS, self-assembly mechanism and structure of MMTNS/CS hydrogels were characterized by an atomic force microscope, scanning electron microscope, transmission electron microscope, Fourier transform infrared spectroscope, energy-dispersive x-ray spectroscope and Brunauer-Emmett-Teller analyzer, respectively. The results indicated that MMT could be easily exfoliated to nanosheets with a thickness of 1 ˜ 5 nm in aqueous solution by an ultrasonic base upon interlayer hydration. The formation mechanism of the self-assembly hydrogels was due to the hydrogen bond (-OH ··· +NH3-) and electrostatic interaction between the MMTNS and CS. The MMTNSs were connected consecutively by CS in-plane to form a huge slice. The porous structure of the hydrogels was controllable by adjusting the MMTNS/CS mass ratio. The hydrogels could be used as adsorbents for sewage treatments, carriers for drugs, microorganisms and catalyzers due to their controllable porous structure and tremendous specific surface area which were derived from the completely exfoliated MMTNS.

Conformation-Directed Formation of Self-Healing Diblock Copolypeptide Hydrogels via Polyion Complexation.

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Sun, Yintao; Wollenberg, Alexander L; O'Shea, Timothy Mark; Cui, Yanxiang; Zhou, Z Hong; Sofroniew, Michael V; Deming, Timothy J

2017-10-25

Synthetic diblock copolypeptides were designed to incorporate oppositely charged ionic segments that form β-sheet-structured hydrogel assemblies via polyion complexation when mixed in aqueous media. The observed chain conformation directed assembly was found to be required for efficient hydrogel formation and provided distinct and useful properties to these hydrogels, including self-healing after deformation, microporous architecture, and stability against dilution in aqueous media. While many promising self-assembled materials have been prepared using disordered or liquid coacervate polyion complex (PIC) assemblies, the use of ordered chain conformations in PIC assemblies to direct formation of new supramolecular morphologies is unprecedented. The promising attributes and unique features of the β-sheet-structured PIC hydrogels described here highlight the potential of harnessing conformational order derived from PIC assembly to create new supramolecular materials.

Preparation and Properties of 3D Printed Alginate–Chitosan Polyion Complex Hydrogels for Tissue Engineering

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Qiongqiong Liu

2018-06-01

Full Text Available Three-dimensional (3D printing holds great potential for preparing sophisticated scaffolds for tissue engineering. As a result of the shear thinning properties of an alginate solution, it is often used as 3D printing ink. However, it is difficult to prepare scaffolds with complexity structure and high fidelity, because the alginate solution has a low viscosity and alginate hydrogels prepared with Ca2+ crosslinking are mechanically weak. In this work, chitosan powders were dispersed and swelled in an alginate solution, which could effectively improve the viscosity of an alginate solution by 1.5–4 times. With the increase of chitosan content, the shape fidelity of the 3D printed alginate–chitosan polyion complex (AlCh PIC hydrogels were improved. Scanning electron microscope (SEM photographs showed that the lateral pore structure of 3D printed hydrogels was becoming more obvious. As a result of the increased reaction ion pairs in comparison to the alginate hydrogels that were prepared with Ca2+ crosslinking, AlCh PIC hydrogels were mechanically strong, and the compression stress of hydrogels at a 90% strain could achieve 1.4 MPa without breaking. In addition, human adipose derived stem cells (hASCs adhered to the 3D printed AlCh PIC hydrogels and proliferated with time, which indicated that the obtained hydrogels were biocompatible and could potentially be used as scaffolds for tissue engineering.

In Situ Forming, Cytocompatible, and Self-Recoverable Tough Hydrogels Based on Dual Ionic and Click Cross-Linked Alginate.

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Ghanian, Mohammad Hossein; Mirzadeh, Hamid; Baharvand, Hossein

2018-05-14

A dual cross-linking strategy was developed to answer the urgent need for fatigue-resistant, cytocompatible, and in situ forming tough hydrogels. Clickable, yet calcium-binding derivatives of alginate were synthesized by partial substitution of its carboxyl functionalities with furan, which could come into Diels-Alder click reaction with maleimide end groups of a four arm poly(ethylene glycol) cross-linker. Tuning the cooperative viscoelastic action of transient ionic and permanent click cross-links within the single network of alginate provided a soft tough hydrogel with a set of interesting features: (i) immediate self-recovery under cyclic loading, (ii) highly efficient and autonomous self-healing upon fracture, (iii) in situ forming ability for molding and minimally invasive injection, (iv) capability for viable cell encapsulation, and (v) reactivity for on-demand biomolecule conjugation. The facile strategy is applicable to a wide range of natural and synthetic polymers by introducing the calcium binding and click reacting functional groups and can broaden the use of tough hydrogels in load-bearing, cell-laden applications such as soft tissue engineering and bioactuators.

Photocrosslinked PLA-PEO-PLA Hydrogels from Self-Assembled Physical Networks: Mechanical Properties and Influence of Assumed Constitutive Relationships

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Sanabria-DeLong, Naomi; Crosby, Alfred J.; Tew, Gregory N.

2014-01-01

Poly(lactide) – block – poly(ethylene oxide) – block – poly(lactide) [PLA-PEO-PLA] triblock copolymers are known to form physical hydrogels in water, due to the polymer's amphiphilicity. Their mechanical properties, biocompatibility, and biodegradability have made them attractive for use as soft tissue scaffolds. However, the network junction points are not covalently crosslinked and in a highly aqueous environment these hydrogels adsorb more water, transform from gel to sol, and lose the designed mechanical properties. In this report, a hydrogel was formed by using a novel two step approach. In the first step end-functionalized PLA-PEOPLA triblock was self-assembled into a physical hydrogel through hydrophobic micelle network junctions, and then, in the second step, this self-assembled physical network structure was locked into place by photocrosslinking the terminal acrylate groups. In contrast to physical hydrogels, the photocrosslinked gels remained intact in phosphate buffered solution at body temperature. The swelling, degradation, and mechanical properties were characterized and demonstrated extended degradation time (~ 65 days), exponential decrease in modulus with degradation time, and tunable shear modulus (1.6 – 133 kPa) by varying concentration. We also discuss the various constitutive relationships (Hookean, Neo-Hookean, and Mooney-Rivlin) that can be used to describe the stress-strain behavior of these hydrogels. The chosen model and assumptions used for data fitting influences the obtained modulus values by as much as a factor of 3.5, demonstrating the importance of clearly stating one's data fitting parameters so that accurate comparisons can be made within the literature. PMID:18817440

Mechanically Reinforced Catechol-Containing Hydrogels with Improved Tissue Gluing Performance

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Jun Feng

2017-11-01

Full Text Available In situ forming hydrogels with catechol groups as tissue reactive functionalities are interesting bioinspired materials for tissue adhesion. Poly(ethylene glycol (PEG–catechol tissue glues have been intensively investigated for this purpose. Different cross-linking mechanisms (oxidative or metal complexation and cross-linking conditions (pH, oxidant concentration, etc. have been studied in order to optimize the curing kinetics and final cross-linking degree of the system. However, reported systems still show limited mechanical stability, as expected from a PEG network, and this fact limits their potential application to load bearing tissues. Here, we describe mechanically reinforced PEG–catechol adhesives showing excellent and tunable cohesive properties and adhesive performance to tissue in the presence of blood. We used collagen/PEG mixtures, eventually filled with hydroxyapatite nanoparticles. The composite hydrogels show far better mechanical performance than the individual components. It is noteworthy that the adhesion strength measured on skin covered with blood was >40 kPa, largely surpassing (>6 fold the performance of cyanoacrylate, fibrin, and PEG–catechol systems. Moreover, the mechanical and interfacial properties could be easily tuned by slight changes in the composition of the glue to adapt them to the particular properties of the tissue. The reported adhesive compositions can tune and improve cohesive and adhesive properties of PEG–catechol-based tissue glues for load-bearing surgery applications.

Self-Healing, Inflatable, Rigidizable Shelter

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Haight, Andrea; Gosau, Jan-Michael; Dixit, Anshu; Gleeson, Dan

2012-01-01

An inflatable, rigidizable shelter system was developed based on Rigi dization on Command (ROC) technology incorporating not only the requ ired low-stowage volume and lightweight character achieved from an i nflatable/rigidizable system, but also a self-healing foam system inc orporated between the rigidizable layers of the final structure to m inimize the damage caused by any punctures to the structure.

In vitro-ex vivo correlations between a cell-laden hydrogel and mucosal tissue for screening composite delivery systems.

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Blakney, Anna K; Little, Adam B; Jiang, Yonghou; Woodrow, Kim A

2016-11-01

Composite delivery systems where drugs are electrospun in different layers and vary the drug stacking-order are posited to affect bioavailability. We evaluated how the formulation characteristics of both burst- and sustained-release electrospun fibers containing three physicochemically diverse drugs: dapivirine (DPV), maraviroc (MVC) and tenofovir (TFV) affect in vitro and ex vivo release. We developed a poly(hydroxyethyl methacrylate) (pHEMA) hydrogel release platform for the rapid, inexpensive in vitro evaluation of burst- and sustained-release topical or dermal drug delivery systems with varying microarchitecture. We investigated properties of the hydrogel that could recapitulate ex vivo release into nonhuman primate vaginal tissue. Using a dimethyl sulfoxide extraction protocol and high-performance liquid chromatography analysis, we achieved >93% recovery from the hydrogels and >88% recovery from tissue explants for all three drugs. We found that DPV loading, but not stacking order (layers of fiber containing a single drug) or microarchitecture (layers with isolated drug compared to all drugs in the same layer) impacted the burst release in vitro and ex vivo. Our burst-release formulations showed a correlation for DPV accumulation between the hydrogel and tissue (R 2 =   0.80), but the correlation was not significant for MVC or TFV. For the sustained-release formulations, the PLGA/PCL content did not affect TFV release in vitro or ex vivo. Incorporation of cells into the hydrogel matrix improved the correlation between hydrogel and tissue explant release for TFV. We expect that this hydrogel-tissue mimic may be a promising preclinical model to evaluate topical or transdermal drug delivery systems with complex microarchitectures.

Methylcellulose Based Thermally Reversible Hydrogel System for Tissue Engineering Applications

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Ram V. Devireddy

2013-06-01

Full Text Available The thermoresponsive behavior of a Methylcellulose (MC polymer was systematically investigated to determine its usability in constructing MC based hydrogel systems in cell sheet engineering applications. Solution-gel analyses were made to study the effects of polymer concentration, molecular weight and dissolved salts on the gelation of three commercially available MCs using differential scanning calorimeter and rheology. For investigation of the hydrogel stability and fluid uptake capacity, swelling and degradation experiments were performed with the hydrogel system exposed to cell culture solutions at incubation temperature for several days. From these experiments, the optimal composition of MC-water-salt that was able to produce stable hydrogels at or above 32 °C, was found to be 12% to 16% of MC (Mol. wt. of 15,000 in water with 0.5× PBS (~150mOsm. This stable hydrogel system was then evaluated for a week for its efficacy to support the adhesion and growth of specific cells in culture; in our case the stromal/stem cells derived from human adipose tissue derived stem cells (ASCs. The results indicated that the addition (evenly spread of ~200 µL of 2 mg/mL bovine collagen type -I (pH adjusted to 7.5 over the MC hydrogel surface at 37 °C is required to improve the ASC adhesion and proliferation. Upon confluence, a continuous monolayer ASC sheet was formed on the surface of the hydrogel system and an intact cell sheet with preserved cell–cell and cell–extracellular matrix was spontaneously and gradually detached when the grown cell sheet was removed from the incubator and exposed to room temperature (~30 °C within minutes.

Methylcellulose based thermally reversible hydrogel system for tissue engineering applications.

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Thirumala, Sreedhar; Gimble, Jeffrey M; Devireddy, Ram V

2013-06-25

The thermoresponsive behavior of a Methylcellulose (MC) polymer was systematically investigated to determine its usability in constructing MC based hydrogel systems in cell sheet engineering applications. Solution-gel analyses were made to study the effects of polymer concentration, molecular weight and dissolved salts on the gelation of three commercially available MCs using differential scanning calorimeter and rheology. For investigation of the hydrogel stability and fluid uptake capacity, swelling and degradation experiments were performed with the hydrogel system exposed to cell culture solutions at incubation temperature for several days. From these experiments, the optimal composition of MC-water-salt that was able to produce stable hydrogels at or above 32 °C, was found to be 12% to 16% of MC (Mol. wt. of 15,000) in water with 0.5× PBS (~150mOsm). This stable hydrogel system was then evaluated for a week for its efficacy to support the adhesion and growth of specific cells in culture; in our case the stromal/stem cells derived from human adipose tissue derived stem cells (ASCs). The results indicated that the addition (evenly spread) of ~200 µL of 2 mg/mL bovine collagen type -I (pH adjusted to 7.5) over the MC hydrogel surface at 37 °C is required to improve the ASC adhesion and proliferation. Upon confluence, a continuous monolayer ASC sheet was formed on the surface of the hydrogel system and an intact cell sheet with preserved cell-cell and cell-extracellular matrix was spontaneously and gradually detached when the grown cell sheet was removed from the incubator and exposed to room temperature (~30 °C) within minutes.

Colloidal gas aphron foams: A novel approach to a hydrogel based tissue engineered myocardial patch

Science.gov (United States)

Johnson, Elizabeth Edna

Cardiovascular disease currently affects an estimated 58 million Americans and is the leading cause of death in the US. Over 2.3 million Americans are currently living with heart failure a leading cause of which is acute myocardial infarction, during which a part of the heart muscle is damaged beyond repair. There is a great need to develop treatments for damaged heart tissue. One potential therapy involves replacement of nonfunctioning scar tissue with a patch of healthy, functioning tissue. A tissue engineered cardiac patch would be ideal for such an application. Tissue engineering techniques require the use of porous scaffolds, which serve as a 3-D template for initial cell attachment and grow-th leading to tissue formation. The scaffold must also have mechanical properties closely matching those of the tissues at the site of implantation. Our research presents a new approach to meet these design requirements. A unique interaction between poly(vinyl alcohol) and amino acids has been discovered by our lab, resulting in the production of novel gels. These unique synthetic hydrogels along with one natural hydrogel, alginate (derived from brown seaweed), have been coupled with a new approach to tissue scaffold fabrication using solid colloidal gas aphrons (CGAs). CGAs are colloidal foams containing uniform bubbles with diameters on the order of micrometers. Upon solidification the GCAs form a porous, 3-D network suitable for a tissue scaffold. The project encompasses four specific aims: (I) characterize hydrogel formation mechanism, (II) use colloidal gas aphrons to produce hydrogel scaffolds, (III) chemically and physically characterize scaffold materials and (IV) optimize and evaluate scaffold biocompatibility.

Cytocompatible in situ forming chitosan/hyaluronan hydrogels via a metal-free click chemistry for soft tissue engineering.

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Fan, Ming; Ma, Ye; Mao, Jiahui; Zhang, Ziwei; Tan, Huaping

2015-07-01

Injectable hydrogels are important cell scaffolding materials for tissue engineering and regenerative medicine. Here, we report a new class of biocompatible and biodegradable polysaccharide hydrogels derived from chitosan and hyaluronan via a metal-free click chemistry, without the addition of copper catalyst. For the metal-free click reaction, chitosan and hyaluronan were modified with oxanorbornadiene (OB) and 11-azido-3,6,9-trioxaundecan-1-amine (AA), respectively. The gelation is attributed to the triazole ring formation between OB and azido groups of polysaccharide derivatives. The molecular structures were verified by FT-IR spectroscopy and elemental analysis, giving substitution degrees of 58% and 47% for chitosan-OB and hyaluronan-AA, respectively. The in vitro gelation, morphologies, equilibrium swelling, compressive modulus and degradation of the composite hydrogels were examined. The potential of the metal-free hydrogel as a cell scaffold was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) within the gel matrix in vitro. Cell culture showed that this metal-free hydrogel could support survival and proliferation of ASCs. A preliminary in vivo study demonstrated the usefulness of the hydrogel as an injectable scaffold for adipose tissue engineering. These characteristics provide a potential opportunity to use the metal-free click chemistry in preparation of biocompatible hydrogels for soft tissue engineering applications. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fabrication of Self-Healable and Patternable Polypyrrole/Agarose Hybrid Hydrogels for Smart Bioelectrodes.

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Park, Nokyoung; Chae, Seung Chul; Kim, Il Tae; Hur, Jaehyun

2016-02-01

We present a new class of electrically conductive, mechanically moldable, and thermally self-healable hybrid hydrogels. The hybrid gels consist of polypyrrole and agarose as the conductive component and self-healable matrix, respectively. By using the appropriate oxidizing agent under conditions of mild temperature, the polymerization of pyrrole occurred along the three-dimensional network of the agarose hydrogel matrix. In contrast to most commercially available hydrogels, the physical crosslinking of agarose gel allows for reversible gelation in the case of our hybrid gel, which could be manipulated by temperature variation, which controls the electrical on/off behavior of the hybrid gel electrode. Exploiting this property, we fabricated a hybrid conductive hydrogel electrode which also self-heals thermally. The novel composite material we report here will be useful for many technological and biological applications, especially in reactive biomimetic functions and devices, artificial muscles, smart membranes, smart full organic batteries, and artificial chemical synapses.

Development and characterization of a novel hydrogel adhesive for soft tissue applications

Science.gov (United States)

Sanders, Lindsey Kennedy

With laparoscopic and robotic surgical techniques advancing, the need for an injectable surgical adhesive is growing. To be effective, surgical adhesives for internal organs require bulk strength and compliance to avoid rips and tears, and adhesive strength to avoid leakage at the application site, while not hindering the natural healing process. Although a number of tissue adhesives and sealants approved by the FDA for surgical use are currently available, attaining a useful balance in all of these qualities has proven difficult, particularly when considering applications involving highly expandable tissue, such as bladder and lung. The long-term goal of this project is to develop a hydrogel-based tissue adhesive that provides proper mechanical properties to eliminate the need for sutures in various soft tissue applications. Tetronic (BASF), a 4-arm poly(propylene oxide)-poly(ethylene oxide) (PPO-PEO) block copolymer, has been selected as the base material for the adhesive hydrogel system. Solutions of Tetronic T1107 can support reverse thermal gelation at physiological temperatures, which can be combined with covalent crosslinking to achieve a "tandem gelation" process making it ideal for use as a tissue adhesive. The objective of this doctoral thesis research is to improve the performance of the hydrogel based tissue adhesive developed previously by Cho and co-workers by applying a multi-functionalization of Tetronic. Specifically, this research aimed to improve bonding strength of Tetronic tissue adhesive using bi-functional modification, incorporate hemostatic function to the bi-functional Tetronic hydrogel, and evaluate the safety of bi-functional Tetronic tissue adhesive both in vitro and in vivo. In summary, we have developed a fast-curing, mechanically strong hemostatic tissue adhesive that can control blood loss in wet conditions during wound treatment applications (bladder, liver and muscle). Specifically, the bi-functional Tetronic adhesive (TAS) with a

Click hydrogels, microgels and nanogels: emerging platforms for drug delivery and tissue engineering.

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Jiang, Yanjiao; Chen, Jing; Deng, Chao; Suuronen, Erik J; Zhong, Zhiyuan

2014-06-01

Hydrogels, microgels and nanogels have emerged as versatile and viable platforms for sustained protein release, targeted drug delivery, and tissue engineering due to excellent biocompatibility, a microporous structure with tunable porosity and pore size, and dimensions spanning from human organs, cells to viruses. In the past decade, remarkable advances in hydrogels, microgels and nanogels have been achieved with click chemistry. It is a most promising strategy to prepare gels with varying dimensions owing to its high reactivity, superb selectivity, and mild reaction conditions. In particular, the recent development of copper-free click chemistry such as strain-promoted azide-alkyne cycloaddition, radical mediated thiol-ene chemistry, Diels-Alder reaction, tetrazole-alkene photo-click chemistry, and oxime reaction renders it possible to form hydrogels, microgels and nanogels without the use of potentially toxic catalysts or immunogenic enzymes that are commonly required. Notably, unlike other chemical approaches, click chemistry owing to its unique bioorthogonal feature does not interfere with encapsulated bioactives such as living cells, proteins and drugs and furthermore allows versatile preparation of micropatterned biomimetic hydrogels, functional microgels and nanogels. In this review, recent exciting developments in click hydrogels, microgels and nanogels, as well as their biomedical applications such as controlled protein and drug release, tissue engineering, and regenerative medicine are presented and discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mechanically Robust 3D Nanostructure Chitosan-Based Hydrogels with Autonomic Self-Healing Properties.

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Karimi, Ali Reza; Khodadadi, Azam

2016-10-12

Fabrication of hydrogels based on chitosan (CS) with superb self-healing behavior and high mechanical and electrical properties has become a challenging and fascinating topic. Most of the conventional hydrogels lack these properties at the same time. Our objectives in this research were to synthesize, characterize, and evaluate the general properties of chitosan covalently cross-linked with zinc phthalocyanine tetra-aldehyde (ZnPcTa) framework. Our hope was to access an unprecedented self-healable three-dimensional (3D) nanostructure that would harvest the superior mechanical and electrical properties associated with chitosan. The properties of cross-linker such as the structure, steric effect, and rigidity of the molecule played important roles in determining the microstructure and properties of the resulting hydrogels. The tetra-functionalized phthalocyanines favor a dynamic Schiff-base linkage with chitosan to form a 3D porous nanostructure. Based on this strategy, the self-healing ability, as demonstrated by rheological recovery and macroscopic and microscopic observations, is introduced through dynamic covalent Schiff-base linkage between NH 2 groups in CS and benzaldehyde groups at cross-linker ends. The hydrogel was characterized using FT-IR, NMR, UV/vis, and rheological measurements. In addition, cryogenic scanning electron microscopy (cryo-SEM) was employed as a technique to visualize the internal morphology of the hydrogels. Study of the surface morphology of the hydrogel showed a 3D porous nanostructure with uniform morphology. Furthermore, incorporating the conductive nanofillers, such as carbon nanotubes (CNTs), into the structure can modulate the mechanical and electrical properties of the obtained hydrogels. Interestingly, these hydrogel nanocomposites proved to have very good film-forming properties, high modulus and strength, acceptable electrical conductivity, and excellent self-healing properties at neutral pH. Such properties can be finely tuned

Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix.

Science.gov (United States)

Kuo, Kuan-Chih; Lin, Ruei-Zeng; Tien, Han-Wen; Wu, Pei-Yun; Li, Yen-Cheng; Melero-Martin, Juan M; Chen, Ying-Chieh

2015-11-01

Tissue engineering promises to restore or replace diseased or damaged tissue by creating functional and transplantable artificial tissues. The development of artificial tissues with large dimensions that exceed the diffusion limitation will require nutrients and oxygen to be delivered via perfusion instead of diffusion alone over a short time period. One approach to perfusion is to vascularize engineered tissues, creating a de novo three-dimensional (3D) microvascular network within the tissue construct. This significantly shortens the time of in vivo anastomosis, perfusion and graft integration with the host. In this study, we aimed to develop injectable allogeneic collagen-phenolic hydroxyl (collagen-Ph) hydrogels that are capable of controlling a wide range of physicochemical properties, including stiffness, water absorption and degradability. We tested whether collagen-Ph hydrogels could support the formation of vascularized engineered tissue graft by human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSC) in vivo. First, we studied the growth of adherent ECFCs and MSCs on or in the hydrogels. To examine the potential formation of functional vascular networks in vivo, a liquid pre-polymer solution of collagen-Ph containing human ECFCs and MSCs, horseradish peroxidase and hydrogen peroxide was injected into the subcutaneous space or abdominal muscle defect of an immunodeficient mouse before gelation, to form a 3D cell-laden polymerized construct. These results showed that extensive human ECFC-lined vascular networks can be generated within 7 days, the engineered vascular density inside collagen-Ph hydrogel constructs can be manipulated through refinable mechanical properties and proteolytic degradability, and these networks can form functional anastomoses with the existing vasculature to further support the survival of host muscle tissues. Finally, optimized conditions of the cell-laden collagen

Enzymatically crosslinked gelatin hydrogel promotes the proliferation of adipose tissue-derived stromal cells

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Gang Yang

2016-09-01

Full Text Available Gelatin hydrogel crosslinked by microbial transglutaminase (mTG exhibits excellent performance in cell adhesion, proliferation, and differentiation. We examined the gelation time and gel strength of gelatin/mTG hydrogels in various proportions to investigate their physical properties and tested their degradation performances in vitro. Cell morphology and viability of adipose tissue-derived stromal cells (ADSCs cultured on the 2D gel surface or in 3D hydrogel encapsulation were evaluated by immunofluorescence staining. Cell proliferation was tested via Alamar Blue assay. To investigate the hydrogel effect on cell differentiation, the cardiac-specific gene expression levelsof Nkx2.5, Myh6, Gja1, and Mef2c in encapsulated ADSCs with or without cardiac induction medium were detected by real-time RT-PCR. Cell release from the encapsulated status and cell migration in a 3D hydrogel model were assessed in vitro. Results show that the gelatin/mTG hydrogels are not cytotoxic and that their mechanical properties are adjustable. Hydrogel degradation is related to gel concentration and the resident cells. Cell growth morphology and proliferative capability in both 2D and 3D cultures were mainly affected by gel concentration. PCR result shows that hydrogel modulus together with induction medium affects the cardiac differentiation of ADSCs. The cell migration experiment and subcutaneous implantation show that the hydrogels are suitable for cell delivery.

A Bioactive Hydrogel and 3D Printed Polycaprolactone System for Bone Tissue Engineering

Directory of Open Access Journals (Sweden)

Ivan Hernandez

2017-07-01

Full Text Available In this study, a hybrid system consisting of 3D printed polycaprolactone (PCL filled with hydrogel was developed as an application for reconstruction of long bone defects, which are innately difficult to repair due to large missing segments of bone. A 3D printed gyroid scaffold of PCL allowed a larger amount of hydrogel to be loaded within the scaffolds as compared to 3D printed mesh and honeycomb scaffolds of similar volumes and strut thicknesses. The hydrogel was a mixture of alginate, gelatin, and nano-hydroxyapatite, infiltrated with human mesenchymal stem cells (hMSC to enhance the osteoconductivity and biocompatibility of the system. Adhesion and viability of hMSC in the PCL/hydrogel system confirmed its cytocompatibility. Biomineralization tests in simulated body fluid (SBF showed the nucleation and growth of apatite crystals, which confirmed the bioactivity of the PCL/hydrogel system. Moreover, dissolution studies, in SBF revealed a sustained dissolution of the hydrogel with time. Overall, the present study provides a new approach in bone tissue engineering to repair bone defects with a bioactive hybrid system consisting of a polymeric scaffold, hydrogel, and hMSC.

A Bioactive Hydrogel and 3D Printed Polycaprolactone System for Bone Tissue Engineering.

Science.gov (United States)

Hernandez, Ivan; Kumar, Alok; Joddar, Binata

2017-09-01

In this study, a hybrid system consisting of 3D printed polycaprolactone (PCL) filled with hydrogel was developed as an application for reconstruction of long bone defects, which are innately difficult to repair due to large missing segments of bone. A 3D printed gyroid scaffold of PCL allowed a larger amount of hydrogel to be loaded within the scaffolds as compared to 3D printed mesh and honeycomb scaffolds of similar volumes and strut thicknesses. The hydrogel was a mixture of alginate, gelatin, and nano-hydroxyapatite, infiltrated with human mesenchymal stem cells (hMSC) to enhance the osteoconductivity and biocompatibility of the system. Adhesion and viability of hMSC in the PCL/hydrogel system confirmed its cytocompatibility. Biomineralization tests in simulated body fluid (SBF) showed the nucleation and growth of apatite crystals, which confirmed the bioactivity of the PCL/hydrogel system. Moreover, dissolution studies, in SBF revealed a sustained dissolution of the hydrogel with time. Overall, the present study provides a new approach in bone tissue engineering to repair bone defects with a bioactive hybrid system consisting of a polymeric scaffold, hydrogel, and hMSC.

Preparation and properties of polyvinyl alcohol (PVA) and hydroxylapatite (HA) hydrogels for cartilage tissue engineering.

Science.gov (United States)

Yuan, F; Ma, M; Lu, L; Pan, Z; Zhou, W; Cai, J; Luo, S; Zeng, W; Yin, F

2017-05-20

A novel bioactive hydrogel for cartilage tissue based on polyvinyl alcohol (PVA) and hydroxylapatite (HA) were prepared, the effects of its component contents on the mechanical properties and microstructure of the hydrogel were investigated. The important properties of the scaffold composites, such as density, porosity, compressive modulus and microstructure were studied and analyzed through various measurements and methods. The biodegradability of hydrogel was evaluated by soaking the samples into artificial degradation solution at body temperature (36 - 37 oC) in vitro. Experimental results showed that the PVA/HA hydrogels had a density of 0.572 - 0.683 g/cm3, a porosity of 63.25 - 96.14% and a compressive modulus of 5.62 - 8.24 MP. The HA compound in the hydrogels enhanced the biodegradation significantly and linearly increased the rate of biodegradation by 2.3 - 8.5 %. The compressive modulus of PVA/HA exhibited a linear reduce to 0.86 - 1.53 MP with the time of degradation. The scaffold composites PVA/HA possess a high porosity, decent compressive modulus and good biodegradability. After further optimizing the structure and properties, this composite might be considered as novel hydrogel biomaterials to be applied in the field of cartilage tissue engineering.

Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

Energy Technology Data Exchange (ETDEWEB)

Luo, Chunhong; Xu, Guoguang; Wang, Xinghui [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Tu, Mei; Zeng, Rong; Rong, Jianhua [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China); Zhao, Jianhao, E-mail: jhzhao@jnu.edu.cn [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China)

2015-01-01

A series of self-reinforcing hyaluronan hydrogels were developed to improve mechanical properties and protein sustained delivery thanks to a dually cross-linked network. Hyaluronan gel particles (HGPs, 1–5 μm in diameter) with different cross-linking densities, i.e. HGPs-1.5, HGPs-3 and HGPs-15, were prepared in an inverse emulsion system and used as the reinforcing phase after glycidyl methacrylation, while glycidyl methacrylated hyaluronan with a substitution degree of 45.2% was synthesized as the matrix phase. These two phases were cross-linked under ultraviolet irradiation to form self-reinforcing hyaluronan hydrogels (srHAs) that showed typical cross-linked structure of HGPs connecting the matrix phase by cross-section observation. In comparison to hyaluronan bulk gels and their blends with HGPs, srHAs distinctly enhanced the mechanical properties and BSA long-term sustained delivery, especially srHA-1.5 showed the highest compressive modulus of 220 ± 15 kPa and the slowest BSA delivery (67% release at 14 d). The 3T3 fibroblast cell culture showed that all the srHAs had no cytotoxicity. - Highlights: • New self-reinforcing HA hydrogels with a dually cross-linked network were developed. • Self-reinforcing HA hydrogels greatly enhanced the mechanical properties. • Self-reinforcing HA hydrogels prolonged the sustained delivery of BSA. • The self-reinforcing mechanism and BSA diffusion mechanism were discussed. • Self-reinforcing HA hydrogels had no cytotoxicity to 3T3 fibroblast cells.

Self-reinforcement and protein sustained delivery of hyaluronan hydrogel by tailoring a dually cross-linked network

International Nuclear Information System (INIS)

Luo, Chunhong; Xu, Guoguang; Wang, Xinghui; Tu, Mei; Zeng, Rong; Rong, Jianhua; Zhao, Jianhao

2015-01-01

A series of self-reinforcing hyaluronan hydrogels were developed to improve mechanical properties and protein sustained delivery thanks to a dually cross-linked network. Hyaluronan gel particles (HGPs, 1–5 μm in diameter) with different cross-linking densities, i.e. HGPs-1.5, HGPs-3 and HGPs-15, were prepared in an inverse emulsion system and used as the reinforcing phase after glycidyl methacrylation, while glycidyl methacrylated hyaluronan with a substitution degree of 45.2% was synthesized as the matrix phase. These two phases were cross-linked under ultraviolet irradiation to form self-reinforcing hyaluronan hydrogels (srHAs) that showed typical cross-linked structure of HGPs connecting the matrix phase by cross-section observation. In comparison to hyaluronan bulk gels and their blends with HGPs, srHAs distinctly enhanced the mechanical properties and BSA long-term sustained delivery, especially srHA-1.5 showed the highest compressive modulus of 220 ± 15 kPa and the slowest BSA delivery (67% release at 14 d). The 3T3 fibroblast cell culture showed that all the srHAs had no cytotoxicity. - Highlights: • New self-reinforcing HA hydrogels with a dually cross-linked network were developed. • Self-reinforcing HA hydrogels greatly enhanced the mechanical properties. • Self-reinforcing HA hydrogels prolonged the sustained delivery of BSA. • The self-reinforcing mechanism and BSA diffusion mechanism were discussed. • Self-reinforcing HA hydrogels had no cytotoxicity to 3T3 fibroblast cells

Encapsulation of Curcumin in Self-Assembling Peptide Hydrogels as Injectable Drug Delivery Vehicles

Science.gov (United States)

Altunbas, Aysegul; Lee, Seung Joon; Rajasekaran, Sigrid A.; Schneider, Joel P.; Pochan, Darrin J.

2011-01-01

Curcumin, a hydrophobic polyphenol, is an extract of turmeric root with antioxidant, anti-inflammatory and anti-tumorigenic properties. Its lack of water solubility and relatively low bioavailability set major limitations for its therapeutic use. In this study, a self-assembling peptide hydrogel is demonstrated to be an effective vehicle for the localized delivery of curcumin over sustained periods of time. The curcumin-hydrogel is prepared in-situ where curcumin encapsulation within the hydrogel network is accomplished concurrently with peptide self-assembly. Physical and in vitro biological studies were used to demonstrate the effectiveness of curcumin-loaded β-hairpin hydrogels as injectable agents for localized curcumin delivery. Notably, rheological characterization of the curcumin loaded hydrogel before and after shear flow have indicated solid-like properties even at high curcumin payloads. In vitro experiments with a medulloblastoma cell line confirm that the encapsulation of the curcumin within the hydrogel does not have an adverse effect on its bioactivity. Most importantly, the rate of curcumin release and its consequent therapeutic efficacy can be conveniently modulated as a function of the concentration of the MAX8 peptide. PMID:21601921

Skin-Inspired Multifunctional Autonomic-Intrinsic Conductive Self-Healing Hydrogels with Pressure Sensitivity, Stretchability, and 3D Printability.

Science.gov (United States)

Darabi, Mohammad Ali; Khosrozadeh, Ali; Mbeleck, Rene; Liu, Yuqing; Chang, Qiang; Jiang, Junzi; Cai, Jun; Wang, Quan; Luo, Gaoxing; Xing, Malcolm

2017-08-01

The advent of conductive self-healing (CSH) hydrogels, a class of novel materials mimicking human skin, may change the trajectory of the industrial process because of their potential applications in soft robots, biomimetic prostheses, and health-monitoring systems. Here, the development of a mechanically and electrically self-healing hydrogel based on physically and chemically cross-linked networks is reported. The autonomous intrinsic self-healing of the hydrogel is attained through dynamic ionic interactions between carboxylic groups of poly(acrylic acid) and ferric ions. A covalent cross-linking is used to support the mechanical structure of the hydrogel. Establishing a fair balance between the chemical and physical cross-linking networks together with the conductive nanostructure of polypyrrole networks leads to a double network hydrogel with bulk conductivity, mechanical and electrical self-healing properties (100% mechanical recovery in 2 min), ultrastretchability (1500%), and pressure sensitivity. The practical potential of CSH hydrogels is further revealed by their application in human motion detection and their 3D-printing performance. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cross-linkable graphene oxide embedded nanocomposite hydrogel with enhanced mechanics and cytocompatibility for tissue engineering.

Science.gov (United States)

Liu, Xifeng; Miller, A Lee; Waletzki, Brian E; Lu, Lichun

2018-05-01

Graphene oxide (GO) is an attractive material that can be utilized to enhance the modulus and conductivities of substrates and hydrogels. To covalently cross-link graphene oxide sheets into hydrogels, abundant cross-linkable double bonds were introduced to synthesize the graphene-oxide-tris-acrylate sheet (GO-TrisA). Polyacrylamide (PAM) nanocomposite hydrogels were then fabricated with inherent covalently and permanently cross-linked GO-TrisA sheets. Results showed that the covalently cross-linked GO-TrisA/PAM nanocomposite hydrogel had enhanced mechanical strength, thermo stability compared with GO/PAM hydrogel maintained mainly by hydrogen bonding between PAM chains and GO sheets. In vitro cell study showed that the covalently cross-linked rGO-TrisA/PAM nanocomposite hydrogel had excellent cytocompatibility after in situ reduction. These results suggest that rGO-TrisA/PAM nanocomposite hydrogel holds great potential for tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1247-1257, 2018. © 2018 Wiley Periodicals, Inc.

Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering.

Science.gov (United States)

Zhang, Xing; Xu, Bin; Puperi, Daniel S; Yonezawa, Aline L; Wu, Yan; Tseng, Hubert; Cuchiara, Maude L; West, Jennifer L; Grande-Allen, K Jane

2015-03-01

The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1-6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG↓IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micro-patterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

In situ spray deposition of cell-loaded, thermally and chemically gelling hydrogel coatings for tissue regeneration.

Science.gov (United States)

Pehlivaner Kara, Meryem O; Ekenseair, Adam K

2016-10-01

In this study, the efficacy of creating cellular hydrogel coatings on warm tissue surfaces through the minimally invasive, sprayable delivery of thermoresponsive liquid solutions was investigated. Poly(N-isopropylacrylamide)-based (pNiPAAm) thermogelling macromers with or without addition of crosslinking polyamidoamine (PAMAM) macromers were synthesized and used to produce in situ forming thermally and chemically gelling hydrogel systems. The effect of solution and process parameters on hydrogel physical properties and morphology was evaluated and compared to poly(ethylene glycol) and injection controls. Smooth, fast, and conformal hydrogel coatings were obtained when pNiPAAm thermogelling macromers were sprayed with high PAMAM concentration at low pressure. Cellular hydrogel coatings were further fabricated by different spraying techniques: single-stream, layer-by-layer, and dual stream methods. The impact of spray technique, solution formulation, pressure, and spray solution viscosity on the viability of fibroblast and osteoblast cells encapsulated in hydrogels was elucidated. In particular, the early formation of chemically crosslinked micronetworks during bulk liquid flow was shown to significantly affect cell viability under turbulent conditions compared to injectable controls. The results demonstrated that sprayable, in situ forming hydrogels capable of delivering cell populations in a homogeneous therapeutic coating on diseased tissue surfaces offer promise as novel therapies for applications in regenerative medicine. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2383-2393, 2016. © 2016 Wiley Periodicals, Inc.

Enzymatic mineralization of gellan gum hydrogel for bone tissue-engineering applications and its enhancement by polydopamine

NARCIS (Netherlands)

Douglas, T.E.L.; Wlodarczyk, M.; Pamula, E.; Declercq, H.A.; Mulder, E.L.W. de; Bucko, M.M.; Balcaen, L.; Vanhaecke, F.; Cornelissen, R.; Dubruel, P.; Jansen, J.A.; Leeuwenburgh, S.C.G.

2014-01-01

Interest is growing in the use of hydrogels as bone tissue-engineering (TE) scaffolds due to advantages such as injectability and ease of incorporation of active substances such as enzymes. Hydrogels consisting of gellan gum (GG), an inexpensive calcium-crosslinkable polysaccharide, have been

Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

Science.gov (United States)

Salamon, Achim; van Vlierberghe, Sandra; van Nieuwenhove, Ine; Baudisch, Frank; Graulus, Geert-Jan; Benecke, Verena; Alberti, Kristin; Neumann, Hans-Georg; Rychly, Joachim; Martins, José C.; Dubruel, Peter; Peters, Kirsten

2014-01-01

Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands. In order to prove their chondrogenesis-supporting potential, a hydrogel film was developed and compared with standard cell culture polystyrene regarding the differentiation behavior of human mesenchymal stem cells. Cellular basis for this study were human adipose tissue-derived mesenchymal stem cells, which exhibit differentiation potential along the adipogenic, osteogenic and chondrogenic lineage. The results obtained show a promotive effect of gelatin-based hydrogels on chondrogenic differentiation of mesenchymal stem cells in vitro and therefore encourage subsequent in vivo studies. PMID:28788517

Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological properties dictate antimicrobial activity

Science.gov (United States)

Jiang, Linhai; Xu, Dawei; Sellati, Timothy J.; Dong, He

2015-11-01

Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would also protect the hydrogel itself from being adversely affected by microbial attachment to its surface. We have previously demonstrated the broad-spectrum antimicrobial activity of supramolecular assemblies of cationic multi-domain peptides (MDPs) in solution. Here, we extend the 1-D soluble supramolecular assembly to 3-D hydrogels to investigate the effect of the supramolecular nanostructure and its rheological properties on the antimicrobial activity of self-assembled hydrogels. Among designed MDPs, the bactericidal activity of peptide hydrogels was found to follow an opposite trend to that in solution. Improved antimicrobial activity of self-assembled peptide hydrogels is dictated by the combined effect of supramolecular surface chemistry and storage modulus of the bulk materials, rather than the ability of individual peptides/peptide assemblies to penetrate bacterial cell membrane as observed in solution. The structure-property-activity relationship developed through this study will provide important guidelines for designing biocompatible peptide hydrogels with built-in antimicrobial activity for various biomedical applications.Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would

Viscoelastic behaviour of hydrogel-based composites for tissue engineering under mechanical load.

Science.gov (United States)

Kocen, Rok; Gasik, Michael; Gantar, Ana; Novak, Saša

2017-03-06

Along with biocompatibility, bioinductivity and appropriate biodegradation, mechanical properties are also of crucial importance for tissue engineering scaffolds. Hydrogels, such as gellan gum (GG), are usually soft materials, which may benefit from the incorporation of inorganic particles, e.g. bioactive glass, not only due to the acquired bioactivity, but also due to improved mechanical properties. They exhibit complex viscoelastic properties, which can be evaluated in various ways. In this work, to reliably evaluate the effect of the bioactive glass (BAG) addition on viscoelastic properties of the composite hydrogel, we employed and compared the three most commonly used techniques, analyzing their advantages and limitations: monotonic uniaxial unconfined compression, small amplitude oscillatory shear (SAOS) rheology and dynamic mechanical analysis (DMA). Creep and small amplitude dynamic strain-controlled tests in DMA are suggested as the best ways for the characterization of mechanical properties of hydrogel composites, whereas the SAOS rheology is more useful for studying the hydrogel's processing kinetics, as it does not induce volumetric changes even at very high strains. Overall, the results confirmed a beneficial effect of BAG (nano)particles on the elastic modulus of the GG-BAG composite hydrogel. The Young's modulus of 6.6 ± 0.8 kPa for the GG hydrogel increased by two orders of magnitude after the addition of 2 wt.% BAG particles (500-800 kPa).

New perspectives in cell delivery systems for tissue regeneration: natural-derived injectable hydrogels.

Science.gov (United States)

Munarin, Fabiola; Petrini, Paola; Bozzini, Sabrina; Tanzi, Maria Cristina

2012-09-27

Natural polymers, because of their biocompatibility, availability, and physico-chemical properties have been the materials of choice for the fabrication of injectable hydrogels for regenerative medicine. In particular, they are appealing materials for delivery systems and provide sustained and controlled release of drugs, proteins, gene, cells, and other active biomolecules immobilized.In this work, the use of hydrogels obtained from natural source polymers as cell delivery systems is discussed. These materials were investigated for the repair of cartilage, bone, adipose tissue, intervertebral disc, neural, and cardiac tissue. Papers from the last ten years were considered, with a particular focus on the advances of the last five years. A critical discussion is centered on new perspectives and challenges in the regeneration of specific tissues, with the aim of highlighting the limits of current systems and possible future advancements.

