Development of keratin–chitosan–gelatin composite scaffold for soft tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Kakkar, Prachi [Central Leather Research Institute (Council of Scientific and Industrial Research), Adyar, Chennai 600020 (India); Verma, Sudhanshu; Manjubala, I. [Biomedical Engineering Division, School of Bio Sciences and Technology, VIT University, Vellore 632014 (India); Madhan, B., E-mail: bmadhan76@yahoo.co.in [Central Leather Research Institute (Council of Scientific and Industrial Research), Adyar, Chennai 600020 (India)

2014-12-01

Keratin has gained much attention in the recent past as a biomaterial for wound healing owing to its biocompatibility, biodegradability, intrinsic biological activity and presence of cellular binding motifs. In this paper, a novel biomimetic scaffold containing keratin, chitosan and gelatin was prepared by freeze drying method. The prepared keratin composite scaffold had good structural integrity. Fourier Transform Infrared (FTIR) spectroscopy showed the retention of the native structure of individual biopolymers (keratin, chitosan, and gelatin) used in the scaffold. Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) results revealed a high thermal denaturation temperature of the scaffold (200–250 °C). The keratin composite scaffold exhibited tensile strength (96 kPa), compression strength (8.5 kPa) and water uptake capacity (> 1700%) comparable to that of a collagen scaffold, which was used as control. The morphology of the keratin composite scaffold observed using a Scanning Electron Microscope (SEM) exhibited good porosity and interconnectivity of pores. MTT assay using NIH 3T3 fibroblast cells demonstrated that the cell viability of the keratin composite scaffold was good. These observations suggest that the keratin–chitosan–gelatin composite scaffold is a promising alternative biomaterial for tissue engineering applications. - Highlights: • Fabrication of novel Keratin-Chitosan-Gelatin composite scaffold • Keratin composite scaffold shows excellent water uptake capacity and porosity • Keratin composite scaffold shows good thermal and physical stability • Biocompatibility of the developed scaffold is comparable to collagen scaffolds • Developed scaffold is a promising material for soft tissue engineering applications.

Biaxial mechanics and inter-lamellar shearing of stem-cell seeded electrospun angle-ply laminates for annulus fibrosus tissue engineering.

Science.gov (United States)

Driscoll, Tristan P; Nakasone, Ryan H; Szczesny, Spencer E; Elliott, Dawn M; Mauck, Robert L

2013-06-01

The annulus fibrosus (AF) of the intervertebral disk plays a critical role in vertebral load transmission that is heavily dependent on the microscale structure and composition of the tissue. With degeneration, both structure and composition are compromised, resulting in a loss of AF mechanical function. Numerous tissue engineering strategies have addressed the issue of AF degeneration, but few have focused on recapitulation of AF microstructure and function. One approach that allows for generation of engineered AF with appropriate (+/-)30° lamellar microstructure is the use of aligned electrospun scaffolds seeded with mesenchymal stem cells (MSCs) and assembled into angle-ply laminates (APL). Previous work indicates that opposing lamellar orientation is necessary for development of near native uniaxial tensile properties. However, most native AF tensile loads are applied biaxially, as the disk is subjected to multi-axial loads and is constrained by its attachments to the vertebral bodies. Thus, the objective of this study was to evaluate the biaxial mechanical response of engineered AF bilayers, and to determine the importance of opposing lamellar structure under this loading regime. Opposing bilayers, which replicate native AF structure, showed a significantly higher modulus in both testing directions compared to parallel bilayers, and reached ∼60% of native AF biaxial properties. Associated with this increase in biaxial properties, significantly less shear, and significantly higher stretch in the fiber direction, was observed. These results provide additional insight into native tissue structure-function relationships, as well as new benchmarks for engineering functional AF tissue constructs. Copyright © 2013 Orthopaedic Research Society.

Biomimetic composite coating on rapid prototyped scaffolds for bone tissue engineering.

Science.gov (United States)

Arafat, M Tarik; Lam, Christopher X F; Ekaputra, Andrew K; Wong, Siew Yee; Li, Xu; Gibson, Ian

2011-02-01

The objective of this present study was to improve the functional performance of rapid prototyped scaffolds for bone tissue engineering through biomimetic composite coating. Rapid prototyped poly(ε-caprolactone)/tri-calcium phosphate (PCL/TCP) scaffolds were fabricated using the screw extrusion system (SES). The fabricated PCL/TCP scaffolds were coated with a carbonated hydroxyapatite (CHA)-gelatin composite via biomimetic co-precipitation. The structure of the prepared CHA-gelatin composite coating was studied by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Compressive mechanical testing revealed that the coating process did not have any detrimental effect on the mechanical properties of the scaffolds. The cell-scaffold interaction was studied by culturing porcine bone marrow stromal cells (BMSCs) on the scaffolds and assessing the proliferation and bone-related gene and protein expression capabilities of the cells. Confocal laser microscopy and SEM images of the cell-scaffold constructs showed a uniformly distributed cell sheet and accumulation of extracellular matrix in the interior of CHA-gelatin composite-coated PCL/TCP scaffolds. The proliferation rate of BMSCs on CHA-gelatin composite-coated PCL/TCP scaffolds was about 2.3 and 1.7 times higher than that on PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds, respectively, by day 10. Furthermore, reverse transcription polymerase chain reaction and Western blot analysis revealed that CHA-gelatin composite-coated PCL/TCP scaffolds stimulate osteogenic differentiation of BMSCs the most, compared with PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds. These results demonstrate that CHA-gelatin composite-coated rapid prototyped PCL/TCP scaffolds are promising for bone tissue engineering. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Refinement of elastic, poroelastic, and osmotic tissue properties of intervertebral disks to analyze behavior in compression.

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Stokes, Ian A F; Laible, Jeffrey P; Gardner-Morse, Mack G; Costi, John J; Iatridis, James C

2011-01-01

Intervertebral disks support compressive forces because of their elastic stiffness as well as the fluid pressures resulting from poroelasticity and the osmotic (swelling) effects. Analytical methods can quantify the relative contributions, but only if correct material properties are used. To identify appropriate tissue properties, an experimental study and finite element analytical simulation of poroelastic and osmotic behavior of intervertebral disks were combined to refine published values of disk and endplate properties to optimize model fit to experimental data. Experimentally, nine human intervertebral disks with adjacent hemi-vertebrae were immersed sequentially in saline baths having concentrations of 0.015, 0.15, and 1.5 M and the loss of compressive force at constant height (force relaxation) was recorded over several hours after equilibration to a 300-N compressive force. Amplitude and time constant terms in exponential force-time curve-fits for experimental and finite element analytical simulations were compared. These experiments and finite element analyses provided data dependent on poroelastic and osmotic properties of the disk tissues. The sensitivities of the model to alterations in tissue material properties were used to obtain refined values of five key material parameters. The relaxation of the force in the three bath concentrations was exponential in form, expressed as mean compressive force loss of 48.7, 55.0, and 140 N, respectively, with time constants of 1.73, 2.78, and 3.40 h. This behavior was analytically well represented by a model having poroelastic and osmotic tissue properties with published tissue properties adjusted by multiplying factors between 0.55 and 2.6. Force relaxation and time constants from the analytical simulations were most sensitive to values of fixed charge density and endplate porosity.

Self-assembled high-strength hydroxyapatite/graphene oxide/chitosan composite hydrogel for bone tissue engineering.

Science.gov (United States)

Yu, Peng; Bao, Rui-Ying; Shi, Xiao-Jun; Yang, Wei; Yang, Ming-Bo

2017-01-02

Graphene hydrogel has shown greatly potentials in bone tissue engineering recently, but it is relatively weak in the practical use. Here we report a facile method to synthesize high strength composite graphene hydrogel. Graphene oxide (GO), hydroxyapatite (HA) nanoparticles (NPs) and chitosan (CS) self-assemble into a 3-dimensional hydrogel with the assistance of crosslinking agent genipin (GNP) for CS and reducing agent sodium ascorbate (NaVC) for GO simultaneously. The dense and oriented microstructure of the resulted composite gel endows it with high mechanical strength, high fixing capacity of HA and high porosity. These properties together with the good biocompatibility make the ternary composite gel a promising material for bone tissue engineering. Such a simultaneous crosslinking and reduction strategy can also be applied to produce a variety of 3D graphene-polymer based nanocomposites for biomaterials, energy storage materials and adsorbent materials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chitosan composite three dimensional macrospheric scaffolds for bone tissue engineering.

Science.gov (United States)

Vyas, Veena; Kaur, Tejinder; Thirugnanam, Arunachalam

2017-11-01

The present work deals with the fabrication of chitosan composite scaffolds with controllable and predictable internal architecture for bone tissue engineering. Chitosan (CS) based composites were developed by varying montmorillonite (MMT) and hydroxyapatite (HA) combinations to fabricate macrospheric three dimensional (3D) scaffolds by direct agglomeration of the sintered macrospheres. The fabricated CS, CS/MMT, CS/HA and CS/MMT/HA 3D scaffolds were characterized for their physicochemical, biological and mechanical properties. The XRD and ATR-FTIR studies confirmed the presence of the individual constituents and the molecular interaction between them, respectively. The reinforcement with HA and MMT showed reduced swelling and degradation rate. It was found that in comparison to pure CS, the CS/HA/MMT composites exhibited improved hemocompatibility and protein adsorption. The sintering of the macrospheres controlled the swelling ability of the scaffolds which played an important role in maintaining the mechanical strength of the 3D scaffolds. The CS/HA/MMT composite scaffold showed 14 folds increase in the compressive strength when compared to pure CS scaffolds. The fabricated scaffolds were also found to encourage the MG 63 cell proliferation. Hence, from the above studies it can be concluded that the CS/HA/MMT composite 3D macrospheric scaffolds have wider and more practical application in bone tissue regeneration applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Porous starch/cellulose nanofibers composite prepared by salt leaching technique for tissue engineering.

Science.gov (United States)

Nasri-Nasrabadi, Bijan; Mehrasa, Mohammad; Rafienia, Mohammad; Bonakdar, Shahin; Behzad, Tayebeh; Gavanji, Shahin

2014-08-08

Starch/cellulose nanofibers composites with proper porosity pore size, mechanical strength, and biodegradability for cartilage tissue engineering have been reported in this study. The porous thermoplastic starch-based composites were prepared by combining film casting, salt leaching, and freeze drying methods. The diameter of 70% nanofibers was in the range of 40-90 nm. All samples had interconnected porous morphology; however an increase in pore interconnectivity was observed when the sodium chloride ratio was increased in the salt leaching. Scaffolds with the total porogen content of 70 wt% exhibited adequate mechanical properties for cartilage tissue engineering applications. The water uptake ratio of nanocomposites was remarkably enhanced by adding 10% cellulose nanofibers. The scaffolds were partially destroyed due to low in vitro degradation rate after more than 20 weeks. Cultivation of isolated rabbit chondrocytes on the fabricated scaffold proved that the incorporation of nanofibers in starch structure improves cell attachment and proliferation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Feasibility of minimally-invasive fiber-based evaluation of chondrodystrophoid canine intervertebral discs by light absorption and scattering spectroscopy

Science.gov (United States)

Jiang, Yuanyuan; McKeirnan, Kelci; Piao, Daqing; Bartels, Kenneth E.

2011-03-01

Extrusion or protrusion of an intervertebral disc is a common, frequently debilitating, painful, and sometimes fatal neurologic disease in the chondrodystrophic dog (dachshund, Pekingese, etc.). A similar condition of intervertebral disc degeneration with extrusion/protrusion is also a relatively common neurologic condition in human patients. Degeneration of the relatively avascular chondrodystrophoid intervertebral disc is associated with loss of water content, increased collagen, and deposits of calcified mineral in the nucleus pulposus. Current diagnostic methods have many limitations for providing accurate information regarding disc composition in situ prior to surgical intervention. Disc composition (i.e., mineralization), can influence the type of treatment regime and potentially prognosis and recurrence rates. The objective of this study is to investigate the feasibility of using a fiber-needle spectroscopy sensor to analyze the changes of tissue compositions involved in the chondrodystrophoid condition of the canine intervertebral disc. The nucleous pulposus, in which the metaplastic process / degeneration develops, is approximately 2mm thick and 5mm in diameter in the dachshund-sized dog. It lies in the center of the disc, surrounded by the annulus fibrosis and is enclosed by cartilaginous vertebral endplates cranially and caudally. This "shallow-and-small-slab" geometry limits the configuration of a fiber probe to sense the disc tissue volume without interference from the vertebrae. A single-fiber sensor is inserted into a 20 gauge myelographic spinal needle for insertion into the disc in situ and connected via a bifurcated fiber to the light source and a spectrometer. A tungsten light source and a 940nm light-emitting-diode are combined for spectral illumination covering VIS/NIR with expected improved sensitivity to water. Analysis of the reflectance spectra is expected to provide information of scattering and absorption compositions of tissue in

Variation in tissue outcome of ovine and human engineered heart valve constructs : relevance for tissue engineering

NARCIS (Netherlands)

Geemen, van D.; Driessen - Mol, A.; Grootzwagers, L.G.M.; Soekhradj - Soechit, R.S.; Riem Vis, P.W.; Baaijens, F.P.T.; Bouten, C.V.C.

AIM: Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and

Single walled carbon nanotube composites for bone tissue engineering.

Science.gov (United States)

Gupta, Ashim; Woods, Mia D; Illingworth, Kenneth David; Niemeier, Ryan; Schafer, Isaac; Cady, Craig; Filip, Peter; El-Amin, Saadiq F

2013-09-01

The purpose of this study was to develop single walled carbon nanotubes (SWCNT) and poly lactic-co-glycolic acid (PLAGA) composites for orthopedic applications and to evaluate the interaction of human stem cells (hBMSCs) and osteoblasts (MC3T3-E1 cells) via cell growth, proliferation, gene expression, extracellular matrix production and mineralization. PLAGA and SWCNT/PLAGA composites were fabricated with various amounts of SWCNT (5, 10, 20, 40, and 100 mg), characterized and degradation studies were performed. Cells were seeded and cell adhesion/morphology, growth/survival, proliferation and gene expression analysis were performed to evaluate biocompatibility. Imaging studies demonstrated uniform incorporation of SWCNT into the PLAGA matrix and addition of SWCNT did not affect the degradation rate. Imaging studies revealed that MC3T3-E1 and hBMSCs cells exhibited normal, non-stressed morphology on the composites and all were biocompatible. Composites with 10 mg SWCNT resulted in highest rate of cell proliferation (p PLAGA composites imparted beneficial cellular growth capabilities and gene expression, and mineralization abilities were well established. These results demonstrate the potential of SWCNT/PLAGA composites for musculoskeletal regeneration and bone tissue engineering (BTE) and are promising for orthopedic applications. Copyright © 2013 Orthopaedic Research Society.

Elastin in the human intervertebral disk. A histological and biochemical study comparing it with elastin in the human yellow ligament.