Design of protein-responsive micro-sized hydrogels for self-regulating microfluidic systems

Science.gov (United States)

Hirayama, Mayu; Tsuruta, Kazuhiro; Kawamura, Akifumi; Ohara, Masayuki; Shoji, Kan; Kawano, Ryuji; Miyata, Takashi

2018-03-01

Diagnosis sensors using micro-total analysis systems (µ-TAS) have been developed for detecting target biomolecules such as proteins and saccharides because they are signal biomolecules for monitoring body conditions and diseases. In this study, biomolecularly stimuli-responsive micro-sized hydrogels that exhibited quick shrinkage in response to lectin concanavalinA (ConA) were prepared in a microchannel by photopolymerization using a fluorescence microscope. In preparing the micro-size hydrogels, glycosyloxyethyl methacrylate (GEMA) as a ligand monomer was copolymerized with a crosslinker in the presence of template ConA in molecular imprinting. The ConA-imprinted micro-hydrogel showed greater shrinkage in response to target ConA than nonimprinted micro-hydrogel. When a buffer solution was switched to an aqueous ConA solution in the Y-shaped microchannel, the flow rates changed quickly because of the responsive shrinkage of the micro-hydrogel prepared in the microchannel. These results suggest that the ConA-imprinted micro-hydrogel acted as a self-regulated microvalve in microfluidic systems.

Hydrogels for lung tissue engineering: Biomechanical properties of thin collagen-elastin constructs.

Science.gov (United States)

Dunphy, Siobhán E; Bratt, Jessica A J; Akram, Khondoker M; Forsyth, Nicholas R; El Haj, Alicia J

2014-10-01

In this study, collagen-elastin constructs were prepared with the aim of producing a material capable of mimicking the mechanical properties of a single alveolar wall. Collagen has been used in a wide range of tissue engineering applications; however, due to its low mechanical properties its use is limited to non load-bearing applications without further manipulation using methods such as cross-linking or mechanical compression. Here, it was hypothesised that the addition of soluble elastin to a collagen hydrogel could improve its mechanical properties. Hydrogels made from collagen only and collagen plus varying amounts elastin were prepared. Young׳s modulus of each membrane was measured using the combination of a non-destructive indentation and a theoretical model previously described. An increase in Young׳s modulus was observed with increasing concentration of elastin. The use of non-destructive indentation allowed for online monitoring of the elastic moduli of cell-seeded constructs over 8 days. The addition of lung fibroblasts into the membrane increased the stiffness of the hydrogels further and cell-seeded collagen hydrogels were found to have a stiffness equal to the theoretical value for a single alveolar wall (≈5kPa). Through provision of some of the native extracellular matrix components of the lung parenchyma these scaffolds may be able to provide an initial building block toward the regeneration of new functional lung tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biologically inspired rosette nanotubes and nanocrystalline hydroxyapatite hydrogel nanocomposites as improved bone substitutes

International Nuclear Information System (INIS)

Zhang Lijie; Webster, Thomas J; Rodriguez, Jose; Raez, Jose; Myles, Andrew J; Fenniri, Hicham

2009-01-01

Today, bone diseases such as bone fractures, osteoporosis and bone cancer represent a common and significant public health problem. The design of biomimetic bone tissue engineering materials that could restore and improve damaged bone tissues provides exciting opportunities to solve the numerous problems associated with traditional orthopedic implants. Therefore, the objective of this in vitro study was to create a biomimetic orthopedic hydrogel nanocomposite based on the self-assembly properties of helical rosette nanotubes (HRNs), the osteoconductive properties of nanocrystalline hydroxyapatite (HA), and the biocompatible properties of hydrogels (specifically, poly(2-hydroxyethyl methacrylate), pHEMA). HRNs are self-assembled nanomaterials that are formed from synthetic DNA base analogs in water to mimic the helical nanostructure of collagen in bone. In this study, different geometries of nanocrystalline HA were controlled by either hydrothermal or sintering methods. 2 and 10 wt% nanocrystalline HA particles were well dispersed into HRN hydrogels using ultrasonication. The nanocrystalline HA and nanocrystalline HA/HRN hydrogels were characterized by x-ray diffraction, transmission electron microscopy, and scanning electron microscopy. Mechanical testing studies revealed that the well dispersed nanocrystalline HA in HRN hydrogels possessed improved mechanical properties compared to hydrogel controls. In addition, the results of this study provided the first evidence that the combination of either 2 or 10 wt% nanocrystalline HA and 0.01 mg ml -1 HRNs in hydrogels greatly increased osteoblast (bone-forming cell) adhesion up to 236% compared to hydrogel controls. Moreover, this study showed that HRNs stimulated HA nucleation and mineralization along their main axis in a way that is very reminiscent of the HA/collagen assembly pattern in natural bone. In summary, the presently observed excellent properties of the biomimetic nanocrystalline HA/HRN hydrogel composites

Self-resonance after inflation: Oscillons, transients, and radiation domination

Science.gov (United States)

Lozanov, Kaloian D.; Amin, Mustafa A.

2018-01-01

Homogeneous oscillations of the inflaton after inflation can be unstable to small spatial perturbations even without coupling to other fields. We show that for inflaton potentials ∝|ϕ |2n near |ϕ |=0 and flatter beyond some |ϕ |=M , the inflaton condensate oscillations can lead to self-resonance, followed by its complete fragmentation. We find that for nonquadratic minima (n >1 ), shortly after backreaction, the equation of state parameter, w →1 /3 . If M ≪mPl, radiation domination is established within less than an e -fold of expansion after the end of inflation. In this case self-resonance is efficient and the condensate fragments into transient, localised spherical objects which are unstable and decay, leaving behind them a virialized field with mean kinetic and gradient energies much greater than the potential energy. This end-state yields w =1 /3 . When M ˜mPl we observe slow and steady, self-resonance that can last many e -folds before backreaction eventually shuts it off, followed by fragmentation and w →1 /3 . We provide analytical estimates for the duration to w →1 /3 after inflation, which can be used as an upper bound (under certain assumptions) on the duration of the transition between the inflationary and the radiation dominated states of expansion. This upper bound can reduce uncertainties in CMB observables such as the spectral tilt ns, and the tensor-to-scalar ratio r . For quadratic minima (n =1 ), w →0 regardless of the value of M . This is because when M ≪mPl, long-lived oscillons form within an e -fold after inflation, and collectively behave as pressureless dust thereafter. For M ˜mPl, the self-resonance is inefficient and the condensate remains intact (ignoring long-term gravitational clustering) and keeps oscillating about the quadratic minimum, again implying w =0 .

Characterization of human adipose tissue-derived stem cells in vitro culture and in vivo differentiation in a temperature-sensitive chitosan/β- glycerophosphate/collagen hybrid hydrogel

Energy Technology Data Exchange (ETDEWEB)

Song, Kedong, E-mail: Kedongsong@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Li, Liying; Yan, Xinyu; Zhang, Wen; Zhang, Yu [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China); Wang, Yiwei [Burns Research Group, ANZAC Research Institute, University of Sydney, Concord, NSW, 2139 (Australia); Liu, Tianqing, E-mail: liutq@dlut.edu.cn [State Key Laboratory of Fine Chemicals, Dalian R& D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024 (China)

2017-01-01

In this study, the interaction of human adipose tissue-derived stem cells (ADSCs) with chitosan/β-glycerophosphate/collagen (C/GP/Co) hybrid hydrogel was test, followed by investigating the capability of engineered adipose tissue formation using this ADSCs seeded hydrogel. The ADSCs were harvested and mixed with a C/GP/Co hydrogel followed by a gelation at 37 °C and an in vitro culture. The results showed that the ADSCs within C/GP/Co hydrogels achieved a 30% of expansion over 7 days in culture medium and encapsulated cell in C/GP/Co hydrogel demonstrated a characteristic morphology with high viability over 5 days. C/GP/Co hydrogel were subcutaneous injected into SD-rats to assess the biocompatibility. The induced ADSCs-C/GP/Co hydrogel and non-induced ADSCs-C/GP/Co hydrogel were subcutaneously injected into nude mice for detecting potential of adipogenic differentiation. It has shown that C/GP/Co hydrogel were well tolerated in SD rats where they had persisted over 4 weeks post implantation. Histology analysis indicated that induced ADSCs-C/GP/Co hydrogel has a greater number of adipocytes and vascularized adipose tissues compared with non-induced ADSCs-C/GP/Co hydrogel. - Highlights: • The hydrogel scaffold was produced using chitosan, β-glycerophosphate and collagen. • This novel hydrogel is in liquid phase at low temperature and is gelatinized at 37 °C. • The new hydrogel provides ADSCs a favorable 3D environment with highly maintenance of proliferation and cytoactive. • ADSCs seeded hydrogel differentiated into adipose tissue, indicating favorable ability of adipogenesis. • This attractive property of C/GP/CO hydrogel points to its value as an excellent scaffold for tissue engineering.

Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

Directory of Open Access Journals (Sweden)

Achim Salamon

2014-02-01

Full Text Available Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands. In order to prove their chondrogenesis-supporting potential, a hydrogel film was developed and compared with standard cell culture polystyrene regarding the differentiation behavior of human mesenchymal stem cells. Cellular basis for this study were human adipose tissue-derived mesenchymal stem cells, which exhibit differentiation potential along the adipogenic, osteogenic and chondrogenic lineage. The results obtained show a promotive effect of gelatin-based hydrogels on chondrogenic differentiation of mesenchymal stem cells in vitro and therefore encourage subsequent in vivo studies.

Transport of silver nanoparticles from nanocomposite Ag/alginate hydrogels under conditions mimicking tissue implantation

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Kostić Danijela D.

2017-01-01

Full Text Available The aim of this work was to assess phenomena occurring during AgNP transport from nanocomposite Ag/alginate hydrogels under conditions relevant for potential biomedical applications as antimicrobial soft tissue implants. First, we have studied AgNP migration from the nanocomposite to the adjacent alginate hydrogel mimicking soft tissue next to the implant. AgNP deposition was carried out by the initial burst release lasting for ∼24 h yielding large aggregates on hydrogel surfaces and smaller clusters (∼400 nm in size inside. However, the overall released content was low (0.67% indicating high nanocomposite stability. In the next experimental series, release of AgNPs, 10–30 nm in size, from Ag/alginate microbeads in water was investigated under static conditions as well as under continuous perfusion mimicking vascularized tissues. Mathematical modeling has revealed AgNP release by diffusion under static conditions with the diffusion coefficient within the Ag/alginate hydrogel of 6.9x10–19 m2 s–1. Conversely, continuous perfusion induced increased AgNP release by convection with the interstitial fluid velocity estimated as 4.6 nm s–1. Overall, the obtained results indicated the influence of hydrodynamic conditions at the implantation site on silver release and potential implant functionality, which should be investigated at the experimentation beginning using appropriate in vitro systems. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III 45019

Biopolymer-based hydrogels as injectable materials for tissue repair scaffolds

International Nuclear Information System (INIS)

Fiejdasz, Sylwia; Szczubiałka, Krzysztof; Lewandowska-Łańcucka, Joanna; Nowakowska, Maria; Osyczka, Anna M

2013-01-01

The progress in tissue regeneration is strongly dependent on the development of biocompatible materials with properties resembling those of a native tissue. Also, the application of noninvasive methods of delivering the scaffold into the tissue defect is of great importance. In this study we present a group of biopolymer-based materials as potential injectable scaffolds. In contrast to other studies involving collagen neutralization or additional incubation of gel in genipin solution, we propose collagen and collagen–chitosan gels crosslinked in situ with genipin. Since some parameters of the cells should be considered in the microscale, the steady-state fluorescence anisotropy was applied to study the microenvironment of the gels. To our knowledge we are the first to report on microrheological properties, such as gel time and microviscosity, for this group of hydrogels. Rapid gelation at physiological temperatures found makes these materials of special interest in applications requiring gel injectability. Physico-chemical investigation showed the influence of the crosslinking agent concentration and chitosan addition on the crosslinking degree, swelling ratio, gel microviscosity, and the degradation rate. Strong correlation was revealed between the surface wettability and the viability of cultured mesenchymal stem cells. Cytotoxicity studies indicated that the collagen–chitosan hydrogels showed the best biocompatibility. (paper)

Recent advances on gradient hydrogels in biomimetic cartilage tissue engineering [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Ivana Gadjanski

2017-12-01

Full Text Available Articular cartilage (AC is a seemingly simple tissue that has only one type of constituting cell and no blood vessels and nerves. In the early days of tissue engineering, cartilage appeared to be an easy and promising target for reconstruction and this was especially motivating because of widespread AC pathologies such as osteoarthritis and frequent sports-induced injuries. However, AC has proven to be anything but simple. Recreating the varying properties of its zonal structure is a challenge that has not yet been fully answered. This caused the shift in tissue engineering strategies toward bioinspired or biomimetic approaches that attempt to mimic and simulate as much as possible the structure and function of the native tissues. Hydrogels, particularly gradient hydrogels, have shown great potential as components of the biomimetic engineering of the cartilaginous tissue.

Photo-cross-linked PLA-PEO-PLA hydrogels from self-assembled physical networks: mechanical properties and influence of assumed constitutive relationships.

Science.gov (United States)

Sanabria-DeLong, Naomi; Crosby, Alfred J; Tew, Gregory N

2008-10-01

Poly(lactide)-block-poly(ethylene oxide)-block-poly(lactide) (PLA-PEO-PLA) triblock copolymers are known to form physical hydrogels in water as a result of the polymer's amphiphilicity. Their mechanical properties, biocompatibility, and biodegradability have made them attractive for use as soft tissue scaffolds. However, the network junction points are not covalently cross-linked, and in a highly aqueous environment these hydrogels adsorb more water, transform from gel to sol, and lose the designed mechanical properties. In this article, a hydrogel was formed by the use of a novel two-step approach. In the first step, the end-functionalized PLA-PEO-PLA triblock was self-assembled into a physical hydrogel through hydrophobic micelle network junctions, and in the second step, this self-assembled physical network structure was locked into place by photo-cross-linking the terminal acrylate groups. In contrast with physical hydrogels, the photo-cross-linked gels remained intact in phosphate-buffered solution at body temperature. The swelling, degradation, and mechanical properties were characterized, and they demonstrated an extended degradation time (approximately 65 days), an exponential decrease in modulus with degradation time, and a tunable shear modulus (1.6-133 kPa). We also discuss the various constitutive relationships (Hookean, neo-Hookean, and Mooney-Rivlin) that can be used to describe the stress-strain behavior of these hydrogels. The chosen model and assumptions used for data fitting influenced the obtained modulus values by as much as a factor of 3.5, which demonstrates the importance of clearly stating one's data fitting parameters so that accurate comparisons can be made within the literature.

Self-Healable and Cold-Resistant Supercapacitor Based on a Multifunctional Hydrogel Electrolyte.

Science.gov (United States)

Tao, Feng; Qin, Liming; Wang, Zhikui; Pan, Qinmin

2017-05-10

Excellent self-healability and cold resistance are attractive properties for a portable/wearable energy-storage device. However, achieving the features is fundamentally dependent on an intrinsically self-healable electrolyte with high ionic conduction at low temperature. Here we report such a hydrogel electrolyte comprising sodium alginate cross-linked by dynamic catechol-borate ester bonding. Since its dynamically cross-linked alginate network can tolerate high-content inorganic salts, the electrolyte possesses excellent healing efficiency/cyclability but also high ionic conduction at both room temperature and low temperature. A supercapacitor with the multifunctional hydrogel electrolyte completely restores its capacitive properties even after breaking/healing for 10 cycles without external stimulus. At a low temperature of -10 °C, the capacitor is even able to maintain at least 80% of its room-temperature capacitance. Our investigations offer a strategy to assemble self-healable and cold-resistant energy storage devices by using a multifunctional hydrogel electrolyte with rationally designed polymeric networks, which has potential application in portable/wearable electronics, intelligent apparel or flexible robot, and so on.

Exploiting Bisphosphonate-Bioactive-Glass Interactions for the Development of Self-Healing and Bioactive Composite Hydrogels

NARCIS (Netherlands)

Diba, M.; An, J.; Schmidt, S.; Hembury, M.; Ossipov, D.; Boccaccini, A.R.; Leeuwenburgh, S.C.G.

2016-01-01

Hydrogels are widely recognized as promising candidates for various biomedical applications, such as tissue engineering. Recently, extensive research efforts have been devoted to the improvement of the biological and mechanical performance of hydrogel systems by incorporation of functional groups

PEGDA hydrogels as a replacement for animal tissues in mucoadhesion testing.

Science.gov (United States)

Eshel-Green, Tal; Eliyahu, Shaked; Avidan-Shlomovich, Shlomit; Bianco-Peled, Havazelet

2016-06-15

Utilization of animal parts in ex-vivo mucoadhesion assays is a common approach that presents many difficulties due to animal rights issues and large variance between animals. This study examines the suitability of two PEGDA (poly(ethylene glycol) diacrylate) based hydrogels to serve as tissue mimetics for mucoadhesion evaluation. One hydrogel, termed PEGDA-QT, was composed of pentaerythritol tetrakis (3-mercaptopropionate) and PEG and contained free thiol groups mimicking those found in natural mucosa. The other hydrogel was formed by UV (ultraviolet) curing of PEGDA and mimicked the mechanical property of mucosa but not its chemical constitute. When ranking different first generation mucoadhesive polymers using a tensile assay, both hydrogels showed good agreement with the ranking achieved for porcine small intestine. However, only PEGDA-QT and porcine small intestine shared a similar displacement curve. The same ranking for PEGDA-QT and porcine small intestine was also observed when comparing a second-generation mucoadhesive polymer, thiolated alginate, to native alginate. Our findings suggest that PEGDA-QT could serve as a replacement for porcine small intestine in both mucoadhesion evaluations using a tensile machine and the flow-through method for first and second-generation mucoadhesive polymers. Copyright © 2016 Elsevier B.V. All rights reserved.

"That's not just beautiful--that's incredibly beautiful!": the adverse impact of inflated praise on children with low self-esteem.

Science.gov (United States)

Brummelman, Eddie; Thomaes, Sander; Orobio de Castro, Bram; Overbeek, Geertjan; Bushman, Brad J

2014-03-01

In current Western society, children are often lavished with inflated praise (e.g., "You made an incredibly beautiful drawing!"). Inflated praise is often given in an attempt to raise children's self-esteem. An experiment (Study 1) and naturalistic study (Study 2) found that adults are especially inclined to give inflated praise to children with low self-esteem. This inclination may backfire, however. Inflated praise might convey to children that they should continue to meet very high standards-a message that might discourage children with low self-esteem from taking on challenges. Another experiment (Study 3) found that inflated praise decreases challenge seeking in children with low self-esteem and has the opposite effect on children with high self-esteem. These findings show that inflated praise, although well intended, may cause children with low self-esteem to avoid crucial learning experiences.

Hydrogel tissue expanders for stomatology. Part I. methacrylate-based polymers

Czech Academy of Sciences Publication Activity Database

Hrib, Jakub; Širc, Jakub; Lesný, P.; Hobzová, Radka; Dušková-Smrčková, Miroslava; Michálek, Jiří; Šmucler, R.

2017-01-01

Roč. 28, č. 1 (2017), s. 1-8, č. článku 12. ISSN 0957-4530 R&D Projects: GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : hydrogel * tissue expander * methacrylates Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 2.325, year: 2016

Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

International Nuclear Information System (INIS)

Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

2013-01-01

Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds

Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Mirahmadi, Fereshteh [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad, E-mail: Tafazoli@aut.ac.ir [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali, E-mail: mashokrgozar@pasteur.ac.ir [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Bonakdar, Shahin [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of)

2013-12-01

Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds.

Rational design and application of responsive α-helical peptide hydrogels

Science.gov (United States)

Banwell, Eleanor F.; Abelardo, Edgardo S.; Adams, Dave J.; Birchall, Martin A.; Corrigan, Adam; Donald, Athene M.; Kirkland, Mark; Serpell, Louise C.; Butler, Michael F.; Woolfson, Derek N.

2009-01-01

Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs; and as supports for cell growth and tissue engineering1. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials2-4. Here we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks melt upon heating, whereas those formed via hydrophobic interactions strengthen when warmed. The hSAFs are dual-peptide systems that only gel on mixing, which gives tight control over assembly5. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture. PMID:19543314

Design of Decorated Self-Assembling Peptide Hydrogels as Architecture for Mesenchymal Stem Cells

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Annj Zamuner

2016-08-01

Full Text Available Hydrogels from self-assembling ionic complementary peptides have been receiving a lot of interest from the scientific community as mimetic of the extracellular matrix that can offer three-dimensional supports for cell growth or can become vehicles for the delivery of stem cells, drugs or bioactive proteins. In order to develop a 3D “architecture” for mesenchymal stem cells, we propose the introduction in the hydrogel of conjugates obtained by chemoselective ligation between a ionic-complementary self-assembling peptide (called EAK and three different bioactive molecules: an adhesive sequence with 4 Glycine-Arginine-Glycine-Aspartic Acid-Serine-Proline (GRGDSP motifs per chain, an adhesive peptide mapped on h-Vitronectin and the growth factor Insulin-like Growth Factor-1 (IGF-1. The mesenchymal stem cell adhesion assays showed a significant increase in adhesion and proliferation for the hydrogels decorated with each of the synthesized conjugates; moreover, such functionalized 3D hydrogels support cell spreading and elongation, validating the use of this class of self-assembly peptides-based material as very promising 3D model scaffolds for cell cultures, at variance of the less realistic 2D ones. Furthermore, small amplitude oscillatory shear tests showed that the presence of IGF-1-conjugate did not alter significantly the viscoelastic properties of the hydrogels even though differences were observed in the nanoscale structure of the scaffolds obtained by changing their composition, ranging from long, well-defined fibers for conjugates with adhesion sequences to the compact and dense film for the IGF-1-conjugate.

Novel antifouling self-healing poly(carboxybetaine methacrylamide-co-HEMA) nanocomposite hydrogels with superior mechanical properties

NARCIS (Netherlands)

Kostina, Nina Yu.; Sharifi, Shahriar; Pereira, Andres de los Santos; Michalek, Jiri; Grijpma, Dirk W.; Rodriguez-Emmenegger, Cesar

2013-01-01

Novel antifouling highly wettable hydrogels with superior mechanical and self-healing properties are presented. Hydrogels were prepared by UV-initiated copolymerisation of non-fouling zwitterionic carboxybetaine methacrylamide (CBMAA-3) and 2-hydroxyethyl methacrylate (HEMA) in the presence of

Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications

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Miguel Gama

2010-02-01

Full Text Available Hydrogel nanoparticles—also referred to as polymeric nanogels or macromolecular micelles—are emerging as promising drug carriers for therapeutic applications. These nanostructures hold versatility and properties suitable for the delivery of bioactive molecules, namely of biopharmaceuticals. This article reviews the latest developments in the use of self-assembled polymeric nanogels for drug delivery applications, including small molecular weight drugs, proteins, peptides, oligosaccharides, vaccines and nucleic acids. The materials and techniques used in the development of self-assembling nanogels are also described.

Self-healable mussel-mimetic nanocomposite hydrogel based on catechol-containing polyaspartamide and graphene oxide

International Nuclear Information System (INIS)

Wang, Bo; Jeon, Young Sil; Park, Ho Seok; Kim, Ji-Heung

2016-01-01

Stimuli-responsive and self-healing materials have a wide range of potential uses, and some significant research has focused on cross-linking of hydrogel materials by means of reversible coordination bonding. The resulting materials, however, tend to have poor mechanical properties with pronounced weakness and brittleness. In this work, we present a novel mussel-inspired graphene oxide(GO)–containing hydrogel based on modified polyaspartamide with γ-amino butyric acid (GABA), 3.4-dihydroxyphenethylamine (DOPA), and ethanolamine (EA), termed PolyAspAm(GABA/DOPA/EA). Here both GO nanosheets and boric acid (H 3 BO 3 ) act as cross-linkers, interacting with polar functional groups of the PolyAspAm(GABA/DOPA/EA). Compared to PolyAspAm(GABA/DOPA/EA)/B 3+ gel without GO, the same containing 5 wt% of GO yielded a 10-fold increase in both the storage and loss moduli, as well as 134% and 104% increases in the tensile and compressive strengths, respectively. In addition, the GO-containing polyaspartamide hydrogel exhibited rapid and autonomous self-healing property. Two types of bonding, boron–catechol coordination and strong hydrogen bonding interactions between PolyAspAm side chains and GO nanosheets, would impart the enhanced mechanical strength and good reversible gelation behavior upon pH stimulation to the hydrogel, making this biocompatible hydrogel a promising soft matter for biomedical applications. - Highlights: • Novel GO-containing nanocomposite hydrogels based on dopamine-conjugated polyaspartamide derivative was prepared. • Improvement in the mechanical property of composite gel by GO incorporation was elucidated. • The “smart” characteristics of pH-responsive gelation and rapid self-healing were demonstrated.

Self-healable mussel-mimetic nanocomposite hydrogel based on catechol-containing polyaspartamide and graphene oxide

Energy Technology Data Exchange (ETDEWEB)

Wang, Bo; Jeon, Young Sil; Park, Ho Seok; Kim, Ji-Heung, E-mail: kimjh@skku.edu

2016-12-01

Stimuli-responsive and self-healing materials have a wide range of potential uses, and some significant research has focused on cross-linking of hydrogel materials by means of reversible coordination bonding. The resulting materials, however, tend to have poor mechanical properties with pronounced weakness and brittleness. In this work, we present a novel mussel-inspired graphene oxide(GO)–containing hydrogel based on modified polyaspartamide with γ-amino butyric acid (GABA), 3.4-dihydroxyphenethylamine (DOPA), and ethanolamine (EA), termed PolyAspAm(GABA/DOPA/EA). Here both GO nanosheets and boric acid (H{sub 3}BO{sub 3}) act as cross-linkers, interacting with polar functional groups of the PolyAspAm(GABA/DOPA/EA). Compared to PolyAspAm(GABA/DOPA/EA)/B{sup 3+} gel without GO, the same containing 5 wt% of GO yielded a 10-fold increase in both the storage and loss moduli, as well as 134% and 104% increases in the tensile and compressive strengths, respectively. In addition, the GO-containing polyaspartamide hydrogel exhibited rapid and autonomous self-healing property. Two types of bonding, boron–catechol coordination and strong hydrogen bonding interactions between PolyAspAm side chains and GO nanosheets, would impart the enhanced mechanical strength and good reversible gelation behavior upon pH stimulation to the hydrogel, making this biocompatible hydrogel a promising soft matter for biomedical applications. - Highlights: • Novel GO-containing nanocomposite hydrogels based on dopamine-conjugated polyaspartamide derivative was prepared. • Improvement in the mechanical property of composite gel by GO incorporation was elucidated. • The “smart” characteristics of pH-responsive gelation and rapid self-healing were demonstrated.

Zinc-Triggered Hydrogelation of Self-assembled Small Molecules to Inhibit Bacterial Growth

Science.gov (United States)

Xu, Chao; Cai, Yanbin; Ren, Chunhua; Gao, Jie; Hao, Jihui

2015-01-01

There is a significant need to develop antibacterial materials that could be applied locally and directly to the places surrounded by large amount of bacteria, in order to address the problems of bacterial antibiotic-resistance or irreversible biofilm formation. Hydrogels are thought to be suitable candidates due to their versatile applications in biomedical field. Among them, small molecular hydrogels have been paid lots of attention because they are easy to design and fabricate and often sensitive to external stimuli. Meanwhile, the antibacterial activity of metal ions are attracting more and more attention because resistance to them are not yet found within bacteria. We therefore designed the zinc ion binding peptide of Nap-GFFYGGGHGRGD, who can self-assemble into hydrogels after binds Zn2+ and inhibit the growth of bacteria due to the excellent antibacterial activity of Zn2+. Upon the addition of zinc ions, solutions containing Nap-GFFYGGGHGRGD transformed into supramolecular hydrogels composed of network of long nano-fibers. Bacterial tests revealed an antibacterial effect of the zinc triggered hydrogels on E. coli. The studied small molecular hydrogel shows great potential in locally addressing bacterial infections.

Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold.

Science.gov (United States)

Kim, Dong Wook; Kim, Eun Ji; Kim, Eun Na; Sung, Myung Whun; Kwon, Tack-Kyun; Cho, Yong Woo; Kwon, Seong Keun

2016-01-01

Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM) grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM) and methylcellulose (MC) for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps-ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.

Biomedical hydrogels biochemistry, manufacture and medical applications

CERN Document Server

Rimmer, Steve

2011-01-01

Hydrogels are very important for biomedical applications because they can be chemically manipulated to alter and control the hydrogel's interaction with cells and tissues. Their flexibility and high water content is similar to that of natural tissue, making them extremely suitable for biomaterials applications. Biomedical hydrogels explores the diverse range and use of hydrogels, focusing on processing methods and novel applications in the field of implants and prostheses. Part one of this book concentrates on the processing of hydrogels, covering hydrogel swelling behaviour, superabsorbent cellulose-based hydrogels and regulation of novel hydrogel products, as well as chapters focusing on the structure and properties of hydrogels and different fabrication technologies. Part two covers existing and novel applications of hydrogels, including chapters on spinal disc and cartilage replacement implants, hydrogels for ophthalmic prostheses and hydrogels for wound healing applications. The role of hydrogels in imag...

Mechanical evaluation of a tissue-engineered zone of calcification in a bone–hydrogel osteochondral construct

Science.gov (United States)

Hollenstein, Jérôme; Terrier, Alexandre; Cory, Esther; Chen, Albert C.; Sah, Robert L.; Pioletti, Dominique P.

2016-01-01

The objective of this study was to test the hypothesis that mechanical properties of artificial osteochondral constructs can be improved by a tissue-engineered zone of calcification (teZCC) at the bone–hydrogel interface. Experimental push-off tests were performed on osteochondral constructs with or without a teZCC. In parallel, a numerical model of the osteochondral defect treatment was developed and validated against experimental results. Experimental results showed that the shear strength at the bone–hydrogel interface increased by 100% with the teZCC. Numerical predictions of the osteochondral defect treatment showed that the shear stress at the bone–hydrogel interface was reduced with the teZCC. We conclude that a teZCC in osteochondral constructs can provide two improvements. First, it increases the strength of the bone–hydrogel interface and second, it reduces the stress at this interface. PMID:23706035

A facile route to the synthesis of anilinic electroactive colloidal hydrogels for neural tissue engineering applications.

Science.gov (United States)

Zarrintaj, Payam; Urbanska, Aleksandra M; Gholizadeh, Saman Seyed; Goodarzi, Vahabodin; Saeb, Mohammad Reza; Mozafari, Masoud

2018-04-15

An innovative drug-loaded colloidal hydrogel was synthesized for applications in neural interfaces in tissue engineering by reacting carboxyl capped aniline dimer and gelatin molecules. Dexamethasone was loaded into the gelatin-aniline dimer solution as a model drug to form an in situ drug-loaded colloidal hydrogel. The conductivity of the hydrogel samples fluctuated around 10 -5  S/cm which appeared suitable for cellular activities. Cyclic voltammetry was used for electroactivity determination, in which 2 redox states were observed, suggesting that the short chain length and steric hindrance prevented the gel from achieving a fully oxidized state. Rheological data depicted the modulus decreasing with aniline dimer increment due to limited hydrogen bonds accessibility. Though the swelling ratio of pristine gelatin (600%) decreased by the introduction and increasing the concentration of aniline dimer because of its hydrophobic nature, it took the value of 300% at worst, which still seems promising for drug delivery uses. Degradation rate of hydrogel was similarly decreased by adding aniline dimer. Drug release was evaluated in passive and stimulated patterns demonstrating tendency of aniline dimer to form a vesicle that controls the drug release behavior. The optimal cell viability, proper cell attachment and neurite extension was achieved in the case of hydrogel containing 10 wt% aniline dimer. Based on tissue/organ behavior, it was promisingly possible to adjust the characteristics of the hydrogels for an optimal drug release. The outcome of this simple and effective approach can potentially offer additional tunable characteristics for recording and stimulating purposes in neural interfaces. Copyright © 2018 Elsevier Inc. All rights reserved.

Dynamic compression of human and ovine meniscal tissue compared with a potential thermoplastic elastomer hydrogel replacement.

Science.gov (United States)

Fischenich, Kristine M; Boncella, Katie; Lewis, Jackson T; Bailey, Travis S; Haut Donahue, Tammy L

2017-10-01

Understanding how human meniscal tissue responds to loading regimes mimetic of daily life as well as how it compares to larger animal models is critical in the development of a functionally accurate synthetic surrogate. Seven human and eight ovine cadaveric meniscal specimens were regionally sectioned into cylinders 5 mm in diameter and 3 mm thick along with 10 polystyrene-b-polyethylene oxide block copolymer-based thermoplastic elastomer (TPE) hydrogels. Samples were compressed to 12% strain at 1 Hz for 5000 cycles, unloaded for 24 h, and then retested. No differences were found within each group between test one and test two. Human and ovine tissue exhibited no regional dependency (p Human samples relaxed quicker than ovine tissue or the TPE hydrogel with modulus values at cycle 50 not significantly different from cycle 5000. Ovine menisci were found to be similar to human menisci in relaxation profile but had significantly higher modulus values (3.44 MPa instantaneous and 0.61 MPa after 5000 cycles compared with 1.97 and 0.11 MPa found for human tissue) and significantly different power law fit coefficients. The TPE hydrogel had an initial modulus of 0.58 MPa and experienced less than a 20% total relaxation over the 5000. Significant differences in the magnitude of compressive modulus between human and ovine menisci were observed, however the relaxation profiles were similar. Although statistically different than the native tissues, modulus values of the TPE hydrogel material were similar to those of the human and ovine menisci, making it a material worth further investigation for use as a synthetic replacement. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2722-2728, 2017. © 2017 Wiley Periodicals, Inc.

The effect of hypoxia on thermosensitive poly(N-vinylcaprolactam) hydrogels with tunable mechanical integrity for cartilage tissue engineering.

Science.gov (United States)

Lynch, Brandon; Crawford, Kristopher; Baruti, Omari; Abdulahad, Asem; Webster, Martial; Puetzer, Jennifer; Ryu, Chang; Bonassar, Lawrence J; Mendenhall, Juana

2017-10-01

Cartilage repair presents a daunting challenge in tissue engineering applications due to the low oxygen conditions (hypoxia) affiliated in diseased states. Hence, the use of biomaterial scaffolds with unique variability is imperative to treat diseased or damaged cartilage. Thermosensitive hydrogels show promise as injectable materials that can be used as tissue scaffolds for cartilage tissue regeneration. However, uses in clinical applications are limited to due mechanical stability and therapeutic efficacy to treat diseased tissue. In this study, several composite hydrogels containing poly(N-vinylcaprolactam) (PVCL) and methacrylated hyaluronic acid (meHA) were prepared using free radical polymerization to produce PVCL-graft-HA (PVCL-g-HA) and characterized using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and scanning electron microscopy. Lower critical solution temperatures and gelation temperatures were confirmed in the range of 33-34°C and 41-45°C, respectively. Using dynamic sheer rheology, the temperature dependence of elastic (G') and viscous (G″) modulus between 25°C and 45°C, revealed that PVCL-g-HA hydrogels at 5% (w/v) concentration exhibited the moduli of 7 Pa (G') to 4 Pa (G″). After 10 days at 1% oxygen, collagen production on PVCL-g-HA hydrogels was 153 ± 25 μg/mg (20%) and 106 ± 18 μg/mg showing a 10-fold increase compared to meHA controls. These studies show promise in PVCL-g-HA hydrogels for the treatment of diseased or damaged articular cartilage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1863-1873, 2017. © 2016 Wiley Periodicals, Inc.

Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering.

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Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

2013-12-01

Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber-hydrogel composite for GAG content and in two-layer electrospun fiber-hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. © 2013.

Human Adipose Tissue Derived Extracellular Matrix and Methylcellulose Hydrogels Augments and Regenerates the Paralyzed Vocal Fold.

Directory of Open Access Journals (Sweden)

Dong Wook Kim

Full Text Available Vocal fold paralysis results from various etiologies and can induce voice changes, swallowing complications, and issues with aspiration. Vocal fold paralysis is typically managed using injection laryngoplasty with fat or synthetic polymers. Injection with autologous fat has shown excellent biocompatibility. However, it has several disadvantages such as unpredictable resorption rate, morbidities associated with liposuction procedure which has to be done in operating room under general anesthesia. Human adipose-derived extracellular matrix (ECM grafts have been reported to form new adipose tissue and have greater biostability than autologous fat graft. Here, we present an injectable hydrogel that is constructed from adipose tissue derived soluble extracellular matrix (sECM and methylcellulose (MC for use in vocal fold augmentation. Human sECM derived from adipose tissue was extracted using two major steps-ECM was isolated from human adipose tissue and was subsequently solubilized. Injectable sECM/MC hydrogels were prepared by blending of sECM and MC. Sustained vocal fold augmentation and symmetric vocal fold vibration were accomplished by the sECM/MC hydrogel in paralyzed vocal fold which were confirmed by laryngoscope, histology and a high-speed imaging system. There were increased number of collagen fibers and fatty granules at the injection site without significant inflammation or fibrosis. Overall, these results indicate that the sECM/MC hydrogel can enhance vocal function in paralyzed vocal folds without early resorption and has potential as a promising material for injection laryngoplasty for stable vocal fold augmentation which can overcome the shortcomings of autologous fat such as unpredictable duration and morbidity associated with the fat harvest.

An interpenetrating HA/G/CS biomimic hydrogel via Diels-Alder click chemistry for cartilage tissue engineering.

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Yu, Feng; Cao, Xiaodong; Zeng, Lei; Zhang, Qing; Chen, Xiaofeng

2013-08-14

In order to mimic the natural cartilage extracellular matrix, a novel biological degradable interpenetrating network hydrogel was synthesized from the gelatin (G), hyaluronic acid (HA) and chondroitin sulfate (CS) by Diels-Alder "click" chemistry. HA was modified with furylamine and G was modified with furancarboxylic acid respectively. (1)H NMR spectra and elemental analysis showed that the substitution degrees of HA-furan and G-furan were 71.5% and 44.5%. Then the hydrogels were finally synthesized by cross-linking furan-modified HA and G derivatives with dimaleimide poly(ethylene glycol) (MAL-PEG-MAL). The mechanical and degradation properties of the hydrogels could be tuned simply through varying the molar ratio between furan and maleimide. Rheological, mechanical and degradation studies demonstrated that the Diels-Alder "click" chemistry is an efficient method for preparing high performance biological interpenetrating hydrogels. This biomimic hydrogel with improved mechanical properties could have great potential applications in cartilage tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve.

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Huang, Lanfeng; Li, Rui; Liu, Wanguo; Dai, Jin; Du, Zhenwu; Wang, Xiaonan; Ma, Jianchao; Zhao, Jinsong

2014-07-15

Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, but cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhesion stage. Moreover, seeded cells were distributed throughout the material.

A bio-inspired, microchanneled hydrogel with controlled spacing of cell adhesion ligands regulates 3D spatial organization of cells and tissue.

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Lee, Min Kyung; Rich, Max H; Lee, Jonghwi; Kong, Hyunjoon

2015-07-01

Bioactive hydrogels have been extensively studied as a platform for 3D cell culture and tissue regeneration. One of the key desired design parameters is the ability to control spatial organization of biomolecules and cells and subsequent tissue in a 3D matrix. To this end, this study presents a simple but advanced method to spatially organize microchanneled, cell adherent gel blocks and non-adherent ones in a single construct. This hydrogel system was prepared by first fabricating a bimodal hydrogel in which the microscale, alginate gel blocks modified with cell adhesion peptides containing Arg-Gly-Asp sequence (RGD peptides), and those free of RGD peptides, were alternatingly presented. Then, anisotropically aligned microchannels were introduced by uniaxial freeze-drying of the bimodal hydrogel. The resulting gel system could drive bone marrow stromal cells to adhere to and differentiate into neuron and glial cells exclusively in microchannels of the alginate gel blocks modified with RGD peptides. Separately, the bimodal gel loaded with microparticles releasing vascular endothelial growth factor stimulated vascular growth solely into microchannels of the RGD-alginate gel blocks in vivo. These results were not attained by the bimodal hydrogel fabricated to present randomly oriented micropores. Overall, the bimodal gel system could regulate spatial organization of nerve-like tissue or blood vessels at sub-micrometer length scale. We believe that the hydrogel assembly demonstrated in this study will be highly useful in developing a better understanding of diverse cellular behaviors in 3D tissue and further improve quality of a wide array of engineered tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Three-dimensional hydrogel cell culture systems for modeling neural tissue

Science.gov (United States)

Frampton, John

Two-dimensional (2-D) neural cell culture systems have served as physiological models for understanding the cellular and molecular events that underlie responses to physical and chemical stimuli, control sensory and motor function, and lead to the development of neurological diseases. However, the development of three-dimensional (3-D) cell culture systems will be essential for the advancement of experimental research in a variety of fields including tissue engineering, chemical transport and delivery, cell growth, and cell-cell communication. In 3-D cell culture, cells are provided with an environment similar to tissue, in which they are surrounded on all sides by other cells, structural molecules and adhesion ligands. Cells grown in 3-D culture systems display morphologies and functions more similar to those observed in vivo, and can be cultured in such a way as to recapitulate the structural organization and biological properties of tissue. This thesis describes a hydrogel-based culture system, capable of supporting the growth and function of several neural cell types in 3-D. Alginate hydrogels were characterized in terms of their biomechanical and biochemical properties and were functionalized by covalent attachment of whole proteins and peptide epitopes. Methods were developed for rapid cross-linking of alginate hydrogels, thus permitting the incorporation of cells into 3-D scaffolds without adversely affecting cell viability or function. A variety of neural cell types were tested including astrocytes, microglia, and neurons. Cells remained viable and functional for longer than two weeks in culture and displayed process outgrowth in 3-D. Cell constructs were created that varied in cell density, type and organization, providing experimental flexibility for studying cell interactions and behavior. In one set of experiments, 3-D glial-endothelial cell co-cultures were used to model blood-brain barrier (BBB) structure and function. This co-culture system was

Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects.

Science.gov (United States)

Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin

2018-06-01

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy

Bioactive gyroid scaffolds formed by sacrificial templating of nanocellulose and nanochitin hydrogels as instructive platforms for biomimetic tissue engineering.