Science.gov (United States)

Mikawa, Y; Hamagami, H; Shikata, J; Yamamuro, T

1986-01-01

The elastic fiber and elastin in the human yellow ligament and intervertebral disk were studied histologically and biochemically. The elastic fiber in the human intervertebral disk, which until now had not been clearly identified microscopically, was observed clearly. We found the distribution of the elastic fiber in the intervertebral disk to be very sparse and irregular, and its diameter was small, being about one-tenth of that found in the yellow ligament. The elastin contents of the yellow ligament and intervertebral disk were 46.7% +/- 0.9% and 1.7% +/- 0.2% respectively (mean +/- SE) of the total dry weight. The amino acid composition of elastin in the yellow ligament is similar to that of other tissue, as reported in the literature; however, that found in the intervertebral disk is significantly different. It would appear, therefore, that the elastin in the intervertebral disk is of a different type from that found elsewhere.

Custom-tailored tissue engineered polycaprolactone scaffolds for total disc replacement

International Nuclear Information System (INIS)

Van Uden, S; Silva-Correia, J; Correlo, V M; Oliveira, J M; Reis, R L

2015-01-01

Degeneration of the intervertebral disc (IVD) represents a significant musculoskeletal disease burden. Tissue engineering has proposed several strategies comprising the use of biodegradable materials to prepare scaffolds that can present mechanical properties similar to those of native IVD tissues. However, this might be insufficient, since the patient’s intervertebral space geometry must be replicated to allow for appropriate implant fixation and integration. Herein, we propose the use of reverse engineering and rapid prototyping techniques with the goal of preparing custom-tailored annulus fibrosus scaffolds; these techniques have previously been applied to rabbit models. The IVD reverse-engineered architecture was obtained by means of microcomputed tomography acquisition and three-dimensional modelling, resulting in a computer-aided design (CAD) that replicates the original rabbit IVD. Later, a fused deposition-modelling three-dimensional printer was used to produce the scaffolds with different geometries provided by the CAD, using polycaprolactone (PCL) with 100% infill density. The microstructure of the PCL scaffolds was investigated by scanning electron microscopy (SEM), which allowed us to observe an adequate fusion adhesion between the layers. The SEM images revealed that, up to the point of moderate resolution, the porosities manually designed in the CAD model were successfully replicated. The PCL scaffolds’ three-dimensional architecture was also assessed by means of microcomputed tomography analysis. Compressive stiffness was determined using a mechanical testing system. Results showed higher values than those of human IVDs (5.9–6.7 kN mm −1 versus 1.2 kN mm −1 , respectively). In vitro studies were performed to investigate the possible cytotoxicity of the polycaprolactone scaffolds’ leachables. The results showed that the custom-tailored PCL scaffolds do not have any deleterious cytotoxic effect over annulus fibrosus cells or the mouse lung

Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics.

Science.gov (United States)

Weber, Kathryn T; Jacobsen, Timothy D; Maidhof, Robert; Virojanapa, Justin; Overby, Chris; Bloom, Ona; Quraishi, Shaheda; Levine, Mitchell; Chahine, Nadeen O

2015-03-01

Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in disc diseases, including cytokines, chemokines, and proteases; advancements in disc disease diagnostics using imaging modalities; updates on studies examining the response of the intervertebral disc to injury; and recent developments in repair strategies, including cell-based repair, biomaterials, and tissue engineering. Findings on the effects of the omega-6 fatty acid, linoleic acid, on nucleus pulposus tissue engineering are presented. Studies described in this review provide greater insights into the pathogenesis of disc degeneration and may define new paradigms for early or differential diagnostics of degeneration using new techniques such as systemic biomarkers. In addition, research on the mechanobiology of disease enriches the development of therapeutics for disc repair, with potential to diminish pain and disability associated with disc degeneration.

Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

International Nuclear Information System (INIS)

Zeng, Chao; Yang, Qiang; Zhu, Meifeng; Du, Lilong; Zhang, Jiamin; Ma, Xinlong; Xu, Baoshan; Wang, Lianyong

2014-01-01

Intervertebral discs (IVDs) are structurally complex tissue that hold the vertebrae together and provide mobility to spine. The nucleus pulposus (NP) degeneration often results in degenerative IVD disease that is one of the most common causes of back and neck pain. Tissue engineered nucleus pulposus offers an alternative approach to regain the function of the degenerative IVD. The aim of this study is to determine the feasibility of porous silk fibroin (SF) scaffolds fabricated by paraffin-sphere-leaching methods with freeze-drying in the application of nucleus pulposus regeneration. The prepared scaffold possessed high porosity of 92.38 ± 5.12% and pore size of 165.00 ± 8.25 μm as well as high pore interconnectivity and appropriate mechanical properties. Rabbit NP cells were seeded and cultured on the SF scaffolds. Scanning electron microscopy, histology, biochemical assays and mechanical tests revealed that the porous scaffolds could provide an appropriate microstructure and environment to support adhesion, proliferation and infiltration of NP cells in vitro as well as the generation of extracellular matrix. The NP cell–scaffold construction could be preliminarily formed after subcutaneously implanted in a nude mice model. In conclusion, The SF porous scaffold offers a potential candidate for tissue engineered NP tissue. - Highlights: • Paraffin microsphere-leaching method is used to fabricate silk fibroin scaffold. • The scaffold has appropriate mechanical property, porosity and pore size • The scaffold supports growth and infiltration of nucleus pulposus cells. • Nucleus pulposus cells can secrete extracellular matrix in the scaffolds. • The scaffold is a potential candidate for tissue engineered nucleus pulposus

Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Zeng, Chao; Yang, Qiang [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhu, Meifeng [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Du, Lilong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhang, Jiamin [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ma, Xinlong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Xu, Baoshan, E-mail: xubaoshan99@126.com [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Wang, Lianyong, E-mail: wly@nankai.edu.cn [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China)

2014-04-01

Intervertebral discs (IVDs) are structurally complex tissue that hold the vertebrae together and provide mobility to spine. The nucleus pulposus (NP) degeneration often results in degenerative IVD disease that is one of the most common causes of back and neck pain. Tissue engineered nucleus pulposus offers an alternative approach to regain the function of the degenerative IVD. The aim of this study is to determine the feasibility of porous silk fibroin (SF) scaffolds fabricated by paraffin-sphere-leaching methods with freeze-drying in the application of nucleus pulposus regeneration. The prepared scaffold possessed high porosity of 92.38 ± 5.12% and pore size of 165.00 ± 8.25 μm as well as high pore interconnectivity and appropriate mechanical properties. Rabbit NP cells were seeded and cultured on the SF scaffolds. Scanning electron microscopy, histology, biochemical assays and mechanical tests revealed that the porous scaffolds could provide an appropriate microstructure and environment to support adhesion, proliferation and infiltration of NP cells in vitro as well as the generation of extracellular matrix. The NP cell–scaffold construction could be preliminarily formed after subcutaneously implanted in a nude mice model. In conclusion, The SF porous scaffold offers a potential candidate for tissue engineered NP tissue. - Highlights: • Paraffin microsphere-leaching method is used to fabricate silk fibroin scaffold. • The scaffold has appropriate mechanical property, porosity and pore size • The scaffold supports growth and infiltration of nucleus pulposus cells. • Nucleus pulposus cells can secrete extracellular matrix in the scaffolds. • The scaffold is a potential candidate for tissue engineered nucleus pulposus.

Natural Polymer-Cell Bioconstructs for Bone Tissue Engineering.

Science.gov (United States)

Titorencu, Irina; Albu, Madalina Georgiana; Nemecz, Miruna; Jinga, Victor V

2017-01-01

The major goal of bone tissue engineering is to develop bioconstructs which substitute the functionality of damaged natural bone structures as much as possible if critical-sized defects occur. Scaffolds that mimic the structure and composition of bone tissue and cells play a pivotal role in bone tissue engineering applications. First, composition, properties and in vivo synthesis of bone tissue are presented for the understanding of bone formation. Second, potential sources of osteoprogenitor cells have been investigated for their capacity to induce bone repair and regeneration. Third, taking into account that the main property to qualify one scaffold as a future bioconstruct for bone tissue engineering is the biocompatibility, the assessments which prove it are reviewed in this paper. Forth, various types of natural polymer- based scaffolds consisting in proteins, polysaccharides, minerals, growth factors etc, are discussed, and interaction between scaffolds and cells which proved bone tissue engineering concept are highlighted. Finally, the future perspectives of natural polymer-based scaffolds for bone tissue engineering are considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Thermogel-Coated Poly(ε-Caprolactone Composite Scaffold for Enhanced Cartilage Tissue Engineering

Directory of Open Access Journals (Sweden)

Shao-Jie Wang

2016-05-01

Full Text Available A three-dimensional (3D composite scaffold was prepared for enhanced cartilage tissue engineering, which was composed of a poly(ε-caprolactone (PCL backbone network and a poly(lactide-co-glycolide-block-poly(ethylene glycol-block-poly(lactide-co-glycolide (PLGA–PEG–PLGA thermogel surface. The composite scaffold not only possessed adequate mechanical strength similar to native osteochondral tissue as a benefit of the PCL backbone, but also maintained cell-friendly microenvironment of the hydrogel. The PCL network with homogeneously-controlled pore size and total pore interconnectivity was fabricated by fused deposition modeling (FDM, and was impregnated into the PLGA–PEG–PLGA solution at low temperature (e.g., 4 °C. The PCL/Gel composite scaffold was obtained after gelation induced by incubation at body temperature (i.e., 37 °C. The composite scaffold showed a greater number of cell retention and proliferation in comparison to the PCL platform. In addition, the composite scaffold promoted the encapsulated mesenchymal stromal cells (MSCs to differentiate chondrogenically with a greater amount of cartilage-specific matrix production compared to the PCL scaffold or thermogel. Therefore, the 3D PCL/Gel composite scaffold may exhibit great potential for in vivo cartilage regeneration.

The extracellular matrix: Structure, composition, age-related differences, tools for analysis and applications for tissue engineering.

Science.gov (United States)

Kular, Jaspreet K; Basu, Shouvik; Sharma, Ram I

2014-01-01

The extracellular matrix is a structural support network made up of diverse proteins, sugars and other components. It influences a wide number of cellular processes including migration, wound healing and differentiation, all of which is of particular interest to researchers in the field of tissue engineering. Understanding the composition and structure of the extracellular matrix will aid in exploring the ways the extracellular matrix can be utilised in tissue engineering applications especially as a scaffold. This review summarises the current knowledge of the composition, structure and functions of the extracellular matrix and introduces the effect of ageing on extracellular matrix remodelling and its contribution to cellular functions. Additionally, the current analytical technologies to study the extracellular matrix and extracellular matrix-related cellular processes are also reviewed.

Neoproteoglycans in tissue engineering

Science.gov (United States)

Weyers, Amanda; Linhardt, Robert J.

2014-01-01

Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein–glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer–glycosaminoglycan complexes. PMID:23399318

[Research advances of three-dimension printing technology in vertebrae and intervertebral disc tissue engineering].

Science.gov (United States)

Yang, Zechuan; Li, Chunde; Sun, Haolin

2016-03-01

Three-dimensional (3D) printing technology is characterized by "inside-out" stack manufacturing. Compared with conventional technologies, 3D printing has the advantage of personalization and precision. Therefore, the shape and internal structure of the scaffolds made by 3D printing technology are highly biomimetic. Besides, 3D bioprinting can precisely deposit the biomaterials, seeding cells and cytokines at the same time, which is a breakthrough in printing technique and material science. With the development of 3D printing, it will make great contributions to the reconstruction of vertebrae and intervertebral disc in the future.

Fabrication of nanocrystalline hydroxyapatite doped degradable composite hollow fiber for guided and biomimetic bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Zhang Ning [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Nichols, Heather L. [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Tylor, Shila [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Wen Xuejun [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States)]. E-mail: xjwen@clemson.edu

2007-04-15

Natural bone tissue possesses a nanocomposite structure interwoven in a three-dimensional (3-D) matrix, which plays critical roles in conferring appropriate physical and biological properties to the bone tissue. Single type of material may not be sufficient to mimic the composition, structure and properties of native bone, therefore, composite materials consisting of both polymers, bioceramics, and other inorganic materials have to be designed. Among a variety of candidate materials, polymer-nanoparticle composites appear most promising for bone tissue engineering applications because of superior mechanical properties, improved durability, and surface bioactivity when compared with conventional polymers or composites. The long term objective of this project is to use highly aligned, bioactive, biodegradable scaffold mimicking natural histological structure of human long bone, and to engineer and regenerate human long bone both in vitro and in vivo. In this study, bioactive, degradable, and highly permeable composite hollow fiber membranes (HFMs) were fabricated using a wet phase phase-inversion approach. The structure of the hollow fiber membranes was examined using scanning electron microscopy (SEM); degradation behavior was examined using weigh loss assay, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC); and bioactivity was evaluated with the amount of calcium deposition from the culture media onto HFM surface. Doping PLGA HFMs with nanoHA results in a more bioactive and slower degrading HFM than pure PLGA HFMs.

Engineering complex orthopaedic tissues via strategic biomimicry.

Science.gov (United States)

Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

2015-03-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

Science.gov (United States)

Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

2014-01-01

The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

Biomaterials for Tissue Engineering

Science.gov (United States)

Lee, Esther J.; Kasper, F. Kurtis; Mikos, Antonios G.

2013-01-01

Biomaterials serve as an integral component of tissue engineering. They are designed to provide architectural framework reminiscent of native extracellular matrix in order to encourage cell growth and eventual tissue regeneration. Bone and cartilage represent two distinct tissues with varying compositional and mechanical properties. Despite these differences, both meet at the osteochondral interface. This article presents an overview of current biomaterials employed in bone and cartilage applications, discusses some design considerations, and alludes to future prospects within this field of research. PMID:23820768

Highly Concentrated Alginate-Gellan Gum Composites for 3D Plotting of Complex Tissue Engineering Scaffolds

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Ashwini Rahul Akkineni

2016-04-01

Full Text Available In tissue engineering, additive manufacturing (AM technologies have brought considerable progress as they allow the fabrication of three-dimensional (3D structures with defined architecture. 3D plotting is a versatile, extrusion-based AM technology suitable for processing a wide range of biomaterials including hydrogels. In this study, composites of highly concentrated alginate and gellan gum were prepared in order to combine the excellent printing properties of alginate with the favorable gelling characteristics of gellan gum. Mixtures of 16.7 wt % alginate and 2 or 3 wt % gellan gum were found applicable for 3D plotting. Characterization of the resulting composite scaffolds revealed an increased stiffness in the wet state (15%–20% higher Young’s modulus and significantly lower volume swelling in cell culture medium compared to pure alginate scaffolds (~10% vs. ~23%. Cytocompatibility experiments with human mesenchymal stem cells (hMSC revealed that cell attachment was improved—the seeding efficiency was ~2.5–3.5 times higher on the composites than on pure alginate. Additionally, the composites were shown to support hMSC proliferation and early osteogenic differentiation. In conclusion, print fidelity of highly concentrated alginate-gellan gum composites was comparable to those of pure alginate; after plotting and crosslinking, the scaffolds possessed improved qualities regarding shape fidelity, mechanical strength, and initial cell attachment making them attractive for tissue engineering applications.

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

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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.

Tissue engineering

CERN Document Server

Fisher, John P; Bronzino, Joseph D

2007-01-01

Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

Engineering of Corneal Tissue through an Aligned PVA/Collagen Composite Nanofibrous Electrospun Scaffold.

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Wu, Zhengjie; Kong, Bin; Liu, Rui; Sun, Wei; Mi, Shengli

2018-02-24

Corneal diseases are the main reason of vision loss globally. Constructing a corneal equivalent which has a similar strength and transparency with the native cornea, seems to be a feasible way to solve the shortage of donated cornea. Electrospun collagen scaffolds are often fabricated and used as a tissue-engineered cornea, but the main drawback of poor mechanical properties make it unable to meet the requirement for surgery suture, which limits its clinical applications to a large extent. Aligned polyvinyl acetate (PVA)/collagen (PVA-COL) scaffolds were electrospun by mixing collagen and PVA to reinforce the mechanical strength of the collagen electrospun scaffold. Human keratocytes (HKs) and human corneal epithelial cells (HCECs) inoculated on aligned and random PVA-COL electrospun scaffolds adhered and proliferated well, and the aligned nanofibers induced orderly HK growth, indicating that the designed PVA-COL composite nanofibrous electrospun scaffold is suitable for application in tissue-engineered cornea.

Osteochondral tissue engineering: scaffolds, stem cells and applications

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Nooeaid, Patcharakamon; Salih, Vehid; Beier, Justus P; Boccaccini, Aldo R

2012-01-01

Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment. PMID:22452848

Multilayer scaffolds in orthopaedic tissue engineering.

Science.gov (United States)

Atesok, Kivanc; Doral, M Nedim; Karlsson, Jon; Egol, Kenneth A; Jazrawi, Laith M; Coelho, Paulo G; Martinez, Amaury; Matsumoto, Tomoyuki; Owens, Brett D; Ochi, Mitsuo; Hurwitz, Shepard R; Atala, Anthony; Fu, Freddie H; Lu, Helen H; Rodeo, Scott A

2016-07-01

The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future.

Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Qian, Junmin; Xu, Weijun; Yong, Xueqing; Jin, Xinxia; Zhang, Wei

2014-01-01

In this study, biomorphic poly(DL-lactic-co-glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164 ± 52 μm and 13 ± 8 μm, respectively, with a porosity of 89.3 ± 1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400 μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering. - Highlights: • Novel biomimetic PLGA/nHA composite scaffolds were successfully prepared. • nHA addition improved elastic modulus of PLGA scaffold and decreased its crystallinity. • PLGA/nHA composite scaffolds had better biocompatibility than PLGA scaffolds. • Biomorphic PLGA/nHA composite scaffold had great potential in bone tissue engineering

Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Qian, Junmin, E-mail: jmqian@mail.xjtu.edu.cn; Xu, Weijun; Yong, Xueqing; Jin, Xinxia; Zhang, Wei

2014-03-01

In this study, biomorphic poly(DL-lactic-co-glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164 ± 52 μm and 13 ± 8 μm, respectively, with a porosity of 89.3 ± 1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400 μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering. - Highlights: • Novel biomimetic PLGA/nHA composite scaffolds were successfully prepared. • nHA addition improved elastic modulus of PLGA scaffold and decreased its crystallinity. • PLGA/nHA composite scaffolds had better biocompatibility than PLGA scaffolds. • Biomorphic PLGA/nHA composite scaffold had great potential in bone tissue engineering.

Pullulan-based composite scaffolds for bone tissue engineering: Improved osteoconductivity by pore wall mineralization.

Science.gov (United States)

Amrita; Arora, Aditya; Sharma, Poonam; Katti, Dhirendra S

2015-06-05

Porous hydrogels have been explored for bone tissue engineering; however their poor mechanical properties make them less suitable as bone graft substitutes. Since incorporation of fillers is a well-accepted method for improving mechanical properties of hydrogels, in this work pullulan hydrogels were reinforced with nano-crystalline hydroxyapatite (nHAp) (5 wt% nHAp in hydrogel) and poly(3-hydroxybutyrate) (PHB) fibers (3 wt% fibers in hydrogel) containing nHAp (3 wt% nHAp in fibers). Addition of these fillers to pullulan hydrogel improved compressive modulus of the scaffold by 10 fold. However, the hydrophilicity of pullulan did not support adhesion and spreading of cells. To overcome this limitation, porous composite scaffolds were modified using a double diffusion method that enabled deposition of hydroxyapatite on pore walls. This method resulted in rapid and uniform coating of HAp throughout the three-dimensional scaffolds which not only rendered them osteoconductive in vitro but also led to an improvement in their compressive modulus. These results demonstrate the potential of mineralized pullulan-based composite scaffolds in non-load bearing bone tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

A review of fibrin and fibrin composites for bone tissue engineering.

Science.gov (United States)

Noori, Alireza; Ashrafi, Seyed Jamal; Vaez-Ghaemi, Roza; Hatamian-Zaremi, Ashraf; Webster, Thomas J

2017-01-01

Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient's own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the

Preparation and comparative characterization of keratin–chitosan and keratin–gelatin composite scaffolds for tissue engineering applications

International Nuclear Information System (INIS)

Balaji, S.; Kumar, Ramadhar; Sripriya, R.; Kakkar, Prachi; Ramesh, D. Vijaya; Reddy, P. Neela Kanta; Sehgal, P.K.

2012-01-01

We report fabrication of three dimensional scaffolds with well interconnected matrix of high porosity using keratin, chitosan and gelatin for tissue engineering and other biomedical applications. Scaffolds were fabricated using porous Keratin–Gelatin (KG), Keratin–Chitosan (KC) composites. The morphology of both KG and KC was investigated using SEM. The scaffolds showed high porosity with interconnected pores in the range of 20–100 μm. They were further tested by FTIR, DSC, CD, tensile strength measurement, water uptake and swelling behavior. In vitro cell adhesion and cell proliferation tests were carried out to study the biocompatibility behavior and their application as an artificial skin substitute. Both KG and KC composite scaffolds showed similar properties and patterns for cell proliferation. Due to rapid degradation of gelatin in KG, we found that it has limited application as compared to KC scaffold. We conclude that KC scaffold owing to its slow degradation and antibacterial properties would be a better substrate for tissue engineering and other biomedical application. Highlights: ► Extraction of reduced keratin from horn meal. ► Preparation of keratin–gelatin and keratin–chitosan composite scaffolds. ► Characterizations of the composite scaffolds. ► Comparative cytotoxicity analysis on NIH3T3 fibroblasts.

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

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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.

Greener synthesis of electrospun collagen/hydroxyapatite composite fibers with an excellent microstructure for bone tissue engineering

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Zhou YY

2015-04-01

Full Text Available Yuanyuan Zhou,1,2 Hongchang Yao,1 Jianshe Wang,1 Dalu Wang,1 Qian Liu,1 Zhongjun Li11College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Institute of Enviromental and Municipal Engineering, North China University of Water Resources and Electric Power, Zhengzhou, People’s Republic of ChinaAbstract: In bone tissue engineering, collagen/hydroxyapatite (HAP fibrous composite obtained via electrospinning method has been demonstrated to support the cells’ adhesion and bone regeneration. However, electrospinning of natural collagen often requires the use of cytotoxic organic solvents, and the HAP crystals were usually aggregated and randomly distributed within a fibrous matrix of collagen, limiting their clinical potential. Here, an effective and greener method for the preparation of collagen/HAP composite fibers was developed for the first time, and this green product not only had 40 times higher mechanical properties than that previously reported, but also had an excellent microstructure similar to that of natural bone. By dissolving type I collagen in environmentally friendly phosphate buffered saline/ethanol solution instead of the frequently-used cytotoxic organic solvents, followed with the key step of desalination, co-electrospinning the collagen solution with the HAP sol, generates a collagen/HAP composite with a uniform and continuous fibrous morphology. Interestingly, the nano-HAP needles were found to preferentially orient along the longitudinal direction of the collagen fibers, which mimicked the nanostructure of natural bones. Based on the characterization of the related products, the formation mechanism for this novel phenomenon was proposed. After cross-linking with 1-ethyl-3-(3-dimethyl-aminopropyl-1-carbodiimide hydrochloride/N-hydroxysuccinimide, the obtained composite exhibited a significant enhancement in mechanical properties. In addition, the biocompatibility of the

Preparation of dexamethasone-loaded biphasic calcium phosphate nanoparticles/collagen porous composite scaffolds for bone tissue engineering.

Science.gov (United States)

Chen, Ying; Kawazoe, Naoki; Chen, Guoping

2018-02-01

Although bone is regenerative, its regeneration capacity is limited. For bone defects beyond a critical size, further intervention is required. As an attractive strategy, bone tissue engineering (bone TE) has been widely investigated to repair bone defects. However, the rapid and effective bone regeneration of large non-healing defects is still a great challenge. Multifunctional scaffolds having osteoinductivity and osteoconductivity are desirable to fasten functional bone tissue regeneration. In the present study, biomimetic composite scaffolds of collagen and biphasic calcium phosphate nanoparticles (BCP NPs) with a controlled release of dexamethasone (DEX) and the controlled pore structures were prepared for bone TE. DEX was introduced in the BCP NPs during preparation of the BCP NPs and hybridized with collagen scaffolds, which pore structures were controlled by using pre-prepared ice particulates as a porogen material. The composite scaffolds had well controlled and interconnected pore structures, high mechanical strength and a sustained release of DEX. The composite scaffolds showed good biocompatibility and promoted osteogenic differentiation of hMSCs when used for three-dimensional culture of human bone marrow-derived mesenchymal stem cells. Subcutaneous implantation of the composite scaffolds at the dorsa of athymic nude mice demonstrated that they facilitated the ectopic bone tissue regeneration. The results indicated the DEX-loaded BCP NPs/collagen composite scaffolds had high potential for bone TE. Scaffolds play a crucial role for regeneration of large bone defects. Biomimetic scaffolds having the same composition of natural bone and a controlled release of osteoinductive factors are desirable for promotion of bone regeneration. In this study, composite scaffolds of collagen and biphasic CaP nanoparticles (BCP NPs) with a controlled release nature of dexamethasone (DEX) were prepared and their porous structures were controlled by using ice particulates

A review of fibrin and fibrin composites for bone tissue engineering

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Noori A

2017-07-01

Full Text Available Alireza Noori,1 Seyed Jamal Ashrafi,2 Roza Vaez-Ghaemi,3 Ashraf Hatamian-Zaremi,4 Thomas J Webster5 1Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 2School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran; 3Department of Chemical and Biological Engineering, Faculty of Biomedical Engineering, The University of British Columbia, Vancouver, BC, Canada; 4Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran; 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA Abstract: Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels, there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the

Composite microsphere-functionalized scaffold for the controlled release of small molecules in tissue engineering

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Laura Pandolfi

2016-01-01

Full Text Available Current tissue engineering strategies focus on restoring damaged tissue architectures using biologically active scaffolds. The ideal scaffold would mimic the extracellular matrix of any tissue of interest, promoting cell proliferation and de novo extracellular matrix deposition. A plethora of techniques have been evaluated to engineer scaffolds for the controlled and targeted release of bioactive molecules to provide a functional structure for tissue growth and remodeling, as well as enhance recruitment and proliferation of autologous cells within the implant. Recently, novel approaches using small molecules, instead of growth factors, have been exploited to regulate tissue regeneration. The use of small synthetic molecules could be very advantageous because of their stability, tunability, and low cost. Herein, we propose a chitosan–gelatin scaffold functionalized with composite microspheres consisting of mesoporous silicon microparticles and poly(dl-lactic-co-glycolic acid for the controlled release of sphingosine-1-phospate, a small molecule of interest. We characterized the platform with scanning electron microscopy, Fourier transform infrared spectroscopy, and confocal microscopy. Finally, the biocompatibility of this multiscale system was analyzed by culturing human mesenchymal stem cells onto the scaffold. The presented strategy establishes the basis of a versatile scaffold for the controlled release of small molecules and for culturing mesenchymal stem cells for regenerative medicine applications.

Fabrication and Characterization of Collagen-Immobilized Porous PHBV/HA Nano composite Scaffolds for Bone Tissue Engineering

International Nuclear Information System (INIS)

Jin-Young, B.; Zhi-Cai, X.; Giseop, K.; Keun-Byoung, Y.; Soo-Young, P.; Lee, S.P.; Inn-Kyu, K.

2012-01-01

The porous composite scaffolds (PHBV/HA) consisting of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and hydroxyapatite (HA) were fabricated using a hot-press machine and salt-leaching. Collagen (type I) was then immobilized on the surface of the porous PHBV/HA composite scaffolds to improve tissue compatibility. The structure and morphology of the collagen-immobilized composite scaffolds (PHBV/HA/Col) were investigated using a scanning electron microscope (SEM), Fourier transform infrared (FTIR), and electron spectroscopy for chemical analysis (ESCA). The potential of the porous PHBV/HA/Col composite scaffolds for use as a bone scaffold was assessed by an experiment with osteoblast cells (MC3T3-E1) in terms of cell adhesion, proliferation, and differentiation. The results showed that the PHBV/HA/Col composite scaffolds possess better cell adhesion and significantly higher proliferation and differentiation than the PHBV/HA composite scaffolds and the PHBV scaffolds. These results suggest that the PHBV/HA/Col composite scaffolds have a high potential for use in the field of bone regeneration and tissue engineering.

Bone tissue engineering using silica-based mesoporous nanobiomaterials:Recent progress.

Science.gov (United States)

Shadjou, Nasrin; Hasanzadeh, Mohammad

2015-10-01

Bone disorders are of significant concern due to increase in the median age of our population. It is in this context that tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Silica based mesostructured nanomaterials possessing pore sizes in the range 2-50 nm and surface reactive functionalities have elicited immense interest due to their exciting prospects in bone tissue engineering. In this review we describe application of silica-based mesoporous nanomaterials for bone tissue engineering. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds and composites. Also, the effect of structural and textural properties of mesoporous materials on development of new biomaterials for production of bone implants and bone cements was discussed. Also, application of different mesoporous materials on construction of manufacture 3-dimensional scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of silica-based mesoporous biomaterials on bone tissue engineering, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone. Copyright © 2015 Elsevier B.V. All rights reserved.

Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhuoyue [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Song, Yue [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Zhang, Jing [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province, 710069 (China); Liu, Wei [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Cui, Jihong, E-mail: cjh@nwu.edu.cn [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Provincial Key Laboratory of Biotechnology of Shaanxi, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province 710069 (China); Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, 229 TaiBai North Road, Xi' an, Shaanxi Province, 710069 (China); and others

2017-03-01

Electrospinning is an effective means to generate nano- to micro-scale polymer fibers resembling native extracellular matrix for tissue engineering. However, a major problem of electrospun materials is that limited pore size and porosity may prevent adequate cellular infiltration and tissue ingrowth. In this study, we first prepared thin layers of hydroxyapatite nanoparticle (nHA)/poly-hydroxybutyrate (PHB) via electrospinning. We then laminated the nHA/PHB thin layers to obtain a scaffold for cell seeding and bone tissue engineering. The results demonstrated that the laminated scaffold possessed optimized cell-loading capacity. Bone marrow mesenchymal stem cells (MSCs) exhibited better adherence, proliferation and osteogenic phenotypes on nHA/PHB scaffolds than on PHB scaffolds. Thereafter, we seeded MSCs onto nHA/PHB scaffolds to fabricate bone grafts. Histological observation showed osteoid tissue formation throughout the scaffold, with most of the scaffold absorbed in the specimens 2 months after implantation, and blood vessels ingrowth into the graft could be observed in the graft. We concluded that electrospun and laminated nanoscaled biocomposite scaffolds hold great therapeutic potential for bone regeneration. - Highlights: • We laminated the nHA/PHB layers to obtain a scaffold for bone tissue engineering. • The laminated scaffold performed optimized cell-loading capacity. • MSCs exhibited osteogenic phenotypes on the laminated scaffold. • Osteoid tissue formed throughout the laminated scaffold after 2 months in vivo. The laminated bio-composite scaffolds can be applied to bone regeneration.

Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering

International Nuclear Information System (INIS)

Chen, Zhuoyue; Song, Yue; Zhang, Jing; Liu, Wei; Cui, Jihong

2017-01-01

Electrospinning is an effective means to generate nano- to micro-scale polymer fibers resembling native extracellular matrix for tissue engineering. However, a major problem of electrospun materials is that limited pore size and porosity may prevent adequate cellular infiltration and tissue ingrowth. In this study, we first prepared thin layers of hydroxyapatite nanoparticle (nHA)/poly-hydroxybutyrate (PHB) via electrospinning. We then laminated the nHA/PHB thin layers to obtain a scaffold for cell seeding and bone tissue engineering. The results demonstrated that the laminated scaffold possessed optimized cell-loading capacity. Bone marrow mesenchymal stem cells (MSCs) exhibited better adherence, proliferation and osteogenic phenotypes on nHA/PHB scaffolds than on PHB scaffolds. Thereafter, we seeded MSCs onto nHA/PHB scaffolds to fabricate bone grafts. Histological observation showed osteoid tissue formation throughout the scaffold, with most of the scaffold absorbed in the specimens 2 months after implantation, and blood vessels ingrowth into the graft could be observed in the graft. We concluded that electrospun and laminated nanoscaled biocomposite scaffolds hold great therapeutic potential for bone regeneration. - Highlights: • We laminated the nHA/PHB layers to obtain a scaffold for bone tissue engineering. • The laminated scaffold performed optimized cell-loading capacity. • MSCs exhibited osteogenic phenotypes on the laminated scaffold. • Osteoid tissue formed throughout the laminated scaffold after 2 months in vivo. The laminated bio-composite scaffolds can be applied to bone regeneration.

The interplay between tissue growth and scaffold degradation in engineered tissue constructs

KAUST Repository

O’Dea, R. D.

2012-09-18

In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (1) differential interactions between cells and the supporting scaffold and their associated ECM, (2) scaffold degradation, and (3) mechanotransduction-regulated cell proliferation and ECM deposition. Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of

Surface modification of nanofibrous polycaprolactone/gelatin composite scaffold by collagen type I grafting for skin tissue engineering

International Nuclear Information System (INIS)

Gautam, Sneh; Chou, Chia-Fu; Dinda, Amit K.; Potdar, Pravin D.; Mishra, Narayan C.

2014-01-01

In the present study, a tri-polymer polycaprolactone (PCL)/gelatin/collagen type I composite nanofibrous scaffold has been fabricated by electrospinning for skin tissue engineering and wound healing applications. Firstly, PCL/gelatin nanofibrous scaffold was fabricated by electrospinning using a low cost solvent mixture [chloroform/methanol for PCL and acetic acid (80% v/v) for gelatin], and then the nanofibrous PCL/gelatin scaffold was modified by collagen type I (0.2–1.5 wt.%) grafting. Morphology of the collagen type I-modified PCL/gelatin composite scaffold that was analyzed by field emission scanning electron microscopy (FE-SEM), showed that the fiber diameter was increased and pore size was decreased by increasing the concentration of collagen type I. Fourier transform infrared (FT-IR) spectroscopy and thermogravimetric (TG) analysis indicated the surface modification of PCL/gelatin scaffold by collagen type I immobilization on the surface of the scaffold. MTT assay demonstrated the viability and high proliferation rate of L929 mouse fibroblast cells on the collagen type I-modified composite scaffold. FE-SEM analysis of cell-scaffold construct illustrated the cell adhesion of L929 mouse fibroblasts on the surface of scaffold. Characteristic cell morphology of L929 was also observed on the nanofiber mesh of the collagen type I-modified scaffold. Above results suggest that the collagen type I-modified PCL/gelatin scaffold was successful in maintaining characteristic shape of fibroblasts, besides good cell proliferation. Therefore, the fibroblast seeded PCL/gelatin/collagen type I composite nanofibrous scaffold might be a potential candidate for wound healing and skin tissue engineering applications. - Highlights: • PCL/gelatin/collagen type I scaffold was fabricated for skin tissue engineering. • PCL/gelatin/collagen type I scaffold showed higher fibroblast growth than PCL/gelatin one. • PCL/gelatin/collagen type I might be one of the ideal scaffold for

Fabrication and Properties of Silica Gel/Calcium Sulfate/Strontium-doped β-tricalcium Phosphate Composite Porous Scaffolds for Bone Tissue Engineering

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QIN Xiao-su

2018-03-01

Full Text Available The calcium sulfate/strontium-doped β-tricalcium phosphate composite spherical pellets was fabricated, using the calcium sulfate/strontium-doped β-TCP as raw material, and through the stirring spray drying method, and then composite spherical pellets were combined with silica gel, porous silica gel/calcium sulfate/strontium-doped β-tricalcium phosphate scaffold was obtained by stacking aggregation method in the mould. The XRD, SEM and FT-IR, etc are employed to examine the chemical composition, composite morphology and structure characteristics, and the degradability, porosity, mechanical properties and cytotoxicity of the scaffolds materials were studied. The results reveal that the composite porous scaffolds have irregular pore structure with pore size between 0.2-1.0mm, and they have a large number of micropores on each of the composite spherical pellets, with the aperture between 50-200μm. Moreover, the porosity of the composite scaffolds is about 62%, which can meet the requirements of scaffolds for bone tissue engineering in porosity; the cytotoxicity tests show the composite scaffolds have no cytotoxic effect and it has good degradation. Therefore, it has good application prospect in bone tissue engineering of the bone defect repair of non-bearing site.

A radiopaque electrospun scaffold for engineering fibrous musculoskeletal tissues: Scaffold characterization and in vivo applications.

Science.gov (United States)

Martin, John T; Milby, Andrew H; Ikuta, Kensuke; Poudel, Subash; Pfeifer, Christian G; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

2015-10-01

strategies for the intervertebral disc, meniscus, tendon and ligament have progressed from in vitro to in vivo evaluation using a variety of animal models, and the clinical application of these technologies is imminent. The composition of most scaffold materials however does not allow for visualization by methods available to clinicians (e.g., radiography), and thus it is not possible to assess their performance in situ. In this work, we describe a radiopaque nanofibrous scaffold that can be visualized radiographically in both small and large animal models and serve as a framework for the development of an engineered fibrous tissue. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Engineering complex tissue-like microgel arrays for evaluating stem cell differentiation

DEFF Research Database (Denmark)

Guermani, Enrico; Shaki, Hossein; Mohanty, Soumyaranjan

2016-01-01

Development of tissue engineering scaffolds with native-like biology and microarchitectures is a prerequisite for stem cell mediated generation of off-the-shelf-tissues. So far, the field of tissue engineering has not full-filled its grand potential of engineering such combinatorial scaffolds...... for engineering functional tissues. This is primarily due to the many challenges associated with finding the right microarchitectures and ECM compositions for optimal tissue regeneration. Here, we have developed a new microgel array to address this grand challenge through robotic printing of complex stem cell...... platform will be used for high-throughput identification of combinatorial and native-like scaffolds for tissue engineering of functional organs....

Synthesis and characterization of injectable composites of poly[D,L-lactide-co-(ε-caprolactone)] reinforced with β-TCP and CaCO3 for intervertebral disk augmentation.

Science.gov (United States)

López, Alejandro; Persson, Cecilia; Hilborn, Jöns; Engqvist, Håkan

2010-10-01

Degeneration of the intervertebral disk constitutes one of the major causes of low back pain in adults aged 20-50 years old. In this study, injectable, in situ setting, degradable composites aimed for intervertebral disk replacement were prepared. β-TCP and calcium carbonate particles were mixed into acrylic-terminated oligo[D,L-lactide-co-(ε-caprolactone)], which were crosslinked at room temperature. The structure of the oligomers was confirmed by 1H-NMR spectroscopy. The composites were examined via SEM, and the mechanical properties of the crosslinked networks were determined. The porous β-TCP particles showed good mechanical anchorage to the matrix due to polymer penetration into the pores. In vitro degradation tests showed that the composites containing β-TCP slowly degraded, whereas the composites containing CaCO3 exhibited apatite formation capacity. It was concluded that the surface area, morphology, and solubility of the fillers might be used to control the degradation properties. The incorporation of fillers also increased both the elastic modulus and the maximum compression strength of the composites, properties that were similar to those of the physiological disk. These materials have potential for long-term intervertebral disk replacement and regenerative scaffolds because of their low degradation rates, bioactivity, and mechanical properties.

Engineering Complex Tissues

Science.gov (United States)

MIKOS, ANTONIOS G.; HERRING, SUSAN W.; OCHAREON, PANNEE; ELISSEEFF, JENNIFER; LU, HELEN H.; KANDEL, RITA; SCHOEN, FREDERICK J.; TONER, MEHMET; MOONEY, DAVID; ATALA, ANTHONY; VAN DYKE, MARK E.; KAPLAN, DAVID; VUNJAK-NOVAKOVIC, GORDANA

2010-01-01

This article summarizes the views expressed at the third session of the workshop “Tissue Engineering—The Next Generation,” which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a “guided interplay” between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from “adult biology” of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician’s perspective for functional tissue

Gel spinning of silk tubes for tissue engineering

Science.gov (United States)

Lovett, Michael; Cannizzaro, Christopher; Vunjak-Novakovic, Gordana; Kaplan, David L.

2011-01-01

Tubular vessels for tissue engineering are typically fabricated using a molding, dipping, or electrospinning technique. While these techniques provide some control over inner and outer diameters of the tube, they lack the ability to align the polymers or fibers of interest throughout the tube. This is an important aspect of biomaterial composite structure and function for mechanical and biological impact of tissue outcomes. We present a novel aqueous process system to spin tubes from biopolymers and proteins such as silk fibroin. Using silk as an example, this method of winding an aqueous solution around a reciprocating rotating mandrel offers substantial improvement in the control of the tube properties, specifically with regard to winding pattern, tube porosity, and composite features. Silk tube properties are further controlled via different post-spinning processing mechanisms such as methanol-treatment, air-drying, and lyophilization. This approach to tubular scaffold manufacture offers numerous tissue engineering applications such as complex composite biomaterial matrices, blood vessel grafts and nerve guides, among others. PMID:18801570

Tissue-engineered collateral ligament composite allografts for scapholunate ligament reconstruction: an experimental study.

Science.gov (United States)

Endress, Ryan; Woon, Colin Y L; Farnebo, Simon J; Behn, Anthony; Bronstein, Joel; Pham, Hung; Yan, Xinrui; Gambhir, Sanjiv S; Chang, James

2012-08-01

In patients with chronic scapholunate (SL) dissociation or dynamic instability, ligament repair is often not possible, and surgical reconstruction is indicated. The ideal graft ligament would recreate both anatomical and biomechanical properties of the dorsal scapholunate ligament (dorsal SLIL). The finger proximal interphalangeal joint (PIP joint) collateral ligament could possibly be a substitute ligament. We harvested human PIP joint collateral ligaments and SL ligaments from 15 cadaveric limbs. We recorded ligament length, width, and thickness, and measured the biomechanical properties (ultimate load, stiffness, and displacement to failure) of native dorsal SLIL, untreated collateral ligaments, decellularized collateral ligaments, and SL repairs with bone-collateral ligament-bone composite collateral ligament grafts. As proof of concept, we then reseeded decellularized bone-collateral ligament-bone composite grafts with green fluorescent protein-labeled adipo-derived mesenchymal stem cells and evaluated them histologically. There was no difference in ultimate load, stiffness, and displacement to failure among native dorsal SLIL, untreated and decellularized collateral ligaments, and SL repairs with tissue-engineered collateral ligament grafts. With pair-matched untreated and decellularized scaffolds, there was no difference in ultimate load or stiffness. However, decellularized ligaments revealed lower displacement to failure compared with untreated ligaments. There was no difference in displacement between decellularized ligaments and native dorsal SLIL. We successfully decellularized grafts with recently described techniques, and they could be similarly reseeded. Proximal interphalangeal joint collateral ligament-based bone-collateral ligament-bone composite allografts had biomechanical properties similar to those of native dorsal SLIL. Decellularization did not adversely affect material properties. These tissue-engineered grafts may offer surgeons another

Greener synthesis of electrospun collagen/hydroxyapatite composite fibers with an excellent microstructure for bone tissue engineering

Science.gov (United States)

Zhou, Yuanyuan; Yao, Hongchang; Wang, Jianshe; Wang, Dalu; Liu, Qian; Li, Zhongjun

2015-01-01

In bone tissue engineering, collagen/hydroxyapatite (HAP) fibrous composite obtained via electrospinning method has been demonstrated to support the cells’ adhesion and bone regeneration. However, electrospinning of natural collagen often requires the use of cytotoxic organic solvents, and the HAP crystals were usually aggregated and randomly distributed within a fibrous matrix of collagen, limiting their clinical potential. Here, an effective and greener method for the preparation of collagen/HAP composite fibers was developed for the first time, and this green product not only had 40 times higher mechanical properties than that previously reported, but also had an excellent microstructure similar to that of natural bone. By dissolving type I collagen in environmentally friendly phosphate buffered saline/ethanol solution instead of the frequently-used cytotoxic organic solvents, followed with the key step of desalination, co-electrospinning the collagen solution with the HAP sol, generates a collagen/HAP composite with a uniform and continuous fibrous morphology. Interestingly, the nano-HAP needles were found to preferentially orient along the longitudinal direction of the collagen fibers, which mimicked the nanostructure of natural bones. Based on the characterization of the related products, the formation mechanism for this novel phenomenon was proposed. After cross-linking with 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride/N-hydroxysuccinimide, the obtained composite exhibited a significant enhancement in mechanical properties. In addition, the biocompatibility of the obtained composite fibers was evaluated by in vitro culture of the human myeloma cells (U2-OS). Taken together, the process outlined herein provides an effective, non-toxic approach for the fabrication of collagen/HAP composite nanofibers that could be good candidates for bone tissue engineering. PMID:25995630

Effect of intervertebral disc disease on scoliosis in the lumbar spine

Directory of Open Access Journals (Sweden)

Wojcik Gustaw

2014-09-01

Full Text Available Lumbar intervertebral discopathy is a common clinical problem and a significant cause of low back pain. Usually it is associated with overload and damage to the intervertebral disc, which directly relates to the instability of the motion segment. Renal normal anatomy between tissues within the spinal canal is a cause of the reflex curvature of the spine, the goal is to increase the volume of the spinal channel and reduce the compression of the nerve tissue. Knee-jerk reaction to pain is an non physiological change of the setting of the spine in the frontal plane.