Science.gov (United States)

Torres-Rendon, Jose Guillermo; Femmer, Tim; De Laporte, Laura; Tigges, Thomas; Rahimi, Khosrow; Gremse, Felix; Zafarnia, Sara; Lederle, Wiltrud; Ifuku, Shinsuke; Wessling, Matthias; Hardy, John G; Walther, Andreas

2015-05-20

A sacrificial templating process using lithographically printed minimal surface structures allows complex de novo geo-metries of delicate hydrogel materials. The hydrogel scaffolds based on cellulose and chitin nanofibrils show differences in terms of attachment of human mesenchymal stem cells, and allow their differentiation into osteogenic outcomes. The approach here serves as a first example toward designer hydrogel scaffolds viable for biomimetic tissue engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechano-responsive hydrogels crosslinked by reactive block copolymer micelles

Science.gov (United States)

Xiao, Longxi

Hydrogels are crosslinked polymeric networks that can swell in water without dissolution. Owing to their structural similarity to the native extracelluar matrices, hydrogels have been widely used in biomedical applications. Synthetic hydrogels have been designed to respond to various stimuli, but mechanical signals have not incorporated into hydrogel matrices. Because most tissues in the body are subjected to various types of mechanical forces, and cells within these tissues have sophisticated mechano-transduction machinery, this thesis is focused on developing hydrogel materials with built-in mechano-sensing mechanisms for use as tissue engineering scaffolds or drug release devices. Self-assembled block copolymer micelles (BCMs) with reactive handles were employed as the nanoscopic crosslinkers for the construction of covalently crosslinked networks. BCMs were assembled from amphiphilic diblock copolymers of poly(n-butyl acrylate) and poly(acrylic acid) partially modified with acrylate. Radical polymerization of acrylamide in the presence of micellar crosslinkers gave rise to elastomeric hydrogels whose mechanical properties can be tuned by varying the BCM composition and concentration. TEM imaging revealed that the covalently integrated BCMs underwent strain-dependent reversible deformation. A model hydrophobic drug, pyrene, loaded into the core of BCMs prior to the hydrogel formation, was dynamically released in response to externally applied mechanical forces, through force-induced reversible micelle deformation and the penetration of water molecules into the micelle core. The mechano-responsive hydrogel has been studied for tissue repair and regeneration purposes. Glycidyl methacrylate (GMA)-modified hyaluronic acid (HA) was photochemically crosslinked in the presence of dexamethasone (DEX)-loaded crosslinkable BCMs. The resultant HA gels (HAxBCM) contain covalently integrated micellar compartments with DEX being sequestered in the hydrophobic core. Compared

Anisotropic polyvinyl alcohol hydrogel phantom for shear wave elastography in fibrous biological soft tissue: a multimodality characterization

International Nuclear Information System (INIS)

Chatelin, Simon; Bernal, Miguel; Deffieux, Thomas; Papadacci, Clément; Nahas, Amir; Boccara, Claude; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu; Flaud, Patrice

2014-01-01

Shear wave elastography imaging techniques provide quantitative measurement of soft tissues elastic properties. Tendons, muscles and cerebral tissues are composed of fibers, which induce a strong anisotropic effect on the mechanical behavior. Currently, these tissues cannot be accurately represented by existing elastography phantoms. Recently, a novel approach for orthotropic hydrogel mimicking soft tissues has been developed (Millon et al 2006 J. Biomed. Mater. Res. B 305–11). The mechanical anisotropy is induced in a polyvinyl alcohol (PVA) cryogel by stretching the physical crosslinks of the polymeric chains while undergoing freeze/thaw cycles. In the present study we propose an original multimodality imaging characterization of this new transverse isotropic (TI) PVA hydrogel. Multiple properties were investigated using a large variety of techniques at different scales compared with an isotropic PVA hydrogel undergoing similar imaging and rheology protocols. The anisotropic mechanical (dynamic and static) properties were studied using supersonic shear wave imaging technique, full-field optical coherence tomography (FFOCT) strain imaging and classical linear rheometry using dynamic mechanical analysis. The anisotropic optical and ultrasonic spatial coherence properties were measured by FFOCT volumetric imaging and backscatter tensor imaging, respectively. Correlation of mechanical and optical properties demonstrates the complementarity of these techniques for the study of anisotropy on a multi-scale range as well as the potential of this TI phantom as fibrous tissue-mimicking phantom for shear wave elastographic applications. (paper)

Anisotropic polyvinyl alcohol hydrogel phantom for shear wave elastography in fibrous biological soft tissue: a multimodality characterization

Science.gov (United States)

Chatelin, Simon; Bernal, Miguel; Deffieux, Thomas; Papadacci, Clément; Flaud, Patrice; Nahas, Amir; Boccara, Claude; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

2014-11-01

Shear wave elastography imaging techniques provide quantitative measurement of soft tissues elastic properties. Tendons, muscles and cerebral tissues are composed of fibers, which induce a strong anisotropic effect on the mechanical behavior. Currently, these tissues cannot be accurately represented by existing elastography phantoms. Recently, a novel approach for orthotropic hydrogel mimicking soft tissues has been developed (Millon et al 2006 J. Biomed. Mater. Res. B 305-11). The mechanical anisotropy is induced in a polyvinyl alcohol (PVA) cryogel by stretching the physical crosslinks of the polymeric chains while undergoing freeze/thaw cycles. In the present study we propose an original multimodality imaging characterization of this new transverse isotropic (TI) PVA hydrogel. Multiple properties were investigated using a large variety of techniques at different scales compared with an isotropic PVA hydrogel undergoing similar imaging and rheology protocols. The anisotropic mechanical (dynamic and static) properties were studied using supersonic shear wave imaging technique, full-field optical coherence tomography (FFOCT) strain imaging and classical linear rheometry using dynamic mechanical analysis. The anisotropic optical and ultrasonic spatial coherence properties were measured by FFOCT volumetric imaging and backscatter tensor imaging, respectively. Correlation of mechanical and optical properties demonstrates the complementarity of these techniques for the study of anisotropy on a multi-scale range as well as the potential of this TI phantom as fibrous tissue-mimicking phantom for shear wave elastographic applications.

A Thixotropic Polyglycerol Sebacate-Based Supramolecular Hydrogel as an Injectable Drug Delivery Matrix

Directory of Open Access Journals (Sweden)

Hongye Ye

2016-04-01

Full Text Available We have developed a “self-healing” polyglycerol sebacate—polyethylene glycol methyl ether methacrylate (PGS-PEGMEMA/α-Cyclodextrin (αCD hydrogel which could be sheared into a liquid during injection and has the potential to quickly “heal” itself back into gel post-injection. This hydrogel was shown to be biocompatible and biodegradable and therefore appropriate for use in vivo. Furthermore, the storage and loss moduli of the hydrogels could be tuned (by varying the concentration of αCD between a fraction of a kPa to a few 100 kPa, a range that coincides with the moduli of cells and human soft tissues. This property would allow for this hydrogel to be used in vivo with maximal mechanical compatibility with human soft tissues. In vitro experiments showed that the hydrogel demonstrated a linear mass erosion profile and a biphasic drug (doxorubicin release profile: Phase I was primarily driven by diffusion and Phase II was driven by hydrogel erosion. The diffusion mechanism was modeled with the First Order equation and the erosion mechanism with the Hopfenberg equation. This established fitting model could be used to predict releases with other drugs and estimate the composition of the hydrogel required to achieve a desired release rate.

Auditing for Score Inflation Using Self-Monitoring Assessments: Findings from Three Pilot Studies

Science.gov (United States)

Koretz, Daniel; Jennings, Jennifer L.; Ng, Hui Leng; Yu, Carol; Braslow, David; Langi, Meredith

2016-01-01

Test-based accountability often produces score inflation. Most studies have evaluated inflation by comparing trends on a high-stakes test and a lower stakes audit test. However, Koretz and Beguin (2010) noted weaknesses of audit tests and suggested self-monitoring assessments (SMAs), which incorporate audit items into high-stakes tests. This…

Characterization of elasticity and hydration of composite hydrogel based on collagen-iota carrageenan as a corneal tissue engineering

Science.gov (United States)

Rinawati, M.; Triastuti, J.; Pursetyo, K. T.

2018-04-01

The cornea is a refractive element of the eye that serves to continue the stimulation of light into the eye it has a clear, transparent, elastic and relatively thick tissue. Factors caused corneal blindness, are dystrophy, keratoconus, corneal scaring. Hydrogels can be made from polysaccharide derivatives that have gelation properties such as iota carrageenan. Therefore, it is a need to develop composite hydrogel based collagen-iota carragenan as an engineeried corneal tissue with high elasticity and hydration properties. Collagen hydrogel has a maximum water content an has equlibrium up to 40 %, less than the human cornea, 81 % and under normal hydration conditions, the human cornea can transmit 87 % of visible light. In addition, the refractive index on the surface of the cornea with air is 1.375-1.380. Based on this study, it is necessary to conduct research on the development and composition of hydrogel composite collagen-iota carrageen hydrogen based on. The best result was K5 (5:5) treatment, which has the equilibrium water content of 87.07 % and viscosity of 10.7346 Pa.s.

Mussel-Inspired Self-Healing Double-Cross-Linked Hydrogels by Controlled Combination of Metal Coordination and Covalent Cross-Linking

DEFF Research Database (Denmark)

Andersen, Amanda; Krogsgaard, Marie; Birkedal, Henrik

2018-01-01

a catechol-based hydrogel design that allows for the degree of oxidative covalent cross-linking to be controlled. Double cross-linked hydrogels with tunable stiffness are constructed by adding the oxidizable catechol analogue, tannic acid, to an oxidation-resistant hydrogel construct held together...... by coordination of the dihydroxy functionality of 1-(2'-carboxyethyl)-2-methyl-3-hydroxy-4-pyridinone to trivalent metal ions. By varying the amount of tannic acid, the hydrogel stiffness can be customized to a given application while retaining the self-healing capabilities of the hydrogel's coordination chemical...

Macroporous modified poly (vinyl alcohol) hydrogels with charged groups for tissue engineering: Preparation and in vitro evaluation

Energy Technology Data Exchange (ETDEWEB)

Drozdova, Maria G., E-mail: drozdovamg@gmail.com [Polymers for Biology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, Moscow 117997 (Russian Federation); Zaytseva-Zotova, Daria S. [Polymers for Biology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, Moscow 117997 (Russian Federation); Akasov, Roman A. [Polymers for Biology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, Moscow 117997 (Russian Federation); Sechenov First Moscow State Medical University, Institute for Regenerative Medicine, Trubetskaya str., 8/2, Moscow 119048 (Russian Federation); Golunova, Anna S.; Artyukhov, Alexander A. [D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Square 9, Moscow 125047 (Russian Federation); Udartseva, Olga O.; Andreeva, Elena R. [Institute of Biomedical Problems of Russian Academy of Sciences, Khoroshevskoe Shosse 76a, Moscow 123007 (Russian Federation); Lisovyy, Denis E.; Shtilman, Michael I. [D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Square 9, Moscow 125047 (Russian Federation); Markvicheva, Elena A. [Polymers for Biology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Miklukho-Maklaya str., 16/10, Moscow 117997 (Russian Federation)

2017-06-01

Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical applications, including tissue engineering, due to their biocompatibility, high water solubility, low protein adsorption, and chemical stability. However, non-charged surface of PVA-based hydrogels is not optimal for cell adhesion and spreading. Here, cross-linked macroporous hydrogels based on low molecular weight acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity, charged groups were introduced to the hydrogel composition. For this purpose, Acr-PVA was copolymerized with either negatively charged acrylic acid (AA) or positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A surface charge of the obtained hydrogels was found to be in function of the co-monomer type and content. Confocal microscopy observations confirmed that adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA monomer content from 5 to 15 mol% resulted in the enhancement of cell viability which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non-modified Acr-PVA hydrogel sample. - Highlights: • To enhance cell affinity, acrylated PVA hydrogel was modified with AA or DEAEMA monomers. • Cell adhesion and spreading were found to depend on the co-monomer type and content. • Proliferation of L929 fibroblasts and stem cells increased on the modified hydrogels.

Macroporous modified poly (vinyl alcohol) hydrogels with charged groups for tissue engineering: Preparation and in vitro evaluation

International Nuclear Information System (INIS)

Drozdova, Maria G.; Zaytseva-Zotova, Daria S.; Akasov, Roman A.; Golunova, Anna S.; Artyukhov, Alexander A.; Udartseva, Olga O.; Andreeva, Elena R.; Lisovyy, Denis E.; Shtilman, Michael I.; Markvicheva, Elena A.

2017-01-01

Poly(vinyl alcohol) (PVA) hydrogels are widely employed for various biomedical applications, including tissue engineering, due to their biocompatibility, high water solubility, low protein adsorption, and chemical stability. However, non-charged surface of PVA-based hydrogels is not optimal for cell adhesion and spreading. Here, cross-linked macroporous hydrogels based on low molecular weight acrylated PVA (Acr-PVA) was synthesized by modification of the pendant alcohol groups on the PVA with glycidyl methacrylate (GMA). To enhance cell affinity, charged groups were introduced to the hydrogel composition. For this purpose, Acr-PVA was copolymerized with either negatively charged acrylic acid (AA) or positively charged 2-(diethylamino) ethyl methacrylate (DEAEMA) monomers. A surface charge of the obtained hydrogels was found to be in function of the co-monomer type and content. Confocal microscopy observations confirmed that adhesion and spreading of both mouse fibroblasts (L929) and human mesenchymal stem cells (hMSC) on the modified Acr-PVA-AA and Acr-PVA-DEAEMA hydrogels were better than those on the non-modified Acr-PVA hydrogel. The increase of DEAEMA monomer content from 5 to 15 mol% resulted in the enhancement of cell viability which was 1.5-fold higher for Acr-PVA-DEAEMA-15 hydrogel than that of the non-modified Acr-PVA hydrogel sample. - Highlights: • To enhance cell affinity, acrylated PVA hydrogel was modified with AA or DEAEMA monomers. • Cell adhesion and spreading were found to depend on the co-monomer type and content. • Proliferation of L929 fibroblasts and stem cells increased on the modified hydrogels.

Soft inflation

Science.gov (United States)

Berkin, Andrew L.; Maeda, Kei-Ichi; Yokoyama, Junichi

1990-01-01

The cosmology resulting from two coupled scalar fields was studied, one which is either a new inflation or chaotic type inflation, and the other which has an exponentially decaying potential. Such a potential may appear in the conformally transformed frame of generalized Einstein theories like the Jordan-Brans-Dicke theory. The constraints necessary for successful inflation are examined. Conventional GUT models such as SU(5) were found to be compatible with new inflation, while restrictions on the self-coupling constant are significantly loosened for chaotic inflation.

Bioinspired Nanocomposite Hydrogels with Highly Ordered Structures.

Science.gov (United States)

Zhao, Ziguang; Fang, Ruochen; Rong, Qinfeng; Liu, Mingjie

2017-12-01

In the human body, many soft tissues with hierarchically ordered composite structures, such as cartilage, skeletal muscle, the corneas, and blood vessels, exhibit highly anisotropic mechanical strength and functionality to adapt to complex environments. In artificial soft materials, hydrogels are analogous to these biological soft tissues due to their "soft and wet" properties, their biocompatibility, and their elastic performance. However, conventional hydrogel materials with unordered homogeneous structures inevitably lack high mechanical properties and anisotropic functional performances; thus, their further application is limited. Inspired by biological soft tissues with well-ordered structures, researchers have increasingly investigated highly ordered nanocomposite hydrogels as functional biological engineering soft materials with unique mechanical, optical, and biological properties. These hydrogels incorporate long-range ordered nanocomposite structures within hydrogel network matrixes. Here, the critical design criteria and the state-of-the-art fabrication strategies of nanocomposite hydrogels with highly ordered structures are systemically reviewed. Then, recent progress in applications in the fields of soft actuators, tissue engineering, and sensors is highlighted. The future development and prospective application of highly ordered nanocomposite hydrogels are also discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Free radical scavenging injectable hydrogels for regenerative therapy

Energy Technology Data Exchange (ETDEWEB)

Komeri, Remya [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State (India); Thankam, Finosh Gnanaprakasam [Dept. of Biomedical Sciences, Creighton University, 2500 California Plaza, Omaha NE68178 (United States); Muthu, Jayabalan, E-mail: mjayabalan52@gmail.com [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State (India)

2017-02-01

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07 kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. - Graphical abstract: Injectable hydrogel with inherent free radical scavenging property for regenerative tissue engineering application. - Highlights: • Novel injectable hydrogel (PEAX-P) is prepared using D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer

Free radical scavenging injectable hydrogels for regenerative therapy

International Nuclear Information System (INIS)

Komeri, Remya; Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2017-01-01

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07 kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. - Graphical abstract: Injectable hydrogel with inherent free radical scavenging property for regenerative tissue engineering application. - Highlights: • Novel injectable hydrogel (PEAX-P) is prepared using D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing (China); Tan, Huaping, E-mail: hptan@njust.edu.cn [School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing (China); Hu, Xiaohong [School of Material Engineering, Jinling Institute of Technology, Nanjing (China)

2015-11-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels–Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37 °C were studied. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. - Highlights: • A biodegradable hyaluronic acid hydrogel was crosslinked via aqueous Diels–Alder chemistry. • Dexamethasone was covalently immobilized into the hyaluronic acid hydrogel via aqueous Diels–Alder chemistry. • Dexamethasone could be released from the Diels–Alder hyaluronic acid hydrogel in a controlled fashion.

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels–Alder chemistry for adipose tissue engineering

International Nuclear Information System (INIS)

Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

2015-01-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels–Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37 °C were studied. The results demonstrated that the aqueous Diels–Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. - Highlights: • A biodegradable hyaluronic acid hydrogel was crosslinked via aqueous Diels–Alder chemistry. • Dexamethasone was covalently immobilized into the hyaluronic acid hydrogel via aqueous Diels–Alder chemistry. • Dexamethasone could be released from the Diels–Alder hyaluronic acid hydrogel in a controlled fashion

Foamed oligo(poly(ethylene glycol)fumarate) hydrogels as versatile prefabricated scaffolds for tissue engineering.

Science.gov (United States)

Henke, Matthias; Baumer, Julia; Blunk, Torsten; Tessmar, Joerg

2014-03-01

Radically cross-linked hydrogels are frequently used as cell carriers due to their excellent biocompatibility and their tissue-like mechanical properties. Through frequent investigation, PEG-based polymers such as oligo(poly(ethylene glycol)fumarate [OPF] have proven to be especially suitable as cell carriers by encapsulating cells during hydrogel formation. In some cases, NaCl or biodegradable gelatin microparticles were added prior to cross-linking in order to provide space for the proliferating cells, which would otherwise stay embedded in the hydrogel matrix. However, all of these immediate cross-linking procedures involve time consuming sample preparation and sterilization directly before cell culture and often show notable swelling after their preparation. In this study, ready to use OPF-hydrogel scaffolds were prepared by gas foaming, freeze drying, individual packing into bags and subsequent γ-sterilization. The scaffolds could be stored and used "off-the-shelf" without any need for further processing prior to cell culture. Thus the handling was simplified and the sterility of the cell carrier was assured. Further improvement of the gel system was achieved using a two component injectable system, which may be used for homogenous injection molding in order to create individually shaped three dimensional scaffolds. In order to evaluate the suitability of the scaffolds for tissue engineering, constructs were seeded with juvenile bovine chondrocytes and cultured for 28 days. Cross-sections of the respective constructs showed an intense and homogenous red staining of GAG with safranin O, indicating a homogenous cell distribution within the scaffolds and the production of substantial amounts of GAG-rich matrix. Copyright © 2012 John Wiley & Sons, Ltd.

Economic benefit of a polyacrylate-based hydrogel compared to an amorphous hydrogel in wound bed preparation of venous leg ulcers

Directory of Open Access Journals (Sweden)

Kaspar D

2015-04-01

Full Text Available Daniela Kaspar,1 Jörg Linder,1 Petra Zöllner,1 Ulrich Simon,2 Hans Smola1,31Medical Competence Centre, Paul Hartmann AG, Heidenheim, Germany; 2Scientific Computing Centre, Ulm University, Ulm, Germany; 3Department of Dermatology, University of Cologne, Cologne, GermanyObjective: To assess the cost-effectiveness of a polyacrylate (PA-based hydrogel compared to an amorphous hydrogel in wound bed preparation for venous leg ulcers.Method: A cost-effectiveness analysis was undertaken alongside a multicenter, randomized controlled trial performed in France. A total of 75 patients with venous leg ulcers extensively covered with fibrin and necrotic tissue were randomized to a PA-containing hydrogel or an amorphous hydrogel. Wounds were treated for 14 days and costs were estimated from the German payer's perspective. Medical costs included study treatment, wound treatment supply, and labor time. The clinical benefit was expressed as the number of patients with wounds >50% covered with granulation tissue within 14 days. The incremental cost-effectiveness ratio (ICER was expressed as the additional cost spent with >50% granulation tissue per day per patient within 14 days of leg ulcer care.Results: Because of individual pricing of wound dressings in hospitals, cost data were derived from the outpatient sector. A total of 33 patients were treated using the PA-based hydrogel and 37 patients using the amorphous hydrogel. The estimated total direct costs per patient and per 14 days of therapy were €306 for both treatment groups. However, with the PA-based hydrogel, 2.5 additional days with wounds covered >50% with granulation tissues were gained within 14 days of leg ulcer care compared to the comparator. The ICER was €0 per additional day spent with >50% granulation tissue.Conclusion: Although there were a greater number of dressing changes in the PA-based hydrogel treatment, the total treatment cost for 14 days of leg ulcer care was the same for both

Hydrogel-Tissue Chemistry: Principles and Applications.

Science.gov (United States)

Gradinaru, Viviana; Treweek, Jennifer; Overton, Kristin; Deisseroth, Karl

2018-05-20

Over the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three-dimensional positioning and/or brain-wide wiring of those very same neurons-even within vertebrate brains. This new approach and its variants, as applied to neuroscience, are beginning to illuminate the fundamental cellular and chemical representations of sensation, cognition, and action. More generally, reimagining metazoans as metareactants-or positionally defined three-dimensional graphs of constituent chemicals made available for ongoing functionalization, transformation, and readout-is stimulating innovation across biology and medicine.

PVA hydrogel properties for biomedical application.

Science.gov (United States)

Jiang, Shan; Liu, Sha; Feng, Wenhao

2011-10-01

PVA has been proposed as a promising biomaterial suitable for tissue mimicking, vascular cell culturing and vascular implanting. In this research, a kind of transparent PVA hydrogel has been investigated in order to mimic the creatural soft tissue deformation during mini-invasive surgery with needle intervention, such as brachytherapy. Three kinds of samples with the same composition of 3 g PVA, 17 g de-ionized water, 80 g dimethyl-sulfoxide but different freeze/thaw cycles have been prepared. In order to investigate the structure and properties of polyvinyl alcohol hydrogel, micro-structure, mechanical property and deformation measurement have been conducted. As the SEM image comparison results show, with the increase of freeze/thaw cycles, PVA hydrogel revealed the similar micro-structure to porcine liver tissue. With uniaxial tensile strength test, the above composition with a five freeze/thaw cycle sample resulted in Young's modulus similar to that of porcine liver's property. Through the comparison of needle insertion deformation experiment and the clinical experiment during brachytherapy, results show that the PVA hydrogel had the same deformation property as prostate tissue. These transparent hydrogel phantom materials can be suitable soft tissue substitutes in needle intervention precision or pre-operation planning studies, particularly in the cases of mimicking creatural tissue deformation and analysing video camera images. Copyright © 2011 Elsevier Ltd. All rights reserved.

Gradient Material Strategies for Hydrogel Optimization in Tissue Engineering Applications

Science.gov (United States)

2018-01-01

Although a number of combinatorial/high-throughput approaches have been developed for biomaterial hydrogel optimization, a gradient sample approach is particularly well suited to identify hydrogel property thresholds that alter cellular behavior in response to interacting with the hydrogel due to reduced variation in material preparation and the ability to screen biological response over a range instead of discrete samples each containing only one condition. This review highlights recent work on cell–hydrogel interactions using a gradient material sample approach. Fabrication strategies for composition, material and mechanical property, and bioactive signaling gradient hydrogels that can be used to examine cell–hydrogel interactions will be discussed. The effects of gradients in hydrogel samples on cellular adhesion, migration, proliferation, and differentiation will then be examined, providing an assessment of the current state of the field and the potential of wider use of the gradient sample approach to accelerate our understanding of matrices on cellular behavior. PMID:29485612

Collagen hydrogels incorporated with surface-aminated mesoporous nanobioactive glass: Improvement of physicochemical stability and mechanical properties is effective for hard tissue engineering.

Science.gov (United States)

El-Fiqi, Ahmed; Lee, Jae Ho; Lee, Eun-Jung; Kim, Hae-Won

2013-12-01

Collagen (Col) hydrogels have poor physicochemical and mechanical properties and are susceptible to substantial shrinkage during cell culture, which limits their potential applications in hard tissue engineering. Here, we developed novel nanocomposite hydrogels made of collagen and mesoporous bioactive glass nanoparticles (mBGns) with surface amination, and addressed the effects of mBGn addition (Col:mBG = 2:1, 1:1 and 1:2) and its surface amination on the physicochemical and mechanical properties of the hydrogels. The amination of mBGn was shown to enable chemical bonding with collagen molecules. As a result, the nanocomposite hydrogels exhibited a significantly improved physicochemical and mechanical stability. The hydrolytic and enzymatic degradation of the Col-mBGn hydrogels were slowed down due to the incorporation of mBGn and its surface amination. The mechanical properties of the hydrogels, specifically the resistance to loading as well as the stiffness, significantly increased with the addition of mBGn and its aminated form, as assessed by a dynamic mechanical analysis. Mesenchymal stem cells cultivated within the Col-mBGn hydrogels were highly viable, with enhanced cytoskeletal extensions, due to the addition of surface aminated mBGn. While the Col hydrogel showed extensive shrinkage (down to ∼20% of initial size) during a few days of culture, the shrinkage of the mBGn-added hydrogel was substantially reduced, and the aminated mBGn-added hydrogel had no observable shrinkage over 21 days. Results demonstrated the effective roles of aminated mBGn in significantly improving the physicochemical and mechanical properties of Col hydrogel, which are ultimately favorable for applications in stem cell culture for bone tissue engineering. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Free radical scavenging injectable hydrogels for regenerative therapy.

Science.gov (United States)

Komeri, Remya; Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

2017-02-01

Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Mussel-Inspired Dopamine and Carbon Nanotube Leading to a Biocompatible Self-Rolling Conductive Hydrogel Film.

Science.gov (United States)

Jiang, Junzi; Huang, Yong; Wang, Yitian; Xu, Hui; Xing, Malcolm; Zhong, Wen

2017-08-18

We report a novel self-rolling, conductive, and biocompatible multiwall carbon nanotube (MWCNT)-dopamine-polyethylene glycol (PEG) hydrogel film. The gel can self-fold into a thin tube when it is transferred from a glass slide to an aqueous environment, regardless of the concentrations of the MWCNT. The film presents a highly organized pattern, which results from the self-assembly of hydrophilic dopamine and hydrophobic carbon nanotubes. By exploring the biomedical potential, we found that MWCNT-included rolled film is nontoxic and can promote cell growth. For further functional verification by qPCR (quantitative polymerase chain reaction), bone marrow derived mesenchymal cells present higher levels of osteogenic differentiations in response to a higher concentration of CNTs. The results suggest that the self-rolling, conductive CNT-dopamine-PEG hydrogel could have multiple potentials, including biomedical usage and as a conductive biosensor.

Self-Healing and Thermo-Responsive Dual-Crosslinked Alginate Hydrogels based on Supramolecular Inclusion Complexes

Science.gov (United States)

Miao, Tianxin; Fenn, Spencer L.; Charron, Patrick N.; Oldinski, Rachael A.

2015-01-01

β-cyclodextrin (β-CD), with a lipophilic inner cavity and hydrophilic outer surface, interacts with a large variety of non-polar guest molecules to form non-covalent inclusion complexes. Conjugation of β-CD onto biomacromolecules can form physically-crosslinked hydrogel networks upon mixing with a guest molecule. Herein describes the development and characterization of self-healing, thermo-responsive hydrogels, based on host-guest inclusion complexes between alginate-graft-β-CD and Pluronic® F108 (poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol)). The mechanics, flow characteristics, and thermal response were contingent on the polymer concentrations, and the host-guest molar ratio. Transient and reversible physical crosslinking between host and guest polymers governed self-assembly, allowing flow under shear stress, and facilitating complete recovery of the material properties within a few seconds of unloading. The mechanical properties of the dual-crosslinked, multi-stimuli responsive hydrogels were tuned as high as 30 kPa at body temperature, and are advantageous for biomedical applications such as drug delivery and cell transplantation. PMID:26509214

Sequentially-crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications.

Science.gov (United States)

Rizwan, Muhammad; Peh, Gary S L; Ang, Heng-Pei; Lwin, Nyein Chan; Adnan, Khadijah; Mehta, Jodhbir S; Tan, Wui Siew; Yim, Evelyn K F

2017-03-01

Naturally-bioactive hydrogels like gelatin provide favorable properties for tissue-engineering but lack sufficient mechanical strength for use as implantable tissue engineering substrates. Complex fabrication or multi-component additives can improve material strength, but often compromises other properties. Studies have shown gelatin methacrylate (GelMA) as a bioactive hydrogel with diverse tissue growth applications. We hypothesize that, with suitable material modifications, GelMA could be employed for growth and implantation of tissue-engineered human corneal endothelial cell (HCEC) monolayer. Tissue-engineered HCEC monolayer could potentially be used to treat corneal blindness due to corneal endothelium dysfunction. Here, we exploited a sequential hybrid (physical followed by UV) crosslinking to create an improved material, named as GelMA+, with over 8-fold increase in mechanical strength as compared to regular GelMA. The presence of physical associations increased the subsequent UV-crosslinking efficiency resulting in robust materials able to withstand standard endothelium insertion surgical device loading. Favorable biodegradation kinetics were also measured in vitro and in vivo. We achieved hydrogels patterning with nano-scale resolution by use of oxygen impermeable stamps that overcome the limitations of PDMS based molding processes. Primary HCEC monolayers grown on GelMA+ carrier patterned with pillars of optimal dimension demonstrated improved zona-occludin-1 expression, higher cell density and cell size homogeneity, which are indications of functionally-superior transplantable monolayers. The hybrid crosslinking and fabrication approach offers potential utility for development of implantable tissue-engineered cell-carrier constructs with enhanced bio-functional properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

A self-standing hydrogel neutral electrolyte for high voltage and safe flexible supercapacitors

Science.gov (United States)

Batisse, N.; Raymundo-Piñero, E.

2017-04-01

The development of safe flexible supercapacitors implies the use of new non-liquid electrolytes for avoiding device leakage which combine mechanical properties and electrochemical performance. In this sense, hydrogel electrolytes composed of a solid non-conductive matrix holding an aqueous electrolytic phase are a reliable solution. In this work, we propose a green physical route for producing self-standing hydrogel films from a PVA polymer based on the freezing/thawing method without using chemical cross-linking agents. Moreover, a neutral electrolytic phase as Na2SO4 is used for reaching higher cell voltages than in an acidic or basic electrolyte. Such new PVA-Na2SO4 hydrogel electrolyte, which also acts as separator, allows reaching voltages windows as high as 1.8 V in a symmetric carbon/carbon supercapacitor with optimal capacitance retention through thousands of cycles. Additionally, in reason of the fast mobility of the ions inside of the polymeric matrix, the hydrogel electrolyte based supercapacitor keeps the power density of the liquid electrolyte device.

A Hydrogel Model Incorporating 3D-Plotted Hydroxyapatite for Osteochondral Tissue Engineering

Directory of Open Access Journals (Sweden)

Michal Bartnikowski

2016-04-01

Full Text Available The concept of biphasic or multi-layered compound scaffolds has been explored within numerous studies in the context of cartilage and osteochondral regeneration. To date, no system has been identified that stands out in terms of superior chondrogenesis, osteogenesis or the formation of a zone of calcified cartilage (ZCC. Herein we present a 3D plotted scaffold, comprising an alginate and hydroxyapatite paste, cast within a photocrosslinkable hydrogel made of gelatin methacrylamide (GelMA, or GelMA with hyaluronic acid methacrylate (HAMA. We hypothesized that this combination of 3D plotting and hydrogel crosslinking would form a high fidelity, cell supporting structure that would allow localization of hydroxyapatite to the deepest regions of the structure whilst taking advantage of hydrogel photocrosslinking. We assessed this preliminary design in terms of chondrogenesis in culture with human articular chondrocytes, and verified whether the inclusion of hydroxyapatite in the form presented had any influence on the formation of the ZCC. Whilst the inclusion of HAMA resulted in a better chondrogenic outcome, the effect of HAP was limited. We overall demonstrated that formation of such compound structures is possible, providing a foundation for future work. The development of cohesive biphasic systems is highly relevant for current and future cartilage tissue engineering.

Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair

NARCIS (Netherlands)

Lu, S.; Lam, J.; Trachtenberg, J.E.; Lee, E.J.; Seyednejad, H.; van den Beucken, J.J.; Tabata, Y.; Wong, M.E.; Jansen, J.A.; Mikos, A.G.; Kasper, F.K.

2014-01-01

The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the

Effect of microcavitary alginate hydrogel with different pore sizes on chondrocyte culture for cartilage tissue engineering

International Nuclear Information System (INIS)

Zeng, Lei; Yao, Yongchang; Wang, Dong-an; Chen, Xiaofeng

2014-01-01

In our previous work, a novel microcavitary hydrogel was proven to be effective for proliferation of chondrocytes and maintenance of chondrocytic phenotype. In present work, we further investigated whether the size of microcavity would affect the growth and the function of chondrocytes. By changing the stirring rate, gelatin microspheres in different sizes including small size (80–120 μm), middle size (150–200 μm) and large size (250–300 μm) were prepared. And then porcine chondrocytes were encapsulated into alginate hydrogel with various sizes of gelatin microspheres. Cell Counting Kit-8 (CCK-8), Live/dead staining and real-time PCR were used to analyze the effect of the pore size on cell proliferation and expression of specific chondrocytic genes. According to all the data, cells cultivated in microcavitary hydrogel, especially in small size, had preferable abilities of proliferation and higher expression of cartilaginous markers including type II collagen, aggrecan and cartilage oligomeric matrix protein (COMP). Furthermore, it was shown by western blot assay that the culture of chondrocytes in microcavitary hydrogel could improve the proliferation of cells potentially by inducing the Erk1/2-MAPK pathway. Taken together, this study demonstrated that chondrocytes favored microcavitary alginate hydrogel with pore size within the range of 80–120 μm for better growth and ECM synthesis, in which Erk1/2 pathway was involved. This culture system would be promising for cartilage tissue engineering. - Highlights: • A novel model with microcavitary structure was set up to study the interaction between cells and materials. • Microcavitary alginate hydrogel could enhance the proliferation of chondrocytes and promote the expression of cartilaginous genes as compared with plain alginate hydrogel. • Cells in microcavitary alginate hydrogel with pore size within the range of 80–120 μm were capable of better growth and ECM synthesis

Effect of microcavitary alginate hydrogel with different pore sizes on chondrocyte culture for cartilage tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Zeng, Lei; Yao, Yongchang [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Wang, Dong-an, E-mail: DAWang@ntu.edu.sg [National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457 (Singapore); Chen, Xiaofeng, E-mail: chenxf@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China)

2014-01-01

In our previous work, a novel microcavitary hydrogel was proven to be effective for proliferation of chondrocytes and maintenance of chondrocytic phenotype. In present work, we further investigated whether the size of microcavity would affect the growth and the function of chondrocytes. By changing the stirring rate, gelatin microspheres in different sizes including small size (80–120 μm), middle size (150–200 μm) and large size (250–300 μm) were prepared. And then porcine chondrocytes were encapsulated into alginate hydrogel with various sizes of gelatin microspheres. Cell Counting Kit-8 (CCK-8), Live/dead staining and real-time PCR were used to analyze the effect of the pore size on cell proliferation and expression of specific chondrocytic genes. According to all the data, cells cultivated in microcavitary hydrogel, especially in small size, had preferable abilities of proliferation and higher expression of cartilaginous markers including type II collagen, aggrecan and cartilage oligomeric matrix protein (COMP). Furthermore, it was shown by western blot assay that the culture of chondrocytes in microcavitary hydrogel could improve the proliferation of cells potentially by inducing the Erk1/2-MAPK pathway. Taken together, this study demonstrated that chondrocytes favored microcavitary alginate hydrogel with pore size within the range of 80–120 μm for better growth and ECM synthesis, in which Erk1/2 pathway was involved. This culture system would be promising for cartilage tissue engineering. - Highlights: • A novel model with microcavitary structure was set up to study the interaction between cells and materials. • Microcavitary alginate hydrogel could enhance the proliferation of chondrocytes and promote the expression of cartilaginous genes as compared with plain alginate hydrogel. • Cells in microcavitary alginate hydrogel with pore size within the range of 80–120 μm were capable of better growth and ECM synthesis.

Anisotropic dehydration of hydrogel surfaces.

Science.gov (United States)

Kaklamani, Georgia; Cheneler, David; Grover, Liam M; Adams, Michael J; Anastasiadis, Spiros H; Bowen, James

2017-12-01

Efforts to develop tissue-engineered skin for regenerative medicine have explored natural, synthetic, and hybrid hydrogels. The creation of a bilayer material, with the stratification exhibited by native skin, is a complex problem. The mechanically robust, waterproof epidermis presents the stratum corneum at the tissue/air interface, which confers many of these protective properties. In this work, we explore the effect of high temperatures on alginate hydrogels, which are widely employed for tissue engineering due to their excellent mechanical properties and cellular compatibility. In particular, we investigate the rapid dehydration of the hydrogel surface which occurs following local exposure to heated surfaces with temperatures in the range 100-200 °C. We report the creation of a mechanically strengthened hydrogel surface, with improved puncture resistance and increased coefficient of friction, compared to an unheated surface. The use of a mechanical restraint during heating promoted differences in the rate of mass loss; the rate of temperature increase within the hydrogel, in the presence and absence of restraint, is simulated and discussed. It is hoped that the results will be of use in the development of processes suitable for preparing skin-like analogues; application areas could include wound healing and skin restoration.

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels-Alder chemistry for adipose tissue engineering.

Science.gov (United States)

Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

2015-11-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels-Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37°C were studied. The results demonstrated that the aqueous Diels-Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. Copyright © 2015. Published by Elsevier B.V.

Tissue integration of polyacrylamide hydrogel: an experimental study of periurethral, perivesical, and mammary gland tissue in the pig

DEFF Research Database (Denmark)

Christensen, Lise H; Nielsen, John B; Mouritsen, Lone

2008-01-01

BACKGROUND Polyacrylamide hydrogel (PAAG) is a nondegradable water-based polymer with high viscoelasticity. The gel is used as a tissue filler, the only risk being prolonged infection with anaerobic, contaminating microorganisms if not treated early with broad-spectrum antibiotics. OBJECTIVE...... With silicone gel as reference, PAAG tissue integration and migration was studied in a longitudinal study of the pig. MATERIALS AND METHODS Forty-one pigs were used. PAAG and silicone gel were injected into mammary tissue, and PAAG was injected into urethral or bladder wall or the anal canal. Tissues...... and regional lymph nodes were examined at 1, 1 1/2, 3, 3 1/2, 6, 12, and 14 months, and other lymph nodes and organs were examined at 1, 6, 12, and 14 months. RESULTS PAAG was invaded by macrophages and giant cells that were gradually replaced by a network of fibrous tissue. Silicone gel was seen inside...

An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering

Science.gov (United States)

Zhao, Liang; Weir, Michael D.; Xu, Hockin H. K.

2010-01-01

The need for bone repair has increased as the population ages. Stem cell-scaffold approaches hold immense promise for bone tissue engineering. However, currently, preformed scaffolds for cell delivery have drawbacks including the difficulty to seed cells deep into the scaffold, and inability for injection in minimally invasive surgeries. Current injectable polymeric carriers and hydrogels are too weak for load-bearing orthopedic application. The objective of this study was to develop an injectable and mechanically-strong stem cell construct for bone tissue engineering. Calcium phosphate cement (CPC) paste was combined with hydrogel microbeads encapsulating human umbilical cord mesenchymal stem cells (hUCMSCs). The hUCMSC-encapsulating composite paste was fully injectable under small injection forces. Cell viability after injection matched that in hydrogel without CPC and without injection. Mechanical properties of the construct matched the reported values of cancellous bone, and were much higher than previous injectable polymeric and hydrogel carriers. hUCMSCs in the injectable constructs osteodifferentiated, yielding high alkaline phosphatase, osteocalcin, collagen type I, and osterix gene expressions at 7 d, which were 50–70 fold higher than those at 1 d. Mineralization by the hUCMSCs at 14 d was 100-fold that at 1 d. In conclusion, a fully-injectable, mechanically-strong, stem cell-CPC scaffold construct was developed. The encapsulated hUCMSCs remained viable, osteodifferentiated, and synthesized bone minerals. The new injectable stem cell construct with load-bearing capability may enhance bone regeneration in minimally-invasive and other orthopedic surgeries. PMID:20570346

Elastic hydrogel substrate supports robust expansion of murine myoblasts and enhances their engraftment

International Nuclear Information System (INIS)

Ding, Ke; Yang, Zhong; Xu, Jian-zhong; Liu, Wen-ying; Zeng, Qiang; Hou, Fang; Lin, Sen

2015-01-01

The application of satellite cell-derived myoblasts in regenerative medicine has been restricted by the rapid loss of stemness during in vitro cell expansion using traditional culture systems. However, studies published in the past decade have highlighted the influence of substrate elasticity on stem cell fate and revealed that culture on a soft hydrogel substrate can promote self-renewal and prolong the regenerative potential of muscle stem cells. Whether hydrogel substrates have similar effects after long-term robust expansion remains to be determined. Herein we prepared an elastic chitosan/beta-glycerophosphate/collagen hydrogel mimicking the soft microenvironment of muscle tissues for use as the substrate for satellite cell culture and investigated its influence on long-term cell expansion. After 20 passages in culture, satellite cell-derived myoblasts cultured on our hydrogel substrate exhibited significant improvements in proliferation capability, cell viability, colony forming frequency, and potential for myogenic differentiation compared to those cultured on a routine rigid culture surface. Immunochemical staining and western blot analysis both confirmed that myoblasts cultured on the hydrogel substrate expressed higher levels of several differentiation-related markers, including Pax7, Pax3, and SSEA-1, and a lower level of MyoD compared to myoblasts cultured on rigid culture plates (all p<0.05). After transplantation into the tibialis anterior of nude mice, myoblasts that had been cultured on the hydrogel substrate demonstrated a significantly greater engraftment efficacy than those cultured on the traditional surface. Collectively, these results indicate that the elastic hydrogel substrate supported robust expansion of murine myoblasts and enhanced their engraftment in vivo. - Highlights: • An elastic hydrogel was designed to mimic the pliable muscle tissue microenvironment. • Myoblasts retained their stemness in long-term culture on the elastic

Elastic hydrogel substrate supports robust expansion of murine myoblasts and enhances their engraftment

Energy Technology Data Exchange (ETDEWEB)

Ding, Ke, E-mail: dk1118@yeah.net [Department of Pediatric Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072 (China); Yang, Zhong [Department of Clinical Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xu, Jian-zhong, E-mail: xjzspine@163.com [Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Liu, Wen-ying; Zeng, Qiang; Hou, Fang [Department of Pediatric Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072 (China); Lin, Sen [Department of Anatomy and Histology & Embryology, Chengdu Medical College, Chengdu 610500 (China)

2015-09-10

The application of satellite cell-derived myoblasts in regenerative medicine has been restricted by the rapid loss of stemness during in vitro cell expansion using traditional culture systems. However, studies published in the past decade have highlighted the influence of substrate elasticity on stem cell fate and revealed that culture on a soft hydrogel substrate can promote self-renewal and prolong the regenerative potential of muscle stem cells. Whether hydrogel substrates have similar effects after long-term robust expansion remains to be determined. Herein we prepared an elastic chitosan/beta-glycerophosphate/collagen hydrogel mimicking the soft microenvironment of muscle tissues for use as the substrate for satellite cell culture and investigated its influence on long-term cell expansion. After 20 passages in culture, satellite cell-derived myoblasts cultured on our hydrogel substrate exhibited significant improvements in proliferation capability, cell viability, colony forming frequency, and potential for myogenic differentiation compared to those cultured on a routine rigid culture surface. Immunochemical staining and western blot analysis both confirmed that myoblasts cultured on the hydrogel substrate expressed higher levels of several differentiation-related markers, including Pax7, Pax3, and SSEA-1, and a lower level of MyoD compared to myoblasts cultured on rigid culture plates (all p<0.05). After transplantation into the tibialis anterior of nude mice, myoblasts that had been cultured on the hydrogel substrate demonstrated a significantly greater engraftment efficacy than those cultured on the traditional surface. Collectively, these results indicate that the elastic hydrogel substrate supported robust expansion of murine myoblasts and enhanced their engraftment in vivo. - Highlights: • An elastic hydrogel was designed to mimic the pliable muscle tissue microenvironment. • Myoblasts retained their stemness in long-term culture on the elastic

Mechanical loading regulates human MSC differentiation in a multi-layer hydrogel for osteochondral tissue engineering.

Science.gov (United States)

Steinmetz, Neven J; Aisenbrey, Elizabeth A; Westbrook, Kristofer K; Qi, H Jerry; Bryant, Stephanie J

2015-07-01

A bioinspired multi-layer hydrogel was developed for the encapsulation of human mesenchymal stem cells (hMSCs) as a platform for osteochondral tissue engineering. The spatial presentation of biochemical cues, via incorporation of extracellular matrix analogs, and mechanical cues, via both hydrogel crosslink density and externally applied mechanical loads, were characterized in each layer. A simple sequential photopolymerization method was employed to form stable poly(ethylene glycol)-based hydrogels with a soft cartilage-like layer of chondroitin sulfate and low RGD concentrations, a stiff bone-like layer with high RGD concentrations, and an intermediate interfacial layer. Under a compressive load, the variation in hydrogel stiffness within each layer produced high strains in the soft cartilage-like layer, low strains in the stiff bone-like layer, and moderate strains in the interfacial layer. When hMSC-laden hydrogels were cultured statically in osteochondral differentiation media, the local biochemical and matrix stiffness cues were not sufficient to spatially guide hMSC differentiation after 21 days. However dynamic mechanical stimulation led to differentially high expression of collagens with collagen II in the cartilage-like layer, collagen X in the interfacial layer and collagen I in the bone-like layer and mineral deposits localized to the bone layer. Overall, these findings point to external mechanical stimulation as a potent regulator of hMSC differentiation toward osteochondral cellular phenotypes. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Co-micellized Pluronic mixture with thermo-sensitivity and residence stability as an injectable tissue adhesion barrier hydrogel.

Science.gov (United States)

Oh, Se Heang; Kang, Jun Goo; Lee, Jin Ho

2018-01-01

Although the tissue adhesion which leads to various complications frequently occurs after surgery, the development of an ideal tissue adhesion barrier is still a challenge. In this study, a thermo-sensitive hydrogel, which can fulfill the essential requirements of tissue adhesion barrier (that is, ease of handling for surgeon, flowing down prevention after application, stable residence on the injury during wound healing, and no use of toxic additives), was developed using biocompatible polyethylene glycol-polypropylene glycol copolymers (Pluronic F127/F68/P123 mixture). From the in vitro cell culture and in vivo animal study, it was observed that the Pluronic mixtures showed sol-gel transition at approximately body temperature (for easy injection or coating on the injury site and flowing down prevention after application) and prolonged residence stability in aqueous environment (> ∼7 days for stable protection of injury tissues/organs during wound healing), and thus was highly effective for the prevention of tissue adhesion without adverse tissue responses. Based on these results, the Pluronic F127/F68/P123 mixture itself (without any additives) can be a good candidate as an injectable or coatable tissue adhesion barrier hydrogel applicable to various injury tissues in terms of ease of use, effectiveness, and safety. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 172-182, 2018. © 2016 Wiley Periodicals, Inc.

Prevention of filtering surgery failure by subconjunctival injection of a novel peptide hydrogel into rabbit eyes

Energy Technology Data Exchange (ETDEWEB)

Liang Liang [Department of Ophthalmology, The Central Hospital of Wuhan, Wuhan 430014 (China); Xu Xiaoding; Zhang Xianzheng [Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072 (China); Feng Mei; Peng Chong; Jiang Fagang [Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

2010-08-01

A novel biocompatible hydrogel was prepared based on the supramolecular self-assembly of a peptide containing a bioactive RGD (arginine-glycine-aspartic acid) sequence and a hydrophobic N-fluorenyl-9-methoxycarbonyl (FMOC) tail. When the self-assembled peptide hydrogel was administered after the filtering surgery of rabbit eyes, the level of connective tissue growth factor (CTGF) mRNA as well as the mean intraocular pressure (IOP) was significantly lower than that of the control eyes during the 21 postoperative days. The filtration bleb and ultrasound biomicroscopy (UBM) images showed that a patent bleb and a filtration fistula could be found in the surgical site of a rabbit eye during the whole experimental period. Histological analysis further evidenced that the filtering surgical wound healing was a normal healing process without scar formation. This new approach, making use of a self-assembled peptide hydrogel to normalize filtering surgical wound healing, may have potential for glaucoma filtering surgery.

Cellularized cylindrical fiber/hydrogel composites for ligament tissue engineering.

Science.gov (United States)

Thayer, Patrick S; Dimling, Anna F; Plessl, Daniel S; Hahn, Mariah R; Guelcher, Scott A; Dahlgren, Linda A; Goldstein, Aaron S

2014-01-13

Electrospun meshes suffer from poor cell infiltration and limited thickness, which restrict their use to thin tissue applications. Herein, we demonstrate two complementary processes to overcome these limitations and achieve elastomeric composites that may be suitable for ligament repair. First, C3H10T1/2 mesenchymal stem cells were incorporated into electrospun meshes using a hybrid electrospinning/electrospraying process. Second, electrospun meshes were rolled and formed into composites with an interpenetrating polyethylene glycol (PEG) hydrogel network. Stiffer composites were formed from poly(lactic-co-glycolic acid) (PLGA) meshes, while softer and more elastic composites were formed from poly(ester-urethane urea) (PEUUR) meshes. As-spun PLGA and PEUUR rolled meshes had tensile moduli of 19.2 ± 1.9 and 0.86 ± 0.34 MPa, respectively, which changed to 11.6 ± 4.8 and 1.05 ± 0.39 MPa with the incorporation of a PEG hydrogel phase. In addition, cyclic tensile testing indicated that PEUUR-based composites deformed elastically to at least 10%. Finally, C3H10T1/2 cells incorporated into electrospun meshes survived the addition of the PEG phase and remained viable for up to 5 days. These results indicate that the fabricated cellularized composites are support cyclic mechanical conditioning, and have potential application in ligament repair.

RANKL release from self-assembling nanofiber hydrogels for inducing osteoclastogenesis in vitro.

Science.gov (United States)

Xing, James Z; Lu, Lei; Unsworth, Larry D; Major, Paul W; Doschak, Michael R; Kaipatur, Neelambar R

2017-02-01

To develop a nanofiber hydrogel (NF-hydrogel) for sustained and controlled release of the recombinant receptor activator of NF-kB ligand; (RANKL) and to characterize the release kinetics and bioactivity of the released RANKL. Various concentrations of fluorescently-labelled RANKL protein were added to NF-hydrogels, composed of Acetyl-(Arg-Ala-Asp-Ala) 4 -CONH 2 [(RADA) 4 ] of different concentrations, to investigate the resulting in vitro release rates. The nano-structures of NF-hydrogel, with and without RANKL, were determined using atomic force microscopy (AFM). Released RANKL was further analyzed for changes in secondary and tertiary structure using CD spectroscopy and fluorescent emission spectroscopy, respectively. Bioactivity of released RANKL protein was determined using NFATc1 gene expression and tartrate resistant acid phosphatase (TRAP) activity of osteoclast cells as biomarkers. NF-hydrogel concentration dependent sustained release of RANKL protein was measured at concentrations between 0.5 and 2%(w/v). NF-hydrogel at 2%(w/v) concentration exhibited a sustained and slow-release of RANKL protein up to 48h. Secondary and tertiary structure analyses confirmed no changes to the RANKL protein released from NF-hydrogel in comparison to native RANKL. The results of NFATc1 gene mRNA expression and TRAP activities of osteoclast, showed that the release process did not affect the bioactivity of released RANKL. This novel study is the first of its kind to attempt in vitro characterization of NF-hydrogel based delivery of RANKL protein to induce osteoclastogenesis. We have shown the self-assembling NF-hydrogel peptide system is amenable to the sustained and controlled release of RANKL locally; that could in turn increase local concentration of RANKL to induce osteoclastogenesis, for application to the controlled mobilization of tooth movement in orthodontic procedures. Orthodontic tooth movement (OTM) occurs through controlled application of light forces to teeth

Biomolecule-Responsive Hydrogels in Medicine.

Science.gov (United States)

Sharifzadeh, Ghorbanali; Hosseinkhani, Hossein

2017-12-01

Recent advances and applications of biomolecule-responsive hydrogels, namely, glucose-responsive hydrogels, protein-responsive hydrogels, and nucleic-acid-responsive hydrogels are highlighted. However, achieving the ultimate purpose of using biomolecule-responsive hydrogels in preclinical and clinical areas is still at the very early stage and calls for more novel designing concepts and advance ideas. On the way toward the real/clinical application of biomolecule-responsive hydrogels, plenty of factors should be extensively studied and examined under both in vitro and in vivo conditions. For example, biocompatibility, biointegration, and toxicity of biomolecule-responsive hydrogels should be carefully evaluated. From the living body's point of view, biocompatibility is seriously depended on the interactions at the tissue/polymer interface. These interactions are influenced by physical nature, chemical structure, surface properties, and degradation of the materials. In addition, the developments of advanced hydrogels with tunable biological and mechanical properties which cause no/low side effects are of great importance. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

THE USE OF A NOVEL ALDEHYDE-FUNCTIONALIZED CHITOSAN HYDROGEL TO PREPARE POROUS TUBULAR SCAFFOLDS FOR VASCULAR TISSUE ENGINEERING APPLICATIONS

Directory of Open Access Journals (Sweden)

Eduardo P. Azevedo

Full Text Available In this work, porous tubular scaffolds were prepared from a novel water soluble aldehyde-functionalized chitosan (ALDCHIT hydrogel, which was obtained by dissolving this chitosan derivative in water and using oxidized dextrose (OXDEXT as the crosslinking agent at different ALDCHIT:OXDEXT mole ratios (10:1, 10:2 and 10:4. By increasing the amount of OXDEXT in respect to ALDCHIT the hydrogels became more rigid and could absorb more than 200% of its weight in water. Since the ALDCHIT:OXDEXT 10:4 was the most stable hydrogel, its ability to form porous tubular scaffolds was investigated. The tubular scaffolds were prepared by the lyophilization method, where the orientation of the pores was controlled by exposing either the internal or the external surface of the frozen hydrogel during the sublimation step. When only the inner surface of the frozen hydrogel was exposed, tubular scaffolds with a highly porous lumen and a sealed outer surface were obtained, where the orientation of the pores, their sizes and interconnectivity seem to be optimum for vascular tissue engineering application.

Fabrication of micropatterned hydrogels for neural culture systems using dynamic mask projection photolithography.

Science.gov (United States)

Curley, J Lowry; Jennings, Scott R; Moore, Michael J

2011-02-11

Increasingly, patterned cell culture environments are becoming a relevant technique to study cellular characteristics, and many researchers believe in the need for 3D environments to represent in vitro experiments which better mimic in vivo qualities. Studies in fields such as cancer research, neural engineering, cardiac physiology, and cell-matrix interaction have shown cell behavior differs substantially between traditional monolayer cultures and 3D constructs. Hydrogels are used as 3D environments because of their variety, versatility and ability to tailor molecular composition through functionalization. Numerous techniques exist for creation of constructs as cell-supportive matrices, including electrospinning, elastomer stamps, inkjet printing, additive photopatterning, static photomask projection-lithography, and dynamic mask microstereolithography. Unfortunately, these methods involve multiple production steps and/or equipment not readily adaptable to conventional cell and tissue culture methods. The technique employed in this protocol adapts the latter two methods, using a digital micromirror device (DMD) to create dynamic photomasks for crosslinking geometrically specific poly-(ethylene glycol) (PEG) hydrogels, induced through UV initiated free radical polymerization. The resulting "2.5D" structures provide a constrained 3D environment for neural growth. We employ a dual-hydrogel approach, where PEG serves as a cell-restrictive region supplying structure to an otherwise shapeless but cell-permissive self-assembling gel made from either Puramatrix or agarose. The process is a quick simple one step fabrication which is highly reproducible and easily adapted for use with conventional cell culture methods and substrates. Whole tissue explants, such as embryonic dorsal root ganglia (DRG), can be incorporated into the dual hydrogel constructs for experimental assays such as neurite outgrowth. Additionally, dissociated cells can be encapsulated in the

Self-degradation of tissue adhesive based on oxidized dextran and poly-L-lysine.

Science.gov (United States)

Matsumura, Kazuaki; Nakajima, Naoki; Sugai, Hajime; Hyon, Suong-Hyu

2014-11-26

We have developed a low-toxicity bioadhesive based on oxidized dextran and poly-L-lysine. Here, we report that the mechanical properties and degradation of this novel hydrogel bioadhesive can be controlled by changing the extent of oxidation of the dextran and the type or concentration of the anhydride species in the acylated poly-L-lysine. The dynamic moduli of the hydrogels can be controlled from 120 Pa to 20 kPa, suggesting that they would have mechanical compatibility with various tissues, and could have applications as tissue adhesives. Development of the hydrogel color from clear to brown indicates that the reaction between the dextran aldehyde groups and the poly-L-lysine amino groups may be induced by a Maillard reaction via Schiff base formation. Degradation of the aldehyde dextran may begin by reaction of the amino groups in the poly-L-lysine. The gel degradation can be ascribed to degradation of the aldehyde dextran in the hydrogel, although the aldehyde dextran itself is relatively stable in water. The oxidized dextran and poly-L-lysine, and the degraded hydrogel showed low cytotoxicities. These findings indicate that a hydrogel consisting of oxidized dextran and poly-L-lysine has low toxicity and a well-controlled degradation rate, and has potential clinical applications as a bioadhesive. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polypeptide based hydrogels

OpenAIRE

Hanay, Saltuk

2018-01-01

There is a need for biocompatible, biodegradable, 3-D printable and stable hydrogels especially in the areas of tissue engineering, drug delivery, bio-sensing technologies and antimicrobial coatings. The main aim of this Ph.D. work was to fabricate polypeptide based hydrogel which may find a potential application in those fields. Focusing on tyrosine or tryptophan-containing copolypeptides prepared by NCarboxyanhydride (NCA) polymerizations, three different crosslinking strategies have been t...

Fabrication of Chitin/Poly(butylene succinate/Chondroitin Sulfate Nanoparticles Ternary Composite Hydrogel Scaffold for Skin Tissue Engineering

Directory of Open Access Journals (Sweden)

S. Deepthi

2014-12-01

Full Text Available Skin loss is one of the oldest and still not totally resolved problems in the medical field. Since spontaneous healing of the dermal defects would not occur, the regeneration of full thickness of skin requires skin substitutes. Tissue engineering constructs would provide a three dimensional matrix for the reconstruction of skin tissue and the repair of damage. The aim of the present work is to develop a chitin based scaffold, by blending it with poly(butylene succinate (PBS, an aliphatic, biodegradable and biocompatible synthetic polymer with excellent mechanical properties. The presence of chondroitin sulfate nanoparticles (CSnp in the scaffold would favor cell adhesion. A chitin/PBS/CSnp composite hydrogel scaffold was developed and characterized by SEM (Scanning Electron Microscope, FTIR (Fourier Transform Infrared Spectroscopy, and swelling ratio of scaffolds were analyzed. The scaffolds were evaluated for the suitability for skin tissue engineering application by cytotoxicity, cell attachment, and cell proliferation studies using human dermal fibroblasts (HDF. The cytotoxicity and cell proliferation studies using HDF confirm the suitability of the scaffold for skin regeneration. In short, these results show promising applicability of the developed chitin/PBS/CSnps ternary composite hydrogel scaffolds for skin tissue regeneration.

Biomimetic Membrane Arrays on Cast Hydrogel Supports

DEFF Research Database (Denmark)

Roerdink-Lander, Monique; Ibragimova, Sania; Rein Hansen, Christian

2011-01-01

, provides mechanical support but at the cost of small molecule transport through the membrane−support sandwich. To stabilize biomimetic membranes while allowing transport through a membrane−support sandwich, we have investigated the feasibility of using an ethylene tetrafluoroethylene (ETFE......)/hydrogel sandwich as the support. The sandwich is realized as a perforated surface-treated ETFE film onto which a hydrogel composite support structure is cast. We report a simple method to prepare arrays of lipid bilayer membranes with low intrinsic electrical conductance on the highly permeable, self......-supporting ETFE/hydrogel sandwiches. We demonstrate how the ETFE/hydrogel sandwich support promotes rapid self-thinning of lipid bilayers suitable for hosting membrane-spanning proteins....

Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering.

Science.gov (United States)

Jang, Jinah; Seol, Young-Joon; Kim, Hyeon Ji; Kundu, Joydip; Kim, Sung Won; Cho, Dong-Woo

2014-09-01

An effective cross-linking of alginate gel was made through reaction with calcium carbonate (CaCO3). We used human chondrocytes as a model cell to study the effects of cross-linking density. Three different pore size ranges of cross-linked alginate hydrogels were fabricated. The morphological, mechanical, and rheological properties of various alginate hydrogels were characterized and responses of biosynthesis of cells encapsulated in each gel to the variation in cross-linking density were investigated. Desired outer shape of structure was maintained when the alginate solution was cross-linked with the applied method. The properties of alginate hydrogel could be tailored through applying various concentrations of CaCO3. The rate of synthesized GAGs and collagens was significantly higher in human chondrocytes encapsulated in the smaller pore structure than that in the larger pore structure. The expression of chondrogenic markers, including collagen type II and aggrecan, was enhanced in the smaller pore structure. It was found that proper structural morphology is a critical factor to enhance the performance and tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Extracellular matrix-derived hydrogels for dental stem cell delivery.

Science.gov (United States)

Viswanath, Aiswarya; Vanacker, Julie; Germain, Loïc; Leprince, Julian G; Diogenes, Anibal; Shakesheff, Kevin M; White, Lisa J; des Rieux, Anne

2017-01-01

Decellularized mammalian extracellular matrices (ECM) have been widely accepted as an ideal substrate for repair and remodelling of numerous tissues in clinical and pre-clinical studies. Recent studies have demonstrated the ability of ECM scaffolds derived from site-specific homologous tissues to direct cell differentiation. The present study investigated the suitability of hydrogels derived from different source tissues: bone, spinal cord and dentine, as suitable carriers to deliver human apical papilla derived mesenchymal stem cells (SCAP) for spinal cord regeneration. Bone, spinal cord, and dentine ECM hydrogels exhibited distinct structural, mechanical, and biological characteristics. All three hydrogels supported SCAP viability and proliferation. However, only spinal cord and bone derived hydrogels promoted the expression of neural lineage markers. The specific environment of ECM scaffolds significantly affected the differentiation of SCAP to a neural lineage, with stronger responses observed with spinal cord ECM hydrogels, suggesting that site-specific tissues are more likely to facilitate optimal stem cell behavior for constructive spinal cord regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 319-328, 2017. © 2016 Wiley Periodicals, Inc.

Polyisocyanopeptide hydrogels: A novel thermo-responsive hydrogel supporting pre-vascularization and the development of organotypic structures.

Science.gov (United States)

Zimoch, Jakub; Padial, Joan Simó; Klar, Agnes S; Vallmajo-Martin, Queralt; Meuli, Martin; Biedermann, Thomas; Wilson, Christopher J; Rowan, Alan; Reichmann, Ernst

2018-04-01

Molecular and mechanical interactions with the 3D extracellular matrix are essential for cell functions such as survival, proliferation, migration, and differentiation. Thermo-responsive biomimetic polyisocyanopeptide (PIC) hydrogels are promising new candidates for 3D cell, tissue, and organ cultures. This is a synthetic, thermo-responsive and stress-stiffening material synthesized via polymerization of the corresponding monomers using a nickel perchlorate as a catalyst. It can be tailored to meet various demands of cells by modulating its stiffness and through the decoration of the polymer with short GRGDS peptides using copper free click chemistry. These peptides make the hydrogels biocompatible by mimicking the binding sites of certain integrins. This study focuses on the optimization of the PIC polymer properties for efficient cell, tissue and organ development. Screening for the optimal stiffness of the hydrogel and the ideal concentration of the GRGDS ligand conjugated with the polymer, enabled cell proliferation, migration and differentiation of various primary cell types of human origin. We demonstrate that fibroblasts, endothelial cells, adipose-derived stem cells and melanoma cells, do survive, thrive and differentiate in optimized PIC hydrogels. Importantly, these hydrogels support the spontaneous formation of complex structures like blood capillaries in vitro. Additionally, we utilized the thermo-responsive properties of the hydrogels for a rapid and gentle recovery of viable cells. Finally, we show that organotypic structures of human origin grown in PIC hydrogels can be successfully transplanted subcutaneously onto immune-compromised rats, on which they survive and integrate into the surrounding tissue. Molecular and mechanical interactions with the surrounding environment are essential for cell functions. Although 2D culture systems greatly contributed to our understanding of complex biological phenomena, they cannot substitute for crucial

Gelatin- and starch-based hydrogels. Part A: Hydrogel development, characterization and coating.

Science.gov (United States)

Van Nieuwenhove, Ine; Salamon, Achim; Peters, Kirsten; Graulus, Geert-Jan; Martins, José C; Frankel, Daniel; Kersemans, Ken; De Vos, Filip; Van Vlierberghe, Sandra; Dubruel, Peter

2016-11-05

The present work aims at constructing the ideal scaffold matrix of which the physico-chemical properties can be altered according to the targeted tissue regeneration application. Ideally, this scaffold should resemble the natural extracellular matrix (ECM) as close as possible both in terms of chemical composition and mechanical properties. Therefore, hydrogel films were developed consisting of methacrylamide-modified gelatin and starch-pentenoate building blocks because the ECM can be considered as a crosslinked hydrogel network consisting of both polysaccharides and structural, signaling and cell-adhesive proteins. For the gelatin hydrogels, three different substitution degrees were evaluated including 31%, 72% and 95%. A substitution degree of 32% was applied for the starch-pentenoate building block. Pure gelatin hydrogels films as well as interpenetrating networks with gelatin and starch were developed. Subsequently, these films were characterized using gel fraction and swelling experiments, high resolution-magic angle spinning (1)H NMR spectroscopy, rheology, infrared mapping and atomic force microscopy. The results indicate that both the mechanical properties and the swelling extent of the developed hydrogel films can be controlled by varying the chemical composition and the degree of substitution of the methacrylamide-modified gelatin applied. The storage moduli of the developed materials ranged between 14 and 63kPa. Phase separation was observed for the IPNs for which separated starch domains could be distinguished located in the surrounding gelatin matrix. Furthermore, we evaluated the affinity of aggrecan for gelatin by atomic force microscopy and radiolabeling experiments. We found that aggrecan can be applied as a bioactive coating for gelatin hydrogels by a straightforward physisorption procedure. Thus, we achieved distinct fine-tuning of the physico-chemical properties of these hydrogels which render them promising candidates for tissue engineering

Alcohol expectancies longitudinally predict drinking and the alcohol myopia effects of relief, self-inflation, and excess.

Science.gov (United States)

Lac, Andrew; Brack, Nathaniel

2018-02-01

Alcohol myopia theory posits that alcohol consumption attenuates information processing capacity, and that expectancy beliefs together with intake level are responsible for experiences in myopic effects (relief, self-inflation, and excess). Adults (N=413) averaging 36.39 (SD=13.02) years of age completed the Comprehensive Effects of Alcohol questionnaire at baseline, followed by alcohol use measures (frequency and quantity) and the Alcohol Myopia Scale one month later. Three structural equation models based on differing construct manifestations of alcohol expectancies served to longitudinally forecast alcohol use and myopia. In Model 1, overall expectancy predicted greater alcohol use and higher levels of all three myopic effects. In Model 2, specifying separate positive and negative expectancy factors, positive but not negative expectancy predicted greater use. Furthermore, positive expectancy and use explained higher myopic relief and higher self-inflation, whereas positive expectancy, negative expectancy, and use explained higher myopic excess. In Model 3, the seven specific expectancy subscales (sociability, tension reduction, liquid courage, sexuality, cognitive and behavioral impairment, risk and aggression, and self-perception) were simultaneously specified as predictors. Tension reduction expectancy, sexuality expectancy, and use contributed to higher myopic relief; sexuality expectancy and use explained higher myopic self-inflation; and risk and aggression expectancy and use accounted for higher myopic excess. Across all three predictive models, the total variance explained ranged from 12 to 19% for alcohol use, 50 to 51% for relief, 29 to 34% for self-inflation, and 32 to 35% for excess. Findings support that the type of alcohol myopia experienced is a concurrent function of self-fulfilling alcohol prophecies and drinking levels. The interpreted measurement manifestation of expectancy yielded different prevention implications. Copyright © 2017 Elsevier

Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment

Science.gov (United States)

Conde, João; Oliva, Nuria; Atilano, Mariana; Song, Hyun Seok; Artzi, Natalie

2016-03-01

The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs--a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)--provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional in vitro and in vivo, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.

Dialing in the Ratio of Covalent and Coordination Cross-links in Self-healing Hydrogels

DEFF Research Database (Denmark)

Andersen, Amanda; Krogsgaard, Marie; Birkedal, Henrik

; it is of great interest to control the degree of which these are present; i.e. controlling the degree of catechol oxidation. Here, we report hydrogels in which the catechols participating in reversible (oxidation resistant catechol-analogue6) and irreversible oxidation cross-links are separated, enabling one...... to predefine the ratio of the two by altering the composition. The oxidation-resistant catechol-analogue was grafted onto polyallylamine,4 while the oxidation cross-links are introduced by addition of tannic acid that has the same useful properties as catechols.5,7,8 This affords hydrogels that retain self......-healing abilities even at high pH but that can be stiffened at will by dialing in the required degree of covalent crosslinking. This dial-in method thus harnesses two aspects of catechol-type chemistries to yield double network hydrogels in a straightforward and highly controllable manner....

Alkylation of human hair keratin for tunable hydrogel erosion and drug delivery in tissue engineering applications.

Science.gov (United States)

Han, Sangheon; Ham, Trevor R; Haque, Salma; Sparks, Jessica L; Saul, Justin M

2015-09-01

Polymeric biomaterials that provide a matrix for cell attachment and proliferation while achieving delivery of therapeutic agents are an important component of tissue engineering and regenerative medicine strategies. Keratins are a class of proteins that have received attention for numerous tissue engineering applications because, like other natural polymers, they promote favorable cell interactions and have non-toxic degradation products. Keratins can be extracted from various sources including human hair, and they are characterized by a high percentage of cysteine residues. Thiol groups on reductively extracted keratin (kerateine) form disulfide bonds, providing a more stable cross-linked hydrogel network than oxidatively extracted keratin (keratose) that cannot form disulfide crosslinks. We hypothesized that an iodoacetamide alkylation (or "capping") of cysteine thiol groups on the kerateine form of keratin could be used as a simple method to modulate the levels of disulfide crosslinking in keratin hydrogels, providing tunable rates of gel erosion and therapeutic agent release. After alkylation, the alkylated kerateines still formed hydrogels and the alkylation led to changes in the mechanical and visco-elastic properties of the materials consistent with loss of disulfide crosslinking. The alkylated kerateines did not lead to toxicity in MC3T3-E1 pre-osteoblasts. These cells adhered to keratin at levels comparable to fibronectin and greater than collagen. Alkylated kerateine gels eroded more rapidly than non-alkylated kerateine and this control over erosion led to tunable rates of delivery of rhBMP-2, rhIGF-1, and ciprofloxacin. These results demonstrate that alkylation of kerateine cysteine residues provides a cell-compatible approach to tune rates of hydrogel erosion and therapeutic agent release within the context of a naturally-derived polymeric system. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Two-component thermosensitive hydrogels : Phase separation affecting rheological behavior

NARCIS (Netherlands)

Abbadessa, Anna; Landín, Mariana; Oude Blenke, Erik; Hennink, Wim E.; Vermonden, Tina

2017-01-01

Extracellular matrices are mainly composed of a mixture of different biopolymers and therefore the use of two or more building blocks for the development of tissue-mimicking hydrogels is nowadays an attractive strategy in tissue-engineering. Multi-component hydrogel systems may undergo phase

Injectable MMP-sensitive alginate hydrogels as hMSC delivery systems.

Science.gov (United States)

Fonseca, Keila B; Gomes, David B; Lee, Kangwon; Santos, Susana G; Sousa, Aureliana; Silva, Eduardo A; Mooney, David J; Granja, Pedro L; Barrias, Cristina C

2014-01-13

Hydrogels with the potential to provide minimally invasive cell delivery represent a powerful tool for tissue-regeneration therapies. In this context, entrapped cells should be able to escape the matrix becoming more available to actively participate in the healing process. Here, we analyzed the performance of proteolytically degradable alginate hydrogels as vehicles for human mesenchymal stem cells (hMSC) transplantation. Alginate was modified with the matrix metalloproteinase (MMP)-sensitive peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG), which did not promote dendritic cell maturation in vitro, neither free nor conjugated to alginate chains, indicating low immunogenicity. hMSC were entrapped within MMP-sensitive and MMP-insensitive alginate hydrogels, both containing cell-adhesion RGD peptides. Softer (2 wt % alginate) and stiffer (4 wt % alginate) matrices were tested. When embedded in a Matrigel layer, hMSC-laden MMP-sensitive alginate hydrogels promoted more extensive outward cell migration and invasion into the tissue mimic. In vivo, after 4 weeks of subcutaneous implantation in a xenograft mouse model, hMSC-laden MMP-sensitive alginate hydrogels showed higher degradation and host tissue invasion than their MMP-insensitive equivalents. In both cases, softer matrices degraded faster than stiffer ones. The transplanted hMSC were able to produce their own collagenous extracellular matrix, and were located not only inside the hydrogels, but also outside, integrated in the host tissue. In summary, injectable MMP-sensitive alginate hydrogels can act as localized depots of cells and confer protection to transplanted cells while facilitating tissue regeneration.

HLC/pullulan and pullulan hydrogels: their microstructure, engineering process and biocompatibility

Energy Technology Data Exchange (ETDEWEB)

Li, Xian [College of chemistry & materials science, Northwest University, Taibai North Road 229, Xi’an, Shaanxi 710069 (China); Shaanxi Key Laboratory of Degradable Biomedical Materials, Department of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an, Shaanxi 710069 (China); Xue, Wenjiao [Shannxi provincial institute of microbiology, Xi’ an 710043 (China); Liu, Yannan; Li, Weina [Shaanxi Key Laboratory of Degradable Biomedical Materials, Department of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an, Shaanxi 710069 (China); Fan, Daidi, E-mail: fandaidi@nwu.edu.cn [Shaanxi Key Laboratory of Degradable Biomedical Materials, Department of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an, Shaanxi 710069 (China); Zhu, Chenhui [Shaanxi Key Laboratory of Degradable Biomedical Materials, Department of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an, Shaanxi 710069 (China); Wang, Yaoyu, E-mail: wyaoyu@nwu.edu.cn [College of chemistry & materials science, Northwest University, Taibai North Road 229, Xi’an, Shaanxi 710069 (China)

2016-01-01

New locally injectable biomaterials that are suitable for use as soft tissue fillers are needed to address a significant unmet medical need. In this study, we used pullulan and human-like collagen (HLC) based hydrogels with various molecular weights (MWs) in combination therapy against tissue defects. Briefly, pullulan was crosslinked with NaIO{sub 4} to form a pullulan hydrogel and then may coupled with HLC using the reaction between the –NH{sub 2} end-group of HLC and the –CHO group present on the aldehyde pullulan to form the HLC/pullulan hydrogel, wherein the NaIO{sub 4} acted as the crosslinking and oxidizing agent. The good miscibility of pullulan and HLC in the hydrogels was confirmed via Fourier transform infrared spectroscopy, scanning electron microscopy, compression testing, enzyme degradation testing, cell adhesions, live/dead staining and subcutaneous filling assays. Here, pullulan hydrogels with various MWs were fabricated and physicochemically characterized. Limitations of the pullulan hydrogels included inflammation, poor mechanical strength, and degradation. By contrast, the properties of the HLC/pullulan hydrogels strongly enhanced. The efficacy of these hydrogels was evaluated both in vitro and in vivo. Our results indicate that HLC/pullulan hydrogels may have therapeutic value as efficient soft tissue fillers, with reduced inflammation, improved cell adhesion and delayed hydrogel degradation. - Graphical abstract: The HLC/pullulan hydrogels were prepared by dialysis, wet granulation and UV radiation after various MWs of pullulan and HLC were crosslinked with NaIO{sub 4}, and injected subcutaneously into Kunming mouse. The formation of HLC/pullulan hydrogels is due to the amide bond linkage with the amino group of HLC and the aldehyde groups in pullulan aqueous media after crosslinking by NaIO{sub 4}. HLC/pullulan hydrogels may have therapeutic value as efficient soft tissue fillers, with reduced inflammation, improved cell adhesion and

Multi-scale Multi-mechanism Toughening of Hydrogels

Science.gov (United States)

Zhao, Xuanhe

Hydrogels are widely used as scaffolds for tissue engineering, vehicles for drug delivery, actuators for optics and fluidics, and model extracellular matrices for biological studies. The scope of hydrogel applications, however, is often severely limited by their mechanical properties. Inspired by the mechanics and hierarchical structures of tough biological tissues, we propose that a general principle for the design of tough hydrogels is to implement two mechanisms for dissipating mechanical energy and maintaining high elasticity in hydrogels. A particularly promising strategy for the design is to integrate multiple pairs of mechanisms across multiple length scales into a hydrogel. We develop a multiscale theoretical framework to quantitatively guide the design of tough hydrogels. On the network level, we have developed micro-physical models to characterize the evolution of polymer networks under deformation. On the continuum level, we have implemented constitutive laws formulated from the network-level models into a coupled cohesive-zone and Mullins-effect model to quantitatively predict crack propagation and fracture toughness of hydrogels. Guided by the design principle and quantitative model, we will demonstrate a set of new hydrogels, based on diverse types of polymers, yet can achieve extremely high toughness superior to their natural counterparts such as cartilages. The work was supported by NSF(No. CMMI- 1253495) and ONR (No. N00014-14-1-0528).

Rapid and annealing-free self-assembly of DNA building blocks for 3D hydrogel chaperoned by cationic comb-type copolymers.

Science.gov (United States)

Zhang, Zheng; Wu, Yuyang; Yu, Feng; Niu, Chaoqun; Du, Zhi; Chen, Yong; Du, Jie

2017-10-01

The construction and self-assembly of DNA building blocks are the foundation of bottom-up development of three-dimensional DNA nanostructures or hydrogels. However, most self-assembly from DNA components is impeded by the mishybridized intermediates or the thermodynamic instability. To enable rapid production of complicated DNA objects with high yields no need for annealing process, herein different DNA building blocks (Y-shaped, L- and L'-shaped units) were assembled in presence of a cationic comb-type copolymer, poly (L-lysine)-graft-dextran (PLL-g-Dex), under physiological conditions. The results demonstrated that PLL-g-Dex not only significantly promoted the self-assembly of DNA blocks with high efficiency, but also stabilized the assembled multi-level structures especially for promoting the complicated 3D DNA hydrogel formation. This study develops a novel strategy for rapid and high-yield production of DNA hydrogel even derived from instable building blocks at relatively low DNA concentrations, which would endow DNA nanotechnology for more practical applications.

Hydrogels and their medical applications

Science.gov (United States)

Rosiak, Janusz M.; Yoshii, Fumio

1999-05-01

Biomaterials play a key role in most approaches for engineering tissues as substitutes for functional replacement, for components of devices related to therapy and diagnosis, for drug delivery systems and supportive scaffolds for guided tissue growth. Modern biomaterials could be composed of various components, e.g. metals, ceramics, natural tissues, polymers. In this last group, the hydrogels, hydrophilic polymeric gels with requested biocompatibility and designed interaction with living surrounding seem to be one of the most promising group of biomaterials. Especially, if they are formed by means of ionizing radiation. In early 1950s, the pioneers of the radiation chemistry of polymers began some experiments with radiation crosslinking of hydrophilic polymers. However, hydrogels were analyzed mainly from the point of view of the phenomenon associated with radiation synthesis, with topology of network and relation between radiation parameters of the processes. Fundamental monographs on radiation polymer physics and chemistry written by A. Charlesby (Atomic Radition and polymers, Pergamon Press, Oxford, 1960) and A. Chapiro (Radiation Chemistry of Polymeric Systems, Interscience, New York, 1962) proceed from this time. The noticeable interest in the application of radiation techniques to obtain hydrogels for biomedical purposes began in the late sixties as a result of the papers and patents invented by Japanese and American scientists, headed by Kaetsu in Japan and Hoffman in USA. Immobilization of biologically active species in hydrogel matrices, their use as drug delivery systems and enzyme traps as well as the modification of material surfaces to improve biocompatibility and their ability to bond antigens and antibodies had been the main subjects of these investigations. In this article a brief summary of investigations on mechanism and kinetics of radiation formation of hydrogels as well as some examples of commercialized hydrogel biomaterials have been

Hydrogels and their medical applications

International Nuclear Information System (INIS)

Rosiak, Janusz M.; Yoshii, Fumio

1999-01-01

Biomaterials play a key role in most approaches for engineering tissues as substitutes for functional replacement, for components of devices related to therapy and diagnosis, for drug delivery systems and supportive scaffolds for guided tissue growth. Modern biomaterials could be composed of various components, e.g. metals, ceramics, natural tissues, polymers. In this last group, the hydrogels, hydrophilic polymeric gels with requested biocompatibility and designed interaction with living surrounding seem to be one of the most promising group of biomaterials. Especially, if they are formed by means of ionizing radiation. In early 1950s, the pioneers of the radiation chemistry of polymers began some experiments with radiation crosslinking of hydrophilic polymers. However, hydrogels were analyzed mainly from the point of view of the phenomenon associated with radiation synthesis, with topology of network and relation between radiation parameters of the processes. Fundamental monographs on radiation polymer physics and chemistry written by A. Charlesby (Atomic Radition and polymers, Pergamon Press, Oxford, 1960) and A. Chapiro (Radiation Chemistry of Polymeric Systems, Interscience, New York, 1962) proceed from this time. The noticeable interest in the application of radiation techniques to obtain hydrogels for biomedical purposes began in the late sixties as a result of the papers and patents invented by Japanese and American scientists, headed by Kaetsu in Japan and Hoffman in USA. Immobilization of biologically active species in hydrogel matrices, their use as drug delivery systems and enzyme traps as well as the modification of material surfaces to improve biocompatibility and their ability to bond antigens and antibodies had been the main subjects of these investigations. In this article a brief summary of investigations on mechanism and kinetics of radiation formation of hydrogels as well as some examples of commercialized hydrogel biomaterials have been

A Self-Assembling Protein Hydrogel Technology for Enzyme Incorporation onto Electrodes in Biofuel Cells

Science.gov (United States)

2015-10-26

an ordered 3-dimentional space. In the first stage, we constructed protein building blocks able to self-assemble into 3D protein hydrogel upon...Chem 23, 1891-1901 (2012). 26. Jung, S. & Yi, H. Facile Strategy for Protein Conjugation with Chitosan -Poly(ethylene glycol) Hybrid Microparticle...multiple enzymes in an ordered 3-dimentional space. In the first stage, we constructed protein building blocks able to self-assemble into 3D protein

New bioactive motifs and their use in functionalized self-assembling peptides for NSC differentiation and neural tissue engineering

Science.gov (United States)

Gelain, F.; Cigognini, D.; Caprini, A.; Silva, D.; Colleoni, B.; Donegá, M.; Antonini, S.; Cohen, B. E.; Vescovi, A.

2012-04-01

Developing functionalized biomaterials for enhancing transplanted cell engraftment in vivo and stimulating the regeneration of injured tissues requires a multi-disciplinary approach customized for the tissue to be regenerated. In particular, nervous tissue engineering may take a great advantage from the discovery of novel functional motifs fostering transplanted stem cell engraftment and nervous fiber regeneration. Using phage display technology we have discovered new peptide sequences that bind to murine neural stem cell (NSC)-derived neural precursor cells (NPCs), and promote their viability and differentiation in vitro when linked to LDLK12 self-assembling peptide (SAPeptide). We characterized the newly functionalized LDLK12 SAPeptides via atomic force microscopy, circular dichroism and rheology, obtaining nanostructured hydrogels that support human and murine NSC proliferation and differentiation in vitro. One functionalized SAPeptide (Ac-FAQ), showing the highest stem cell viability and neural differentiation in vitro, was finally tested in acute contusive spinal cord injury in rats, where it fostered nervous tissue regrowth and improved locomotor recovery. Interestingly, animals treated with the non-functionalized LDLK12 had an axon sprouting/regeneration intermediate between Ac-FAQ-treated animals and controls. These results suggest that hydrogels functionalized with phage-derived peptides may constitute promising biomimetic scaffolds for in vitro NSC differentiation, as well as regenerative therapy of the injured nervous system. Moreover, this multi-disciplinary approach can be used to customize SAPeptides for other specific tissue engineering applications.Developing functionalized biomaterials for enhancing transplanted cell engraftment in vivo and stimulating the regeneration of injured tissues requires a multi-disciplinary approach customized for the tissue to be regenerated. In particular, nervous tissue engineering may take a great advantage from the

Hyaluronic acid based hydrogel system for soft tissue regeneration and drug delivery

Science.gov (United States)

Jha, Amit Kumar

the gels. Human MSCs were undifferentiated during the early time points of culture, however differentiated into osteoblast phenotype after 28 days of culture. In summary, the HA-based hydrogel matrices are hierarchically structured, mechanically robust and enzymatically stable, capable of mediating cellular functions through the spatial and temporal presentation of defined biological cues. These hydrogel systems are promising candidates for soft tissue regeneration.

Fabrication of keratin-silica hydrogel for biomedical applications

Energy Technology Data Exchange (ETDEWEB)

Kakkar, Prachi; Madhan, Balaraman, E-mail: bmadhan76@yahoo.co.in

2016-09-01

In the recent past, keratin has been fabricated into different forms of biomaterials like scaffold, gel, sponge, film etc. In lieu of the myriad advantages of the hydrogels for biomedical applications, a keratin-silica hydrogel was fabricated using tetraethyl orthosilicate (TEOS). Textural analysis shed light on the physical properties of the fabricated hydrogel, inturn enabling the optimization of the hydrogel. The optimized keratin-silica hydrogel was found to exhibit instant springiness, optimum hardness, with ease of spreadability. Moreover, the hydrogel showed excellent swelling with highly porous microarchitecture. MTT assay and DAPI staining revealed that keratin-silica hydrogel was biocompatible with fibroblast cells. Collectively, these properties make the fabricated keratin-silica hydrogel, a suitable dressing material for biomedical applications. - Highlights: • Keratin-silica hydrogel has been fabricated using sol–gel technique. • The hydrogel shows appropriate textural properties. • The hydrogel promotes fibroblast cells proliferation. • The hydrogel has potential soft tissue engineering applications like wound healing.

Hydrogels for efficient light delivery in optogenetic applications

Science.gov (United States)

Johannsmeier, S.; Torres, M. L.; Ripken, T.; Heinemann, D.; Heisterkamp, A.

2018-02-01

Light-based therapies have been established for various indications, such as skin conditions, cancer or neonatal jaundice. Advances in the field of optogenetics open up new horizons for light-tissue interactions with an organism-wide impact. Excitable tissues, such as nerve and muscle tissues, can be controlled by light after the introduction of light-sensitive ion channels. Since these organs are generally not easily accessible to illumination in vivo, there is an increasing need for effective biocompatible waveguides for light delivery. These devices not only have to guide and distribute the light as desired with minimal losses, they should also mimic the mechanical properties of the surrounding tissue to ensure compatibility. In this project, we are tuning the properties of hydrogels from poly(ethylene glycol) derivatives to achieve compatibility with muscle tissue as well as optimal light guiding and distribution for optogenetic applications at the heart. The excitation light is coupled into the hydrogel with a biocompatible fiber. Properties of the hydrogel are mainly tuned by monomer length and concentration. Total reflection can be achieved by embedding a fiber-like hydrogel with a high refractive index into a second, low refractive index gel. Different geometries and scattering microparticles are used for light distribution in a flat gel patch. Targeted cell attachment can be achieved by introducing a protein layer to the otherwise bioinert gel. After optimization, the hydrogel may be used to deliver light for the excitation of genetically altered cardiomyocytes for controlled contraction.

Photocrosslinked PLA-PEO-PLA Hydrogels from Self-Assembled Physical Networks: Mechanical Properties and Influence of Assumed Constitutive Relationships

OpenAIRE

Sanabria-DeLong, Naomi; Crosby, Alfred J.; Tew, Gregory N.

2008-01-01

Poly(lactide) – block – poly(ethylene oxide) – block – poly(lactide) [PLA-PEO-PLA] triblock copolymers are known to form physical hydrogels in water, due to the polymer's amphiphilicity. Their mechanical properties, biocompatibility, and biodegradability have made them attractive for use as soft tissue scaffolds. However, the network junction points are not covalently crosslinked and in a highly aqueous environment these hydrogels adsorb more water, transform from gel to sol, and lose the des...

Self-organized dysprosium-directed alginate hydrogels and its chemical features

Energy Technology Data Exchange (ETDEWEB)

Ma, Qianmin [School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China); Gao, Jinwei [Institute for Advanced Materials, Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510006 (China); Peng, Huojun [School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China); Wang, Qianming, E-mail: qmwang@scnu.edu.cn [Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education, School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China); School of Chemistry and Environment, South China Normal University, Guangzhou 510006 (China); Guangzhou Key Laboratory of Materials for Energy Conversion and Storage, Guangzhou 510006 (China)

2016-09-15

Rational use of self-organized materials may contribute in developing new structures and devices in practical technology. Synthetic metallo-supramolecular gels are generally designed with transitional metal-directed process. However, the assembly of both lanthanide and sodium alginate in macromolecular systems would find a new way of utilizing its physical properties. The stimuli-responsive molecule (alginate) could firmly form stable hydrogels upon the encapsulation of dysprosium ions. In addition, the immobilization of YVO{sub 4}: Eu{sup 3+} nanoparticle in the soft matrix has been achieved and it has never been explored in the fabrication of phosphor-incorporated luminescent alginate gels. The key feature of the present soft matter is that its red emission could be switched off in the presence of sodium ascorbate and the results may have a tremendous impact on the extension of photophysical application based on soft nanoscale devices. - Highlights: • Dy{sup 3+} can be used for the gelation of the dissolved alginate. • Lanthanide hydrogels could exhibit red emissions under excitations. • Luminescence could be switched “off” in the presence of sodium ascorbate.