Stem cell therapy for intervertebral disc regeneration: review article

Directory of Open Access Journals (Sweden)

Mohsen Sheykhhasan

2017-02-01

Full Text Available Intervertebral disks (IVD acts as shock absorber between each of the vertebrae in the spinal column by keeping the vertebrae separated when the shock caused by the action. They also serve to protect the nerves that run down the middle of the spine and intervertebral disks. The disks are made of fibrocartilaginous material. The outside of the disk is made of a strong material called the annulus fibrosus. Inside this protective covering is a jelly-like substance known as mucoprotein gel. This interior is known as the nucleus pulposus. The nucleus pulposus consists of large vacuolated notochord cells, small chondrocyte-like cells, collagen fibrils, and aggrecan, a proteoglycan that aggregates by binding to hyaluronan. Attached to each aggrecan molecule are glycosaminoglycan (GAG chains of chondroitin sulfate and keratan sulfate. Intervertebral disks degeneration is frequently associated with low back and neck pain, which accounts as a disability. Despite the known outcomes of the Intervertebral disks degeneration cascade, the treatment of IVD degeneration is limited in that available conservative and surgical treatments do not reverse the pathology or restore the IVD tissue. Regenerative medicine for IVD degeneration, by injection of Intervertebral disks cells, chondrocytes or stem cells, has been extensively studied in the past decade in various animal models of induced IVD degeneration, and has progressed to clinical trials in the treatment of various spinal disease. Despite preliminary results showing positive effects of cell-injection strategies for IVD regeneration, detailed basic research on Intervertebral disks cells and their niche demonstrates that transplanted cells are unable to survive and adapt in the avascular niche of the IVD. For this therapeutic strategy to succeed, the indications for its use and the patients who would benefit need to be better defined. To surmount these obstacles, the solution will be identified only by focused

Bioactive glass in tissue engineering

Science.gov (United States)

Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

2011-01-01

This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances.

Science.gov (United States)

Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul; Vrana, Nihal Engin

2014-01-01

In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

Directory of Open Access Journals (Sweden)

Julien Barthes

2014-01-01

Full Text Available In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells’ behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

Fiber/collagen composites for ligament tissue engineering: influence of elastic moduli of sparse aligned fibers on mesenchymal stem cells.

Science.gov (United States)

Thayer, Patrick S; Verbridge, Scott S; Dahlgren, Linda A; Kakar, Sanjeev; Guelcher, Scott A; Goldstein, Aaron S

2016-08-01

Electrospun microfibers are attractive for the engineering of oriented tissues because they present instructive topographic and mechanical cues to cells. However, high-density microfiber networks are too cell-impermeable for most tissue applications. Alternatively, the distribution of sparse microfibers within a three-dimensional hydrogel could present instructive cues to guide cell organization while not inhibiting cell behavior. In this study, thin (∼5 fibers thick) layers of aligned microfibers (0.7 μm) were embedded within collagen hydrogels containing mesenchymal stem cells (MSCs), cultured for up to 14 days, and assayed for expression of ligament markers and imaged for cell organization. These microfibers were generated through the electrospinning of polycaprolactone (PCL), poly(ester-urethane) (PEUR), or a 75/25 PEUR/PCL blend to produce microfiber networks with elastic moduli of 31, 15, and 5.6 MPa, respectively. MSCs in composites containing 5.6 MPa fibers exhibited increased expression of the ligament marker scleraxis and the contractile phenotype marker α-smooth muscle actin versus the stiffer fiber composites. Additionally, cells within the 5.6 MPa microfiber composites were more oriented compared to cells within the 15 and 31 MPa microfiber composites. Together, these data indicate that the mechanical properties of microfiber/collagen composites can be tuned for the engineering of ligament and other target tissues. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1894-1901, 2016. © 2016 Wiley Periodicals, Inc.

Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

Science.gov (United States)

Tran, Cassie M; Shapiro, Irving M; Risbud, Makarand V

2013-08-08

Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration. © 2013 Elsevier B.V. All rights reserved.

The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

Science.gov (United States)

Babur, Betul Kul; Kabiri, Mahboubeh; Klein, Travis Jacob; Lott, William B; Doran, Michael Robert

2015-01-01

We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage tissues; the incorporation of CD enhanced tissue size and matrix content, but did not enhance chondrogenic gene expression.

In vitro cytocompatibility evaluation of chitosan/graphene oxide 3D scaffold composites designed for bone tissue engineering.

Science.gov (United States)

Dinescu, Sorina; Ionita, Mariana; Pandele, Andreea Madalina; Galateanu, Bianca; Iovu, Horia; Ardelean, Aurel; Costache, Marieta; Hermenean, Anca

2014-01-01

Extensively studied nowadays, graphene oxide (GO) has a benefic effect on cell proliferation and differentiation, thus holding promise for bone tissue engineering (BTE) approaches. The aim of this study was not only to design a chitosan 3D scaffold improved with GO for optimal BTE, but also to analyze its physicochemical properties and to evaluate its cytocompatibility and ability to support cell metabolic activity and proliferation. Overall results show that the addition of GO in the scaffold's composition improved mechanical properties and pore formation and enhanced the bioactivity of the scaffold material for tissue engineering. The new developed CHT/GO 3 wt% scaffold could be a potential candidate for further in vitro and in vivo osteogenesis studies and BTE approaches.

A computational study of intervertebral disc degeneration in relation to changes in regional tissue composition and disc nutrition

OpenAIRE

Ruiz Wills, Carlos

2015-01-01

Up to 85% of the world population suffers from low back pain, a clinical condition often related to the intervertebral disc (IVD) degeneration (DD). Altered disc cell nutrition affects cell viability and can generate catabolic cascades that degrade the extracellular matrix (ECM). Also, a major degenerative biochemical change in the disc is the proteoglycan (PG) loss, which affects the osmotic pressure and hydration that is critical for cell nutrition. However, the relationship between biochem...

[Strategies to choose scaffold materials for tissue engineering].

Science.gov (United States)

Gao, Qingdong; Zhu, Xulong; Xiang, Junxi; Lü, Yi; Li, Jianhui

2016-02-01

Current therapies of organ failure or a wide range of tissue defect are often not ideal. Transplantation is the only effective way for long time survival. But it is hard to meet huge patients demands because of donor shortage, immune rejection and other problems. Tissue engineering could be a potential option. Choosing a suitable scaffold material is an essential part of it. According to different sources, tissue engineering scaffold materials could be divided into three types which are natural and its modified materials, artificial and composite ones. The purpose of tissue engineering scaffold is to repair the tissues or organs damage, so could reach the ideal recovery in its function and structure aspect. Therefore, tissue engineering scaffold should even be as close as much to the original tissue or organs in function and structure. We call it "organic scaffold" and this strategy might be the drastic perfect substitute for the tissues or organs in concern. Optimized organization with each kind scaffold materials could make up for biomimetic structure and function of the tissue or organs. Scaffold material surface modification, optimized preparation procedure and cytosine sustained-release microsphere addition should be considered together. This strategy is expected to open new perspectives for tissue engineering. Multidisciplinary approach including material science, molecular biology, and engineering might find the most ideal tissue engineering scaffold. Using the strategy of drawing on each other strength and optimized organization with each kind scaffold material to prepare a multifunctional biomimetic tissue engineering scaffold might be a good method for choosing tissue engineering scaffold materials. Our research group had differentiated bone marrow mesenchymal stem cells into bile canaliculi like cells. We prepared poly(L-lactic acid)/poly(ε-caprolactone) biliary stent. The scaffold's internal played a part in the long-term release of cytokines which

Current Concepts in Scaffolding for Bone Tissue Engineering.

Science.gov (United States)

Ghassemi, Toktam; Shahroodi, Azadeh; Ebrahimzadeh, Mohammad H; Mousavian, Alireza; Movaffagh, Jebraeel; Moradi, Ali

2018-03-01

Bone disorders are of significant worry due to their increased prevalence in the median age. Scaffold-based bone tissue engineering holds great promise for the future of osseous defects therapies. Porous composite materials and functional coatings for metallic implants have been introduced in next generation of orthopedic medicine for tissue engineering. While osteoconductive materials such as hydroxyapatite and tricalcium phosphate ceramics as well as some biodegradable polymers are suggested, much interest has recently focused on the use of osteoinductive materials like demineralized bone matrix or bone derivatives. However, physiochemical modifications in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, mineralization and osteogenic differentiation are required. This paper reviews studies on bone tissue engineering from the biomaterial point of view in scaffolding. Level of evidence: I.

Notochord Cells in Intervertebral Disc Development and Degeneration

Science.gov (United States)

McCann, Matthew R.; Séguin, Cheryle A.

2016-01-01

The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

Notochord Cells in Intervertebral Disc Development and Degeneration

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Matthew R. McCann

2016-01-01

Full Text Available The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches.

High Definition Confocal Imaging Modalities for the Characterization of Tissue-Engineered Substitutes.

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Mayrand, Dominique; Fradette, Julie

2018-01-01

Optimal imaging methods are necessary in order to perform a detailed characterization of thick tissue samples from either native or engineered tissues. Tissue-engineered substitutes are featuring increasing complexity including multiple cell types and capillary-like networks. Therefore, technical approaches allowing the visualization of the inner structural organization and cellular composition of tissues are needed. This chapter describes an optical clearing technique which facilitates the detailed characterization of whole-mount samples from skin and adipose tissues (ex vivo tissues and in vitro tissue-engineered substitutes) when combined with spectral confocal microscopy and quantitative analysis on image renderings.

Bioactive polymeric scaffolds for tissue engineering

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Scott Stratton

2016-12-01

Full Text Available A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

The materials used in bone tissue engineering

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Tereshchenko, V. P., E-mail: tervp@ngs.ru; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M. [Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Novosibirsk (Russian Federation)

2015-11-17

Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering

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Aldo R. Boccaccini

2010-07-01

Full Text Available Traditionally, bioactive glasses have been used to fill and restore bone defects. More recently, this category of biomaterials has become an emerging research field for bone tissue engineering applications. Here, we review and discuss current knowledge on porous bone tissue engineering scaffolds on the basis of melt-derived bioactive silicate glass compositions and relevant composite structures. Starting with an excerpt on the history of bioactive glasses, as well as on fundamental requirements for bone tissue engineering scaffolds, a detailed overview on recent developments of bioactive glass and glass-ceramic scaffolds will be given, including a summary of common fabrication methods and a discussion on the microstructural-mechanical properties of scaffolds in relation to human bone (structure-property and structure-function relationship. In addition, ion release effects of bioactive glasses concerning osteogenic and angiogenic responses are addressed. Finally, areas of future research are highlighted in this review.

Cell-laden hydrogels for osteochondral and cartilage tissue engineering.

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Yang, Jingzhou; Zhang, Yu Shrike; Yue, Kan; Khademhosseini, Ali

2017-07-15

Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry. Particularly, advances in the development of cell-laden hydrogels have opened up new possibilities for cell therapy. In this article, we describe the problems encountered in this field and review recent progress in designing cell-hydrogel hybrid constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel type, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation matrices with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing technologies (e.g. molding, bioprinting, and assembly) for fabrication of hydrogel-based osteochondral and cartilage constructs with complex compositions and microarchitectures to mimic their native counterparts. Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered biomaterials that replace the damaged regions and promote tissue regeneration. Cell-laden hydrogel systems have emerged as a promising tissue-engineering

Titanium dioxide (TiO2) nanoparticles filled poly(d,l lactid acid) (PDLLA) matrix composites for bone tissue engineering

NARCIS (Netherlands)

Gerhardt, L.C.; Jell, G.M.R.; Boccaccini, A.R.

2007-01-01

Titanium dioxide (TiO2) nanoparticles were investigated for bone tissue engineering applications with regard to bioactivity and particle cytotoxicity. Composite films on the basis of poly(d,l lactid acid) (PDLLA) filled with 0, 5 and 30 wt% TiO2 nanoparticles were processed by solvent casting.

A chondroitinase-ABC and TGF-β1 treatment regimen for enhancing the mechanical properties of tissue engineered fibrocartilage

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MacBarb, Regina F.; Makris, Eleftherios A.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2012-01-01

The development of functionally equivalent fibrocartilage remains elusive despite efforts to engineer tissues such as the knee menisci, intervertebral disc, and TMJ disc. Attempts to engineer these structures often fail to create tissues with mechanical properties on par with native tissue, resulting in constructs unsuitable for clinical applications. The objective of this study was to engineer a spectrum of biomimetic fibrocartilages representative of the distinct functional properties found in native tissues. Using the self-assembly process, different co-cultures of meniscus cells (MCs) and articular chondrocytes (ACs) were seeded into agarose wells and treated with the catabolic agent chondroitinase-ABC (C-ABC) and the anabolic agent transforming growth factor-β1 (TGF-β1) via a two-factor (cell ratio and bioactive treatment), full factorial study design. Application of both C-ABC and TGF-β1 resulted in a beneficial or positive increase in the collagen content of treated constructs compared to controls. Significant increases in both the collagen density and fiber diameter were also seen with this treatment, increasing these values 32% and 15%, respectively, over control values. Mechanical testing found the combined bioactive treatment to synergistically increase the Young’s modulus and ultimate tensile strength of the engineered fibrocartilages compared to controls, with values reaching the lower spectrum of those found in native tissues. Together, these data demonstrate that C-ABC and TGF-β1 interact to develop a denser collagen matrix better able to withstand tensile loading. This study highlights a way to optimize the tensile properties of engineered fibrocartilage using a biochemical and biophysical agent together to create distinct fibrocartilages with functional properties mimicking those of native tissue. PMID:23041782

The rapid manufacture of uniform composite multicellular-biomaterial micropellets, their assembly into macroscopic organized tissues, and potential applications in cartilage tissue engineering.

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Betul Kul Babur

Full Text Available We and others have published on the rapid manufacture of micropellet tissues, typically formed from 100-500 cells each. The micropellet geometry enhances cellular biological properties, and in many cases the micropellets can subsequently be utilized as building blocks to assemble complex macrotissues. Generally, micropellets are formed from cells alone, however when replicating matrix-rich tissues such as cartilage it would be ideal if matrix or biomaterials supplements could be incorporated directly into the micropellet during the manufacturing process. Herein we describe a method to efficiently incorporate donor cartilage matrix into tissue engineered cartilage micropellets. We lyophilized bovine cartilage matrix, and then shattered it into microscopic pieces having average dimensions < 10 μm diameter; we termed this microscopic donor matrix "cartilage dust (CD". Using a microwell platform, we show that ~0.83 μg CD can be rapidly and efficiently incorporated into single multicellular aggregates formed from 180 bone marrow mesenchymal stem/stromal cells (MSC each. The microwell platform enabled the rapid manufacture of thousands of replica composite micropellets, with each micropellet having a material/CD core and a cellular surface. This micropellet organization enabled the rapid bulking up of the micropellet core matrix content, and left an adhesive cellular outer surface. This morphological organization enabled the ready assembly of the composite micropellets into macroscopic tissues. Generically, this is a versatile method that enables the rapid and uniform integration of biomaterials into multicellular micropellets that can then be used as tissue building blocks. In this study, the addition of CD resulted in an approximate 8-fold volume increase in the micropellets, with the donor matrix functioning to contribute to an increase in total cartilage matrix content. Composite micropellets were readily assembled into macroscopic cartilage

Ozone therapy for t he complex prolapse of lumbar intervertebral disc: a clinical observation

International Nuclear Information System (INIS)

Peng Yong; Wei Mengqi; Wu Juan; Zhou Jianshou; Yang Yong; Zhao Hongliang; Shi Mingguo

2010-01-01

Objective: To evaluate the therapeutic outcome of ozone injection therapy for the treatment of complex prolapse of lumbar intervertebral disc, which is accompanied with spinal stenosis due to hypertrophy of ligamentum flavum, degeneration of intervertebral facet joints, intervertebral hyperosteogeny and degeneration, lumbar muscle strain and negative pressure in intervertebral discs. Methods: Seventy patients with simple intervertebral disc prolapse (simple group) and 70 patients with complex intervertebral disc prolapse (complex group) were selected for the study. The complex intervertebral disc prolapse included negative pressure in intervertebral disc (n=11), recurrence after resection of nucleus polposus of intervertebral disc (n=5), spinal stenosis (n=10), degeneration of intervertebral facet joints and interver-tebral hyperosteogeny (n=30), stenosis of lateral recess (n=4) and lumbar muscle strain (n=10). All patients were treated with ozone injection under the CT guidance. A total of 2-3 ml ozone with the concentration of 40-50 μg / ml was injected into the intervertebral disk and a total of 5-8 ml ozone with the concentration of 30-40 μg / ml was injected into the paraspinal space. Infiltration injection into the pain spots with 20 ml ozone was carried out in patients with lumbar muscle strain. Results: A comparison of the therapeutic outcomes between simple group and complex group was made. Immediate relief from clinical symptoms was obtained in 80% of all treated patients. The effective rate one week after the procedure was 95%, which became 96% at 3-6 months after the treatment. Conclusion: Correct clinical diagnosis, skilled and accurate manipulation during the surgery and reasonable use of ozone injection in the treatment of soft tissue injury, etc. can markedly improve the therapeutic effect for complex lumbar intervertebral disc prolase. (authors)

The composition of engineered cartilage at the time of implantation determines the likelihood of regenerating tissue with a normal collagen architecture.

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Nagel, Thomas; Kelly, Daniel J

2013-04-01

The biomechanical functionality of articular cartilage is derived from both its biochemical composition and the architecture of the collagen network. Failure to replicate this normal Benninghoff architecture in regenerating articular cartilage may in turn predispose the tissue to failure. In this article, the influence of the maturity (or functionality) of a tissue-engineered construct at the time of implantation into a tibial chondral defect on the likelihood of recapitulating a normal Benninghoff architecture was investigated using a computational model featuring a collagen remodeling algorithm. Such a normal tissue architecture was predicted to form in the intact tibial plateau due to the interplay between the depth-dependent extracellular matrix properties, foremost swelling pressures, and external mechanical loading. In the presence of even small empty defects in the articular surface, the collagen architecture in the surrounding cartilage was predicted to deviate significantly from the native state, indicating a possible predisposition for osteoarthritic changes. These negative alterations were alleviated by the implantation of tissue-engineered cartilage, where a mature implant was predicted to result in the formation of a more native-like collagen architecture than immature implants. The results of this study highlight the importance of cartilage graft functionality to maintain and/or re-establish joint function and suggest that engineering a tissue with a native depth-dependent composition may facilitate the establishment of a normal Benninghoff collagen architecture after implantation into load-bearing defects.

Electrospun nanofibrous materials for tissue engineering and drug delivery

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Wenguo Cui, Yue Zhou and Jiang Chang

2010-01-01

Full Text Available The electrospinning technique, which was invented about 100 years ago, has attracted more attention in recent years due to its possible biomedical applications. Electrospun fibers with high surface area to volume ratio and structures mimicking extracellular matrix (ECM have shown great potential in tissue engineering and drug delivery. In order to develop electrospun fibers for these applications, different biocompatible materials have been used to fabricate fibers with different structures and morphologies, such as single fibers with different composition and structures (blending and core-shell composite fibers and fiber assemblies (fiber bundles, membranes and scaffolds. This review summarizes the electrospinning techniques which control the composition and structures of the nanofibrous materials. It also outlines possible applications of these fibrous materials in skin, blood vessels, nervous system and bone tissue engineering, as well as in drug delivery.

The biocompatibility of carbon hydroxyapatite/β-glucan composite for bone tissue engineering studied with Raman and FTIR spectroscopic imaging.

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Sroka-Bartnicka, Anna; Kimber, James A; Borkowski, Leszek; Pawlowska, Marta; Polkowska, Izabela; Kalisz, Grzegorz; Belcarz, Anna; Jozwiak, Krzysztof; Ginalska, Grazyna; Kazarian, Sergei G

2015-10-01

The spectroscopic approaches of FTIR imaging and Raman mapping were applied to the characterisation of a new carbon hydroxyapatite/β-glucan composite developed for bone tissue engineering. The composite is an artificial bone material with an apatite-forming ability for the bone repair process. Rabbit bone samples were tested with an implanted bioactive material for a period of several months. Using spectroscopic and chemometric methods, we were able to determine the presence of amides and phosphates and the distribution of lipid-rich domains in the bone tissue, providing an assessment of the composite's bioactivity. Samples were also imaged in transmission using an infrared microscope combined with a focal plane array detector. CaF2 lenses were also used on the infrared microscope to improve spectral quality by reducing scattering artefacts, improving chemometric analysis. The presence of collagen and lipids at the bone/composite interface confirmed biocompatibility and demonstrate the suitability of FTIR microscopic imaging with lenses in studying these samples. It confirmed that the composite is a very good background for collagen growth and increases collagen maturity with the time of the bone growth process. The results indicate the bioactive and biocompatible properties of this composite and demonstrate how Raman and FTIR spectroscopic imaging have been used as an effective tool for tissue characterisation.

In vitro evaluation of alginate/halloysite nanotube composite scaffolds for tissue engineering

International Nuclear Information System (INIS)

Liu, Mingxian; Dai, Libing; Shi, Huizhe; Xiong, Sheng; Zhou, Changren

2015-01-01

In this study, a series of alginate/halloysite nanotube (HNTs) composite scaffolds were prepared by solution-mixing and freeze-drying method. HNTs are incorporated into alginate to improve both the mechanical and cell-attachment properties of the scaffolds. The interfacial interactions between alginate and HNTs were confirmed by the atomic force microscope (AFM), transmission electron microscope (TEM) and FTIR spectroscopy. The mechanical, morphological, and physico-chemical properties of the composite scaffolds were investigated. The composite scaffolds exhibit significant enhancement in compressive strength and compressive modulus compared with pure alginate scaffold both in dry and wet states. A well-interconnected porous structure with size in the range of 100–200 μm and over 96% porosity is found in the composite scaffolds. X-ray diffraction (XRD) result shows that HNTs are uniformly dispersed and partly oriented in the composite scaffolds. The incorporation of HNTs leads to increase in the scaffold density and decrease in the water swelling ratio of alginate. HNTs improve the stability of alginate scaffolds against enzymatic degradation in PBS solution. Thermogravimetrica analysis (TGA) shows that HNTs can improve the thermal stability of the alginate. The mouse fibroblast cells display better attachment to the alginate/HNT composite than those to the pure alginate, suggesting the good cytocompatibility of the composite scaffolds. Alginate/HNT composite scaffolds exhibit great potential for applications in tissue engineering. - Highlights: • We fabricated HNTs reinforced alginate composite scaffolds for biomedical applications. • The hydrogen bond interactions between HNTs and alginate are confirmed. • HNTs can significantly enhance the mechanical properties of alginate scaffold. • The scaffolds exhibit a highly porous structure with interconnected pores. • HNTs can improve the cell attachment and proliferation on alginate

In vitro evaluation of alginate/halloysite nanotube composite scaffolds for tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Liu, Mingxian [Department of Materials Science and Engineering, Jinan University, Guangzhou 510632 (China); Dai, Libing [Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital Medical College, Jinan University, Guangzhou 510220 (China); Shi, Huizhe; Xiong, Sheng [Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632 (China); Zhou, Changren, E-mail: tcrz9@jnu.edu.cn [Department of Materials Science and Engineering, Jinan University, Guangzhou 510632 (China)

2015-04-01

In this study, a series of alginate/halloysite nanotube (HNTs) composite scaffolds were prepared by solution-mixing and freeze-drying method. HNTs are incorporated into alginate to improve both the mechanical and cell-attachment properties of the scaffolds. The interfacial interactions between alginate and HNTs were confirmed by the atomic force microscope (AFM), transmission electron microscope (TEM) and FTIR spectroscopy. The mechanical, morphological, and physico-chemical properties of the composite scaffolds were investigated. The composite scaffolds exhibit significant enhancement in compressive strength and compressive modulus compared with pure alginate scaffold both in dry and wet states. A well-interconnected porous structure with size in the range of 100–200 μm and over 96% porosity is found in the composite scaffolds. X-ray diffraction (XRD) result shows that HNTs are uniformly dispersed and partly oriented in the composite scaffolds. The incorporation of HNTs leads to increase in the scaffold density and decrease in the water swelling ratio of alginate. HNTs improve the stability of alginate scaffolds against enzymatic degradation in PBS solution. Thermogravimetrica analysis (TGA) shows that HNTs can improve the thermal stability of the alginate. The mouse fibroblast cells display better attachment to the alginate/HNT composite than those to the pure alginate, suggesting the good cytocompatibility of the composite scaffolds. Alginate/HNT composite scaffolds exhibit great potential for applications in tissue engineering. - Highlights: • We fabricated HNTs reinforced alginate composite scaffolds for biomedical applications. • The hydrogen bond interactions between HNTs and alginate are confirmed. • HNTs can significantly enhance the mechanical properties of alginate scaffold. • The scaffolds exhibit a highly porous structure with interconnected pores. • HNTs can improve the cell attachment and proliferation on alginate.

Surface modification of nanofibrous polycaprolactone/gelatin composite scaffold by collagen type I grafting for skin tissue engineering.

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Gautam, Sneh; Chou, Chia-Fu; Dinda, Amit K; Potdar, Pravin D; Mishra, Narayan C

2014-01-01

In the present study, a tri-polymer polycaprolactone (PCL)/gelatin/collagen type I composite nanofibrous scaffold has been fabricated by electrospinning for skin tissue engineering and wound healing applications. Firstly, PCL/gelatin nanofibrous scaffold was fabricated by electrospinning using a low cost solvent mixture [chloroform/methanol for PCL and acetic acid (80% v/v) for gelatin], and then the nanofibrous PCL/gelatin scaffold was modified by collagen type I (0.2-1.5wt.%) grafting. Morphology of the collagen type I-modified PCL/gelatin composite scaffold that was analyzed by field emission scanning electron microscopy (FE-SEM), showed that the fiber diameter was increased and pore size was decreased by increasing the concentration of collagen type I. Fourier transform infrared (FT-IR) spectroscopy and thermogravimetric (TG) analysis indicated the surface modification of PCL/gelatin scaffold by collagen type I immobilization on the surface of the scaffold. MTT assay demonstrated the viability and high proliferation rate of L929 mouse fibroblast cells on the collagen type I-modified composite scaffold. FE-SEM analysis of cell-scaffold construct illustrated the cell adhesion of L929 mouse fibroblasts on the surface of scaffold. Characteristic cell morphology of L929 was also observed on the nanofiber mesh of the collagen type I-modified scaffold. Above results suggest that the collagen type I-modified PCL/gelatin scaffold was successful in maintaining characteristic shape of fibroblasts, besides good cell proliferation. Therefore, the fibroblast seeded PCL/gelatin/collagen type I composite nanofibrous scaffold might be a potential candidate for wound healing and skin tissue engineering applications. © 2013.

[Expression and distribution of xenoantigen alpha-Gal in intervertebral disk of Chinese banna minipig inbred line].

Science.gov (United States)

Shou, Jian-guo; Mi, Jian-hong; Ying, Da-jun

2002-09-01

To investigate the expression and distribution of xenoantigen in intervertebral disk of Chinese banna minipig inbred line, and to study the availability of xenograft transplantation of intervertebral disk. Samples of intervertebral disk were collected from six Banna pigs of 8 to 11-month-old. The fixation, embedment and slice were performed. alpha-Gal specific binding lection (BSI-B4) were used as affinity reagents and affinity-immunohistochemistry assays (SABC methods and DAB stain) were conducted to detect the expression and distribution of xenoantigen (alpha-Gal). alpha-Gal was found in chondrocyte cell and chondrocyte-like cell in intervertebral disk which have the positive yellow-stained particulate aggradation. There was no stain in the matrix, elastic fiber and collagen fiber. The distribution of xenoantigen is locally in the tissue of intervertebral disk and its expression is weak. This suggests that the intervertebral disk of Banna pig may be alternative donor for xenotransplantation.

Articular cartilage: from formation to tissue engineering.

Science.gov (United States)

Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

2016-05-26

Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue.

Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

Science.gov (United States)

Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

2013-10-01

Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review.