Stochastic quantum inflation for a canonical scalar field with linear self-interaction potential

Energy Technology Data Exchange (ETDEWEB)

Panotopoulos, Grigoris [CENTRA, Instituto Superior Tecnico, Universidade de Lisboa, Lisboa (Portugal)

2017-10-15

We apply Starobinsky's formalism of stochastic inflation to the case of a massless minimally coupled scalar field with linear self-interaction potential. We solve the corresponding Fokker-Planck equation exactly, and we obtain analytical expressions for the stochastic expectation values. (orig.)

Dilute self-healing hydrogels of silk-collagen-like block copolypeptides at neutral pH

NARCIS (Netherlands)

Golinska, M.D.; Wlodarczyk-Biegun, M.K.; Werten, M.W.T.; Cohen Stuart, M.A.; Wolf, de F.A.; Vries, de R.J.

2014-01-01

We report on self-healing, pH-responsive hydrogels that are entirely protein-based. The protein is a denovo designed recombinant triblock polypeptide of 66 kg/mol consisting of a silk-like middle block (GAGAGAGH)48, flanked by two long collagen-inspired hydrophilic random coil side blocks. The

Nondestructive mechanical characterization of developing biological tissues using inflation testing.

Science.gov (United States)

Oomen, P J A; van Kelle, M A J; Oomens, C W J; Bouten, C V C; Loerakker, S

2017-10-01

One of the hallmarks of biological soft tissues is their capacity to grow and remodel in response to changes in their environment. Although it is well-accepted that these processes occur at least partly to maintain a mechanical homeostasis, it remains unclear which mechanical constituent(s) determine(s) mechanical homeostasis. In the current study a nondestructive mechanical test and a two-step inverse analysis method were developed and validated to nondestructively estimate the mechanical properties of biological tissue during tissue culture. Nondestructive mechanical testing was achieved by performing an inflation test on tissues that were cultured inside a bioreactor, while the tissue displacement and thickness were nondestructively measured using ultrasound. The material parameters were estimated by an inverse finite element scheme, which was preceded by an analytical estimation step to rapidly obtain an initial estimate that already approximated the final solution. The efficiency and accuracy of the two-step inverse method was demonstrated on virtual experiments of several material types with known parameters. PDMS samples were used to demonstrate the method's feasibility, where it was shown that the proposed method yielded similar results to tensile testing. Finally, the method was applied to estimate the material properties of tissue-engineered constructs. Via this method, the evolution of mechanical properties during tissue growth and remodeling can now be monitored in a well-controlled system. The outcomes can be used to determine various mechanical constituents and to assess their contribution to mechanical homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Three-Dimensional Calcium Alginate Hydrogel Assembly via TiOPc-Based Light-Induced Controllable Electrodeposition

Directory of Open Access Journals (Sweden)

Yang Liu

2017-06-01

Full Text Available Artificial reconstruction of three-dimensional (3D hydrogel microstructures would greatly contribute to tissue assembly in vitro, and has been widely applied in tissue engineering and drug screening. Recent technological advances in the assembly of functional hydrogel microstructures such as microfluidic, 3D bioprinting, and micromold-based 3D hydrogel fabrication methods have enabled the formation of 3D tissue constructs. However, they still lack flexibility and high efficiency, which restrict their application in 3D tissue constructs. Alternatively, we report a feasible method for the fabrication and reconstruction of customized 3D hydrogel blocks. Arbitrary hydrogel microstructures were fabricated in situ via flexible and rapid light-addressable electrodeposition. To demonstrate the versatility of this method, the higher-order assembly of 3D hydrogel blocks was investigated using a constant direct current (DC voltage (6 V applied between two electrodes for 20–120 s. In addition to the plane-based two-dimensional (2D assembly, hierarchical structures—including multi-layer 3D hydrogel structures and vessel-shaped structures—could be assembled using the proposed method. Overall, we developed a platform that enables researchers to construct complex 3D hydrogel microstructures efficiently and simply, which has the potential to facilitate research on drug screening and 3D tissue constructs.

One-Pot Automated Synthesis of Quasi Triblock Copolymers for Self-Healing Physically Crosslinked Hydrogels.

Science.gov (United States)

Voorhaar, Lenny; De Meyer, Bernhard; Du Prez, Filip; Hoogenboom, Richard

2016-10-01

The preparation of physically crosslinked hydrogels from quasi ABA-triblock copolymers with a water-soluble middle block and hydrophobic end groups is reported. The hydrophilic monomer N-acryloylmorpholine is copolymerized with hydrophobic isobornyl acrylate via a one-pot sequential monomer addition through reversible addition fragmentation chain-transfer (RAFT) polymerization in an automated parallel synthesizer, allowing systematic variation of polymer chain length and hydrophobic-hydrophilic ratio. Hydrophobic interactions between the outer blocks cause them to phase-separate into larger hydrophobic domains in water, forming physical crosslinks between the polymers. The resulting hydrogels are studied using rheology and their self-healing ability after large strain damage is shown. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fluorescence Imaging in Genipin Crosslinked Chitosan–Poly(vinyl pyrrolidone Hydrogels

Directory of Open Access Journals (Sweden)

Simon Matcham

2016-10-01

Full Text Available Recent research has identified genipin as a promising natural crosslinking agent for biocompatible hydrogels as genipin is significantly less cytotoxic than current synthetic crosslinking agents, such as glutaraldehyde. Conveniently, fluorophores can be produced when genipin crosslinks. In this study, fluorescence intensity measurements of genipin crosslinked chitosan-poly(vinyl pyrrolidone hydrogels have been explored as a dynamic, in situ method for tracing sol-gel transition. These pH-responsive smart materials have a future in medical applications, in particular in tissue engineering and drug delivery, where methods to follow the process in situ and in real-time are crucial for future advancement. Samples were prepared using deionised water, pH 4, and pH 10 solutions, and studied at 24 and 37 °C over a 24 h period. Both temperature and pH have been found to affect sol-gel transition in the hydrogels studied. The transition from acidic (pH 4 to basic (pH 10 solution resulted in reduced fluorescence intensity suggesting that, under more basic conditions, genipin molecules self-polymerise, reducing the number of molecules available for reaction with the amino groups of chitosan. Three-dimensional representations of the fluorescence present in a hydrogel sample have also been produced from the data, enabling the visualisation of variation in fluorescence with time at the surface of the hydrogel.

The synthesis of hydrogels with controlled distribution of polymer brushes in hydrogel network

Energy Technology Data Exchange (ETDEWEB)

Sun, YuWei; Zhou, Chao; Zhang, AoKai; Xu, LiQun; Yao, Fang [School of Chemistry and Chemical Engineering, Southeast University, Jiangning District, Nanjing, Jiangsu Province, 211189 (China); Cen, Lian, E-mail: cenlian@hotmail.com [National Tissue Engineering Center of China, No.68, East Jiang Chuan Road, Shanghai, 200241 (China); School of Chemical Engineering, East China University of Science and Technology, No.130, Mei Long Road, Shanghai, 200237 (China); Fu, Guo-Dong, E-mail: fu7352@seu.edu.cn [School of Chemistry and Chemical Engineering, Southeast University, Jiangning District, Nanjing, Jiangsu Province, 211189 (China)

2014-11-30

Highlights: • Many biological tissues are 3-dimensionally asymmetric in structure and properties, it would be desirable if hydrogels could bear such structural similarity with specialized surface and bulk properties. Moreover, gradual but continuous variation in spatial structural and property is also a common phenomenon in biological tissues, such as interfaces between bone and tendon, or between bone and cartilage. Hence, the development of a method to introduce well-defined functional polymer brushes on PEG hydrogels, especially with precisely controlled spatial structure in 3-dimensions, would impart the hydrogels with special functionalities and wider applications. Poly(ethylene glycol) (PEG) hydrogels with 3-dimensionally controlled well-defined poly(N-isopropylacrylamide) (poly(NIPAAm)) brushes were prepared by combined copper(I)-catalyzed azide-alkyne cycloaddition (“Click Chemistry”) and atom transfer radical polymerization (ATRP). The resulting hydrogels were presented as representatives with their detailed synthesis routes and characterization. H{sub PEG}-S-poly(NIPAAm) is a hydrogel with poly(NIPAAm) brushes mainly grafted on surface, whereas H{sub PEG}-G-poly(NIPAAm) has a gradiently decreased poly(NIPAAm) brushes in their chain length from surface to inside. On the other hand, poly(NIPAAm) brushes in H{sub PEG}-U-poly(NIPAAm) are uniformly dispersed throughout the whole hydrogel network. Successful preparation of H{sub PEG}-S-poly(NIPAAm), H{sub PEG}-G-poly(NIPAAm) and H{sub PEG}-U-poly(NIPAAm) were ascertained by X-ray photoelectron spectroscopy (XPS) and water contact angle measurement. Hence, the flexibility and controllability of the synthetic strategy in varying the distribution of polymer brushes and hydrogel surface properties was demonstrated. Hydrogels with tunable and well-defined 3-dimensional poly(NIPAAm) polymer brushes could be tailor-designed to find potential applications in smart devices or skin dressing, such as for diabetics

Hydrogels for Cartilage Regeneration, from Polysaccharides to Hybrids

Directory of Open Access Journals (Sweden)

Daniela Anahí Sánchez-Téllez

2017-12-01

Full Text Available The aims of this paper are: (1 to review the current state of the art in the field of cartilage substitution and regeneration; (2 to examine the patented biomaterials being used in preclinical and clinical stages; (3 to explore the potential of polymeric hydrogels for these applications and the reasons that hinder their clinical success. The studies about hydrogels used as potential biomaterials selected for this review are divided into the two major trends in tissue engineering: (1 the use of cell-free biomaterials; and (2 the use of cell seeded biomaterials. Preparation techniques and resulting hydrogel properties are also reviewed. More recent proposals, based on the combination of different polymers and the hybridization process to improve the properties of these materials, are also reviewed. The combination of elements such as scaffolds (cellular solids, matrices (hydrogel-based, growth factors and mechanical stimuli is needed to optimize properties of the required materials in order to facilitate tissue formation, cartilage regeneration and final clinical application. Polymer combinations and hybrids are the most promising materials for this application. Hybrid scaffolds may maximize cell growth and local tissue integration by forming cartilage-like tissue with biomimetic features.

Nanocomposite hydrogels stabilized by self-assembled multivalent bisphosphonate-magnesium nanoparticles mediate sustained release of magnesium ion and promote in-situ bone regeneration.

Science.gov (United States)

Zhang, Kunyu; Lin, Sien; Feng, Qian; Dong, Chaoqun; Yang, Yanhua; Li, Gang; Bian, Liming

2017-12-01

Hydrogels are appealing biomaterials for applications in regenerative medicine due to their tunable physical and bioactive properties. Meanwhile, therapeutic metal ions, such as magnesium ion (Mg 2+ ), not only regulate the cellular behaviors but also stimulate local bone formation and healing. However, the effective delivery and tailored release of Mg 2+ remains a challenge, with few reports on hydrogels being used for Mg 2+ delivery. Bisphosphonate exhibits a variety of specific bioactivities and excellent binding affinity to multivalent cations such as Mg 2+ . Herein, we describe a nanocomposite hydrogel based on hyaluronic acid and self-assembled bisphosphonate-magnesium (BP-Mg) nanoparticles. These nanoparticles bearing acrylate groups on the surface not only function as effective multivalent crosslinkers to strengthen the hydrogel network structure, but also promote the mineralization of hydrogels and mediate sustained release of Mg 2+ . The released Mg 2+ ions facilitate stem cell adhesion and spreading on the hydrogel substrates in the absence of cell adhesion ligands, and promote osteogenesis of the seeded hMSCs in vitro. Furthermore, the acellular porous hydrogels alone can support in situ bone regeneration without using exogenous cells and inductive agents, thereby greatly simplifying the approaches of bone regeneration therapy. In this study, we developed a novel bioactive nanocomposite hydrogel based on hyaluronic acid and self-assembled bisphosphonate-magnesium (BP-Mg) nanoparticles. Such hydrogels are stabilized by the multivalent crosslinking domains formed by the aggregation of Ac-BP-Mg NPs, and therefore show enhanced mechanical properties, improved capacity for mineralization, and controlled release kinetics of Mg 2+ . Moreover, the released Mg 2+ can enhance cell adhesion and spreading, and further promote the osteogenic differentiation of hMSCs. Owing to these unique properties, these acellular hydrogels alone can well facilitate the in vivo

Co-assembly of chitosan and phospholipids into hybrid hydrogels

DEFF Research Database (Denmark)

Mendes, Ana Carina Loureiro; Shekarforoush, Elhamalsadat; Engwer, Christoph

2016-01-01

Novel hybrid hydrogels were formed by adding chitosan (Ch) to phospholipids (P) self-assembled particles in lactic acid. The effect of the phospholipid concentration on the hydrogel properties was investigated and was observed to affect the rate of hydrogel formation and viscoelastic properties...

Direct-write Bioprinting of Cell-laden Methacrylated Gelatin Hydrogels

Science.gov (United States)

Bertassoni, Luiz E.; Cardoso, Juliana C.; Manoharan, Vijayan; Cristino, Ana L.; Bhise, Nupura S.; Araujo, Wesleyan A.; Zorlutuna, Pinar; Vrana, Nihal E.; Ghaemmaghami, Amir M.

2014-01-01

Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least 8 days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms. PMID:24695367

Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels

International Nuclear Information System (INIS)

Bertassoni, Luiz E; Cardoso, Juliana C; Manoharan, Vijayan; Cristino, Ana L; Bhise, Nupura S; Araujo, Wesleyan A; Zorlutuna, Pinar; Vrana, Nihal E; Dokmeci, Mehmet R; Khademhosseini, Ali; Ghaemmaghami, Amir M

2014-01-01

Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least eight days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms. (paper)

Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels.

Science.gov (United States)

Bertassoni, Luiz E; Cardoso, Juliana C; Manoharan, Vijayan; Cristino, Ana L; Bhise, Nupura S; Araujo, Wesleyan A; Zorlutuna, Pinar; Vrana, Nihal E; Ghaemmaghami, Amir M; Dokmeci, Mehmet R; Khademhosseini, Ali

2014-06-01

Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least eight days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms.

Synthesis and characterization of hyaluronic acid/human-like collagen hydrogels

International Nuclear Information System (INIS)

Zhang, Jingjing; Ma, Xiaoxuan; Fan, Daidi; Zhu, Chenhui; Deng, Jianjun; Hui, Junfeng; Ma, Pei

2014-01-01

Injectable hydrogel plays an important role in soft tissue filling and repair. We report an injectable hydrogel based on hyaluronic acid (HA) and human-like collagen (HLC), both with favorable biocompatibility and biodegradability. These two types of biomacromolecules were crosslinked with 1,4-butanediol diglycidyl ether to form a three-dimensional network. The redundant crosslinker was removed by dialysis and distillation. An HA-based hydrogel prepared by the same method was used as a control. The cytocompatibility was studied with a Cell Counting Kit-8 (CCK-8) test. Carbazole colorimetry was used to analyze the in vitro degradation rate. The histocompatibility was evaluated by hematoxylin and eosin (H and E) staining analysis and immunohistochemical analysis. The CCK-8 assay demonstrated that the HA/HLC hydrogel was less cytotoxic than the HA-based hydrogel and could promote baby hamster kidney cell (BHK) proliferation. The cell adhesion indicated that BHK could grow well on the surface of the materials and maintain good cell viability. The in vitro degradation test showed that the HA/HLC hydrogel had a longer degradation time and an excellent antienzyme ability. In vivo injection showed that there was little inflammatory response to HA/HLC after 1, 2, and 4 weeks. Therefore, the HA/HLC hydrogel is a promising biomaterial for soft tissue filling and repair. - Highlights: • Human-like collagen was used with hyaluronic acid to prepare soft tissue filling meterials. • 1,4-Butanediol diglycidyl ether (BDDE) was introduced to treat the hydrogels. • The addition of human-like collagen could improve the biological properties of hydrogels

Synthesis and characterization of hyaluronic acid/human-like collagen hydrogels

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jingjing; Ma, Xiaoxuan, E-mail: xiaoxuanma@163.com; Fan, Daidi, E-mail: fandaidi@nwu.edu.cn; Zhu, Chenhui; Deng, Jianjun; Hui, Junfeng; Ma, Pei

2014-10-01

Injectable hydrogel plays an important role in soft tissue filling and repair. We report an injectable hydrogel based on hyaluronic acid (HA) and human-like collagen (HLC), both with favorable biocompatibility and biodegradability. These two types of biomacromolecules were crosslinked with 1,4-butanediol diglycidyl ether to form a three-dimensional network. The redundant crosslinker was removed by dialysis and distillation. An HA-based hydrogel prepared by the same method was used as a control. The cytocompatibility was studied with a Cell Counting Kit-8 (CCK-8) test. Carbazole colorimetry was used to analyze the in vitro degradation rate. The histocompatibility was evaluated by hematoxylin and eosin (H and E) staining analysis and immunohistochemical analysis. The CCK-8 assay demonstrated that the HA/HLC hydrogel was less cytotoxic than the HA-based hydrogel and could promote baby hamster kidney cell (BHK) proliferation. The cell adhesion indicated that BHK could grow well on the surface of the materials and maintain good cell viability. The in vitro degradation test showed that the HA/HLC hydrogel had a longer degradation time and an excellent antienzyme ability. In vivo injection showed that there was little inflammatory response to HA/HLC after 1, 2, and 4 weeks. Therefore, the HA/HLC hydrogel is a promising biomaterial for soft tissue filling and repair. - Highlights: • Human-like collagen was used with hyaluronic acid to prepare soft tissue filling meterials. • 1,4-Butanediol diglycidyl ether (BDDE) was introduced to treat the hydrogels. • The addition of human-like collagen could improve the biological properties of hydrogels.

"That's Not Just Beautiful-That's Incredibly Beautiful!" : The Adverse Impact of Inflated Praise on Children With Low Self-Esteem

NARCIS (Netherlands)

Brummelman, Eddie; Thomaes, Sander; Orobio de Castro, Bram; Overbeek, Geertjan; Bushman, Brad J.

2014-01-01

In current Western society, children are often lavished with inflated praise (e.g., "You made an incredibly beautiful drawing!"). Inflated praise is often given in an attempt to raise children's self-esteem. An experiment (Study 1) and naturalistic study (Study 2) found that adults are especially

Polyampholyte hydrogel electrolytes for flexible and self-healing aqueous supercapacitor for low temperature applications

Science.gov (United States)

Chung, Hyun-Joong; Li, Xinda

Quenched polyampholytes provide a novel class of tough hydrogel that has self-healing ability, strong adhesion, and mechanical flexibility. In this study, we show that the polyampholyte hydrogels can be utilized as an aqueous gel electrolyte material that is especially useful for low temperature operations; at -30 °C, energy density of 10.5 Wh/kg at a power density of 500 W/kg was achieved. The high performance at the low temperature is associated to the concept of non-freezable water near the hydrophilic polymer chains. A comparison between differential scanning calorimetry (DSC) measurements for polyampholytes that contained KOH and neat KOH solution revealed that increased amount of water molecules become non-freezable when the solution is contained in the hydrogel networks. In addition, the crosslinked network structure of the polyampholyte chains disrupts the crystalline growth of ice, resulting in `slush-like' ice formation. The interplay between the increased amount of unfrozen water and the limited growth of ice crystals leads to the enhanced supercapacitor performance at low temperatures.

3D Printing and Electrospinning of Composite Hydrogels for Cartilage and Bone Tissue Engineering

Directory of Open Access Journals (Sweden)

Arianna De Mori

2018-03-01

Full Text Available Injuries of bone and cartilage constitute important health issues costing the National Health Service billions of pounds annually, in the UK only. Moreover, these damages can become cause of disability and loss of function for the patients with associated social costs and diminished quality of life. The biomechanical properties of these two tissues are massively different from each other and they are not uniform within the same tissue due to the specific anatomic location and function. In this perspective, tissue engineering (TE has emerged as a promising approach to address the complexities associated with bone and cartilage regeneration. Tissue engineering aims at developing temporary three-dimensional multicomponent constructs to promote the natural healing process. Biomaterials, such as hydrogels, are currently extensively studied for their ability to reproduce both the ideal 3D extracellular environment for tissue growth and to have adequate mechanical properties for load bearing. This review will focus on the use of two manufacturing techniques, namely electrospinning and 3D printing, that present promise in the fabrication of complex composite gels for cartilage and bone tissue engineering applications.

Scalable robotic biofabrication of tissue spheroids

International Nuclear Information System (INIS)

Mehesz, A Nagy; Hajdu, Z; Visconti, R P; Markwald, R R; Mironov, V; Brown, J; Beaver, W; Da Silva, J V L

2011-01-01

Development of methods for scalable biofabrication of uniformly sized tissue spheroids is essential for tissue spheroid-based bioprinting of large size tissue and organ constructs. The most recent scalable technique for tissue spheroid fabrication employs a micromolded recessed template prepared in a non-adhesive hydrogel, wherein the cells loaded into the template self-assemble into tissue spheroids due to gravitational force. In this study, we present an improved version of this technique. A new mold was designed to enable generation of 61 microrecessions in each well of a 96-well plate. The microrecessions were seeded with cells using an EpMotion 5070 automated pipetting machine. After 48 h of incubation, tissue spheroids formed at the bottom of each microrecession. To assess the quality of constructs generated using this technology, 600 tissue spheroids made by this method were compared with 600 spheroids generated by the conventional hanging drop method. These analyses showed that tissue spheroids fabricated by the micromolded method are more uniform in diameter. Thus, use of micromolded recessions in a non-adhesive hydrogel, combined with automated cell seeding, is a reliable method for scalable robotic fabrication of uniform-sized tissue spheroids.

Scalable robotic biofabrication of tissue spheroids

Energy Technology Data Exchange (ETDEWEB)

Mehesz, A Nagy; Hajdu, Z; Visconti, R P; Markwald, R R; Mironov, V [Advanced Tissue Biofabrication Center, Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC (United States); Brown, J [Department of Mechanical Engineering, Clemson University, Clemson, SC (United States); Beaver, W [York Technical College, Rock Hill, SC (United States); Da Silva, J V L, E-mail: mironovv@musc.edu [Renato Archer Information Technology Center-CTI, Campinas (Brazil)

2011-06-15

Development of methods for scalable biofabrication of uniformly sized tissue spheroids is essential for tissue spheroid-based bioprinting of large size tissue and organ constructs. The most recent scalable technique for tissue spheroid fabrication employs a micromolded recessed template prepared in a non-adhesive hydrogel, wherein the cells loaded into the template self-assemble into tissue spheroids due to gravitational force. In this study, we present an improved version of this technique. A new mold was designed to enable generation of 61 microrecessions in each well of a 96-well plate. The microrecessions were seeded with cells using an EpMotion 5070 automated pipetting machine. After 48 h of incubation, tissue spheroids formed at the bottom of each microrecession. To assess the quality of constructs generated using this technology, 600 tissue spheroids made by this method were compared with 600 spheroids generated by the conventional hanging drop method. These analyses showed that tissue spheroids fabricated by the micromolded method are more uniform in diameter. Thus, use of micromolded recessions in a non-adhesive hydrogel, combined with automated cell seeding, is a reliable method for scalable robotic fabrication of uniform-sized tissue spheroids.

Inflation and the Higgs Scalar

Energy Technology Data Exchange (ETDEWEB)

Green, Dan [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States)

2014-12-05

This note makes a self-contained exposition of the basic facts of big bang cosmology as they relate to inflation. The fundamental problems with that model are then explored. A simple scalar model of inflation is evaluated which provides the solution of those problems and makes predictions which will soon be definitively tested. The possibility that the recently discovered fundamental Higgs scalar field drives inflation is explored.

Phase separation of in situ forming poly (lactide-co-glycolide acid) implants investigated using a hydrogel-based subcutaneous tissue surrogate and UV-vis imaging.

Science.gov (United States)

Sun, Yu; Jensen, Henrik; Petersen, Nickolaj J; Larsen, Susan W; Østergaard, Jesper

2017-10-25

Phase separation of in situ forming poly (lactide-co-glycolide acid) (PLGA) implants with agarose hydrogels as the provider of nonsolvent (water) mimicking subcutaneous tissue was investigated using a novel UV-vis imaging-based analytical platform. In situ forming implants of PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin representing fast and slow phase separating systems, respectively, were evaluated using this platform. Upon contact with the agarose hydrogel, the phase separation of the systems was followed by the study of changes in light transmission and absorbance as a function of time and position. For the PLGA-1-methyl-2-pyrrolidinone system, the rate of spatial phase separation was determined and found to decrease with increasing the PLGA concentration from 20% to 40% (w/w). Hydrogels with different agarose concentrations (1% and 10% (w/v)) were prepared for providing the nonsolvent, water, to the in situ forming PLGA implants simulating the injection site environment. The resulting implant morphology depended on the stiffness of hydrogel matrix, indicating that the matrix in which implants are formed is of importance. Overall, the work showed that the UV-vis imaging-based platform with an agarose hydrogel mimicking the subcutaneous tissue holds potential in providing bio-relevant and mechanistic information on the phase separation processes of in situ forming implants. Copyright © 2017 Elsevier B.V. All rights reserved.

Changes in myopia with low-Dk hydrogel and high-Dk silicone hydrogel extended wear.

Science.gov (United States)

Jalbert, Isabelle; Stretton, Serina; Naduvilath, Thomas; Holden, Brien; Keay, Lisa; Sweeney, Deborah

2004-08-01

This study compared changes in myopia between wearers of high-oxygen permeability (Dk) silicone hydrogel lenses and low-Dk hydrogel lenses after 1 year of extended wear (EW). Ninety-two adult subjects were randomly assigned to a lens type. Subjective refraction and autokeratometry were performed at baseline and at 6 and 12 months. After 6 months of EW, myopia (spherical equivalent) regressed by 0.18 +/- 0.33 D (p Dk silicone hydrogel group and progressed by -0.23 +/- 0.36 D (p Dk hydrogel group. There were no further changes after 12 months. Previous lens wear history, baseline refractive error, and age and gender did not have an impact on the change in myopia, and only 35% of the variation could be accounted for by changes in corneal curvature and lens type. Soft contact lens type significantly affects the direction of change in myopia during EW. We hypothesize that these changes are driven by pressure-related redistribution of corneal tissue in high-Dk silicone hydrogel lens wearers and by hypoxia-associated corneal thinning in low-Dk hydrogel wearers. More long-term studies are required to confirm whether the effects of high-Dk silicone hydrogel lens wear on myopia are permanent.

Artificial Auricular Cartilage Using Silk Fibroin and Polyvinyl Alcohol Hydrogel

Science.gov (United States)

Lee, Jung Min; Sultan, Md. Tipu; Kim, Soon Hee; Kumar, Vijay; Yeon, Yeung Kyu; Lee, Ok Joo; Park, Chan Hum

2017-01-01

Several methods for auricular cartilage engineering use tissue engineering techniques. However, an ideal method for engineering auricular cartilage has not been reported. To address this issue, we developed a strategy to engineer auricular cartilage using silk fibroin (SF) and polyvinyl alcohol (PVA) hydrogel. We constructed different hydrogels with various ratios of SF and PVA by using salt leaching, silicone mold casting, and freeze-thawing methods. We characterized each of the hydrogels in terms of the swelling ratio, tensile strength, pore size, thermal properties, morphologies, and chemical properties. Based on the cell viability results, we found a blended hydrogel composed of 50% PVA and 50% SF (P50/S50) to be the best hydrogel among the fabricated hydrogels. An intact 3D ear-shaped auricular cartilage formed six weeks after the subcutaneous implantation of a chondrocyte-seeded 3D ear-shaped P50/S50 hydrogel in rats. We observed mature cartilage with a typical lacunar structure both in vitro and in vivo via histological analysis. This study may have potential applications in auricular tissue engineering with a human ear-shaped hydrogel. PMID:28777314

Inflation and quantum cosmology

International Nuclear Information System (INIS)

Linde, A.

1991-01-01

In this article a review of the present status of inflationary cosmology is given. We start with a discussion of the simplest version of the chaotic inflation scenario. Then we discuss some recent develoments in the inflationary cosmology, including the theory of a self-reproducing inflationary universe (eternal chaotic inflation). We do it with the help of stochastic approach to inflation. The results obtained within this approach are compared with the results obtained in the context of Euclidean quantum cosmology. (WL)

Synthesis and characterization of biodegradable poly (ethylene glycol) and poly (caprolactone diol) end capped poly (propylene fumarate) cross linked amphiphilic hydrogel as tissue engineering scaffold material.

Science.gov (United States)

Krishna, Lekshmi; Jayabalan, Muthu

2009-12-01

Biodegradable poly (caprolactone diol-co-propylene fumarate-co-ethylene glycol) amphiphilic polymer with poly (ethylene glycol) and poly (caprolactone diol) chain ends (PCL-PPF-PEG) was prepared. PCL-PPF-PEG undergoes fast setting with acrylamide (aqueous solution) by free radical polymerization and produces a crosslinked hydrogel. The cross linked and freeze-dried amphiphilic material has porous and interconnected network. It undergoes higher degree of swelling and water absorption to form hydrogel with hydrophilic and hydrophobic domains at the surface and appreciable tensile strength. The present hydrogel is compatible with L929 fibroblast cells. PCL-PPF-PEG/acrylamide hydrogel is a candidate scaffold material for tissue engineering applications.

Multifunctional magnetic-responsive hydrogels to engineer tendon-to-bone interface.

Science.gov (United States)

Silva, Elsa D; Babo, Pedro S; Costa-Almeida, Raquel; Domingues, Rui M A; Mendes, Bárbara B; Paz, Elvira; Freitas, Paulo; Rodrigues, Márcia T; Granja, Pedro L; Gomes, Manuela E

2017-06-11

Photocrosslinkable magnetic hydrogels are attracting great interest for tissue engineering strategies due to their versatility and multifunctionality, including their remote controllability ex vivo, thus enabling engineering complex tissue interfaces. This study reports the development of a photocrosslinkable magnetic responsive hydrogel made of methacrylated chondroitin sulfate (MA-CS) enriched with platelet lysate (PL) with tunable features, envisioning their application in tendon-to-bone interface. MA-CS coated iron-based magnetic nanoparticles were incorporated to provide magnetic responsiveness to the hydrogel. Osteogenically differentiated adipose-derived stem cells and/or tendon-derived cells were encapsulated within the hydrogel, proliferating and expressing bone- and tendon-related markers. External magnetic field (EMF) application modulated the swelling, degradation and release of PL-derived growth factors, and impacted both cell morphology and the expression and synthesis of tendon- and bone-like matrix with a more evident effect in co-cultures. Overall, the developed magnetic responsive hydrogel represents a potential cell carrier system for interfacial tissue engineering with EMF-controlled properties. Copyright © 2017 Elsevier Inc. All rights reserved.

Self-cleaned electrochemical protein imprinting biosensor basing on a thermo-responsive memory hydrogel.

Science.gov (United States)

Wei, Yubo; Zeng, Qiang; Hu, Qiong; Wang, Min; Tao, Jia; Wang, Lishi

2018-01-15

Herein, the self-cleaned electrochemical protein imprinting biosensor basing on a thermo-responsive memory hydrogel was constructed on a glassy carbon electrode (GCE) with a free radical polymerization method. Combining the advantages of thermo-responsive molecular imprinted polymers and electrochemistry, the resulted biosensor presents a novel self-cleaned ability for bovine serum albumin (BSA) in aqueous media. As a temperature controlled gate, the hydrogel film undergoes the adsorption and desorption of BSA basing on a reversible structure change with the external temperature stimuli. In particular, these processes have been revealed by the response of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) of electroactive [Fe(CN) 6 ] 3-/4- . The results have been supported by the evidences of scanning electron microscopy (SEM) and contact angles measurements. Under the optimal conditions, a wide detection range from 0.02μmolL -1 to 10μmolL -1 with a detection limit of 0.012 μmolL -1 (S/N = 3) was obtained for BSA. This proposed BSA sensor also possesses high selectivity, excellent stability, acceptable recovery and good reproducibility in its practical applications. Copyright © 2017. Published by Elsevier B.V.

Development of soy lecithin based novel self-assembled emulsion hydrogels.

Science.gov (United States)

Singh, Vinay K; Pandey, Preeti M; Agarwal, Tarun; Kumar, Dilip; Banerjee, Indranil; Anis, Arfat; Pal, Kunal

2015-03-01

The current study reports the development and characterization of soy lecithin based novel self-assembled emulsion hydrogels. Sesame oil was used as the representative oil phase. Emulsion gels were formed when the concentration of soy lecithin was >40% w/w. Metronidazole was used as the model drug for the drug release and the antimicrobial tests. Microscopic study showed the apolar dispersed phase in an aqueous continuum phase, suggesting the formation of emulsion hydrogels. FTIR study indicated the formation of intermolecular hydrogen bonding, whereas, the XRD study indicated predominantly amorphous nature of the emulsion gels. Composition dependent mechanical and drug release properties of the emulsion gels were observed. In-depth analyses of the mechanical studies were done using Ostwald-de Waele power-law, Kohlrausch and Weichert models, whereas, the drug release profiles were modeled using Korsmeyer-Peppas and Peppas-Sahlin models. The mechanical analyses indicated viscoelastic nature of the emulsion gels. The release of the drug from the emulsion gels was diffusion mediated. The drug loaded emulsion gels showed good antimicrobial activity. The biocompatibility test using HaCaT cells (human keratinocytes) suggested biocompatibility of the emulsion gels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Laminin Peptide-Immobilized Hydrogels Modulate Valve Endothelial Cell Hemostatic Regulation.

Directory of Open Access Journals (Sweden)

Liezl Rae Balaoing

Full Text Available Valve endothelial cells (VEC have unique phenotypic responses relative to other types of vascular endothelial cells and have highly sensitive hemostatic functions affected by changes in valve tissues. Furthermore, effects of environmental factors on VEC hemostatic function has not been characterized. This work used a poly(ethylene glycol diacrylate (PEGDA hydrogel platform to evaluate the effects of substrate stiffness and cell adhesive ligands on VEC phenotype and expression of hemostatic genes. Hydrogels of molecular weights (MWs 3.4, 8, and 20 kDa were polymerized into platforms of different rigidities and thiol-modified cell adhesive peptides were covalently bound to acrylate groups on the hydrogel surfaces. The peptide RKRLQVQLSIRT (RKR is a syndecan-1 binding ligand derived from laminin, a trimeric protein and a basement membrane matrix component. Conversely, RGDS is an integrin binding peptide found in many extracellular matrix (ECM proteins including fibronectin, fibrinogen, and von Willebrand factor (VWF. VECs adhered to and formed a stable monolayer on all RKR-coated hydrogel-MW combinations. RGDS-coated platforms supported VEC adhesion and growth on RGDS-3.4 kDa and RGDS-8 kDa hydrogels. VECs cultured on the softer RKR-8 kDa and RKR-20 kDa hydrogel platforms had significantly higher gene expression for all anti-thrombotic (ADAMTS-13, tissue factor pathway inhibitor, and tissue plasminogen activator and thrombotic (VWF, tissue factor, and P-selectin proteins than VECs cultured on RGDS-coated hydrogels and tissue culture polystyrene controls. Stimulated VECs promoted greater platelet adhesion than non-stimulated VECs on their respective culture condition; yet stimulated VECs on RGDS-3.4 kDa gels were not as responsive to stimulation relative to the RKR-gel groups. Thus, the syndecan binding, laminin-derived peptide promoted stable VEC adhesion on the softer hydrogels and maintained VEC phenotype and natural hemostatic function. In

Functionalized D-form self-assembling peptide hydrogels for bone regeneration

Directory of Open Access Journals (Sweden)

He B

2016-04-01

Full Text Available Bin He,1 Yunsheng Ou,1 Ao Zhou,1 Shuo Chen,1 Weikang Zhao,1 Jinqiu Zhao,2 Hong Li,3 Yong Zhu,1 Zenghui Zhao,1 Dianming Jiang1 1Department of Orthopedics, 2Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3School of Physical Science and Technology, Sichuan University, Chengdu, People’s Republic of China Abstract: Bone defects are very common in orthopedics, and there is great need to develop suitable bone grafts for transplantation in vivo. However, current bone grafts still encounter some limitations, including limited availability, immune rejection, poor osteoinduction and osteoconduction, poor biocompatibility and degradation properties, etc. Self-assembling peptide nanofiber scaffolds have emerged as an important substrate for cell culture and bone regeneration. We report on the structural features (eg, Congo red staining, circular dichroism spectroscopy, transmission electron microscopy, and rheometry assays and osteogenic ability of D-RADA16-RGD peptide hydrogels (with or without basic fibroblast growth factor due to the better stability of peptide bonds formed by these peptides compared with those formed by L-form peptides, and use them to fill the femoral condyle defect of Sprague Dawley rat model. The bone morphology change, two-dimensional reconstructions using microcomputed tomography, quantification of the microcomputed tomography analyses as well as histological analyses have demonstrated that RGD-modified D-form peptide scaffolds are able to enhance extensive bone regeneration. Keywords: bone defect, functionalized D-form self-assembling peptide, D-RADA16-RGD, peptide hydrogel, bone regeneration

Reinforcement of hydrogels using three-dimensionally printed microfibres

NARCIS (Netherlands)

Visser, Jetze; Melchels, Ferry P. W.; Jeon, June E.; van Bussel, Erik M.; Kimpton, Laura S.; Byrne, Helen M.; Dhert, Wouter J. A.; Dalton, Paul D.; Hutmacher, Dietmar W.; Malda, J

Despite intensive research, hydrogels currently available for tissue repair in the musculoskeletal system are unable to meet the mechanical, as well as the biological, requirements for successful outcomes. Here we reinforce soft hydrogels with highly organized, high-porosity microfibre networks that

The matrix reloaded: the evolution of regenerative hydrogels

NARCIS (Netherlands)

Jabbari, E.; Leijten, Jeroen Christianus Hermanus; Xu, Q.; Khademhosseini, A.

2016-01-01

Cell-laden hydrogels can regenerate lost, damaged or malfunctioning tissues. Clinical success of such hydrogels is strongly dependent on the ability to tune their chemical, physico-mechanical, and biological properties to a specific application. In particular, mimicking the intricate arrangement of

Injectable self-gelling composites for bone tissue engineering based on gellan gum hydrogel enriched with different bioglasses

NARCIS (Netherlands)

Douglas, T.E.; Piwowarczyk, W.; Pamula, E.; Liskova, J.; Schaubroeck, D.; Leeuwenburgh, S.C.; Brackman, G.; Balcaen, L.; Detsch, R.; Declercq, H.; Cholewa-Kowalska, K.; Dokupil, A.; Cuijpers, V.M.; Vanhaecke, F.; Cornelissen, R.; Coenye, T.; Boccaccini, A.R.; Dubruel, P.

2014-01-01

Hydrogels of biocompatible calcium-crosslinkable polysaccharide gellan gum (GG) were enriched with bioglass particles to enhance (i) mineralization with calcium phosphate (CaP); (ii) antibacterial properties and (iii) growth of bone-forming cells for future bone regeneration applications. Three

On the role of hydrogel structure and degradation in controlling the transport of cell-secreted matrix molecules for engineered cartilage.

Science.gov (United States)

Dhote, Valentin; Skaalure, Stacey; Akalp, Umut; Roberts, Justine; Bryant, Stephanie J; Vernerey, Franck J

2013-03-01

Damage to cartilage caused by injury or disease can lead to pain and loss of mobility, diminishing one's quality of life. Because cartilage has a limited capacity for self-repair, tissue engineering strategies, such as cells encapsulated in synthetic hydrogels, are being investigated as a means to restore the damaged cartilage. However, strategies to date are suboptimal in part because designing degradable hydrogels is complicated by structural and temporal complexities of the gel and evolving tissue along multiple length scales. To address this problem, this study proposes a multi-scale mechanical model using a triphasic formulation (solid, fluid, unbound matrix molecules) based on a single chondrocyte releasing extracellular matrix molecules within a degrading hydrogel. This model describes the key players (cells, proteoglycans, collagen) of the biological system within the hydrogel encompassing different length scales. Two mechanisms are included: temporal changes of bulk properties due to hydrogel degradation, and matrix transport. Numerical results demonstrate that the temporal change of bulk properties is a decisive factor in the diffusion of unbound matrix molecules through the hydrogel. Transport of matrix molecules in the hydrogel contributes both to the development of the pericellular matrix and the extracellular matrix and is dependent on the relative size of matrix molecules and the hydrogel mesh. The numerical results also demonstrate that osmotic pressure, which leads to changes in mesh size, is a key parameter for achieving a larger diffusivity for matrix molecules in the hydrogel. The numerical model is confirmed with experimental results of matrix synthesis by chondrocytes in biodegradable poly(ethylene glycol)-based hydrogels. This model may ultimately be used to predict key hydrogel design parameters towards achieving optimal cartilage growth. Copyright © 2012 Elsevier Ltd. All rights reserved.

3D-Printable Bioactivated Nanocellulose-Alginate Hydrogels.

Science.gov (United States)

Leppiniemi, Jenni; Lahtinen, Panu; Paajanen, Antti; Mahlberg, Riitta; Metsä-Kortelainen, Sini; Pinomaa, Tatu; Pajari, Heikki; Vikholm-Lundin, Inger; Pursula, Pekka; Hytönen, Vesa P

2017-07-05

We describe herein a nanocellulose-alginate hydrogel suitable for 3D printing. The composition of the hydrogel was optimized based on material characterization methods and 3D printing experiments, and its behavior during the printing process was studied using computational fluid dynamics simulations. The hydrogel was biofunctionalized by the covalent coupling of an enhanced avidin protein to the cellulose nanofibrils. Ionic cross-linking of the hydrogel using calcium ions improved the performance of the material. The resulting hydrogel is suitable for 3D printing, its mechanical properties indicate good tissue compatibility, and the hydrogel absorbs water in moist conditions, suggesting potential in applications such as wound dressings. The biofunctionalization potential was shown by attaching a biotinylated fluorescent protein and a biotinylated fluorescent small molecule via avidin and monitoring the material using confocal microscopy. The 3D-printable bioactivated nanocellulose-alginate hydrogel offers a platform for the development of biomedical devices, wearable sensors, and drug-releasing materials.

Osteochondral defect repair using a polyvinyl alcohol-polyacrylic acid (PVA-PAAc) hydrogel.

Science.gov (United States)

Bichara, David A; Bodugoz-Sentruk, Hatice; Ling, Doris; Malchau, Erik; Bragdon, Charles R; Muratoglu, Orhun K

2014-08-01

Poly(vinyl alcohol) (PVA) hydrogels can be candidates for articular cartilage repair due to their high water content. We synthesized a PVA-poly(acrylic acid) (PAAc) hydrogel formulation and determined its ability to function as a treatment option for condylar osteochondral (OC) defects in a New Zealand white rabbit (NZWR) model for 12 weeks and 24 weeks. In addition to hydrogel OC implants, tensile bar-shaped hydrogels were also implanted subcutaneously to evaluate changes in mechanical properties as a function of in vivo duration. There were no statistically significant differences (p > 0.05) in the water content measured in the OC hydrogel implant that was harvested after 12 weeks and 24 weeks, and non-implanted controls. There were no statistically significant differences (p > 0.05) in the break stress, strain at break or modulus of the tensile bars either between groups. Histological analysis of the OC defect, synovial capsule and fibrous tissue around the tensile bars determined hydrogel biocompatibility. Twelve-week hydrogels were found to be in situ flush with the articular cartilage; meniscal tissue demonstrated an intact surface. Twenty-four week hydrogels protruded from the defect site due to lack of integration with subchondral tissue, causing fibrillation to the meniscal surface. Condylar micro-CT scans ruled out osteolysis and bone cysts of the subchondral bone, and no PVA-PAAc hydrogel contents were found in the synovial fluid. The PVA-PAAc hydrogel was determined to be fully biocompatible, maintained its properties over time, and performed well at the 12 week time point. Physical fixation of the PVA-PAAc hydrogel to the subchondral bone is required to ensure long-term performance of hydrogel plugs for OC defect repair.