Science.gov (United States)

Chaudhari, Atul A; Vig, Komal; Baganizi, Dieudonné Radé; Sahu, Rajnish; Dixit, Saurabh; Dennis, Vida; Singh, Shree Ram; Pillai, Shreekumar R

2016-11-25

Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Degradable polymers for tissue engineering

NARCIS (Netherlands)

van Dijkhuizen-Radersma, Riemke; Moroni, Lorenzo; van Apeldoorn, Aart A.; Zhang, Zheng; Grijpma, Dirk W.; van Blitterswijk, Clemens A.

2008-01-01

This chapter elaborates the degradable polymers for tissue engineering and their required scaffold material in tissue engineering. It recognizes the examples of degradable polymers broadly used in tissue engineering. Tissue engineering is the persuasion of the body to heal itself through the

The Application of Corals in Bone Tissue Engineering

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Iraj Nabipour

2017-05-01

Full Text Available Natural coral exoskeleton and coralline hydroxyapatite have been used as bone replacement graft for repairing of bone defects in animal models and humans since two decades ago. These bone replacement grafts have an osteoconductive, biodegradable and biocompatible features. Currently, three lines of researches in bone tissue engineering are conducting on corals. Corals have been used for construction of bony composites, stem cells attachments, and the growth factors-scaffold-based approaches. This review have paid to the wide range of coral use in clinical experiments as a bone graft substitute and cell-scaffold-based approaches in bone tissue engineering.

The Study on Biocompatibility of Porous nHA/PLGA Composite Scaffolds for Tissue Engineering with Rabbit Chondrocytes In Vitro

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Lei Chen

2013-01-01

Full Text Available Objective. To examine the biocompatibility of a novel nanohydroxyapatite/poly[lactic-co-glycolic acid] (nHA/PLGA composite and evaluate its feasibility as a scaffold for cartilage tissue engineering. Methods. Chondrocytes of fetal rabbit were cultured with nHA/PLGA scaffold in vitro and the cell viability was assessed by MTT assay first. Cells adhering to nHA/PLGA scaffold were then observed by inverted microscope and scanning electron microscope (SEM. The cell cycle profile was analyzed by flow cytometry. Results. The viability of the chondrocytes on the scaffold was not affected by nHA/PLGA comparing with the control group as it was shown by MTT assay. Cells on the surface and in the pores of the scaffold increased in a time-dependent manner. Results obtained from flow cytometry showed that there was no significant difference in cell cycle profiles between the coculture group and control (P>0.05. Conclusion. The porous nHA/PLGA composite scaffold is a biocompatible and good kind of scaffold for cartilage tissue engineering.

Electrospun Nanofibrous Materials for Neural Tissue Engineering

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Yee-Shuan Lee

2011-02-01

Full Text Available The use of biomaterials processed by the electrospinning technique has gained considerable interest for neural tissue engineering applications. The tissue engineering strategy is to facilitate the regrowth of nerves by combining an appropriate cell type with the electrospun scaffold. Electrospinning can generate fibrous meshes having fiber diameter dimensions at the nanoscale and these fibers can be nonwoven or oriented to facilitate neurite extension via contact guidance. This article reviews studies evaluating the effect of the scaffold’s architectural features such as fiber diameter and orientation on neural cell function and neurite extension. Electrospun meshes made of natural polymers, proteins and compositions having electrical activity in order to enhance neural cell function are also discussed.

Intervertebral disc (IVD): Structure, degeneration, repair and regeneration

Energy Technology Data Exchange (ETDEWEB)

Whatley, Benjamin R.; Wen Xuejun, E-mail: xjwen@clemson.edu

2012-02-01

Low back pain affects a large portion of the population, resulting in high care costs for therapy and treatment. One primary cause of low back pain is the degeneration of the intervertebral disc (IVD) resulting in the compression of the spinal nerves and adjacent vertebrae. Exact causes of degeneration are unknown, but it is thought that natural aging, and both biological and genetic factors may play a significant role in the degenerative process. Conventional methods to alleviate low back pain include spinal fusion and artificial disc replacement. Traditional treatments through spinal fusion may eliminate pain yet do not restore disc function and lead to further degeneration of adjacent levels by altering disc biomechanics and natural kinematics. Recently, artificial IVD replacements have started to gain interest, with two IVD implants currently approved in the United States. Although these implants facilitate the preservation of motions and disc space height, they are unable to sustain compressive forces due to their lack of elasticity. In addition, the implants may produce wear debris that can cause osteolysis and other deleterious effects. As an alternative to these conventional approaches, tissue engineered IVD constructs offer the advantage of biointegration while preserving the essential attributes of natural motion and disc space restoration. There is a great need for the development of tissue engineered scaffolds that simulate the natural 3D morphology and microenvironment of the targeted tissue. Scaffolds should facilitate biological transport to satisfy nutrition and waste removal requirements within the IVD. The discrete tissue architectures of the nucleus pulposus (NP) and annulus fibrosus (AF) have posed great challenges to IVD tissue engineering. Current attempts have not been able to satisfy the biological functions and/or mechanical properties of native tissue. Therefore, these current scaffolds are far from satisfactory. This review highlights the

Engineering Musculoskeletal Tissue Interfaces

Directory of Open Access Journals (Sweden)

Ece Bayrak

2018-04-01

Full Text Available Tissue engineering aims to bring together biomaterials, cells, and signaling molecules within properly designed microenvironments in order to create viable treatment options for the lost or malfunctioning tissues. Design and production of scaffolds and cell-laden grafts that mimic the complex structural and functional features of tissues are among the most important elements of tissue engineering strategy. Although all tissues have their own complex structure, an even more complex case in terms of engineering a proper carrier material is encountered at the tissue interfaces, where two distinct tissues come together. The interfaces in the body can be examined in four categories; cartilage-bone and ligament-bone interfaces at the knee and the spine, tendon-bone interfaces at the shoulder and the feet, and muscle-tendon interface at the skeletal system. These interfaces are seen mainly at the soft-to-hard tissue transitions and they are especially susceptible to injury and tear due to the biomechanical inconsistency between these tissues where high strain fields are present. Therefore, engineering the musculoskeletal tissue interfaces remain a challenge. This review focuses on recent advancements in strategies for musculoskeletal interface engineering using different biomaterial-based platforms and surface modification techniques.

Tissue engineering in dentistry.

Science.gov (United States)

Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Salih, Vehid M; Kim, Hae-Won; Knowles, Jonathan C

2014-08-01

of this review is to inform practitioners with the most updated information on tissue engineering and its potential applications in dentistry. The authors used "PUBMED" to find relevant literature written in English and published from the beginning of tissue engineering until today. A combination of keywords was used as the search terms e.g., "tissue engineering", "approaches", "strategies" "dentistry", "dental stem cells", "dentino-pulp complex", "guided tissue regeneration", "whole tooth", "TMJ", "condyle", "salivary glands", and "oral mucosa". Abstracts and full text articles were used to identify causes of craniofacial tissue loss, different approaches for craniofacial reconstructions, how the tissue engineering emerges, different strategies of tissue engineering, biomaterials employed for this purpose, the major attempts to engineer different dental structures, finally challenges and future of tissue engineering in dentistry. Only those articles that dealt with the tissue engineering in dentistry were selected. There have been a recent surge in guided tissue engineering methods to manage periodontal diseases beyond the traditional approaches. However, the predictable reconstruction of the innate organisation and function of whole teeth as well as their periodontal structures remains challenging. Despite some limited progress and minor successes, there remain distinct and important challenges in the development of reproducible and clinically safe approaches for oral tissue repair and regeneration. Clearly, there is a convincing body of evidence which confirms the need for this type of treatment, and public health data worldwide indicates a more than adequate patient resource. The future of these therapies involving more biological approaches and the use of dental tissue stem cells is promising and advancing. Also there may be a significant interest of their application and wider potential to treat disorders beyond the craniofacial region. Considering the

Cell and Tissue Engineering

CERN Document Server

2012-01-01

“Cell and Tissue Engineering” introduces the principles and new approaches in cell and tissue engineering. It includes both the fundamentals and the current trends in cell and tissue engineering, in a way useful both to a novice and an expert in the field. The book is composed of 13 chapters all of which are written by the leading experts. It is organized to gradually assemble an insight in cell and tissue function starting form a molecular nano-level, extending to a cellular micro-level and finishing at the tissue macro-level. In specific, biological, physiological, biophysical, biochemical, medical, and engineering aspects are covered from the standpoint of the development of functional substitutes of biological tissues for potential clinical use. Topics in the area of cell engineering include cell membrane biophysics, structure and function of the cytoskeleton, cell-extracellular matrix interactions, and mechanotransduction. In the area of tissue engineering the focus is on the in vitro cultivation of ...

In Vitro Degradation of PHBV Scaffolds and nHA/PHBV Composite Scaffolds Containing Hydroxyapatite Nanoparticles for Bone Tissue Engineering

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Naznin Sultana

2012-01-01

Full Text Available This paper investigated the long-term in vitro degradation properties of scaffolds based on biodegradable polymers and osteoconductive bioceramic/polymer composite materials for the application of bone tissue engineering. The three-dimensional porous scaffolds were fabricated using emulsion-freezing/freeze-drying technique using poly(hydroxybutyrate-co-hydroxyvalerate (PHBV which is a natural biodegradable and biocompatible polymer. Nanosized hydroxyapatite (nHA particles were successfully incorporated into the PHBV scaffolds to render the scaffolds osteoconductive. The PHBV and nHA/PHBV scaffolds were systematically evaluated using various techniques in terms of mechanical strength, porosity, porous morphology, and in vitro degradation. PHBV and nHA/PHBV scaffolds degraded over time in phosphate-buffered saline at 37°C. PHBV polymer scaffolds exhibited slow molecular weight loss and weight loss in the in vitro physiological environment. Accelerated weight loss was observed in nHA incorporated PHBV composite scaffolds. An increasing trend of crystallinity was observed during the initial period of degradation time. The compressive properties decreased more than 40% after 5-month in vitro degradation. Together with interconnected pores, high porosity, suitable mechanical properties, and slow degradation profile obtained from long-term degradation studies, the PHBV scaffolds and osteoconductive nHA/PHBV composite scaffolds showed promises for bone tissue engineering application.

A chondroitinase-ABC and TGF-β1 treatment regimen for enhancing the mechanical properties of tissue-engineered fibrocartilage.

Science.gov (United States)

MacBarb, Regina F; Makris, Eleftherios A; Hu, Jerry C; Athanasiou, Kyriacos A

2013-01-01

The development of functionally equivalent fibrocartilage remains elusive despite efforts to engineer tissues such as knee meniscus, intervertebral disc and temporomandibular joint disc. Attempts to engineer these structures often fail to create tissues with mechanical properties on a par with native tissue, resulting in constructs unsuitable for clinical applications. The objective of this study was to engineer a spectrum of biomimetic fibrocartilages representative of the distinct functional properties found in native tissues. Using the self-assembly process, different co-cultures of meniscus cells and articular chondrocytes were seeded into agarose wells and treated with the catabolic agent chondroitinase-ABC (C-ABC) and the anabolic agent transforming growth factor-β1 (TGF-β1) via a two-factor (cell ratio and bioactive treatment), full factorial study design. Application of both C-ABC and TGF-β1 resulted in a beneficial or positive increase in the collagen content of treated constructs compared to controls. Significant increases in both the collagen density and fiber diameter were also seen with this treatment, increasing these values by 32 and 15%, respectively, over control values. Mechanical testing found the combined bioactive treatment to synergistically increase the Young's modulus and ultimate tensile strength of the engineered fibrocartilages compared to controls, with values reaching the lower spectrum of those found in native tissues. Together, these data demonstrate that C-ABC and TGF-β1 interact to develop a denser collagen matrix better able to withstand tensile loading. This study highlights a way to optimize the tensile properties of engineered fibrocartilage using a biochemical and a biophysical agent together to create distinct fibrocartilages with functional properties mimicking those of native tissue. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Novel scalable silicone elastomer and poly(2-hydroxyethyl methacrylate) (PHEMA) composite materials for tissue engineering and drug delivery applications

DEFF Research Database (Denmark)

Mohanty, Soumyaranjan; Hemmingsen, Mette; Wojcik, Magdalena

2013-01-01

material with increased hydrophilicity in regard to virgin silicone elastomer, making it suitable as a scaffold for tissue engineering and with the concomitant possibility for delivering drug from the scaffold to the tissue. Interpenetrating polymer networks (IPNs) of silicone elastomer and PHEMA......In recent years hydrogels have received increasing attention as potential materials for applications in regenerative medicine. They can be used for scaffold materials providing structural integrity to tissue constructs, for controlled delivery of drugs and proteins to cell and tissues......, and for support materials in tissue growth. However, the real challenge is to obtain sufficiently good mechanical properties of the hydrogel. The present study shows the combination of two normally non-compatible materials, silicone elastomer and poly(2-hydroxyethyl methacrylate) (PHEMA), into a novel composite...

Fabrication and characterization of PCL/gelatin composite nanofibrous scaffold for tissue engineering applications by electrospinning method

International Nuclear Information System (INIS)

Gautam, Sneh; Dinda, Amit Kumar; Mishra, Narayan Chandra

2013-01-01

In the present study, composite nanofibrous tissue engineering-scaffold consisting of polycaprolactone and gelatin, was fabricated by electrospinning method, using a new cost-effective solvent mixture: chloroform/methanol for polycaprolactone (PCL) and acetic acid for gelatin. The morphology of the nanofibrous scaffold was investigated by using field emission scanning electron microscopy (FE-SEM) which clearly indicates that the morphology of nanofibers was influenced by the weight ratio of PCL to gelatin in the solution. Uniform fibers were produced only when the weight ratio of PCL/gelatin is sufficiently high (10:1). The scaffold was further characterized by Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric (TG) analysis, and X-ray diffraction (XRD). FT-IR and TG analysis indicated some interactions between PCL and gelatin molecules within the scaffold, while XRD results demonstrated crystalline nature of PCL/gelatin composite scaffold. Cytotoxicity effect of scaffold on L929 mouse fibroblast cells was evaluated by MTT assay and cell proliferation on the scaffold was confirmed by DNA quantification. Positive results of MTT assay and DNA quantification L929 mouse fibroblast cells indicated that the scaffold made from the combination of natural polymer (gelatin) and synthetic polymer (PCL) may serve as a good candidate for tissue engineering applications. - Highlights: ► PCL/Gelatin scaffold was successfully fabricated by electrospinning method. ► PCL in CHCl 3 /CH 3 OH and gelatin in acetic acid: a novel polymer-solvent system. ► The morphology of nanofibers was influenced by the weight ratio of PCL/gelatin. ► Chemical interactions between PCL and gelatin molecules enhanced cell growth. ► Cell culture studies indicate the suitability of scaffold for tissue regeneration

Recent Advances in Biomaterials for 3D Printing and Tissue Engineering.