Fabrication of circular microfluidic network in enzymatically-crosslinked gelatin hydrogel

Energy Technology Data Exchange (ETDEWEB)

He, Jiankang, E-mail: jiankanghe@mail.xjtu.edu.cn; Chen, Ruomeng; Lu, Yongjie; Zhan, Li; Liu, Yaxiong; Li, Dichen; Jin, Zhongmin

2016-02-01

It is a huge challenge to engineer vascular networks in vital organ tissue engineering. Although the incorporation of artificial microfluidic network into thick tissue-engineered constructs has shown great promise, most of the existing microfluidic strategies are limited to generate rectangle cross-sectional channels rather than circular vessels in soft hydrogels. Here we present a facile approach to fabricate branched microfluidic network with circular cross-sections in gelatin hydrogels by combining micromolding and enzymatically-crosslinking mechanism. Partially crosslinked hydrogel slides with predefined semi-circular channels were molded, assembled and in situ fully crosslinked to form a seamless and circular microfluidic network. The bonding strength of the resultant gelatin hydrogels was investigated. The morphology and the dimension of the resultant circular channels were characterized using scanning electron microscopy (SEM) and micro-computerized tomography (μCT). Computational fluid dynamic simulation shows that the fabrication error had little effect on the distribution of flow field but affected the maximum velocity in comparison with designed models. The microfluidic gelatin hydrogel facilitates the attachment and spreading of human umbilical endothelial cells (HUVECs) to form a uniform endothelialized layer around the circular channel surface, which successfully exhibited barrier functions. The presented method might provide a simple way to fabricate circular microfluidic networks in biologically-relevant hydrogels to advance various applications of in vitro tissue models, organ-on-a-chip systems and tissue engineering. - Highlights: • A facile method was proposed to build a circular fluidic network in gelatin hydrogel. • The fluidic network is mechanically robust and supports physiological flow. • HUVECs formed endothelialized layer around the channel to express barrier function.

Microengineered 3D cell-laden thermoresponsive hydrogels for mimicking cell morphology and orientation in cartilage tissue engineering.

Science.gov (United States)

Mellati, Amir; Fan, Chia-Ming; Tamayol, Ali; Annabi, Nasim; Dai, Sheng; Bi, Jingxiu; Jin, Bo; Xian, Cory; Khademhosseini, Ali; Zhang, Hu

2017-01-01

Mimicking the zonal organization of native articular cartilage, which is essential for proper tissue functions, has remained a challenge. In this study, a thermoresponsive copolymer of chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) was synthesized as a carrier of mesenchymal stem cells (MSCs) to provide a support for their proliferation and differentiation. Microengineered three-dimensional (3D) cell-laden CS-g-PNIPAAm hydrogels with different microstripe widths were fabricated to control cellular alignment and elongation in order to mimic the superficial zone of natural cartilage. Biochemical assays showed six- and sevenfold increment in secretion of glycosaminoglycans (GAGs) and total collagen from MSCs encapsulated within the synthesized hydrogel after 28 days incubation in chondrogenic medium. Chondrogenic differentiation was also verified qualitatively by histological and immunohistochemical assessments. It was found that 75 ± 6% of cells encapsulated within 50 μm wide microstripes were aligned with an aspect ratio of 2.07 ± 0.16 at day 5, which was more organized than those observed in unpatterned constructs (12 ± 7% alignment and a shape index of 1.20 ± 0.07). The microengineered constructs mimicked the cell shape and organization in the superficial zone of cartilage whiles the unpatterned one resembled the middle zone. Our results suggest that microfabrication of 3D cell-laden thermosensitive hydrogels is a promising platform for creating biomimetic structures leading to more successful multi-zonal cartilage tissue engineering. Biotechnol. Bioeng. 2017;114: 217-231. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hydrogels from feather keratin show higher viscoelastic properties and cell proliferation than those from hair and wool keratins.

Science.gov (United States)

Esparza, Yussef; Bandara, Nandika; Ullah, Aman; Wu, Jianping

2018-09-01

Hydrogel prepared from keratin shows potential applications in tissue engineering. However, the importance of the keratin sources has not been considered. The objectives of this study were to characterize and compare the rheological (storage modulus), physical (porosity, pore size, swelling capacity, and water contact angle) and in vitro cell compatibility of hydrogel scaffolds prepared from various keratin sources. Keratins were characterized by means of their molecular weight, amino acid composition, thermal and conformational properties. Hydrogels from chicken feather keratins demonstrated substantially higher storage modulus (G') than hair and wool keratin hydrogels. However, higher swelling capacity (>3000%) was determined in hair and wool over feather keratin (1500%) hydrogels. Our results suggest that small molecular weight and β-sheet conformation of feather keratin (~10 kDa) facilitated the self-assembly of rigid hydrogels through disulfide bond re-oxidation. Whereas, high molecular weight (10-75 kDa) stretchable α-helix conformation in hair and wool keratins resulted in weaker hydrogels. The cell cultures using fibroblasts showed the highest proliferation rate on chicken feather keratin hydrogel scaffolds. After 15 days of culture, partial breakdown of keratin fibers was observed. Results indicate that stiffer avian keratins can be used to fabricate more mechanically robust biomaterials than mammalian keratins. Copyright © 2018 Elsevier B.V. All rights reserved.

Heparin binding chitosan derivatives for production of pro-angiogenic hydrogels for promoting tissue healing

Energy Technology Data Exchange (ETDEWEB)

Yar, Muhammad, E-mail: drmyar@ciitlahore.edu.pk [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Shahzad, Sohail [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Shahzadi, Lubna [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Shahzad, Sohail Anjum [Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, University of Health Sciences, Lahore (Pakistan); Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Materials Science and Engineering, North Campus, University of Sheffield, Broad Lane, Sheffield S3 7HQ (United Kingdom); MacNeil, Sheila, E-mail: s.macneil@sheffield.ac.uk [Materials Science and Engineering, North Campus, University of Sheffield, Broad Lane, Sheffield S3 7HQ (United Kingdom)

2017-05-01

Our aim was to develop a biocompatible hydrogel that could be soaked in heparin and placed on wound beds to improve the vasculature of poorly vascularized wound beds. In the current study, a methodology was developed for the synthesis of a new chitosan derivative (CSD-1). Hydrogels were synthesized by blending CSD-1 for either 4 or 24 h with polyvinyl alcohol (PVA). The physical/chemical interactions and the presence of specific functional groups were confirmed by Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance ({sup 1}H NMR). The porous nature of the hydrogels was confirmed by scanning electron microscopy (SEM). Thermal gravimetric analysis (TGA) showed that these hydrogels have good thermal stability which was slightly increased as the blending time was increased. Hydrogels produced with 24 h of blending supported cell attachment more and could be loaded with heparin to induce new blood vessel formation in a chick chorionic allantoic membrane assay. - Highlights: • Chitosan based hydrogels were designed to stimulate angiogenesis. • Two new derivatives of chitosan were produced using a Mannich type reaction. • Blending a chitosan derivative with PVA gave a porous biocompatible hydrogel. • Heparin bound to the hydrogel on immersion changing its morphology. • Heparin loaded hydrogel stimulated blood vessel formation in a chick model.

FGL-functionalized self-assembling nanofiber hydrogel as a scaffold for spinal cord-derived neural stem cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Jian [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zheng, Jin [Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qixin, E-mail: zheng-qx@163.com [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Wu, Yongchao; Wu, Bin; Huang, Shuai; Fang, Weizhi; Guo, Xiaodong [Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

2015-01-01

A class of designed self-assembling peptide nanofiber scaffolds has been shown to be a good biomimetic material in tissue engineering. Here, we specifically made a new peptide hydrogel scaffold FGLmx by mixing the pure RADA{sub 16} and designer functional peptide RADA{sub 16}-FGL solution, and we analyzed the physiochemical properties of each peptide with atomic force microscopy (AFM) and circular dichroism (CD). In addition, we examined the biocompatibility and bioactivity of FGLmx as well as RADA{sub 16} scaffold on spinal cord-derived neural stem cells (SC-NSCs) isolated from neonatal rats. Our results showed that RADA{sub 16}-FGL displayed a weaker β-sheet structure and FGLmx could self-assemble into nanofibrous morphology. Moreover, we found that FGLmx was not only noncytotoxic to SC-NSCs but also promoted SC-NSC proliferation and migration into the three-dimensional (3-D) scaffold, meanwhile, the adhesion and lineage differentiation of SC-NSCs on FGLmx were similar to that on RADA{sub 16}. Our results indicated that the FGL-functionalized peptide scaffold might be very beneficial for tissue engineering and suggested its further application for spinal cord injury (SCI) repair. - Highlights: • RADA{sub 16} and RADA{sub 16}-FGL peptides were synthesized and characterized. • Rat spinal cord neural stem cells were successfully isolated and characterized. • We provided an induction method for mixed differentiation of neural stem cells. • FGL scaffold had good biocompatibility and bioactivity with neural stem cells.

Hydrogels That Allow and Facilitate Bone Repair, Remodeling, and Regeneration.

Science.gov (United States)

Short, Aaron R; Koralla, Deepthi; Deshmukh, Ameya; Wissel, Benjamin; Stocker, Benjamin; Calhoun, Mark; Dean, David; Winter, Jessica O

2015-10-28

Bone defects can originate from a variety of causes, including trauma, cancer, congenital deformity, and surgical reconstruction. Success of the current "gold standard" treatment (i.e., autologous bone grafts) is greatly influenced by insufficient or inappropriate bone stock. There is thus a critical need for the development of new, engineered materials for bone repair. This review describes the use of natural and synthetic hydrogels as scaffolds for bone tissue engineering. We discuss many of the advantages that hydrogels offer as bone repair materials, including their potential for osteoconductivity, biodegradability, controlled growth factor release, and cell encapsulation. We also discuss the use of hydrogels in composite devices with metals, ceramics, or polymers. These composites are useful because of the low mechanical moduli of hydrogels. Finally, the potential for thermosetting and photo-cross-linked hydrogels as three-dimensionally (3D) printed, patient-specific devices is highlighted. Three-dimensional printing enables controlled spatial distribution of scaffold materials, cells, and growth factors. Hydrogels, especially natural hydrogels present in bone matrix, have great potential to augment existing bone tissue engineering devices for the treatment of critical size bone defects.

Arct'Alg release from hydrogel membranes

International Nuclear Information System (INIS)

Amaral, Renata H.; Rogero, Sizue O.; Shihomatsu, Helena M.; Lugao, Ademar B.

2009-01-01

The hydrogel properties make them attractive for a variety of biomedical and pharmaceutical applications, primarily in drug delivery system. Synthetic hydrogels have been studied to develop new devices for drugs or cosmetic active agents release. Arct'Alg R is an extract derived from red algae biomass which has antioxidant, anti-inflammatory and tissue regeneration stimulant properties. This extract was incorporated to poly(N-vinyl pyrrolidone) (PVP) and poly(vinyl alcohol) (PVA) hydrogel membranes obtained by gamma rays crosslinking technique. The ionizing radiation presents the advantage to occur polymerization and sterilization simultaneously in the same process. The aim of this work was the in vitro release kinetic study of Arct'Alg R from hydrogel membranes during 24 hours to verify the possibility of use in cosmetic and dermatological treatments. Results showed that about 50% and 30% of incorporated Arct'Alg R was released from PVP and PVA hydrogel membrane devices respectively. (author)

Self-Organization and the Self-Assembling Process in Tissue Engineering

Science.gov (United States)

Eswaramoorthy, Rajalakshmanan; Hadidi, Pasha; Hu, Jerry C.

2015-01-01

In recent years, the tissue engineering paradigm has shifted to include a new and growing subfield of scaffoldless techniques which generate self-organizing and self-assembling tissues. This review aims to provide a cogent description of this relatively new research area, with special emphasis on applications toward clinical use and research models. Particular emphasis is placed on providing clear definitions of self-organization and the self-assembling process, as delineated from other scaffoldless techniques in tissue engineering and regenerative medicine. Significantly, during formation, self-organizing and self-assembling tissues display biological processes similar to those that occur in vivo. These help lead to the recapitulation of native tissue morphological structure and organization. Notably, functional properties of these tissues also approach native tissue values; some of these engineered tissues are already in clinical trials. This review aims to provide a cohesive summary of work in this field, and to highlight the potential of self-organization and the self-assembling process to provide cogent solutions to current intractable problems in tissue engineering. PMID:23701238

Biocompatible Porous Polyester-Ether Hydrogel Scaffolds with Cross-Linker Mediated Biodegradation and Mechanical Properties for Tissue Augmentation

Directory of Open Access Journals (Sweden)

Berkay Ozcelik

2018-02-01

Full Text Available Porous polyester-ether hydrogel scaffolds (PEHs were fabricated using acid chloride/alcohol chemistry and a salt templating approach. The PEHs were produced from readily available and cheap commercial reagents via the reaction of hydroxyl terminated poly(ethylene glycol (PEG derivatives with sebacoyl, succinyl, or trimesoyl chloride to afford ester cross-links between the PEG chains. Through variation of the acid chloride cross-linkers used in the synthesis and the incorporation of a hydrophobic modifier (poly(caprolactone (PCL, it was possible to tune the degradation rates and mechanical properties of the resulting hydrogels. Several of the hydrogel formulations displayed exceptional mechanical properties, remaining elastic without fracture at compressive strains of up to 80%, whilst still displaying degradation over a period of weeks to months. A subcutaneous rat model was used to study the scaffolds in vivo and revealed that the PEHs were infiltrated with well vascularised tissue within two weeks and had undergone significant degradation in 16 weeks without any signs of toxicity. Histological evaluation for immune responses revealed that the PEHs incite only a minor inflammatory response that is reduced over 16 weeks with no evidence of adverse effects.

Hydrogel Macroporosity and the Prolongation of Transgene Expression and the Enhancement of Angiogenesis

Science.gov (United States)

Shepard, Jaclyn A.; Virani, Farrukh R.; Goodman, Ashley G.; Gossett, Timothy D.; Shin, Seungjin; Shea, Lonnie D.

2012-01-01

The utility of hydrogels for regenerative medicine can be improved through localized gene delivery to enhance their bioactivity. However, current systems typically lead to low-level transgene expression located in host tissue surrounding the implant. Herein, we investigated the inclusion of macropores into hydrogels to facilitate cell ingrowth and enhance gene delivery within the macropores in vivo. Macropores were created within PEG hydrogels by gelation around gelatin microspheres, with gelatin subsequently dissolved by incubation at 37°C. The macropores were interconnected, as evidenced by homogeneous cell seeding in vitro and complete cell infiltration in vivo. Lentivirus loaded within hydrogels following gelation retained its activity relative to the unencapsulated control virus. In vivo, macroporous PEG demonstrated sustained, elevated levels of transgene expression for 6 weeks, while hydrogels without macropores had transient expression. Transduced cells were located throughout the macroporous structure, while non-macroporous PEG hydrogels had transduction only in the adjacent host tissue. Delivery of lentivirus encoding for VEGF increased vascularization relative to the control, with vessels throughout the macropores of the hydrogel. The inclusion of macropores within the hydrogel to enhance cell infiltration enhances transduction and influences tissue development, which has implications for multiple regenerative medicine applications. PMID:22800542

Construction of Modular Hydrogel Sheets for Micropatterned Macro-scaled 3D Cellular Architecture.

Science.gov (United States)

Son, Jaejung; Bae, Chae Yun; Park, Je-Kyun

2016-01-11

Hydrogels can be patterned at the micro-scale using microfluidic or micropatterning technologies to provide an in vivo-like three-dimensional (3D) tissue geometry. The resulting 3D hydrogel-based cellular constructs have been introduced as an alternative to animal experiments for advanced biological studies, pharmacological assays and organ transplant applications. Although hydrogel-based particles and fibers can be easily fabricated, it is difficult to manipulate them for tissue reconstruction. In this video, we describe a fabrication method for micropatterned alginate hydrogel sheets, together with their assembly to form a macro-scale 3D cell culture system with a controlled cellular microenvironment. Using a mist form of the calcium gelling agent, thin hydrogel sheets are easily generated with a thickness in the range of 100 - 200 µm, and with precise micropatterns. Cells can then be cultured with the geometric guidance of the hydrogel sheets in freestanding conditions. Furthermore, the hydrogel sheets can be readily manipulated using a micropipette with an end-cut tip, and can be assembled into multi-layered structures by stacking them using a patterned polydimethylsiloxane (PDMS) frame. These modular hydrogel sheets, which can be fabricated using a facile process, have potential applications of in vitro drug assays and biological studies, including functional studies of micro- and macrostructure and tissue reconstruction.

Inflation targeting and core inflation

OpenAIRE

Julie Smith

2005-01-01

This paper examines the interaction of core inflation and inflation targeting as a monetary policy regime. Interest in core inflation has grown because of inflation targeting. Core inflation is defined in numerous ways giving rise to many potential measures; this paper defines core inflation as the best forecaster of inflation. A cross-country study finds before the start of inflation targeting, but not after, core inflation differs between non-inflation targeters and inflation targeters. Thr...

Osteogenic differentiation of human adipose-derived mesenchymal stem cells on gum tragacanth hydrogel.

Science.gov (United States)

Haeri, Seyed Mohammad Jafar; Sadeghi, Yousef; Salehi, Mohammad; Farahani, Reza Masteri; Mohsen, Nourozian

2016-05-01

Currently, natural polymer based hydrogels has attracted great attention of orthopedic surgeons for application in bone tissue engineering. With this aim, osteoinductive capacity of Gum Tragacanth (GT) based hydrogel was compared to collagen hydrogel and tissue culture plate (TCPS). For this purpose, adipose-derived mesenchymal stem cells (AT-MSCs) was cultured on the hydrogels and TCPS and after investigating the biocompatibility of hydrogels using MTT assay, osteoinductivity of hydrogels were evaluated using pan osteogenic markers such as Alizarin red staining, alkaline phosphatase (ALP) activity, calcium content and osteo-related genes. Increasing proliferation trend of AT-MSCs on GT hydrogel demonstrated that TG has no-cytotoxicity and can even be better than the other groups i.e., highest proliferation at day 5. GT hydrogel displayed highest ALP activity and mineralization when compared to the collagen hydrogel and TCPS. Relative gene expression levels have demonstrated that highest expression of Runx2, osteonectin and osteocalcin in the cells cultured GT hydrogel but the expression of collagen type-1 remains constant in hydrogels. Above results demonstrate that GT hydrogel could be an appropriate scaffold for accelerating and supporting the adhesion, proliferation and osteogenic differentiation of stem cells which further can be used for orthopedic applications. Copyright © 2016. Published by Elsevier Ltd.

Triethyl orthoformate mediated a novel crosslinking method for the preparation of hydrogels for tissue engineering applications: characterization and in vitro cytocompatibility analysis

Energy Technology Data Exchange (ETDEWEB)

Yar, Muhammad, E-mail: drmyar@ciitlahore.edu.pk [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Shahzad, Sohail [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Siddiqi, Saadat Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Rauf, Abdul [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Anwar, Muhammad Sabieh [Department of Physics, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences (LUMS), Opposite Sector U, D.H.A., Lahore 54792 (Pakistan); Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Materials Science and Engineering, The Kroto Research Institute, The University of Sheffield, North Campus, Broad Lane, Sheffield S3 7HQ (United Kingdom)

2015-11-01

This paper describes the development of a new crosslinking method for the synthesis of novel hydrogel films from chitosan and PVA for potential use in various biomedical applications. These hydrogel membranes were synthesized by blending different ratios of chitosan (CS) and poly(vinyl alcohol) (PVA) solutions and were crosslinked with 2.5% (w/v) triethyl orthoformate (TEOF) in the presence of 17% (w/v) sulfuric acid. The physical/chemical interactions and the presence of specific functional groups in the synthesized materials were evaluated by Fourier transform infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). Thermal gravimetric analysis (TGA) proved that these crosslinked hydrogel films have good thermal stability which was decreased as the CS ratio was increased. Differential scanning calorimetry (DSC) exhibited that CS and PVA were present in the amorphous form. The solution absorption properties were performed in phosphate buffer saline (PBS) solution of pH 7.4. The 20% PVA–80% CS crosslinked hydrogel films showed a greater degree of solution absorption (183%) as compared to other compositions. The hydrogels with greater CS concentration (60% and 80%) demonstrated relatively more porous structure, better cell viability and proliferation and also revealed good blood clotting ability even after crosslinking. Based on the observed facts these hydrogels can be tailored for their potential utilization in wound healing and skin tissue engineering applications. - Highlights: • A new method for covalently crosslinking of chitosan and PVA. • Triethyl orthoformate (TEOF) a new polymer–polymer crosslinking agent. • Hydrogels displayed a good solution absorption capacity. • Hydrogels demonstrated good cytocompatibility. • Good blood clotting potential was shown by these scaffolds.

Triethyl orthoformate mediated a novel crosslinking method for the preparation of hydrogels for tissue engineering applications: characterization and in vitro cytocompatibility analysis

International Nuclear Information System (INIS)

Yar, Muhammad; Shahzad, Sohail; Siddiqi, Saadat Anwar; Mahmood, Nasir; Rauf, Abdul; Anwar, Muhammad Sabieh; Chaudhry, Aqif Anwar; Rehman, Ihtesham ur

2015-01-01

This paper describes the development of a new crosslinking method for the synthesis of novel hydrogel films from chitosan and PVA for potential use in various biomedical applications. These hydrogel membranes were synthesized by blending different ratios of chitosan (CS) and poly(vinyl alcohol) (PVA) solutions and were crosslinked with 2.5% (w/v) triethyl orthoformate (TEOF) in the presence of 17% (w/v) sulfuric acid. The physical/chemical interactions and the presence of specific functional groups in the synthesized materials were evaluated by Fourier transform infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). Thermal gravimetric analysis (TGA) proved that these crosslinked hydrogel films have good thermal stability which was decreased as the CS ratio was increased. Differential scanning calorimetry (DSC) exhibited that CS and PVA were present in the amorphous form. The solution absorption properties were performed in phosphate buffer saline (PBS) solution of pH 7.4. The 20% PVA–80% CS crosslinked hydrogel films showed a greater degree of solution absorption (183%) as compared to other compositions. The hydrogels with greater CS concentration (60% and 80%) demonstrated relatively more porous structure, better cell viability and proliferation and also revealed good blood clotting ability even after crosslinking. Based on the observed facts these hydrogels can be tailored for their potential utilization in wound healing and skin tissue engineering applications. - Highlights: • A new method for covalently crosslinking of chitosan and PVA. • Triethyl orthoformate (TEOF) a new polymer–polymer crosslinking agent. • Hydrogels displayed a good solution absorption capacity. • Hydrogels demonstrated good cytocompatibility. • Good blood clotting potential was shown by these scaffolds

Injectable, degradable, electroactive nanocomposite hydrogels containing conductive polymer nanoparticles for biomedical applications.

Science.gov (United States)

Wang, Qinmei; Wang, Qiong; Teng, Wei

2016-01-01

Injectable electroactive hydrogels (eGels) are promising in regenerative medicine and drug delivery, however, it is still a challenge to obtain such hydrogels simultaneously possessing other properties including uniform structure, degradability, robustness, and biocompatibility. An emerging strategy to endow hydrogels with desirable properties is to incorporate functional nanoparticles in their network. Herein, we report the synthesis and characterization of an injectable hydrogel based on oxidized alginate (OA) crosslinking gelatin reinforced by electroactive tetraaniline-graft-OA nanoparticles (nEOAs), where nEOAs are expected to impart electroactivity besides reinforcement without significantly degrading the other properties of hydrogels. Assays of transmission electron microscopy, (1)H nuclear magnetic resonance, and dynamic light scattering reveal that EOA can spontaneously and quickly self-assemble into robust nanoparticles in water, and this nanoparticle structure can be kept at pH 3~9. Measurement of the gel time by rheometer and the stir bar method confirms the formation of the eGels, and their gel time is dependent on the weight content of nEOAs. As expected, adding nEOAs to hydrogels does not cause the phase separation (scanning electron microscopy observation), but it improves mechanical strength up to ~8 kPa and conductivity up to ~10(-6) S/cm in our studied range. Incubating eGels in phosphate-buffered saline leads to their further swelling with an increase of water content <6% and gradual degradation. When growing mesenchymal stem cells on eGels with nEOA content ≤14%, the growth curves and morphology of cells were found to be similar to that on tissue culture plastic; when implanting these eGels on a chick chorioallantoic membrane for 1 week, mild inflammation response appeared without any other structural changes, indicating their good in vitro and in vivo biocompatibility. With injectability, uniformity, degradability, electroactivity, relative

Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

Directory of Open Access Journals (Sweden)

Sun HY

2017-04-01

Full Text Available Hongyu Sun,* Jing Zhou,* Zhu Huang,* Linlin Qu,* Ning Lin,* Chengxiao Liang, Ruiwu Dai, Lijun Tang, Fuzhou Tian General Surgery Center, Chengdu Military General Hospital, Chengdu, China *These authors contributed equally to this work Abstract: Carbon nanotubes (CNTs provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt% exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. Keywords: carbon nanotubes, collagen hydrogel, cardiac constructs, cell alignment, tissue functionality

Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

Science.gov (United States)

Sun, Hongyu; Zhou, Jing; Huang, Zhu; Qu, Linlin; Lin, Ning; Liang, Chengxiao; Dai, Ruiwu; Tang, Lijun; Tian, Fuzhou

2017-01-01

Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. PMID:28450785

A phytomodulatory hydrogel with enhanced healing effects.

Science.gov (United States)

Vasconcelos, Mirele S; Souza, Tamiris F G; Figueiredo, Ingrid S; Sousa, Emília T; Sousa, Felipe D; Moreira, Renato A; Alencar, Nylane M N; Lima-Filho, José V; Ramos, Márcio V

2018-04-01

The healing performance of a hydrogel composed of hemicelluloses extracted from seeds of Caesalpinia pulcherrima (Fabaceae) and mixed with phytomodulatory proteins obtained from the latex of Calotropis procera was characterized on excisional wounds. The hydrogel did not induce dermal irritability. When topically used on excisional wounds, the hydrogel enhanced healing by wound contraction. Histology and the measurement of inflammatory mediators (myeloperoxidase, interleukin-1β, and interleukin-6) suggested that the inflammatory phase of the healing process was intensified, stimulating fibroplasia and neovascularization (proliferative phase) and tissue remodeling by increasing new collagen fiber deposition. In addition, reduction on levels of malondialdehyde in the groups that the hydrogel was applied suggested that the oxidative stress was reduced. The hydrogel performed better than the reference drug used, as revealed by the extended thickness of the remodeled epithelium. Copyright © 2018 John Wiley & Sons, Ltd.

Injectable hydrogels derived from phosphorylated alginic acid calcium complexes

Energy Technology Data Exchange (ETDEWEB)

Kim, Han-Sem; Song, Minsoo, E-mail: minsoosong00@gmail.com; Lee, Eun-Jung; Shin, Ueon Sang, E-mail: usshin12@dankook.ac.kr

2015-06-01

Phosphorylation of sodium alginate salt (NaAlg) was carried out using H{sub 3}PO{sub 4}/P{sub 2}O{sub 5}/Et{sub 3}PO{sub 4} followed by acid–base reaction with Ca(OAc){sub 2} to give phosphorylated alginic acid calcium complexes (CaPAlg), as a water dispersible alginic acid derivative. The modified alginate derivatives including phosphorylated alginic acid (PAlg) and CaPAlg were characterized by nuclear magnetic resonance spectroscopy for {sup 1}H, and {sup 31}P nuclei, high resolution inductively coupled plasma optical emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. CaPAlg hydrogels were prepared simply by mixing CaPAlg solution (2 w/v%) with NaAlg solution (2 w/v%) in various ratios (2:8, 4:6, 6:4, 8:2) of volume. No additional calcium salts such as CaSO{sub 4} or CaCl{sub 2} were added externally. The gelation was completed within about 3–40 min indicating a high potential of hydrogel delivery by injection in vivo. Their mechanical properties were tested to be ≤ 6.7 kPa for compressive strength at break and about 8.4 kPa/mm for elastic modulus. SEM analysis of the CaPAlg hydrogels showed highly porous morphology with interconnected pores of width in the range of 100–800 μm. Cell culture results showed that the injectable hydrogels exhibited comparable properties to the pure alginate hydrogel in terms of cytotoxicity and 3D encapsulation of cells for a short time period. The developed injectable hydrogels showed suitable physicochemical and mechanical properties for injection in vivo, and could therefore be beneficial for the field of soft tissue engineering. - Highlights: • Preparation of water-soluble alginic acid complexes with calcium phosphate • Self-assembly of the phosphorylated alginic acid calcium complexes with sodium alginate • Preparation of injectable hydrogels with diverse gelation times within about 3–40 min.

Preparation of Chitosan-based Injectable Hydrogels and Its Application in 3D Cell Culture.

Science.gov (United States)

Li, Yongsan; Zhang, Yaling; Wei, Yen; Tao, Lei

2017-09-29

The protocol presents a facile, efficient, and versatile method to prepare chitosan-based hydrogels using dynamic imine chemistry. The hydrogel is prepared by mixing solutions of glycol chitosan with a synthesized benzaldehyde terminated polymer gelator, and hydrogels are efficiently obtained in several minutes at room temperature. By varying ratios between glycol chitosan, polymer gelator, and water contents, versatile hydrogels with different gelation times and stiffness are obtained. When damaged, the hydrogel can recover its appearances and modulus, due to the reversibility of the dynamic imine bonds as crosslinkages. This self-healable property enables the hydrogel to be injectable since it can be self-healed from squeezed pieces to an integral bulk hydrogel after the injection process. The hydrogel is also multi-responsive to many bio-active stimuli due to different equilibration statuses of the dynamic imine bonds. This hydrogel was confirmed as bio-compatible, and L929 mouse fibroblast cells were embedded following standard procedures and the cell proliferation was easily assessed by a 3D cell cultivation process. The hydrogel can offer an adjustable platform for different research where a physiological mimic of a 3D environment for cells is profited. Along with its multi-responsive, self-healable, and injectable properties, the hydrogels can potentially be applied as multiple carriers for drugs and cells in future bio-medical applications.

initiated small intestinal sub-mucosal wound-healing hydrogel

African Journals Online (AJOL)

In vitro cell culture was carried out on the hydrogels, and cell count was obtained on ... a crucial role in stem cell differentiation. ... biodegradable material, especially in tissue engineering [10,11]. .... The test procedures used were based on the method of ..... responsive hydrogels for controlled drug release. Polymer. 2009 ...

'That’s Not Just Beautiful—That’s Incredibly Beautiful!' : The Adverse Impact of Inflated Praise on Children With Low Self-Esteem

NARCIS (Netherlands)

Brummelman, E.; Thomaes, S.; Orobio de Castro, B.; Overbeek, G.; Bushman, B.J.

In current Western society, children are often lavished with inflated praise (e.g., “You made an incredibly beautiful drawing!”). Inflated praise is often given in an attempt to raise children’s self-esteem. An experiment (Study 1) and naturalistic study (Study 2) found that adults are especially

Proliferation and osteoblastic differentiation of hMSCs on cellulose-based hydrogels.

Science.gov (United States)

Raucci, Maria Grazia; Alvarez-Perez, Marco Antonio; Demitri, Christian; Sannino, Alessandro; Ambrosio, Luigi

2012-01-01

The aim of this project was to study the proliferation and differentiation of human Mesenchymal Stem Cells (hMSCs) onto a cellulose-based hydrogel for bone tissue engineering. Modified-cellulose hydrogel was prepared via double esterification crosslinking using citric acid. The response of human Mesenchymal Stem Cells (hMSCs) in terms of cell proliferation and differentiation into osteoblastic phenotype was evaluated by using Alamar blue assay and Alkaline phosphatase activity. The results showed that CMCNa and CMCNa_CA have no negative effect on hMSC, adhesion and proliferation. Moreover, the increase of the ALP expression for CMCNa_CA confirms the ability of the hydrogels to support the osteoblastic differentiation. The cellulose-based hydrogels have a potential application as filler in bone tissue regeneration.

Hydrogels from Biopolymer Hybrid for Biomedical, Food, and Functional Food Applications

Directory of Open Access Journals (Sweden)

Robert C. Spiro

2012-04-01

Full Text Available Hybrid hydrogels from biopolymers have been applied for various indications across a wide range of biomedical, pharmaceutical, and functional food industries. In particular, hybrid hydrogels synthesized from two biopolymers have attracted increasing attention. The inclusion of a second biopolymer strengthens the stability of resultant hydrogels and enriches its functionalities by bringing in new functional groups or optimizing the micro-environmental conditions for certain biological and biochemical processes. This article presents approaches that have been used by our groups to synthesize biopolymer hybrid hydrogels for effective uses for immunotherapy, tissue regeneration, food and functional food applications. The research has achieved some challenging results, such as stabilizing physical structure, increasing mucoadhesiveness, and the creation of an artificial extracellular matrix to aid in guiding tissue differentiation.

Bioinspired, biomimetic, double-enzymatic mineralization of hydrogels for bone regeneration with calcium carbonate

DEFF Research Database (Denmark)

Lopez-Heredia, Marco A.; Łapa, Agata; Mendes, Ana Carina Loureiro

2017-01-01

Hydrogels are popular materials for tissue regeneration. Incorporation of biologically active substances, e.g. enzymes, is straightforward. Hydrogel mineralization is desirable for bone regeneration. Here, hydrogels of Gellan Gum (GG), a biocompatible polysaccharide, were mineralized biomimetically...... of osteoblast-like cells....

Unitarizing Higgs Inflation

CERN Document Server

Giudice, Gian F

2011-01-01

We consider a simple extension of the Standard Model Higgs inflation with one new real scalar field which preserves unitarity up to the Planck scale. The new scalar field (called sigma) completes in the ultraviolet the theory of Higgs inflation by linearizing the Higgs kinetic term in the Einstein frame, just as the non-linear sigma model is unitarized into its linear version. The unitarity cutoff of the effective theory, obtained by integrating out the sigma field, varies with the background value of the Higgs field. In our setup, both the Higgs field and the sigma field participate in the inflationary dynamics, following the flat direction of the potential. We obtain the same slow-roll parameters and spectral index as in the original Higgs inflation but we find that the Hubble rate during inflation depends not only on the Higgs self-coupling, but also on the unknown couplings of the sigma field.

Unitarizing Higgs inflation

International Nuclear Information System (INIS)

Giudice, Gian F.; Lee, Hyun Min

2011-01-01

We consider a simple extension of the Standard Model Higgs inflation with one new real scalar field which preserves unitarity up to the Planck scale. The new scalar field (called sigma) completes in the ultraviolet the theory of Higgs inflation by linearizing the Higgs kinetic term in the Einstein frame, just as the non-linear sigma model is unitarized into its linear version. The unitarity cutoff of the effective theory, obtained by integrating out the sigma field, varies with the background value of the Higgs field. In our setup, both the Higgs field and the sigma field participate in the inflationary dynamics, following the flat direction of the potential. We obtain the same slow-roll parameters and spectral index as in the original Higgs inflation but we find that the Hubble rate during inflation depends not only on the Higgs self-coupling, but also on the unknown couplings of the sigma field.

Facile synthesis of degradable and electrically conductive polysaccharide hydrogels.

Science.gov (United States)

Guo, Baolin; Finne-Wistrand, Anna; Albertsson, Ann-Christine

2011-07-11

Degradable and electrically conductive polysaccharide hydrogels (DECPHs) have been synthesized by functionalizing polysaccharide with conductive aniline oligomers. DECPHs based on chitosan (CS), aniline tetramer (AT), and glutaraldehyde were obtained by a facile one-pot reaction by using the amine group of CS and AT under mild conditions, which avoids the multistep reactions and tedious purification involved in the synthesis of degradable conductive hydrogels in our previous work. Interestingly, these one-pot hydrogels possess good film-forming properties, electrical conductivity, and a pH-sensitive swelling behavior. The chemical structure and morphology before and after swelling of the hydrogels were verified by FT-IR, NMR, and SEM. The conductivity of the hydrogels was tuned by adjusting the content of AT. The swelling ratio of the hydrogels was altered by the content of tetraaniline and cross-linker. The hydrogels underwent slow degradation in a buffer solution. The hydrogels obtained by this facile approach provide new possibilities in biomedical applications, for example, biodegradable conductive hydrogels, films, and scaffolds for cardiovascular tissue engineering and controlled drug delivery.

3D- Printed Poly(ε-caprolactone) Scaffold Integrated with Cell-laden Chitosan Hydrogels for Bone Tissue Engineering

OpenAIRE

Dong, Liang; Wang, Shao-Jie; Zhao, Xin-Rong; Zhu, Yu-Fang; Yu, Jia-Kuo

2017-01-01

Synthetic polymeric scaffolds are commonly used in bone tissue engineering (BTE) due to their biocompatibility and adequate mechanical properties. However, their hydrophobicity and the lack of specific cell recognition sites confined their practical application. In this study, to improve the cell seeding efficiency and osteoinductivity, an injectable thermo-sensitive chitosan hydrogel (CSG) was incorporated into a 3D-printed poly(ε-caprolactone) (PCL) scaffold to form a hybrid scaffold. To de...

Promotion of peripheral nerve regeneration of a peptide compound hydrogel scaffold

Directory of Open Access Journals (Sweden)

Wei GJ

2013-08-01

Full Text Available Guo-Jun Wei,1 Meng Yao,1 Yan-Song Wang,1 Chang-Wei Zhou,1 De-Yu Wan,1 Peng-Zhen Lei,1 Jian Wen,1 Hong-Wei Lei,2 Da-Ming Dong1 1Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China; 2Department of Rheumatology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China Background: Peripheral nerve injury is a common trauma, but presents a significant challenge to the clinic. Silk-based materials have recently become an important biomaterial for tissue engineering applications due to silk’s biocompatibility and impressive mechanical and degradative properties. In the present study, a silk fibroin peptide (SF16 was designed and used as a component of the hydrogel scaffold for the repair of peripheral nerve injury. Methods: The SF16 peptide’s structure was characterized using spectrophotometry and atomic force microscopy, and the SF16 hydrogel was analyzed using scanning electron microscopy. The effects of the SF16 hydrogel on the viability and growth of live cells was first assessed in vitro, on PC12 cells. The in vivo test model involved the repair of a nerve gap with tubular nerve guides, through which it was possible to identify if the SF16 hydrogel would have the potential to enhance nerve regeneration. In this model physiological saline was set as the negative control, and collagen as the positive control. Walking track analysis and electrophysiological methods were used to evaluate the functional recovery of the nerve at 4 and 8 weeks after surgery. Results: Analysis of the SF16 peptide’s characteristics indicated that it consisted of a well-defined secondary structure and exhibited self-assembly. Results of scanning electron microscopy showed that the peptide based hydrogel may represent a porous scaffold that is viable for repair of peripheral nerve injury. Analysis of cell culture also supported that the hydrogel was an effective

Microscale Strategies for Generating Cell-Encapsulating Hydrogels

Directory of Open Access Journals (Sweden)

Ali Khademhosseini

2012-09-01

Full Text Available Hydrogels in which cells are encapsulated are of great potential interest for tissue engineering applications. These gels provide a structure inside which cells can spread and proliferate. Such structures benefit from controlled microarchitectures that can affect the behavior of the enclosed cells. Microfabrication-based techniques are emerging as powerful approaches to generate such cell-encapsulating hydrogel structures. In this paper we introduce common hydrogels and their crosslinking methods and review the latest microscale approaches for generation of cell containing gel particles. We specifically focus on microfluidics-based methods and on techniques such as micromolding and electrospinning.

How likely are constituent quanta to initiate inflation?

Directory of Open Access Journals (Sweden)

Lasha Berezhiani

2015-10-01

Full Text Available We propose an intuitive framework for studying the problem of initial conditions in slow-roll inflation. In particular, we consider a universe at high, but sub-Planckian energy density and analyze the circumstances under which it is plausible for it to become dominated by inflated patches at late times, without appealing to the idea of self-reproduction. Our approach is based on defining a prior probability distribution for the constituent quanta of the pre-inflationary universe. To test the idea that inflation can begin under very generic circumstances, we make specific – yet quite general and well grounded – assumptions on the prior distribution. As a result, we are led to the conclusion that the probability for a given region to ignite inflation at sub-Planckian densities is extremely small. Furthermore, if one chooses to use the enormous volume factor that inflation yields as an appropriate measure, we find that the regions of the universe which started inflating at densities below the self-reproductive threshold nevertheless occupy a negligible physical volume in the present universe as compared to those domains that have never inflated.

Charged Triazole Cross-Linkers for Hyaluronan-Based Hybrid Hydrogels

Directory of Open Access Journals (Sweden)

Maike Martini

2016-09-01

Full Text Available Polyelectrolyte hydrogels play an important role in tissue engineering and can be produced from natural polymers, such as the glycosaminoglycan hyaluronan. In order to control charge density and mechanical properties of hyaluronan-based hydrogels, we developed cross-linkers with a neutral or positively charged triazole core with different lengths of spacer arms and two terminal maleimide groups. These cross-linkers react with thiolated hyaluronan in a fast, stoichiometric thio-Michael addition. Introducing a positive charge on the core of the cross-linker enabled us to compare hydrogels with the same interconnectivity, but a different charge density. Positively charged cross-linkers form stiffer hydrogels relatively independent of the size of the cross-linker, whereas neutral cross-linkers only form stable hydrogels at small spacer lengths. These novel cross-linkers provide a platform to tune the hydrogel network charge and thus the mechanical properties of the network. In addition, they might offer a wide range of applications especially in bioprinting for precise design of hydrogels.

Spatially and temporally controlled hydrogels for tissue engineering

NARCIS (Netherlands)

J., Leijten; Seo, Jungmok; Yue, Kan; Trujillo-de Santiago, Grissel; Tamayol, Ali; Ruiz-Esparza, Guillermo U.; Ryon Shin, Su; Sharifi, Roholah; Noshadi, Iman; Moises Alvarez, Mario; Shrike Zhang, Yu; Khademhosseini, Ali

2017-01-01

Recent years have seen tremendous advances in the field of hydrogel-based biomaterials. One of the most prominent revolutions in this field has been the integration of elements or techniques that enable spatial and temporal control over hydrogels’ properties and functions. Here, we critically review

Evaluation of fibrin-gelatin hydrogel as biopaper for application in skin bioprinting: An in-vitro study.

Science.gov (United States)

Hakam, Mohammad Sadjad; Imani, Rana; Abolfathi, Nabiollah; Fakhrzadeh, Hossein; Sharifi, Ali Mohammad

2016-01-01

Recent advances in tissue engineering have led to the development of the concept of bioprinting as an interesting alternative to traditional tissue engineering approaches. Biopaper, a biomimetic hydrogel, is an essential component of the bioprinting process. The aim of this work was to synthesize a biopaper made of fibrin-gelatin hybrid hydrogel for application in skin bioprinting. Different composition percentages of the two biopolymer hydrogels, fibrin-gelatin, have been studied for the construction of the biopaper and were examined in terms of water absorption, biodegradability, glucose absorption, mechanical properties and water vapor transmission. Subsequently, tissue fusion study was performed on prepared 3T3 fibroblast cell line pellets embedded into the hydrogel. Based on the obtained results, fibrin-gelatin blend hydrogel with the same proportion of two components provides a natural scaffold for fibroblast-based bioink embedding and culture. The suggested optimized hydrogel was a suitable candidate as a biopaper for skin bioprinting technology.

Enhanced intratumoral uptake of quantum dots concealed within hydrogel nanoparticles

International Nuclear Information System (INIS)

Nair, Ashwin; Shen Jinhui; Thevenot, Paul; Zou Ling; Tang Liping; Cai Tong; Hu Zhibing

2008-01-01

Effective nanomedical devices for tumor imaging and drug delivery are not yet available. In an attempt to construct a more functional device for tumor imaging, we have embedded quantum dots (which have poor circulatory behavior) within hydrogel nanoparticles made of poly-N-isopropylacrylamide. We found that the hydrogel encapsulated quantum dots are more readily taken up by cultured tumor cells. Furthermore, in a melanoma model, hydrogel encapsulated quantum dots also preferentially accumulate in the tumor tissue compared with normal tissue and have ∼16-fold greater intratumoral uptake compared to non-derivatized quantum dots. Our results suggest that these derivatized quantum dots, which have greatly improved tumor localization, may enhance cancer monitoring and chemotherapy.

In-situ crosslinkable and self-assembling elastin-like polypeptide block copolymers for cartilage tissue repair

Science.gov (United States)

Lim, Dong Woo

This work describes the development of genetically engineered elastin-like polypeptide (ELP) block copolymers as in-situ gelling scaffolds for cartilage tissue repair. The central hypothesis underlying this work is that ELP based biopolymers can be exploited as injectable biomaterials by rapid chemical crosslinking. To prove this, gene libraries encoding ELP having different molecular weights and amino acid sequences, and ELP block copolymers composed of various ELP blocks having diverse amino acid composition, length, and phase transition behavior were synthesized by recursive directional ligation, expressed in E. Coli and purified by inverse transition cycling. Mannich-type condensation of hydroxymethylphosphines (HMPs) with primary- and secondary-amines of amino acids was developed as a new crosslinking method of polypeptides. Chemically crosslinked ELP hydrogels were formed rapidly in an aqueous solution by reaction of ELPs containing periodic lysine residues with HMPs. The crosslinking density and mechanical property of the ELP hydrogels were controlled at the sequence level by varying the Lys density in ELPs composed of mono-block as well as by segregation of the Lys residues within specific blocks of tri-block architectures. Fibroblasts embedded in ELP hydrogels survived the crosslinking process and were viable after in vitro culture for at least 3 days. The DNA content of fibroblasts within the tri-block gels was significantly higher than that in the mono-block gels at day 3. These results suggest that the HMP crosslinked ELP block copolymer hydrogels show finely tuned mechanical properties and different microenvironments for cell viability as well as potential as in-situ crosslinkable biopolymers for tissue repair applications with load-bearing environments. As an alternative, rheological behavior of the ELP block copolymers and ELP-grafted hyaluronic acids (HAs) as artificial extracellular matrices (ECMs) showed that they were thermally aggregated into

Novel antifouling self-healing poly(carboxybetaine methacrylamide-co-HEMA) nanocomposite hydrogels with superior mechanical properties

Czech Academy of Sciences Publication Activity Database

Kostina, Nina Yu.; Sharifi, S.; de los Santos Pereira, Andres; Michálek, Jiří; Grijpma, D. W.; Rodriguez-Emmenegger, Cesar

2013-01-01

Roč. 1, č. 41 (2013), s. 5644-5650 ISSN 2050-750X R&D Projects: GA AV ČR KAN200520804; GA ČR GA13-00939S; GA ČR GAP205/12/1702; GA ČR GAP106/12/1451; GA ČR GBP205/12/G118 Institutional support: RVO:61389013 Keywords : hydrogels * self- healing * antifouling Subject RIV: CD - Macromolecular Chemistry

Strengthening injectable thermo-sensitive NIPAAm-g-chitosan hydrogels using chemical cross-linking of disulfide bonds as scaffolds for tissue engineering.

Science.gov (United States)

Wu, Shu-Wei; Liu, Xifeng; Miller, A Lee; Cheng, Yu-Shiuan; Yeh, Ming-Long; Lu, Lichun

2018-07-15

In the present study, we fabricated non-toxic, injectable, and thermo-sensitive NIPAAm-g-chitosan (NC) hydrogels with thiol modification for introduction of disulfide cross-linking strategy. Previously, NIPAAm and chitosan copolymer has been proven to have excellent biocompatibility, biodegradability and rapid phase transition after injection, suitable to serve as cell carriers or implanted scaffolds. However, weak mechanical properties significantly limit their potential for biomedical fields. In order to overcome this issue, we incorporated thiol side chains into chitosan by covalently conjugating N-acetyl-cysteine (NAC) with carbodiimide chemistry to strengthen mechanical properties. After oxidation of thiols into disulfide bonds, modified NC hydrogels did improve the compressive modulus over 9 folds (11.4 kPa). Oscillatory frequency sweep showed a positive correlation between storage modulus and cross-liking density as well. Additionally, there was no cytotoxicity observed to mesenchymal stem cells, fibroblasts and osteoblasts. We suggested that the thiol-modified thermo-sensitive polysaccharide hydrogels are promising to be a cell-laden biomaterial for tissue regeneration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Injectable shear-thinning nanoengineered hydrogels for stem cell delivery

DEFF Research Database (Denmark)

Thakur, Ashish; Jaiswal, Manish K.; Peak, Charles W.

2016-01-01

-thinning characteristics, and enhanced mechanical stiffness, elastomeric properties, and physiological stability. The shear-thinning characteristics of nanocomposite hydrogels are investigated for human mesenchymal stem cell (hMSC) delivery. The hMSCs showed high cell viability after injection and encapsulated cells......Injectable hydrogels are investigated for cell encapsulation and delivery as they can shield cells from high shear forces. One of the approaches to obtain injectable hydrogels is to reinforce polymeric networks with high aspect ratio nanoparticles such as two-dimensional (2D) nanomaterials. 2D...... showed a circular morphology. The proposed shear-thinning nanoengineered hydrogels can be used for cell delivery for cartilage tissue regeneration and 3D bioprinting....

Transient Dynamic Mechanical Analysis of Resilin-based Elastomeric Hydrogels

Science.gov (United States)

Li, Linqing; Kiick, Kristi

2014-04-01

The outstanding high-frequency properties of emerging resilin-like polypeptides (RLPs) have motivated their development for vocal fold tissue regeneration and other applications. Recombinant RLP hydrogels show efficient gelation, tunable mechanical properties, and display excellent extensibility, but little has been reported about their transient mechanical properties. In this manuscript, we describe the transient mechanical behavior of new RLP hydrogels investigated via both sinusoidal oscillatory shear deformation and uniaxial tensile testing. Oscillatory stress relaxation and creep experiments confirm that RLP-based hydrogels display significantly reduced stress relaxation and improved strain recovery compared to PEG-based control hydrogels. Uniaxial tensile testing confirms the negligible hysteresis, reversible elasticity and superior resilience (up to 98%) of hydrated RLP hydrogels, with Young’s modulus values that compare favorably with those previously reported for resilin and that mimic the tensile properties of the vocal fold ligament at low strain (engineering applications, of a range of RLP hydrogels.

An Injectable Composite Gelatin Hydrogel with pH Response Properties

Directory of Open Access Journals (Sweden)

Baoguo Chen

2017-01-01

Full Text Available On account of minimally invasive procedure and of filling irregular defects of tissues, injectable hydrogels are increasingly attractive in biomedical fields. However, traditional hydrogel formed by simple physical interaction or in situ crosslinking had inevitably some drawbacks such as low mechanical strength and lack of multifunctional properties. Though many investigations had successfully modified traditional injectable hydrogel to obtain both mechanical and functional properties, an acetalated β-cyclodextrin (Ac-β-CD nanoparticle composite injectable hydrogel designed in the research was another effective and efficient choice to solve the drawbacks. First of all, gelatin derivative (G-AA and Ac-β-CD were synthesized to prepare hydrogel and nanoparticle, respectively. In order to ensure good compatibility between nanoparticle and macromonomer and provide crosslink points between nanoparticle and macromonomer, G-AA was simultaneously functionalized onto the surface of Ac-β-CD nanoparticle during the fabrication of Ac-β-CD nanoparticle using one-step method. Finally, injectable composite hydrogel was obtained by photoinitiated polymerization in situ. Hydrogel properties like gelation time and swelling ratio were investigated. The viscoelastic behavior of hydrogels confirmed that typical characteristics of crosslinked elastomer for all hydrogel and nanoparticle in hydrogel could improve the mechanical property of hydrogel. Moreover, the transparency with time had verified obvious acid-response properties of hydrogels.

Skin-inspired hydrogel-elastomer hybrids with robust interfaces and functional microstructures

Science.gov (United States)

Yuk, Hyunwoo; Zhang, Teng; Parada, German Alberto; Liu, Xinyue; Zhao, Xuanhe

2016-06-01

Inspired by mammalian skins, soft hybrids integrating the merits of elastomers and hydrogels have potential applications in diverse areas including stretchable and bio-integrated electronics, microfluidics, tissue engineering, soft robotics and biomedical devices. However, existing hydrogel-elastomer hybrids have limitations such as weak interfacial bonding, low robustness and difficulties in patterning microstructures. Here, we report a simple yet versatile method to assemble hydrogels and elastomers into hybrids with extremely robust interfaces (interfacial toughness over 1,000 Jm-2) and functional microstructures such as microfluidic channels and electrical circuits. The proposed method is generally applicable to various types of tough hydrogels and diverse commonly used elastomers including polydimethylsiloxane Sylgard 184, polyurethane, latex, VHB and Ecoflex. We further demonstrate applications enabled by the robust and microstructured hydrogel-elastomer hybrids including anti-dehydration hydrogel-elastomer hybrids, stretchable and reactive hydrogel-elastomer microfluidics, and stretchable hydrogel circuit boards patterned on elastomer.

Ibuprofen-conjugated hyaluronate/polygalacturonic acid hydrogel for the prevention of epidural fibrosis.

Science.gov (United States)

Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Chang, Chih-Ju; Liu, Tse-Ying; Chen, Ming-Hong

2016-05-01

The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D(1)H NMR spectroscopy.In vitroanalysis showed that the ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E2production of the lipopolysaccharide-induced RAW264.7 cells. Histological data inin vivostudies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofenviaa polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis. © The Author(s) 2016.

High-water-content mouldable polyvinyl alcohol-borax hydrogels reinforced by well-dispersed cellulose nanoparticles: dynamic rheological properties and hydrogel formation mechanism.

Science.gov (United States)

Han, Jingquan; Lei, Tingzhou; Wu, Qinglin

2014-02-15

Cellulose nanoparticle (CNP) reinforced polyvinyl alcohol-borax (PB) hydrogels were produced via a facile approach in an aqueous system. The effects of particle size, aspect ratio, crystal structure, and surface charge of CNPs on the rheological properties of the composite hydrogels were investigated. The rheological measurements confirmed the incorporation of well-dispersed CNPs to PB system significantly enhanced the viscoelasticity and stiffness of hydrogels. The obtained free-standing, high elasticity and mouldable hydrogels exhibited self-recovery under continuous step strain and thermo-reversibility under temperature sweep. With the addition of cellulose I nanofibers, a 19-fold increase in the high-frequency plateau of storage modulus was obtained compared with that of the pure PB. CNPs acted as multifunctional crosslinking agents and nanofillers to physically and chemically bridge the 3D network hydrogel. The plausible mechanism for the multi-complexation between CNPs, polyvinyl alcohol and borax was proposed to understand the relationship between the 3D network and hydrogel properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

Injectable, degradable, electroactive nanocomposite hydrogels containing conductive polymer nanoparticles for biomedical applications

Directory of Open Access Journals (Sweden)

Wang QM

2016-01-01

Full Text Available Qinmei Wang,1 Qiong Wang,2 Wei Teng2 1Laboratory of Biomaterials, Key Laboratory on Assisted Circulation, Ministry of Health, Cardiovascular Division, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Prosthodontics, Hospital of Stomatology, Institute of Stomatological Research, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People’s Republic of China Abstract: Injectable electroactive hydrogels (eGels are promising in regenerative medicine and drug delivery, however, it is still a challenge to obtain such hydrogels simultaneously possessing other properties including uniform structure, degradability, robustness, and biocompatibility. An emerging strategy to endow hydrogels with desirable properties is to incorporate functional nanoparticles in their network. Herein, we report the synthesis and characterization of an injectable hydrogel based on oxidized alginate (OA crosslinking gelatin reinforced by electroactive tetraaniline-graft-OA nanoparticles (nEOAs, where nEOAs are expected to impart electroactivity besides reinforcement without significantly degrading the other properties of hydrogels. Assays of transmission electron microscopy, 1H nuclear magnetic resonance, and dynamic light scattering reveal that EOA can spontaneously and quickly self-assemble into robust nanoparticles in water, and this nanoparticle structure can be kept at pH 3~9. Measurement of the gel time by rheometer and the stir bar method confirms the formation of the eGels, and their gel time is dependent on the weight content of nEOAs. As expected, adding nEOAs to hydrogels does not cause the phase separation (scanning electron microscopy observation, but it improves mechanical strength up to ~8 kPa and conductivity up to ~10-6 S/cm in our studied range. Incubating eGels in phosphate-buffered saline leads to their further swelling with an increase of water content <6% and gradual degradation

Gene Therapy Vectors with Enhanced Transfection Based on Hydrogels Modified with Affinity Peptides

Science.gov (United States)

Shepard, Jaclyn A.; Wesson, Paul J.; Wang, Christine E.; Stevans, Alyson C.; Holland, Samantha J.; Shikanov, Ariella; Grzybowski, Bartosz A.; Shea, Lonnie D.

2011-01-01

Regenerative strategies for damaged tissue aim to present biochemical cues that recruit and direct progenitor cell migration and differentiation. Hydrogels capable of localized gene delivery are being developed to provide a support for tissue growth, and as a versatile method to induce the expression of inductive proteins; however, the duration, level, and localization of expression isoften insufficient for regeneration. We thus investigated the modification of hydrogels with affinity peptides to enhance vector retention and increase transfection within the matrix. PEG hydrogels were modified with lysine-based repeats (K4, K8), which retained approximately 25% more vector than control peptides. Transfection increased 5- to 15-fold with K8 and K4 respectively, over the RDG control peptide. K8- and K4-modified hydrogels bound similar quantities of vector, yet the vector dissociation rate was reduced for K8, suggesting excessive binding that limited transfection. These hydrogels were subsequently applied to an in vitro co-culture model to induce NGF expression and promote neurite outgrowth. K4-modified hydrogels promoted maximal neurite outgrowth, likely due to retention of both the vector and the NGF. Thus, hydrogels modified with affinity peptides enhanced vector retention and increased gene delivery, and these hydrogels may provide a versatile scaffold for numerous regenerative medicine applications. PMID:21514659

Evaluation of fibroblasts adhesion and proliferation on alginate-gelatin crosslinked hydrogel.

Directory of Open Access Journals (Sweden)

Bapi Sarker

Full Text Available Due to the relatively poor cell-material interaction of alginate hydrogel, alginate-gelatin crosslinked (ADA-GEL hydrogel was synthesized through covalent crosslinking of alginate di-aldehyde (ADA with gelatin that supported cell attachment, spreading and proliferation. This study highlights the evaluation of the physico-chemical properties of synthesized ADA-GEL hydrogels of different compositions compared to alginate in the form of films. Moreover, in vitro cell-material interaction on ADA-GEL hydrogels of different compositions compared to alginate was investigated by using normal human dermal fibroblasts. Viability, attachment, spreading and proliferation of fibroblasts were significantly increased on ADA-GEL hydrogels compared to alginate. Moreover, in vitro cytocompatibility of ADA-GEL hydrogels was found to be increased with increasing gelatin content. These findings indicate that ADA-GEL hydrogel is a promising material for the biomedical applications in tissue-engineering and regeneration.

Controlled molecular self-assembly of complex three-dimensional structures in soft materials.

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Huang, Changjin; Quinn, David; Suresh, Subra; Hsia, K Jimmy

2018-01-02

Many applications in tissue engineering, flexible electronics, and soft robotics call for approaches that are capable of producing complex 3D architectures in soft materials. Here we present a method using molecular self-assembly to generate hydrogel-based 3D architectures that resembles the appealing features of the bottom-up process in morphogenesis of living tissues. Our strategy effectively utilizes the three essential components dictating living tissue morphogenesis to produce complex 3D architectures: modulation of local chemistry, material transport, and mechanics, which can be engineered by controlling the local distribution of polymerization inhibitor (i.e., oxygen), diffusion of monomers/cross-linkers through the porous structures of cross-linked polymer network, and mechanical constraints, respectively. We show that oxygen plays a role in hydrogel polymerization which is mechanistically similar to the role of growth factors in tissue growth, and the continued growth of hydrogel enabled by diffusion of monomers/cross-linkers into the porous hydrogel similar to the mechanisms of tissue growth enabled by material transport. The capability and versatility of our strategy are demonstrated through biomimetics of tissue morphogenesis for both plants and animals, and its application to generate other complex 3D architectures. Our technique opens avenues to studying many growth phenomena found in nature and generating complex 3D structures to benefit diverse applications. Copyright © 2017 the Author(s). Published by PNAS.

Supramolecular polyaniline hydrogel as a support for urease

International Nuclear Information System (INIS)

Słoniewska, Anna; Pałys, Barbara

2014-01-01

Supramolecular hydrogels of conducting polymers are successfully used in bioelectrochemistry because of their mechanical and swelling properties of gels added to the specific electron transport properties of conducting polymers. We have studied polyaniline-poly(styrene sulfonate) (PANI–PSS) hydrogel as a substrate for the urease. The hydrogels were synthesized at pH = 0 and pH = 5. PANI–PSS hydrogel is a supramolecular self-assembly material consisting of positively-charged PANI chains and negatively-charged PSS chains. The hydrogel was studied by cyclic voltammetry, infrared and Raman spectroscopy and Scanning Electron Microscopy (SEM). Raman spectra revealed presence of phenazine rings in the hydrogel structure. Phenazine rings form covalent cross-linkers contributing to the hydrogel mechanical stability. The covalent cross-linkers influence the cyclic voltammetry responses of the hydrogel in acidic media. We tested the activity of urease immobilized in the PANI–PSS hydrogel by the physical adsorption or by the covalent bonding with the carbodiimide reaction. The enzyme immobilized in hydrogels prepared at higher pH value reveals significantly higher sensitivity. The method of the enzyme immobilization has smaller impact on the sensitivity. All hydrogel sensors reveal largely higher sensitivity to urea comparing to urease immobilized in the typical electrochemically deposited PANI films. The sensitivity of urease covalently bond to the hydrogel obtained at pH = 5 was as high as 1693 μA/(mol dm 3 ). The sensor response was linear in the urea concentration range from 10 −4 to 7 × 10 −2 mol/dm 3

Poly(ethylene glycol) dicarboxylate/poly(ethylene oxide) hydrogel film co-crosslinked by electron beam irradiation as an anti-adhesion barrier

International Nuclear Information System (INIS)

Haryanto,; Singh, Deepti; Han, Sung Soo; Son, Jun Hyuk; Kim, Seong Cheol

2015-01-01

The cross-linked poly(ethylene glycol) dicarboxylate (PEGDC)/poly(ethylene oxide) (PEO) and poly(ethylene glycol) dimethacrylate (PEGDMA)/(PEO) hydrogels were developed for possible biomedical applications such as an anti-adhesion barrier. Various contents of PEGDC/PEO film were irradiated using an electron beam with various beam intensities in order to obtain various degrees of crosslinked hydrogels. The optimum dose (300 kGy) and total crosslinker content of 10% were used to prepare crosslinked hydrogel films with three different compositions (10% PEGDC, 10% PEGDMA, 5% PEGDC–5% PEGDMA). Among them, 10% PEGDC hydrogel film exhibited the highest elongation at break (69.33 ± 6.87%) with high mechanical strength. 10% PEGDC hydrogel film showed the lowest hemolysis activity (6.03 ± 0.01%) and the highest tissue adherence (75.67 ± 1.15 cN). The result also indicated that the carboxyl groups in PEGDC affect the tissue adherence of hydrogel films via H-bonding interactions. In animal studies, 10% PEGDC anti-adhesion hydrogel film degraded within 3 weeks and demonstrated better anti-adhesive effect compared to Guardix-SG®. - Highlights: • The crosslinked PEGDC/PEO hydrogel was developed by e-beam irradiation. • 10% PEGDC hydrogel film showed the highest elongation at break and tissue adhesion. • The COOH group enhanced the tissue adherence of hydrogel films on the intestine. • 10% PEGDC hydrogel film demonstrated a good anti-adhesive effect in animal study. • All of the hydrogel films with 10% PEGDC degraded in vivo within three weeks

A novel platelet lysate hydrogel for endothelial cell and mesenchymal stem cell-directed neovascularization.

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Robinson, Scott T; Douglas, Alison M; Chadid, Tatiana; Kuo, Katie; Rajabalan, Ajai; Li, Haiyan; Copland, Ian B; Barker, Thomas H; Galipeau, Jacques; Brewster, Luke P

2016-05-01

Mesenchymal stem cells (MSC) hold promise in promoting vascular regeneration of ischemic tissue in conditions like critical limb ischemia of the leg. However, this approach has been limited in part by poor cell retention and survival after delivery. New biomaterials offer an opportunity to localize cells to the desired tissue after delivery, but also to improve cell survival after delivery. Here we characterize the mechanical and microstructural properties of a novel hydrogel composed of pooled human platelet lysate (PL) and test its ability to promote MSC angiogenic activity using clinically relevant in vitro and in vivo models. This PL hydrogel had comparable storage and loss modulus and behaved as a viscoelastic solid similar to fibrin hydrogels despite having 1/4-1/10th the fibrin content of standard fibrin gels. Additionally, PL hydrogels enabled sustained release of endogenous PDGF-BB for up to 20days and were resistant to protease degradation. PL hydrogel stimulated pro-angiogenic activity by promoting human MSC growth and invasion in a 3D environment, and enhancing endothelial cell sprouting alone and in co-culture with MSCs. When delivered in vivo, the combination of PL and human MSCs improved local tissue perfusion after 8days compared to controls when assessed with laser Doppler perfusion imaging in a murine model of hind limb ischemia. These results support the use of a PL hydrogel as a scaffold for MSC delivery to promote vascular regeneration. Innovative strategies for improved retention and viability of mesenchymal stem cells (MSCs) are needed for cellular therapies. Human platelet lysate is a potent serum supplement that improves the expansion of MSCs. Here we characterize our novel PL hydrogel's desirable structural and biologic properties for human MSCs and endothelial cells. PL hydrogel can localize cells for retention in the desired tissue, improves cell viability, and augments MSCs' angiogenic activity. As a result of these unique traits, PL

Development and Characterization of UHMWPE Fiber-Reinforced Hydrogels For Meniscal Replacement

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Holloway, Julianne Leigh

Meniscal tears are the most common orthopedic injuries to the human body. The current treatment of choice, however, is a partial meniscectomy that leads to osteoarthritis proportional to the amount of tissue removed. As a result, there is a significant clinical need to develop materials capable of restoring the biomechanical contact stress distribution to the knee after meniscectomy and preventing the onset of osteoarthritis. In this work, a fiber-reinforced hydrogel-based synthetic meniscus was developed that allows for tailoring of the mechanical properties and molding of the implant to match the size, shape, and property distribution of the native tissue. Physically cross-linked poly(vinyl alcohol) (PVA) hydrogels were reinforced with ultrahigh molecular weight polyethylene (UHMWPE) fibers and characterized in compression (0.1-0.8 MPa) and tension (0.1-250 MPa) showing fine control over mechanical properties within the range of the human meniscus. Morphology and crystallinity analysis of PVA hydrogels showed increases in crystallinity and PVA densification, or phase separation, with freeze-thaw cycles. A comparison of freeze-thawed and aged, physically cross-linked hydrogels provided insight on both crystallinity and phase separation as mechanisms for PVA gelation. Results indicated both mechanisms independently contributed to hydrogel modulus for freeze-thawed hydrogels. In vitro swelling studies were performed using osmotic solutions to replicate the swelling pressure present in the knee. Minimal swelling was observed for hydrogels with a PVA concentration of 30-35 wt%, independently of hydrogel freeze-thaw cycles. This allows for independent tailoring of hydrogel modulus and pore structure using freeze-thaw cycles and swelling behavior using polymer concentration to match a wide range of properties needed for various soft tissue applications. The UHMWPE-PVA interface was identified as a significant weakness. To improve interfacial adhesion, a novel

Mechanical properties, structure, bioadhesion, and biocompatibility of pectin hydrogels.

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Markov, Pavel A; Krachkovsky, Nikita S; Durnev, Eugene A; Martinson, Ekaterina A; Litvinets, Sergey G; Popov, Sergey V

2017-09-01

The surface structure, biocompatibility, textural, and adhesive properties of calcium hydrogels derived from 1, 2, and 4% solutions of apple pectin were examined in this study. An increase in the pectin concentration in hydrogels was shown to improve their stability toward elastic and plastic deformation. The elasticity of pectin hydrogels, measured as Young's modulus, ranged from 6 to 100 kPa. The mechanical properties of the pectin hydrogels were shown to correspond to those of soft tissues. The characterization of surface roughness in terms of the roughness profile (Ra) and the root-mean-square deviation of the roughness profile (Rq) indicated an increased roughness profile for hydrogels depending on their pectin concentration. The adhesion of AU2% and AU4% hydrogels to the serosa abdominal wall, liver, and colon was higher than that of the AU1% hydrogel. The adhesion of macrophages and the non-specific adsorption of blood plasma proteins were found to increase as the pectin concentration in the hydrogels increased. The rate of degradation of all hydrogels was higher in phosphate buffered saline (PBS) than that in DMEM and a fibroblast cell monolayer. The pectin hydrogel was also found to have a low cytotoxicity. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2572-2581, 2017. © 2017 Wiley Periodicals, Inc.

Inflation and Inflation Uncertainty in Turkey

OpenAIRE

dogru, bulent

2014-01-01

Abstract: In this study, the relationship between inflation and inflation uncertainty is analyzed using Granger causality tests with annual inflation series covering the time period 1923 to 2012 for Turkish Economy. Inflation uncertainty is measured by Exponential Generalized Autoregressive Conditional Heteroskedastic model. Econometric findings suggest that although in long run the Friedman's hypothesis that high inflation increases inflation ...

Synthesis and characterization of a novel double cross-linked hydrogel based on Diels-Alder click reaction and coordination bonding.

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Li, Shubin; Wang, Lu; Yu, Xuemei; Wang, Chengli; Wang, Zhenyu

2018-01-01

Hydrogels, promising biological materials, need to have both strong mechanical properties and also inherent self-healing properties. In this work a double cross-linked network (DN) hydrogel was designed and prepared by combining a Diels-Alder click reaction and coordination effects. This DN hydrogel had good thermodynamic properties, anti-EDTA performance and self-healing properties. In addition, the mechanical properties, swelling properties and surface morphology of DN hydrogels can be controlled by adjusting the ratio of Fe 3+ -catechol. The adjustment of pH value can change the color, crosslinking mode and mechanical properties of the DN hydrogel. This smart hydrogel created from DA click chemistry and coordination effects has significance for guiding the design of new hydrogels with good mechanical properties, self-healing properties and controlled cross-link density. Copyright © 2017. Published by Elsevier B.V.

Engineering cartilaginous grafts using chondrocyte-laden hydrogels supported by a superficial layer of stem cells.

Science.gov (United States)

Mesallati, Tariq; Buckley, Conor T; Kelly, Daniel J

2017-05-01

During postnatal joint development, progenitor cells that reside in the superficial region of articular cartilage first drive the rapid growth of the tissue and later help direct the formation of mature hyaline cartilage. These developmental processes may provide directions for the optimal structuring of co-cultured chondrocytes (CCs) and multipotent stromal/stem cells (MSCs) required for engineering cartilaginous tissues. The objective of this study was to engineer cartilage grafts by recapitulating aspects of joint development where a population of superficial progenitor cells drives the development of the tissue. To this end, MSCs were either self-assembled on top of CC-laden agarose gels (structured co-culture) or were mixed with CCs before being embedded in an agarose hydrogel (mixed co-culture). Porcine infrapatellar fat pad-derived stem cells (FPSCs) and bone marrow-derived MSCs (BMSCs) were used as sources of progenitor cells. The DNA, sGAG and collagen content of a mixed co-culture of FPSCs and CCs was found to be lower than the combined content of two control hydrogels seeded with CCs and FPSCs only. In contrast, a mixed co-culture of BMSCs and CCs led to increased proliferation and sGAG and collagen accumulation. Of note was the finding that a structured co-culture, at the appropriate cell density, led to greater sGAG accumulation than a mixed co-culture for both MSC sources. In conclusion, assembling MSCs onto CC-laden hydrogels dramatically enhances the development of the engineered tissue, with the superficial layer of progenitor cells driving CC proliferation and cartilage ECM production, mimicking certain aspects of developing cartilage. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Non-invasive monitoring of in vivo hydrogel degradation and cartilage regeneration by multiparametric MR imaging

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Chen, Zelong; Yan, Chenggong; Yan, Shina; Liu, Qin; Hou, Meirong; Xu, Yikai; Guo, Rui

2018-01-01

Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging. Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months. Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo. The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations. Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration. PMID:29464005

Type II collagen-hyaluronan hydrogel – a step towards a scaffold for intervertebral disc tissue engineering

Directory of Open Access Journals (Sweden)

L Calderon

2010-09-01

Full Text Available Intervertebral disc regeneration strategies based on stem cell differentiation in combination with the design of functional scaffolds is an attractive approach towards repairing/regenerating the nucleus pulposus. The specific aim of this study was to optimise a composite hydrogel composed of type II collagen and hyaluronic acid (HA as a carrier for mesenchymal stem cells. Hydrogel stabilisation was achieved by means of 1-ethyl-3(3-dimethyl aminopropyl carbodiimide (EDC and N-hydroxysuccinimide (NHS cross-linking. Optimal hydrogel properties were determined by investigating different concentrations of EDC (8mM, 24mM and 48mM. Stable hydrogels were obtained independent of the concentration of carbodiimide used. The hydrogels cross-linked by the lowest concentration of EDC (8mM demonstrated high swelling properties. Additionally, improved proliferation of seeded rat mesenchymal stem cells (rMSCs and hydrogel stability levels in culture were observed with this 8mM cross-linked hydrogel. Results from this study indicate that EDC/NHS (8mM cross-linked type II collagen/HA hydrogel was capable of supporting viability of rMSCs, and furthermore their differentiation into a chondrogenic lineage. Further investigations should be conducted to determine its potential as scaffold for nucleus pulposus regeneration/repair.

Biocompatible nanomaterials based on dendrimers, hydrogels and hydrogel nanocomposites for use in biomedicine

Science.gov (United States)

Khoa Nguyen, Cuu; Quyen Tran, Ngoc; Phuong Nguyen, Thi; Hai Nguyen, Dai

2017-03-01

Over the past decades, biopolymer-based nanomaterials have been developed to overcome the limitations of other macro- and micro- synthetic materials as well as the ever increasing demand for the new materials in nanotechnology, biotechnology, biomedicine and others. Owning to their high stability, biodegradability, low toxicity, and biocompatibility, biopolymer-based nanomaterials hold great promise for various biomedical applications. The pursuit of this review is to briefly describe our recent studies regarding biocompatible biopolymer-based nanomaterials, particularly in the form of dendrimers, hydrogels, and hydrogel composites along with the synthetic and modification approaches for the utilization in drug delivery, tissue engineering, and biomedical implants. Moreover, in vitro and in vivo studies for the toxicity evaluation are also discussed.

Self-assembling peptide hydrogels immobilized on silicon surfaces

International Nuclear Information System (INIS)

Franchi, Stefano; Battocchio, Chiara; Galluzzi, Martina; Navisse, Emanuele; Zamuner, Annj; Dettin, Monica; Iucci, Giovanna

2016-01-01

The hydrogels of self-assembling ionic complementary peptides have collected in the scientific community increasing consensus as mimetics of the extracellular matrix that can offer 3D supports for cell growth or be vehicles for the delivery of stem cells or drugs. Such scaffolds have also been proposed as bone substitutes for small defects as they promote beneficial effects on human osteoblasts. In this context, our research deals with the introduction of a layer of self-assembling peptides on a silicon surface by covalent anchoring and subsequent physisorption. In this work, we present a spectroscopic investigation of the proposed bioactive scaffolds, carried out by surface-sensitive spectroscopic techniques such as XPS (X-ray photoelectron spectroscopy) and RAIRS (Reflection Absorption Infrared Spectroscopy) and by state-of-the-art synchrotron radiation methodologies such as angle dependent NEXAFS (Near Edge X-ray Absorption Fine Structure). XPS studies confirmed the change in the surface composition in agreement with the proposed enrichments, and led to assess the self-assembling peptide chemical stability. NEXAFS spectra, collected in angular dependent mode at the N K-edge, allowed to investigate the self-assembling behavior of the macromolecules, as well as to determine their molecular orientation on the substrate. Furthermore, Infrared Spectroscopy measurements demonstrated that the peptide maintains its secondary structure (β-sheet anti-parallel) after deposition on the silicon surface. The complementary information acquired by means of XPS, NEXAFS and RAIRS lead to hypothesize a “layer-by-layer” arrangement of the immobilized peptides, giving rise to an ordered 3D nanostructure. - Highlights: • A self-assembling peptide (SAP) was covalently immobilized of on a flat silicon surface. • A physisorbed SAP layer was grown on top of the covalently immobilized peptide layer. • Molecular order and orientation of the peptide overlayer on the flat silicon

Self-assembling peptide hydrogels immobilized on silicon surfaces

Energy Technology Data Exchange (ETDEWEB)

Franchi, Stefano; Battocchio, Chiara; Galluzzi, Martina; Navisse, Emanuele [Department of Sciences, University “Roma Tre”, Via della Vasca Navale 79, Roma, 00146 (Italy); Zamuner, Annj; Dettin, Monica [Department of Industrial Engineering, University of Padua, Via Marzolo, 9, Padua, 35131 (Italy); Iucci, Giovanna, E-mail: giovanna.iucci@uniroma3.it [Department of Sciences, University “Roma Tre”, Via della Vasca Navale 79, Roma, 00146 (Italy)

2016-12-01

The hydrogels of self-assembling ionic complementary peptides have collected in the scientific community increasing consensus as mimetics of the extracellular matrix that can offer 3D supports for cell growth or be vehicles for the delivery of stem cells or drugs. Such scaffolds have also been proposed as bone substitutes for small defects as they promote beneficial effects on human osteoblasts. In this context, our research deals with the introduction of a layer of self-assembling peptides on a silicon surface by covalent anchoring and subsequent physisorption. In this work, we present a spectroscopic investigation of the proposed bioactive scaffolds, carried out by surface-sensitive spectroscopic techniques such as XPS (X-ray photoelectron spectroscopy) and RAIRS (Reflection Absorption Infrared Spectroscopy) and by state-of-the-art synchrotron radiation methodologies such as angle dependent NEXAFS (Near Edge X-ray Absorption Fine Structure). XPS studies confirmed the change in the surface composition in agreement with the proposed enrichments, and led to assess the self-assembling peptide chemical stability. NEXAFS spectra, collected in angular dependent mode at the N K-edge, allowed to investigate the self-assembling behavior of the macromolecules, as well as to determine their molecular orientation on the substrate. Furthermore, Infrared Spectroscopy measurements demonstrated that the peptide maintains its secondary structure (β-sheet anti-parallel) after deposition on the silicon surface. The complementary information acquired by means of XPS, NEXAFS and RAIRS lead to hypothesize a “layer-by-layer” arrangement of the immobilized peptides, giving rise to an ordered 3D nanostructure. - Highlights: • A self-assembling peptide (SAP) was covalently immobilized of on a flat silicon surface. • A physisorbed SAP layer was grown on top of the covalently immobilized peptide layer. • Molecular order and orientation of the peptide overlayer on the flat silicon

Polyvinyl alcohol hydrogels for iontohporesis

Science.gov (United States)

Bera, Prasanta; Alam, Asif Ali; Arora, Neha; Tibarewala, Dewaki Nandan; Basak, Piyali

2013-06-01

Transdermal therapeutic systems propound controlled release of active ingredients through the skin into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. The iontophoresis deal with the systemic delivery of the bioactive agents (drug) by applying an electric current. It is basically an injection without the needle. The iontophoretic system requires a gel-based matrix to accommodate the bioactive agent. Hydrogels have been used by many investigators in controlled-release drug delivery systems because of their good tissue compatibility and easy manipulation of swelling level and, thereby, solute permeability. In this work we have prepared polyvinyl alcohol (PVA) hydrogel. We have cross linked polyvinyl alcohol chemically with Glutaraldehyde with different wt%. FTIR study reveals the chemical changes during cross linking. Swelling in water, is done to have an idea about drug loading and drug release from the membrane. After drug loading to the hydrogels, we have studied the drug release property of the hydrogels using salicylic acid as a model drug.

Independent control of matrix adhesiveness and stiffness within a 3D self-assembling peptide hydrogel.

Science.gov (United States)

Hogrebe, Nathaniel J; Reinhardt, James W; Tram, Nguyen K; Debski, Anna C; Agarwal, Gunjan; Reilly, Matthew A; Gooch, Keith J

2018-04-01

A cell's insoluble microenvironment has increasingly been shown to exert influence on its function. In particular, matrix stiffness and adhesiveness strongly impact behaviors such as cell spreading and differentiation, but materials that allow for independent control of these parameters within a fibrous, stromal-like microenvironment are very limited. In the current work, we devise a self-assembling peptide (SAP) system that facilitates user-friendly control of matrix stiffness and RGD (Arg-Gly-Asp) concentration within a hydrogel possessing a microarchitecture similar to stromal extracellular matrix. In this system, the RGD-modified SAP sequence KFE-RGD and the scrambled sequence KFE-RDG can be directly swapped for one another to change RGD concentration at a given matrix stiffness and total peptide concentration. Stiffness is controlled by altering total peptide concentration, and the unmodified base peptide KFE-8 can be included to further increase this stiffness range due to its higher modulus. With this tunable system, we demonstrate that human mesenchymal stem cell morphology and differentiation are influenced by both gel stiffness and the presence of functional cell binding sites in 3D culture. Specifically, cells 24 hours after encapsulation were only able to spread out in stiffer matrices containing KFE-RGD. Upon addition of soluble adipogenic factors, soft gels facilitated the greatest adipogenesis as determined by the presence of lipid vacuoles and PPARγ-2 expression, while increasing KFE-RGD concentration at a given stiffness had a negative effect on adipogenesis. This three-component hydrogel system thus allows for systematic investigation of matrix stiffness and RGD concentration on cell behavior within a fibrous, three-dimensional matrix. Physical cues from a cell's surrounding environment-such as the density of cell binding sites and the stiffness of the surrounding material-are increasingly being recognized as key regulators of cell function

Mussel-inspired fabrication of konjac glucomannan/microcrystalline cellulose intelligent hydrogel with pH-responsive sustained release behavior.

Science.gov (United States)

Wang, Lin; Du, Yu; Yuan, Yi; Mu, Ruo-Jun; Gong, Jingni; Ni, Yongsheng; Pang, Jie; Wu, Chunhua

2018-07-01

Intelligent hydrogels are attractive biomaterials for various applications, however, fabricating a hydrogel with both adequate self-healing ability and mechanical properties remains a challenge. Herein, a series of novel intelligent konjac glucomannan (KGM)/microcrystalline cellulose (MCC) hydrogels were prepared vis the mussel-inspired chemistry. MCC was firstly functionalized by the oxidative polymerization of dopamine, and the intelligent hydrogels were obtained by mixing aqueous solutions of KGM and functionalized MCC (PDMCC). By introducing PDMCC, a more compact interconnected porous structure formed for the resulting hydrogels. The self-healing ability and mechanical properties of intelligent hydrogels were dependence on the PDMCC content. Compared with KGM hydrogels, KGM/PDMCC hydrogels exhibited a more distinct pH sensitivity and a lower initial burst release, which was attributed to the compact structure and strong intermolecular hydrogen bond interaction between PDMCC and KGM. These results suggest that the KGM/PDMCC intelligent hydrogels may be promising carriers for controlled drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Two-dimensional inverse opal hydrogel for pH sensing.

Science.gov (United States)

Xue, Fei; Meng, Zihui; Qi, Fenglian; Xue, Min; Wang, Fengyan; Chen, Wei; Yan, Zequn

2014-12-07

A novel hydrogel film with a highly ordered macropore monolayer on its surface was prepared by templated photo-polymerization of hydrogel monomers on a two-dimensional (2D) polystyrene colloidal array. The 2D inverse opal hydrogel has prominent advantages over traditional three-dimensional (3D) inverse opal hydrogels. First, the formation of the 2D array template through a self-assembly method is considerably faster and simpler. Second, the stable ordering structure of the 2D array template makes it easier to introduce the polymerization solution into the template. Third, a simple measurement, a Debye diffraction ring, is utilized to characterize the neighboring pore spacing of the 2D inverse opal hydrogel. Acrylic acid was copolymerized into the hydrogel; thus, the hydrogel responded to pH through volume change, which resulted from the formation of the Donnan potential. The 2D inverse opal hydrogel showed that the neighboring pore spacing increased by about 150 nm and diffracted color red-shifted from blue to red as the pH increased from pH 2 to 7. In addition, the pH response kinetics and ionic strength effect of this 2D mesoporous polymer film were also investigated.

Topographical heterogeneity in transparent PVA hydrogels studied by AFM

Energy Technology Data Exchange (ETDEWEB)

Pramanick, Ashit Kumar; Gupta, Siddhi, E-mail: siddhigupta@nmlindia.org; Mishra, Trilochan; Sinha, Arvind

2012-02-01

Physically crosslinked poly (vinyl alcohol) (PVA) hydrogels have a wide range of biomedical applications. Transparent and stable PVA hydrogels synthesized by freeze-thawing method are potential candidates to be used as tissue engineering scaffolds provided they exhibit suitable topographical roughness and surface energy. The effect of processing parameters i.e., polymer concentration and number of freeze-thaw cycles on the resulting topography of the freeze-thawed transparent hydrogels has been studied and quantified using non-contact mode of an atomic force microscope (AFM) and image analysis. Simultaneously captured phase contrast images have revealed significant information about morphological changes in the topographical features and crystallinity of the hydrogels. Topographical roughness was found to decrease as a function of number of freeze-thaw cycles.

In vivo guided vascular regeneration with a non-porous elastin-like polypeptide hydrogel tubular scaffold.

Science.gov (United States)

Mahara, Atsushi; Kiick, Kristi L; Yamaoka, Tetsuji

2017-06-01

Herein, we demonstrate a new approach for small-caliber vascular reconstruction using a non-porous elastin-like polypeptide hydrogel tubular scaffold, based on the concept of guided vascular regeneration (GVR). The scaffolds are composed of elastin-like polypeptide, (Val-Pro-Gly-Ile-Gly) n , for compliance matching and antithrombogenicity and an Arg-Gly-Asp (RGD) motif for connective tissue regeneration. When the polypeptide was mixed with an aqueous solution of β-[Tris(hydroxymethyl)phosphino]propionic acid at 37°C, the polypeptide hydrogel was rapidly formed. The elastic modulus of the hydrogel was 4.4 kPa. The hydrogel tubular scaffold was formed in a mold and reinforced with poly(lactic acid) nanofibers. When tubular scaffolds with an inner diameter of 1 mm and length of 5 mm were implanted into rat abdominal aortae, connective tissue grew along the scaffold luminal surface from the flanking native tissues, resulting in new blood vessel tissue with a thickness of 200 μm in 1 month. In contrast, rats implanted with control scaffolds without the RGD motif died. These results indicate that the non-porous hydrogel tubular scaffold containing the RGD motif effectively induced rapid tissue regeneration and that GVR is a promising strategy for the regeneration of small-diameter blood vessels. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1746-1755, 2017. © 2017 Wiley Periodicals, Inc.

Designer Self-Assembling Peptide Nanofiber Scaffolds Containing Link Protein N-Terminal Peptide Induce Chondrogenesis of Rabbit Bone Marrow Stem Cells

Directory of Open Access Journals (Sweden)

Baichuan Wang

2014-01-01

Full Text Available Designer self-assembling peptide nanofiber hydrogel scaffolds have been considered as promising biomaterials for tissue engineering because of their excellent biocompatibility and biofunctionality. Our previous studies have shown that a novel designer functionalized self-assembling peptide nanofiber hydrogel scaffold (RLN/RADA16, LN-NS containing N-terminal peptide sequence of link protein (link N can promote nucleus pulposus cells (NPCs adhesion and three-dimensional (3D migration and stimulate biosynthesis of type II collagen and aggrecan by NPCs in vitro. The present study has extended these investigations to determine the effects of this functionalized LN-NS on bone marrow stem cells (BMSCs, a potential cell source for NP regeneration. Although the functionalized LN-NS cannot promote BMSCs proliferation, it significantly promotes BMSCs adhesion compared with that of the pure RADA16 hydrogel scaffold. Moreover, the functionalized LN-NS remarkably stimulates biosynthesis and deposition of type II collagen and aggrecan. These data demonstrate that the functionalized peptide nanofiber hydrogel scaffold containing link N peptide as a potential matrix substrate will be very useful in the NP tissue regeneration.

A comparative study on collagen type I and hyaluronic acid dependent cell behavior for osteochondral tissue bioprinting.

Science.gov (United States)

Park, Ju Young; Choi, Jong-Cheol; Shim, Jin-Hyung; Lee, Jung-Seob; Park, Hyoungjun; Kim, Sung Won; Doh, Junsang; Cho, Dong-Woo

2014-09-01

Bioprinting is a promising technique for engineering composite tissues, such as osteochondral tissues. In this study, as a first step toward bioprinting-based osteochondral tissue regeneration, we systematically examined the behavior of chondrocytes and osteoblasts to hyaluronic acid (HA) and type I collagen (Col-1) hydrogels. First, we demonstrated that cells on hydrogels that were comprised of major native tissue extracellular matrix (ECM) components (i.e. chondrocytes on HA hydrogels and osteoblasts on Col-1 hydrogels) exhibited better proliferation and cell function than cells on non-native ECM hydrogels (i.e., chondrocytes on Col-1 hydrogels and osteoblasts on HA hydrogels). In addition, cells located near their native ECM hydrogels migrated towards them. Finally, we bioprinted three-dimensional (3D) osteochondral tissue-mimetic structures composed of two compartments, osteoblast-encapsulated Col-1 hydrogels and chondrocyte-encapsulated HA hydrogels, and found viability and functions of each cell type were well maintained within the 3D structures up to 14 days in vitro. These results suggest that with proper choice of hydrogel materials, bioprinting-based approaches can be successfully applied for osteochondral tissue regeneration.

Engineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells.

Science.gov (United States)

Neufurth, Meik; Wang, Xiaohong; Schröder, Heinz C; Feng, Qingling; Diehl-Seifert, Bärbel; Ziebart, Thomas; Steffen, Renate; Wang, Shunfeng; Müller, Werner E G

2014-10-01

Sodium alginate hydrogel, stabilized with gelatin, is a suitable, biologically inert matrix that can be used for encapsulating and 3D bioprinting of bone-related SaOS-2 cells. However, the cells, embedded in this matrix, remain in a non-proliferating state. Here we show that addition of an overlay onto the bioprinted alginate/gelatine/SaOS-2 cell scaffold, consisting of agarose and the calcium salt of polyphosphate [polyP·Ca(2+)-complex], resulted in a marked increase in cell proliferation. In the presence of 100 μm polyP·Ca(2+)-complex, the cells proliferate with a generation time of approximately 47-55 h. In addition, the hardness of the alginate/gelatin hydrogel substantially increases in the presence of the polymer. The reduced Young's modulus for the alginate/gelatin hydrogel is approximately 13-14 kPa, and this value drops to approximately 0.5 kPa after incubation of the cell containing scaffolds for 5 d. In the presence of 100 μm polyP·Ca(2+)-complex, the reduced Young's modulus increases to about 22 kPa. The hardness of the polyP·Ca(2+)-complex containing hydrogel remains essentially constant if cells are absent in the matrix, but it drops to 3.2 kPa after a 5 d incubation period in the presence of SaOS-2 cells, indicating that polyP·Ca(2+)-complex becomes metabolized, degraded, by the cells. The alginate/gelatine-agarose system with polyP·Ca(2+)-complex cause a significant increase in the mineralization of the cells. SEM analyses revealed that the morphology of the mineral nodules formed on the surface of the cells embedded in the alginate/gelatin hydrogel do not significantly differ from the nodules on cells growing in monolayer cultures. The newly developed technique, using cells encapsulated into an alginate/gelatin hydrogel and a secondary layer containing the morphogenetically active, growth promoting polymer polyP·Ca(2+)-complex opens new possibilities for the application of 3D bioprinting in bone tissue engineering. Copyright �

The chaotic regime of D-term inflation

Energy Technology Data Exchange (ETDEWEB)

Buchmüller, W. [DESY, Notkestrasse 85, 22607 Hamburg (Germany); Domcke, V. [SISSA/INFN, Via Bonomea 265, 34136 Trieste (Italy); Schmitz, K., E-mail: wilfried.buchmueller@desy.de, E-mail: valerie.domcke@sissa.it, E-mail: kai.schmitz@ipmu.jp [Kavli IPMU (WPI), University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa (Japan)

2014-11-01

We consider D-term inflation for small couplings of the inflaton to matter fields. Standard hybrid inflation then ends at a critical value of the inflaton field that exceeds the Planck mass. During the subsequent waterfall transition the inflaton continues its slow-roll motion, whereas the waterfall field rapidly grows by quantum fluctuations. Beyond the decoherence time, the waterfall field becomes classical and approaches a time-dependent minimum, which is determined by the value of the inflaton field and the self-interaction of the waterfall field. During the final stage of inflation, the effective inflaton potential is essentially quadratic, which leads to the standard predictions of chaotic inflation. The model illustrates how the decay of a false vacuum of GUT-scale energy density can end in a period of 'chaotic inflation'.

The chaotic regime of D-term inflation

Energy Technology Data Exchange (ETDEWEB)

Buchmueller, W. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Domcke, V. [SISSA/INFN, Triest (Italy); Schmitz, K. [Kavli IPMU (WPI), Kashiwa (Japan)

2014-08-15

We consider D-term inflation for small couplings of the inflaton to matter fields. Standard hybrid inflation then ends at a critical value of the inflaton field that exceeds the Planck mass. During the subsequent waterfall transition the inflaton continues its slow-roll motion, whereas the waterfall field rapidly grows by quantum fluctuations. Beyond the decoherence time, the waterfall field becomes classical and approaches a time-dependent minimum, which is determined by the value of the inflaton field and the self-interaction of the waterfall field. During the final stage of inflation, the effective inflaton potential is essentially quadratic, which leads to the standard predictions of chaotic inflation. The model illustrates how the decay of a false vacuum of GUT-scale energy density can end in a period of 'chaotic inflation'.

The chaotic regime of D-term inflation

International Nuclear Information System (INIS)

Buchmueller, W.; Domcke, V.; Schmitz, K.

2014-08-01

We consider D-term inflation for small couplings of the inflaton to matter fields. Standard hybrid inflation then ends at a critical value of the inflaton field that exceeds the Planck mass. During the subsequent waterfall transition the inflaton continues its slow-roll motion, whereas the waterfall field rapidly grows by quantum fluctuations. Beyond the decoherence time, the waterfall field becomes classical and approaches a time-dependent minimum, which is determined by the value of the inflaton field and the self-interaction of the waterfall field. During the final stage of inflation, the effective inflaton potential is essentially quadratic, which leads to the standard predictions of chaotic inflation. The model illustrates how the decay of a false vacuum of GUT-scale energy density can end in a period of 'chaotic inflation'.

The chaotic regime of D-term inflation

International Nuclear Information System (INIS)

Buchmüller, W.; Domcke, V.; Schmitz, K.

2014-01-01

We consider D-term inflation for small couplings of the inflaton to matter fields. Standard hybrid inflation then ends at a critical value of the inflaton field that exceeds the Planck mass. During the subsequent waterfall transition the inflaton continues its slow-roll motion, whereas the waterfall field rapidly grows by quantum fluctuations. Beyond the decoherence time, the waterfall field becomes classical and approaches a time-dependent minimum, which is determined by the value of the inflaton field and the self-interaction of the waterfall field. During the final stage of inflation, the effective inflaton potential is essentially quadratic, which leads to the standard predictions of chaotic inflation. The model illustrates how the decay of a false vacuum of GUT-scale energy density can end in a period of 'chaotic inflation'

The chaotic regime of D-term inflation

Science.gov (United States)

Buchmüller, W.; Domcke, V.; Schmitz, K.

2014-11-01

We consider D-term inflation for small couplings of the inflaton to matter fields. Standard hybrid inflation then ends at a critical value of the inflaton field that exceeds the Planck mass. During the subsequent waterfall transition the inflaton continues its slow-roll motion, whereas the waterfall field rapidly grows by quantum fluctuations. Beyond the decoherence time, the waterfall field becomes classical and approaches a time-dependent minimum, which is determined by the value of the inflaton field and the self-interaction of the waterfall field. During the final stage of inflation, the effective inflaton potential is essentially quadratic, which leads to the standard predictions of chaotic inflation. The model illustrates how the decay of a false vacuum of GUT-scale energy density can end in a period of `chaotic inflation'.

Engineering Enriched Microenvironments with Gradients of Platelet Lysate in Hydrogel Fibers.

Science.gov (United States)

Santo, Vítor E; Babo, Pedro; Amador, Miguel; Correia, Cláudia; Cunha, Bárbara; Coutinho, Daniela F; Neves, Nuno M; Mano, João F; Reis, Rui L; Gomes, Manuela E

2016-06-13

Gradients of physical and chemical cues are characteristic of specific tissue microenvironments and contribute toward morphogenesis and tissue regeneration upon injury. Recent advances on microfluidics and hydrogel manipulation raised the possibility of generating biomimetic biomaterials enriched with bioactive factors and encapsulating cells following designs specifically tailored for a target application. The novelty of this work relies on the combination of methacrylated gellan gum (MeGG) with platelet lysate (PL), aiming to generate novel advanced 3D PL-enriched photo-cross-linkable hydrogels and overcoming the lack of adhesion sites provided by the native MeGG hydrogels. This combination takes advantage of the availability, enriched growth factor composition, and potential autologous application of PL while simultaneously preserving the ability provided by MeGG to tailor mechanical properties, protein release kinetics, and shape of the construct according to the desired goal. Incorporation of PL in the hydrogels significantly improved cellular adhesion and viability in the constructs. The use of microfluidic tools allowed the design of a fiber-like hydrogel incorporating a gradient of PL along the length of the fiber. These spatial protein gradients led to the viability and cell number gradients caused by maintenance of human umbilical vein endothelial cells (HUVECs) survival in the fibers toward the PL-enriched sections in comparison with the nonloaded MeGG sections of the fibers. Altogether, we propose a proof of concept strategy to design a PL gradient biomaterial with potential in tissue engineering approaches and analysis of cell-microenvironment interactions.

Engineering Protein Hydrogels Using SpyCatcher-SpyTag Chemistry.

Science.gov (United States)

Gao, Xiaoye; Fang, Jie; Xue, Bin; Fu, Linglan; Li, Hongbin

2016-09-12

Constructing hydrogels from engineered proteins has attracted significant attention within the material sciences, owing to their myriad potential applications in biomedical engineering. Developing efficient methods to cross-link tailored protein building blocks into hydrogels with desirable mechanical, physical, and functional properties is of paramount importance. By making use of the recently developed SpyCatcher-SpyTag chemistry, we successfully engineered protein hydrogels on the basis of engineered tandem modular elastomeric proteins. Our resultant protein hydrogels are soft but stable, and show excellent biocompatibility. As the first step, we tested the use of these hydrogels as a drug carrier, as well as in encapsulating human lung fibroblast cells. Our results demonstrate the robustness of the SpyCatcher-SpyTag chemistry, even when the SpyTag (or SpyCatcher) is flanked by folded globular domains. These results demonstrate that SpyCatcher-SpyTag chemistry can be used to engineer protein hydrogels from tandem modular elastomeric proteins that can find applications in tissue engineering, in fundamental mechano-biological studies, and as a controlled drug release vehicle.

Injectable Anisotropic Nanocomposite Hydrogels Direct in Situ Growth and Alignment of Myotubes

International Nuclear Information System (INIS)

De France, Kevin J.; Yager, Kevin G.; Chan, Katelyn J. W.; Corbett, Brandon; Cranston, Emily D.; Hoare, Todd

2017-01-01

Here, while injectable in situ cross-linking hydrogels have attracted increasing attention as minimally invasive tissue scaffolds and controlled delivery systems, their inherently disorganized and isotropic network structure limits their utility in engineering oriented biological tissues. Traditional methods to prepare anisotropic hydrogels are not easily translatable to injectable systems given the need for external equipment to direct anisotropic gel fabrication and/or the required use of temperatures or solvents incompatible with biological systems. Herein, we report a new class of injectable nanocomposite hydrogels based on hydrazone cross-linked poly(oligoethylene glycol methacrylate) and magnetically aligned cellulose nanocrystals (CNCs) capable of encapsulating skeletal muscle myoblasts and promoting their differentiation into highly oriented myotubes in situ. CNC alignment occurs on the same time scale as network gelation and remains fixed after the removal of the magnetic field, enabling concurrent CNC orientation and hydrogel injection. The aligned hydrogels show mechanical and swelling profiles that can be rationally modulated by the degree of CNC alignment and can direct myotube alignment both in two- and three-dimensions following coinjection of the myoblasts with the gel precursor components. As such, these hydrogels represent a critical advancement in anisotropic biomimetic scaffolds that can be generated noninvasively in vivo following simple injection.

Water-Hydrogel Binding Affinity Modulates Freeze-Drying-Induced Micropore Architecture and Skeletal Myotube Formation.

Science.gov (United States)

Rich, Max H; Lee, Min Kyung; Marshall, Nicholas; Clay, Nicholas; Chen, Jinrong; Mahmassani, Ziad; Boppart, Marni; Kong, Hyunjoon

2015-08-10

Freeze-dried hydrogels are increasingly used to create 3D interconnected micropores that facilitate biomolecular and cellular transports. However, freeze-drying is often plagued by variance in micropore architecture based on polymer choice. We hypothesized that water-polymer binding affinity plays a significant role in sizes and numbers of micropores formed through freeze-drying, influencing cell-derived tissue quality. Poly(ethylene glycol)diacrylate (PEGDA) hydrogels with alginate methacrylate (AM) were used due to AM's higher binding affinity for water than PEGDA. PEGDA-AM hydrogels with larger AM concentrations resulted in larger sizes and numbers of micropores than pure PEGDA hydrogels, attributed to the increased mass of water binding to the PEGDA-AM gel. Skeletal myoblasts loaded in microporous PEGDA-AM hydrogels were active to produce 3D muscle-like tissue, while those loaded in pure PEGDA gels were localized on the gel surface. We propose that this study will be broadly useful in designing and improving the performance of various microporous gels.

On the Interaction between Superabsorbent Hydrogels and Cementitious Materials

Science.gov (United States)

Farzanian, Khashayar

the desorption of hydrogels is investigated in relation to the chemical composition of the hydrogels. In the second set of experiments of this part, the behavior of the hydrogels in a hydrating cement paste is monitored by tracking the size and morphology evolution of hydrogels interacting with the cement paste matrix. It is shown that the changes on the surface characteristics of hydrogels as a result of interactions with the pore solution and cement particles can affect the desorption rate of hydrogels in contact with a porous cementitious material. Scanning electron microscopic (SEM) examination demonstrates two different desorption modes with distinct morphologies of hydrogels depending on the chemical composition of hydrogels. The effect of the interfacial bonding between the hydrogels and the cementitious matrix and its relation to the desorption is illustrated. The desorption of hydrogels with different chemical compositions in blended cement mixture containing different supplementary cementitious materials (SCMs) such as slag, fly ash, silica fume and two types of glass powders, are examined. The absorption/desorption kinetics of hydrogels in different hydrating blended cement mixtures are monitored by freeze drying the samples at different times. The surface characteristics of different hydrogels after interaction with pore solution, cement particles and SCMs particles are examined and their relation to interfacial bonding is illustrated. It is shown that different SCMs can cause distinct changes on interfacial bonding. The understanding of hydrogel behavior in cementitious materials helps with accurate mixture design for internal curing. The kinetics of desorption is crucial for the purpose of internal curing. The understanding of release mechanisms and the change in the hydrogel morphology is important for the self-healing and self-sealing applications. Two major contributions of this research are (1) to show the effect of capillary forces developed at the

Inflation and dark energy from three-forms

International Nuclear Information System (INIS)

Koivisto, Tomi S.; Nunes, Nelson J.

2009-01-01

Three-forms can give rise to viable cosmological scenarios of inflation and dark energy with potentially observable signatures distinct from standard single scalar field models. In this study, the background dynamics and linear perturbations of self-interacting three-form cosmology are investigated. The phase space of cosmological solutions possesses (super)-inflating attractors and saddle points, which can describe three-form driven inflation or dark energy. The quantum generation and the classical evolution of perturbations is considered. The scalar and tensor spectra from a three-form inflation and the impact from the presence of a three-form on matter perturbations are computed. Stability properties and equivalence of the model with alternative formulations are discussed.

A comparative study on collagen type I and hyaluronic acid dependent cell behavior for osteochondral tissue bioprinting

International Nuclear Information System (INIS)

Park, Ju Young; Choi, Jong-Cheol; Lee, Jung-Seob; Park, Hyoungjun; Doh, Junsang; Cho, Dong-Woo; Shim, Jin-Hyung; Kim, Sung Won

2014-01-01

Bioprinting is a promising technique for engineering composite tissues, such as osteochondral tissues. In this study, as a first step toward bioprinting-based osteochondral tissue regeneration, we systematically examined the behavior of chondrocytes and osteoblasts to hyaluronic acid (HA) and type I collagen (Col-1) hydrogels. First, we demonstrated that cells on hydrogels that were comprised of major native tissue extracellular matrix (ECM) components (i.e. chondrocytes on HA hydrogels and osteoblasts on Col-1 hydrogels) exhibited better proliferation and cell function than cells on non-native ECM hydrogels (i.e., chondrocytes on Col-1 hydrogels and osteoblasts on HA hydrogels). In addition, cells located near their native ECM hydrogels migrated towards them. Finally, we bioprinted three-dimensional (3D) osteochondral tissue-mimetic structures composed of two compartments, osteoblast-encapsulated Col-1 hydrogels and chondrocyte-encapsulated HA hydrogels, and found viability and functions of each cell type were well maintained within the 3D structures up to 14 days in vitro. These results suggest that with proper choice of hydrogel materials, bioprinting-based approaches can be successfully applied for osteochondral tissue regeneration. (paper)

Reinforcing the inner phase of the filled hydrogels with CNTs alters drug release properties and human keratinocyte morphology: A study on the gelatin- tamarind gum filled hydrogels.

Science.gov (United States)

Maharana, Vivek; Gaur, Deepanjali; Nayak, Suraj K; Singh, Vinay K; Chakraborty, Subhabrata; Banerjee, Indranil; Ray, Sirsendu S; Anis, Arfat; Pal, Kunal

2017-11-01

The study reports the synthesis and characterization of gelatin-tamarind gum (TG) based filled hydrogels for drug delivery applications. In this study, three different types of carbon nanotubes (CNTs) were incorporated within the dispersed TG phase of the filled hydrogels. The prepared hydrogels were thoroughly characterised using bright field microscope, FESEM, FTIR spectroscopy, differential scanning calorimeter, and mechanical tester. The swelling and the drug (salicylic acid) release properties of the filled hydrogels were also evaluated. The micrographs revealed the formation of biphasic systems. The internal phase appeared as agglomerates, and the CNTs were confined within the dispersed TG phase. FTIR and XRD studies revealed that CNTs promoted associative interactions among the components of the hydrogel, which promoted the formation of large crystallite size. The mechanical study indicated better resistance to the breakdown of the architecture of the CNT-containing filled hydrogels. Drug release studies, both passive and iontophoretic, suggested that the non-Fickian diffusion of the drug was prevalent during its release from hydrogel matrices. The prepared hydrogels were cytocompatible with human keratinocytes. The results suggested the probable use of such hydrogels in wound healing, tissue engineering and drug delivery applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phytase-mediated enzymatic mineralization of chitosan-enriched hydrogels

DEFF Research Database (Denmark)

Lišková, Jana; Douglas, Timothy E.L.; Wijnants, Robbe

2018-01-01

Hydrogels mineralized with calcium phosphate (CaP) are increasingly popular bone regeneration biomaterials. Mineralization can be achieved by phosphatase enzyme incorporation and incubation in calcium glycerophosphate (CaGP). Gellan gum (GG) hydrogels containing the enzyme phytase and chitosan...... oligomer were mineralized in CaGP solution and characterized with human osteoblast-like MG63 cells and adipose tissue-derived stem cells (ADSC). Phytase induced CaP formation. Chitosan concentration determined mineralization extent and hydrogel mechanical reinforcement. Phytase-induced mineralization...... promoted MG63 adhesion and proliferation, especially in the presence of chitosan, and was non-toxic to MG63 cells (with and without chitosan). ADSC adhesion and proliferation were poor without mineralization. Chitosan did not affect ADSC osteogenic differentiation....

Vascularization of soft tissue engineering constructs

DEFF Research Database (Denmark)

Pimentel Carletto, Rodrigo

nanotechnology-based paradigm for engineering vascularised liver tissue for transplantation”) and the Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug delivery and sensing Using microcontainers and Nanomechanics (Danish National Research Foundation (DNRF122).......Vascularization is recognized to be the biggest challenge for the fabrication of tissues and finally, organs in vitro. So far, several fabrication techniques have been proposed to create a perfusable vasculature within hydrogels, however, the vascularization and perfusion of hydrogels...... with mechanical properties in the range of soft tissues has not been fully achieved. My project focused on the fabrication and the active perfusion of hydrogel constructs with multi-dimensional vasculature and controlled mechanical properties targeting soft tissues. Specifically, the initial part of the research...

Photodegradable, Photoadaptable Hydrogels via Radical-Mediated Disulfide Fragmentation Reaction.

Science.gov (United States)

Fairbanks, Benjamin D; Singh, Samir P; Bowman, Christopher N; Anseth, Kristi S

2011-04-26

Various techniques have been adopted to impart a biological responsiveness to synthetic hydrogels for the delivery of therapeutic agents as well as the study and manipulation of biological processes and tissue development. Such techniques and materials include polyelectrolyte gels that swell and deswell with changes in pH, thermosensitive gels that contract at physiological temperatures, and peptide cross-linked hydrogels that degrade upon peptidolysis by cell-secreted enzymes. Herein we report a unique approach to photochemically deform and degrade disulfide cross-linked hydrogels, mitigating the challenges of light attenuation and low quantum yield, permitting the degradation of hydrogels up to 2 mm thick within 120 s at low light intensities (10 mW/cm(2) at 365 nm). Hydrogels were formed by the oxidation of thiol-functionalized 4-armed poly(ethylene glycol) macromolecules. These disulfide cross-linked hydrogels were then swollen in a lithium acylphosphinate photoinitiator solution. Upon exposure to light, photogenerated radicals initiate multiple fragmentation and disulfide exchange reactions, permitting and promoting photodeformation, photowelding, and photodegradation. This novel, but simple, approach to generate photoadaptable hydrogels portends the study of cellular response to mechanically and topographically dynamic substrates as well as novel encapsulations by the welding of solid substrates. The principles and techniques described herein hold implications for more than hydrogel materials but also for photoadaptable polymers more generally.

T-piece resuscitator versus self-inflating bag for preterm resuscitation: an institutional experience.

Science.gov (United States)

Jayaram, Archana; Sima, Adam; Barker, Gail; Thacker, Leroy R

2013-07-01

Manual ventilation in the delivery room is provided with devices such as self-inflating bags (SIBs), flow-inflating bags, and T-piece resuscitators. To compare the effect of type of manual ventilation device on overall response to resuscitation among preterm neonates born at Apgar score. Secondary outcomes were incidence of air leaks, need for chest compressions/epinephrine, need for intubation, and surfactant use. We identified 294 resuscitations requiring ventilation. SIB was used for 135 neonates, and T-piece was used for 159 neonates. There was no significant difference between the 1-min and 5-min Apgar scores between SIB and T-piece (P = .77 and P = .11, respectively), nor were there significant differences in secondary outcomes. The rate of rise of Apgar score was higher, by 0.47, with T-piece, compared to SIB (95% CI 0.08-0.87, P = .02). Although some manikin studies favor T-piece for providing reliable and consistent pressures, our experience did not indicate significant differences in effectiveness of resuscitation between the T-piece and SIB in preterm resuscitations.

Transient rheology of stimuli responsive hydrogels: Integrating microrheology and microfluidics

Science.gov (United States)

Sato, Jun

Stimuli-responsive hydrogels have diverse potential applications in the field of drug delivery, tissue engineering, agriculture, cosmetics, gene therapy, and as sensors and actuators due to their unique responsiveness to external signals, such as pH, temperature, and ionic strength. Understanding the responsiveness of hydrogel structure and rheology to these stimuli is essential for designing materials with desirable performance. However, no instrumentation and well-defined methodology are available to characterize the structural and rheological responses to rapid solvent changes. In this thesis, a new microrheology set-up is described, which allows us to quantitatively measure the transient rheological properties and microstructure of a variety of solvent-responsive complex fluids. The device was constructed by integrating particle tracking microrheology and microfluidics and offers unique experimental capabilities for performing solvent-reponse measurements on soft fragile materials without applying external shear forces. Transient analysis methods to quantitatively obtain rheological properties were also constructed, and guidelines for the trade-off between statistical validity and temporal resolution were developed to accurately capture physical transitions. Employing the new device and methodology, we successfully quantified the transient rheological and microstructural responses during gel formation and break-up, and viscosity changes of solvent-responsive complex fluids. The analysis method was expanded for heterogeneous samples, incorporating methods to quantify the microrheology of samples with broad distributions of individual particle dynamics. Transient microrheology measurements of fragile, heterogeneous, self-assembled block copolypeptide hydrogels revealed that solvent exchange via convective mixing and dialysis can lead to significantly different gel properties and that commonly applied sample preparation protocols for the characterization of soft

Smaller self-inflating bags produce greater guideline consistent ventilation in simulated cardiopulmonary resuscitation.

Science.gov (United States)

Nehme, Ziad; Boyle, Malcolm J

2009-02-20

Suboptimal bag ventilation in cardiopulmonary resuscitation (CPR) has demonstrated detrimental physiological outcomes for cardiac arrest patients. In light of recent guideline changes for resuscitation, there is a need to identify the efficacy of bag ventilation by prehospital care providers. The objective of this study was to evaluate bag ventilation in relation to operator ability to achieve guideline consistent ventilation rate, tidal volume and minute volume when using two different capacity self-inflating bags in an undergraduate paramedic cohort. An experimental study using a mechanical lung model and a simulated adult cardiac arrest to assess the ventilation ability of third year Monash University undergraduate paramedic students. Participants were instructed to ventilate using 1600 ml and 1000 ml bags for a length of two minutes at the correct rate and tidal volume for a patient undergoing CPR with an advanced airway. Ventilation rate and tidal volume were recorded using an analogue scale with mean values calculated. Ethics approval was granted. Suboptimal ventilation with the use of conventional 1600 ml bag was common, with 77% and 97% of participants unable to achieve guideline consistent ventilation rates and tidal volumes respectively. Reduced levels of suboptimal ventilation arouse from the use of the smaller bag with a 27% reduction in suboptimal tidal volumes (p = 0.015) and 23% reduction in suboptimal minute volumes (p = 0.045). Smaller self-inflating bags reduce the incidence of suboptimal tidal volumes and minute volumes and produce greater guideline consistent results for cardiac arrest patients.

Dextran hydrogels incorporated with bioactive glass-ceramic: Nanocomposite scaffolds for bone tissue engineering.

Science.gov (United States)

Nikpour, Parisa; Salimi-Kenari, Hamed; Fahimipour, Farahnaz; Rabiee, Sayed Mahmood; Imani, Mohammad; Dashtimoghadam, Erfan; Tayebi, Lobat

2018-06-15

A series of nanocomposite scaffolds comprised of dextran (Dex) and sol-gel derived bioactive glass ceramic nanoparticles (nBGC: 0-16 (wt%)) were fabricated as bioactive scaffolds for bone tissue engineering. Scanning electron microscopy showed Dex/nBGC scaffolds were consisting of a porous 3D microstructure with an average pore size of 240 μm. Energy-dispersive x-ray spectroscopy illustrated nBGC nanoparticles were homogenously distributed within the Dex matrix at low nBGC content (2 wt%), while agglomeration was observed at higher nBGC contents. It was found that the osmotic pressure and nBGC agglomeration at higher nBGC contents leads to increased water uptake, then reduction of the compressive modulus. Bioactivity of Dex/nBGC scaffolds was validated through apatite formation after submersion in the simulated body fluid. Dex/nBGC composite scaffolds were found to show improved human osteoblasts (HOBs) proliferation and alkaline phosphatase (ALP) activity with increasing nBGC content up to 16 (wt%) over two weeks. Owing to favorable physicochemical and bioactivity properties, the Dex/nBGC composite hydrogels can be offered as promising bioactive scaffolds for bone tissue engineering applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Riboflavin-induced photo-crosslinking of collagen hydrogel and its application in meniscus tissue engineering.

Science.gov (United States)

Heo, Jiseung; Koh, Rachel H; Shim, Whuisu; Kim, Hwan D; Yim, Hyun-Gu; Hwang, Nathaniel S

2016-04-01

A meniscus tear is a common knee injury, but its regeneration remains a clinical challenge. Recently, collagen-based scaffolds have been applied in meniscus tissue engineering. Despite its prevalence, application of natural collagen scaffold in clinical setting is limited due to its extremely low stiffness and rapid degradation. The purpose of the present study was to increase the mechanical properties and delay degradation rate of a collagen-based scaffold by photo-crosslinking using riboflavin (RF) and UV exposure. RF is a biocompatible vitamin B2 that showed minimal cytotoxicity compared to conventionally utilized photo-initiator. Furthermore, collagen photo-crosslinking with RF improved mechanical properties and delayed enzyme-triggered degradation of collagen scaffolds. RF-induced photo-crosslinked collagen scaffolds encapsulated with fibrochondrocytes resulted in reduced scaffold contraction and enhanced gene expression levels for the collagen II and aggrecan. Additionally, hyaluronic acid (HA) incorporation into photo-crosslinked collagen scaffold showed an increase in its retention. Based on these results, we demonstrate that photo-crosslinked collagen-HA hydrogels can be potentially applied in the scaffold-based meniscus tissue engineering.

Biodegradable Thermogel as Culture Matrix of Bone Marrow Mesenchymal Stem Cells for Potential Cartilage Tissue Engineering

Institute of Scientific and Technical Information of China (English)

Yan-bo Zhang; Jian-xun Ding; Wei-guo Xu; Jie Wu; Fei Chang; Xiu-li Zhuang; Xue-si Chen

2014-01-01

Poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was synthesized through the ring-opening polymerization of LA and GA with PEG as macroinitiator and stannous octoate as catalyst.The amphiphilic copolymer self-assembled into micelles in aqueous solutions,and formed hydrogels as the increase of temperature at relatively high concentrations (＞ 15 wt％).The favorable degradability of the hydrogel was confirmed by in vitro and in vivo degradation experiments.The good cellular and tissular compatibilities of the thermogel were demonstrated.The excellent adhesion and proliferation of bone marrow mesenchymal stem cells endowed PLGA-PEG-PLGA thermogelling hydrogel with fascinating prospect for cartilage tissue engineering.

Bioprinting of hybrid tissue constructs with tailorable mechanical properties

Energy Technology Data Exchange (ETDEWEB)

Schuurman, W; Khristov, V; Pot, M W; Dhert, W J A; Malda, J [Department of Orthopaedics, University Medical Center Utrecht (Netherlands); Van Weeren, P R, E-mail: j.malda@umcutrecht.nl [Faculty of Veterinary Sciences, Department of Equine Sciences, Utrecht University (Netherlands)

2011-06-15

Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels. (communication)

Bioprinting of hybrid tissue constructs with tailorable mechanical properties

International Nuclear Information System (INIS)

Schuurman, W; Khristov, V; Pot, M W; Dhert, W J A; Malda, J; Van Weeren, P R

2011-01-01

Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels. (communication)

In Vitro Osteogenic and Odontogenic Differentiation of Human Dental Pulp Stem Cells Seeded on Carboxymethyl Cellulose-Hydroxyapatite Hybrid Hydrogel.

Directory of Open Access Journals (Sweden)

Gabriella eTeti

2015-10-01

Full Text Available Stem cells from human dental pulp have been considered as an alternative source of adult stem cells in tissue engineering because of their potential to differentiate into multiple cell lineages.Recently, polysaccharide based hydrogels have become especially attractive as matrices for the repair and regeneration of a wide variety of tissues and organs. The incorporation of inorganic minerals as hydroxyapatite nanoparticles can modulate the performance of the scaffolds with potential applications in tissue engineering. The aim of this study was to verify the osteogenic and odontogenic differentiation of dental pulp stem cells (DPSCs cultured on a carboxymethyl cellulose—hydroxyapatite hybrid hydrogel. Human DPSCs were seeded on carboxymethyl cellulose—hydroxyapatite hybrid hydrogel and on carboxymethyl cellulose hydrogel for 1, 3, 5, 7, 14 and 21 days. Cell viability assay and ultramorphological analysis were carried out to evaluate biocompatibility and cell adhesion. Real Time PCR was carried out to demonstrate the expression of osteogenic and odontogenic markers. Results showed a good adhesion and viability in cells cultured on carboxymethyl cellulose—hydroxyapatite hybrid hydrogel, while a low adhesion and viability was observed in cells cultured on carboxymethyl cellulose hydrogel. Real Time PCR data demonstrated a temporal up-regulation of osteogenic and odontogenic markers in dental pulp stem cells cultured on carboxymethyl cellulose—hydroxyapatite hybrid hydrogel. In conclusion, our in vitro data confirms the ability of DPSCs to differentiate toward osteogenic and odontogenic lineages in presence of a carboxymethyl cellulose—hydroxyapatite hybrid hydrogel. Taken together, our results provide evidence that DPSCs and carboxymethyl cellulose—hydroxyapatite hybrid hydrogel could be considered promising candidates for dental pulp complex and periodontal tissue engineering.

Engineering zonal cartilaginous tissue by modulating oxygen levels and mechanical cues through the depth of infrapatellar fat pad stem cell laden hydrogels.

Science.gov (United States)

Luo, Lu; O'Reilly, Adam R; Thorpe, Stephen D; Buckley, Conor T; Kelly, Daniel J

2017-09-01

Engineering tissues with a structure and spatial composition mimicking those of native articular cartilage (AC) remains a challenge. This study examined if infrapatellar fat pad-derived stem cells (FPSCs) can be used to engineer cartilage grafts with a bulk composition and a spatial distribution of matrix similar to the native tissue. In an attempt to mimic the oxygen gradients and mechanical environment within AC, FPSC-laden hydrogels (either 2 mm or 4 mm in height) were confined to half of their thickness and/or subjected to dynamic compression (DC). Confining FPSC-laden hydrogels was predicted to accentuate the gradient in oxygen tension through the depth of the constructs (higher in the top and lower in the bottom), leading to enhanced glycosaminoglycan (GAG) and collagen synthesis in 2 mm high tissues. When subjected to DC alone, both GAG and collagen accumulation increased within 2 mm high unconfined constructs. Furthermore, the dynamic modulus of constructs increased from 0.96 MPa to 1.45 MPa following the application of DC. There was no synergistic benefit of coupling confinement and DC on overall levels of matrix accumulation; however in all constructs, irrespective of their height, the combination of these boundary conditions led to the development of engineered tissues that spatially best resembled native AC. The superficial region of these constructs mimicked that of native tissue, staining weakly for GAG, strongly for type II collagen, and in 4 mm high tissues more intensely for proteoglycan 4 (lubricin). This study demonstrated that FPSCs respond to joint-like environmental conditions by producing cartilage tissues mimicking native AC. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery.

Science.gov (United States)

Wollenberg, A L; O'Shea, T M; Kim, J H; Czechanski, A; Reinholdt, L G; Sofroniew, M V; Deming, T J

2018-04-05

Injectable hydrogels with tunable physiochemical and biological properties are potential tools for improving neural stem/progenitor cell (NSPC) transplantation to treat central nervous system (CNS) injury and disease. Here, we developed injectable diblock copolypeptide hydrogels (DCH) for NSPC transplantation that contain hydrophilic segments of modified l-methionine (Met). Multiple Met-based DCH were fabricated by post-polymerization modification of Met to various functional derivatives, and incorporation of different amino acid comonomers into hydrophilic segments. Met-based DCH assembled into self-healing hydrogels with concentration and composition dependent mechanical properties. Mechanical properties of non-ionic Met-sulfoxide formulations (DCH MO ) were stable across diverse aqueous media while cationic formulations showed salt ion dependent stiffness reduction. Murine NSPC survival in DCH MO was equivalent to that of standard culture conditions, and sulfoxide functionality imparted cell non-fouling character. Within serum rich environments in vitro, DCH MO was superior at preserving NSPC stemness and multipotency compared to cell adhesive materials. NSPC in DCH MO injected into uninjured forebrain remained local and, after 4 weeks, exhibited an immature astroglial phenotype that integrated with host neural tissue and acted as cellular substrates that supported growth of host-derived axons. These findings demonstrate that Met-based DCH are suitable vehicles for further study of NSPC transplantation in CNS injury and disease models. Copyright © 2018 Elsevier Ltd. All rights reserved.

Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

Science.gov (United States)

Pradhan, Swati

cells were identified in cultured cells from dispersed tissue. Biomarker studies with the salivary enzyme, alpha-amylase, and tight junction proteins, such as zonula occludens-1 and E-cadherin, confirmed the phenotype of these cells. Strong staining for laminin and perlecan/HSPG2 were noted in basement membranes and perlecan also was secreted and organized by cultured acinar populations, which formed lobular structures that mimicked intact glands when cultured on Matrigel(TM) or a bioactive peptide derived from domain IV of perlecan (PlnDIV). On either matrix, large acini-like lobular structures grew and formed connections between the lobes. alpha-Amylase secretion was confirmed by staining and activity assay. Biomarkers including tight junction protein E-cadherin and water channel protein, aquaporin 5 (AQP5) found in tissue, were expressed in cultured acinar cells. Cells cultured on Matrigel(TM) or PlnDIV peptide organized stress fibers and activated focal adhesion kinase (FAK). HA, a natural polysaccharide and a major component of the ECM, can be used to generate soft and pliable hydrogels. A culture system consisting of HA hydrogel and PlnDIV peptide was used to generate a 2.5D culture system. Acinar cells cultured on these hydrogels self-assembled into lobular structures and expressed tight junction components such as ZO-1. Acini-like structures were stained for the presence of alpha-amylase. Live/dead staining revealed the presence of apoptotic cells in the center of the acini-like structures, indicative of lumen formation. The functionality of these acini-like structures was studied by stimulating them with neurotransmitters to enhance their fluid and protein production. Acini-like structures treated with norepinephrine and isoproterenol showed increased granule formation as observed by phase contrast microscopy and alpha-amylase staining in the structures. Lobular structures on hydrogels were treated with acetylcholine to increase fluid production. The increase

Fabrication and mechanical characterization of graphene oxide-reinforced poly (acrylic acid)/gelatin composite hydrogels

Science.gov (United States)

Faghihi, Shahab; Gheysour, Mahsa; Karimi, Alireza; Salarian, Reza

2014-02-01

Hydrogels have found many practical uses in drug release, wound dressing, and tissue engineering. However, their applications are restricted due to their weak mechanical properties. The role of graphene oxide nanosheets (GONS) as reinforcement agent in poly (acrylic acid) (PAA)/Gelatin (Gel) composite hydrogels is investigated. Composite hydrogels are synthesized by thermal initiated redox polymerization method. Samples are then prepared with 20 and 40 wt. % of PAA, an increasing amount of GONS (0.1, 0.2, and 0.3 wt. %), and a constant amount of Gel. Subsequently, cylindrical hydrogel samples are subjected to a series of compression tests in order to measure their elastic modulus, maximum stress and strain. The results exhibit that the addition of GONS increases the Young's modulus and maximum stress of hydrogels significantly as compared with control (0.0 wt. % GONS). The highest Young's modulus is observed for hydrogel with GO (0.2 wt. %)/PAA (20 wt. %), whereas the highest maximum stress is detected for GO (0.2 wt. %)/PAA (40 wt. %) specimen. The addition of higher amounts of GONS leads to a decrease in the maximum stress of the hydrogel GO (0.3 wt. %)/PAA (40 wt. %). No significant differences are detected for the maximum strain among the hydrogel samples, as the amount of GONS increased. These results suggest that the application of GONS could be used to improve mechanical properties of hydrogel materials. This study may provide an alternative for the fabrication of low-cost graphene/polymer composites with enhanced mechanical properties beneficial for tissue engineering applications.

Construction and characterization of a pure protein hydrogel for drug delivery application.

Science.gov (United States)

Xu, Xu; Xu, ZhaoKang; Yang, XiaoFeng; He, YanHao; Lin, Rong

2017-02-01

Injectable hydrogels have a variety of applications, including regenerative medicine, tissue engineering and controlled drug delivery. In this paper, we reported on a pure protein hydrogel based on tetrameric recombinant proteins for the potential drug delivery application. This protein hydrogel was formed instantly by simply mixing two recombinant proteins (ULD-TIP1 and ULD-GGGWRESAI) through the specific protein-peptide interaction. The protein hydrogel was characterized by rheology and scanning electron microscopy (SEM). In vitro cytotoxicity test indicated that the developed protein hydrogel had no apparent cytotoxicity against L-929 cells and HCEC cells after 48h incubation. The formed protein hydrogels was gradually degraded after incubation in phosphate buffered solution (PBS, pH=7.4) for a period of 144h study, as indicated by in vitro degradation test. Encapsulation of model drug (sodium diclofenac; DIC) were achieved by simple mixing of drugs with hydrogelator and the entrapped drugs was almost completely released from hydrogels within 24h via a diffusion manner. As a conclusion, the simple and mild preparation procedure and good biocompatibility of protein hydrogel would render its good promising candidate for drug delivery applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Design of a hybrid biomaterial for tissue engineering: Biopolymer-scaffold integrated with an autologous hydrogel carrying mesenchymal stem-cells.

Science.gov (United States)

Weinstein-Oppenheimer, Caroline R; Brown, Donald I; Coloma, Rodrigo; Morales, Patricio; Reyna-Jeldes, Mauricio; Díaz, María J; Sánchez, Elizabeth; Acevedo, Cristian A

2017-10-01

Biologically active biomaterials as biopolymers and hydrogels have been used in medical applications providing favorable results in tissue engineering. In this research, a wound dressing device was designed by integration of an autologous clot hydrogel carrying mesenchymal stem-cells onto a biopolymeric scaffold. This hybrid biomaterial was tested in-vitro and in-vivo, and used in a human clinical case. The biopolymeric scaffold was made with gelatin, chitosan and hyaluronic acid, using a freeze-drying method. The scaffold was a porous material which was designed evaluating both physical properties (glass transition, melting temperature and pore size) and biological properties (cell viability and fibronectin expression). Two types of chitosan (120 and 300kDa) were used to manufacture the scaffold, being the high molecular weight the most biologically active and stable after sterilization with gamma irradiation (25kGy). A clot hydrogel was formulated with autologous plasma and calcium chloride, using an approach based on design of experiments. The optimum hydrogel was used to incorporate cells onto the porous scaffold, forming a wound dressing biomaterial. The wound dressing device was firstly tested in-vitro using human cells, and then, its biosecurity was evaluated in-vivo using a rabbit model. The in-vitro results showed high cell viability after one week (99.5%), high mitotic index (19.8%) and high fibronectin expression. The in-vivo application to rabbits showed adequate biodegradability capacity (between 1 and 2weeks), and the histological evaluation confirmed absence of rejection signs and reepithelization on the wound zone. Finally, the wound dressing biomaterial was used in a single human case to implant autologous cells on a skin surgery. The medical examination indicated high biocompatibility, partial biodegradation at one week, early regeneration capacity at 4weeks and absence of rejection signs. Copyright © 2017 Elsevier B.V. All rights reserved.

Dual long memory of inflation and test of the relationship between inflation and inflation uncertainty

OpenAIRE

LIU Jinquan; ZHENG Tingguo; SUI Jianli

2008-01-01

This paper uses the ARFIMA-FIGARCH model to investigate the China¡¯s monthly inflation rate from January 1983 to October 2005. It is found that both first moment and second moment of inflation have remarkable long memory, indicating the existence of long memory properties in both inflation level and inflation uncertainty. By the Granger-causality test on inflation rate and inflation uncertainty, it is shown that the inflation level affects the inflation uncertainty and so supports Friedman hy...