Science.gov (United States)

Jammalamadaka, Udayabhanu; Tappa, Karthik

2018-03-01

Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering. The applications of 3D printing in the field of regenerative medicine and tissue engineering are limited by the variety of biomaterials that can be used in this technology. Many researchers have developed novel biomaterials and compositions to enable their use in 3D printing methods. The advantages of fabricating scaffolds using 3D printing are numerous, including the ability to create complex geometries, porosities, co-culture of multiple cells, and incorporate growth factors. In this review, recently-developed biomaterials for different tissues are discussed. Biomaterials used in 3D printing are categorized into ceramics, polymers, and composites. Due to the nature of 3D printing methods, most of the ceramics are combined with polymers to enhance their printability. Polymer-based biomaterials are 3D printed mostly using extrusion-based printing and have a broader range of applications in regenerative medicine. The goal of tissue engineering is to fabricate functional and viable organs and, to achieve this, multiple biomaterials and fabrication methods need to be researched.

Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs

OpenAIRE

Choi, Kyung-Suk; Harfe, Brian D.

2011-01-01

The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Remo...

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).

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review

Directory of Open Access Journals (Sweden)

Atul A. Chaudhari

2016-11-01

Full Text Available Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL, and poly-ethylene-glycol (PEG, etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Chondroprotective supplementation promotes the mechanical properties of injectable scaffold for human nucleus pulposus tissue engineering.

Science.gov (United States)

Foss, Berit L; Maxwell, Thomas W; Deng, Ying

2014-01-01

A result of intervertebral disc (IVD) degeneration, the nucleus pulposus (NP) is no longer able to withstand applied load leading to pain and disability. The objective of this study is to fabricate a tissue-engineered injectable scaffold with chondroprotective supplementation in vitro to improve the mechanical properties of a degenerative NP. Tissue-engineered scaffolds were fabricated using different concentrations of alginate and calcium chloride and mechanically evaluated. Fabrication conditions were based on structural and mechanical resemblance to the native NP. Chondroprotective supplementation, glucosamine (GCSN) and chondroitin sulfate (CS), were added to scaffolds at concentrations of 0:0µg/mL (0:0-S), 125:100µg/mL (125:100-S), 250:200µg/mL (250:200-S), and 500:400µg/mL (500:400-S), GCSN and CS, respectively. Scaffolds were used to fabricate tissue-engineered constructs through encapsulation of human nucleus pulposus cells (HNPCs). The tissue-engineered constructs were collected at days 1, 14, and 28 for biochemical and biomechanical evaluations. Confocal microscopy showed HNPC viability and rounded morphology over the 28 day period. MTT analysis resulted in significant increases in cell proliferation for each group. Collagen type II ELISA quantification and compressive aggregate moduli (HA) showed increasing trends for both 250:200-S and the 500:400-S groups on Day 28 with significantly greater HA compared to 0:0-S group. Glycosaminoglycan and water content decreased for all groups. Results indicate the increased mechanical properties of the 250:200-S and the 500:400-S was due to production of a functional matrix. This study demonstrated potential for a chondroprotective supplemented injectable scaffold to restore biomechanical function of a degenerative disc through the production of a mechanically functional matrix. Copyright © 2013 Elsevier Ltd. All rights reserved.

A novel squid pen chitosan/hydroxyapatite/β-tricalcium phosphate composite for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Shavandi, Amin, E-mail: amin.shavandi@postgrad.otago.ac.nz [Department of Food Sciences, University of Otago, Dunedin (New Zealand); Department of Applied Sciences, University of Otago, Dunedin (New Zealand); Bekhit, Alaa El-Din A. [Department of Food Sciences, University of Otago, Dunedin (New Zealand); Sun, Zhifa; Ali, Azam [Department of Physics, University of Otago, Dunedin (New Zealand); Gould, Maree [Department of Anatomy, University of Otago, Dunedin (New Zealand)

2015-10-01

Squid pen chitosan was used in the fabrication of biocomposite scaffolds for bone tissue engineering. Hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) obtained from waste mussel shells were used as the calcium phosphate source. The composite was prepared using 2.5% tripolyphosphate (TPP) and 1% glycerol as a cross-linker and plasticizer, respectively. The weight percent (wt.%) ratios of the ceramic components in the composite were 20/10/70, 30/20/50 and 40/30/30 (HA/β-TCP/Chi). The biodegradation rate and structural properties of the scaffolds were investigated. Scanning electron microscopy (SEM) and microCT(μCT) results indicated that the composites have a well defined lamellar structure with an average pore size of 200 μm. The porosity of the composites decreased from 88 to 56% by increasing the ratio of HA/β-TCP from 30 to 70%. After 28 days of incubation in a physiological solution, the scaffolds were degraded by approximately 30%. In vitro investigations showed that the composites were cytocompatible and supported the growth of L929 and Saos-2 cells. The obtained data suggests that the squid pen chitosan composites are potential candidates for bone regeneration. - Highlights: • Biocomposite scaffolds were made from mussel shells HA and β-TCP, and squid pin chitosan. • The porosity of the composites decreased with an increase in HA/β-TCP ratio. • Composites were cytocompatible and supported the growth of L929 and Saos-2 cells. • Composite containing 50% HA and β-TCP had the best mechanical properties.

Bio-based polyurethane for tissue engineering applications: How hydroxyapatite nanoparticles influence the structure, thermal and biological behavior of polyurethane composites.

Science.gov (United States)

Gabriel, Laís P; Santos, Maria Elizabeth M Dos; Jardini, André L; Bastos, Gilmara N T; Dias, Carmen G B T; Webster, Thomas J; Maciel Filho, Rubens

2017-01-01

In this work, thermoset polyurethane composites were prepared by the addition of hydroxyapatite nanoparticles using the reactants polyol polyether and an aliphatic diisocyanate. The polyol employed in this study was extracted from the Euterpe oleracea Mart. seeds from the Amazon Region of Brazil. The influence of hydroxyapatite nanoparticles on the structure and morphology of the composites was studied using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), the structure was evaluated by Fourier transform infrared spectroscopy (FT-IR), thermal properties were analyzed by thermogravimetry analysis (TGA), and biological properties were studied by in vitro and in vivo studies. It was found that the addition of HA nanoparticles promoted fibroblast adhesion while in vivo investigations with histology confirmed that the composites promoted connective tissue adherence and did not induce inflammation. In this manner, this study supports the further investigation of bio-based, polyurethane/hydroxyapatite composites as biocompatible scaffolds for numerous tissue engineering applications. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Imaging Agents Specific for the Annulus Fibrosus of the Intervertebral Disk

Directory of Open Access Journals (Sweden)

Summer L. Gibbs-Strauss

2010-05-01

Full Text Available Low back pain is a prevalent medical condition that is difficult to diagnose and treat. Current imaging methods are unable to correlate pain reliably with spinal structures, and surgical removal of painful damaged or degenerating disks is technically challenging. A contrast agent specific for the intervertebral disk could assist in the detection, diagnosis, and surgical treatment of low back pain. The styryl pyridinium (FM fluorophores were characterized and structure-activity relationships between chemical structure and in vivo uptake were established. Two novel FM fluorophores with improved optical properties for imaging the intervertebral disks were synthesized and evaluated in mice, rats, and pigs. After a single systemic injection, eight of eight FM fluorophores provided high-contrast imaging of the trigeminal ganglia, whereas six of eight provided high-contrast imaging of the dorsal root ganglia. Unexpectedly, three of eight FM fluorophores provided high-contrast imaging of annulus fibrosus tissue of the intervertebral disks, confirmed histologically. We present the first known contrast agent specific for the intervertebral disks and identify the chemical structural motif that mediates uptake. FM fluorophores could be used for image-guided surgery to assist in the removal of intervertebral disk and lay the foundation for derivatives for magnetic resonance imaging and positron emission tomography.

Composite scaffolds for cartilage tissue engineering based on natural polymers of bacterial origin, thermoplastic poly(3-hydroxybutyrate) and micro-fibrillated bacterial cellulose

Czech Academy of Sciences Publication Activity Database

Akaraonye, E.; Filip, J.; Šafaříková, Miroslava; Salih, V.; Keshavarz, T.; Knowles, J.C.; Roy, I.

2016-01-01

Roč. 65, č. 7 (2016), s. 780-791 ISSN 0959-8103 Institutional support: RVO:60077344 Keywords : polyhydroxyalkanoates * poly(3-hydroxybutyrate) * bacterial cellulose * micro-fibrillated cellulose * tissue engineering scaffold * composite materials Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.070, year: 2016

Developing bioactive composite scaffolds for bone tissue engineering

Science.gov (United States)

Chen, Yun

bone-like apatite/collagen composite coating. Saos-2 osteoblast-like cells were used to evaluate the cellular behaviors on these biomimetic coatings. Cell morphologies on the surfaces of PLLA films and scaffolds, PLLA films and scaffolds with apatite coating, and PLLA films and scaffolds with apatite/collagen composite coating were studied by SEM. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasodium bromide (MTT) assay. In addition, differentiated cell function was assessed by measuring alkaline phosphatase activity. These results suggested that the apatite coating and apatite/collagen composite coating fabricated through the accelerated biomimetic processes could improve the interactions between osteoblasts and PLLA. The composite coating was more effective than apatite coating in improving such interactions. PLLA scaffolds coated with submicron collagen fibrils and submicron apatite paticulates are expected to be one of the promising 3D substrates for bone tissue engineering. To facilitate coating into scaffolds, the flowing condition was introduced into the accelerated biomimetic process. The apatite formed in the different sites in the scaffold was characterized using SEM. It was found that the accelerated biomimetic process performed in the flowing condition yielded more uniform spatial distribution of apatite particles than that in the regular shaking condition. This work provides a novel condition for obtaining uniform spatial distribution of bone-like apatite within the scaffolds in a timely manner, which is expected to facilitate uniform distribution of attached cells within the scaffoldsin vitro and in vivo.

Do cell based tissue engineering products for meniscus regeneration influence vascularization?

Science.gov (United States)

Koch, Matthias; Ehrenreich, Tobias; Koehl, Gudrun; Pattappa, Girish; Pfeifer, Christian; Loibl, Markus; Müller, Michael; Nerlich, Michael; Angele, Peter; Zellner, Johannes

2017-01-01

Meniscus regeneration is observed within the peripheral, vascularized zone but decreases in the inner two thirds alongside the vascularization. Within this avascular area, cell-based tissue-engineering-approaches appear to be a promising strategy for the treatment of meniscal defects. Evaluation of the angiogenic potential of cell-based tissue-engineering-products for meniscus healing. Evaluation of angiogenesis induced by rabbit meniscus-pellets, meniscus-cells (MC) or mesenchymal stem-cells (MSC) in cell-based tissue-engineering-products within a rabbit meniscus-ring was performed using a transparent dorsal skin fold chamber in nude mice. Observations were undertaken during a 14 days period. Cell preconditioning differed between experimental groups. Immunohistochemical analysis of the regenerated tissue in the meniscus-ring induced by cell loaded composite scaffolds for differentiation and anti-angiogenic factors were performed. Meniscus-pellets and MSC-/MC-based tissue-engineering-products induced angiogenesis. An accelerated vascularization was detected in the group of meniscus-pellets derived from the vascularized zone compared to avascular meniscus-pellets. In terms of cell-based tissue-engineering-products, chondrogenic preconditioning resulted in significantly increased vessel growth. MSC-constructs showed an accelerated angiogenesis. Immunohistochemical evaluation showed a progressive differentiation and lower content for anti-angiogenic endostatin in the precultured group. Preconditioning of MC-/MSC-based tissue-engineering-products is a promising tool to influence the angiogenic potential of tissue-engineering-products and to adapt these properties according to the aimed tissue qualities.

Ag-loaded MgSrFe-layered double hydroxide/chitosan composite scaffold with enhanced osteogenic and antibacterial property for bone engineering tissue.

Science.gov (United States)

Cao, Dandan; Xu, Zhengliang; Chen, Yixuan; Ke, Qinfei; Zhang, Changqing; Guo, Yaping

2018-02-01

Bone tissue engineering scaffolds for the reconstruction of large bone defects should simultaneously promote osteogenic differentiation and avoid postoperative infection. Herein, we develop, for the first time, Ag-loaded MgSrFe-layered double hydroxide/chitosan (Ag-MgSrFe/CS) composite scaffold. This scaffold exhibits three-dimensional interconnected macroporous structure with a pore size of 100-300 μm. The layered double hydroxide nanoplates in the Ag-MgSrFe/CS show lateral sizes of 200-400 nm and thicknesses of ∼50 nm, and the Ag nanoparticles with particle sizes of ∼20 nm are uniformly dispersed on the scaffold surfaces. Human bone marrow-derived mesenchymal stem cells (hBMSCs) present good adhesion, spreading, and proliferation on the Ag-MgSrFe/CS composite scaffold, suggesting that the Ag and Sr elements in the composite scaffold have no toxicity to hBMSCs. When compared with MgFe/CS composite scaffold, the Ag-MgSrFe/CS composite scaffold has better osteogenic property. The released Sr 2+ ions from the composite scaffold enhance the alkaline phosphatase activity of hBMSCs, promote the extracellular matrix mineralization, and increase the expression levels of osteogenic-related RUNX2 and BMP-2. Moreover, the Ag-MgSrFe/CS composite scaffold possesses good antibacterial property because the Ag nanoparticles in the composite scaffold effectively prevent biofilm formation against S. aureus. Hence, the Ag-MgSrFe/CS composite scaffold with excellent osteoinductivity and antibacterial property has a great potential for bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 863-873, 2018. © 2017 Wiley Periodicals, Inc.

Recent Advances in Biomaterials for 3D Printing and Tissue Engineering

Directory of Open Access Journals (Sweden)

Udayabhanu Jammalamadaka

2018-03-01

Full Text Available Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering. The applications of 3D printing in the field of regenerative medicine and tissue engineering are limited by the variety of biomaterials that can be used in this technology. Many researchers have developed novel biomaterials and compositions to enable their use in 3D printing methods. The advantages of fabricating scaffolds using 3D printing are numerous, including the ability to create complex geometries, porosities, co-culture of multiple cells, and incorporate growth factors. In this review, recently-developed biomaterials for different tissues are discussed. Biomaterials used in 3D printing are categorized into ceramics, polymers, and composites. Due to the nature of 3D printing methods, most of the ceramics are combined with polymers to enhance their printability. Polymer-based biomaterials are 3D printed mostly using extrusion-based printing and have a broader range of applications in regenerative medicine. The goal of tissue engineering is to fabricate functional and viable organs and, to achieve this, multiple biomaterials and fabrication methods need to be researched.

Biomimetic nanoclay scaffolds for bone tissue engineering

Science.gov (United States)

Ambre, Avinash Harishchandra

Tissue engineering offers a significant potential alternative to conventional methods for rectifying tissue defects by evoking natural regeneration process via interactions between cells and 3D porous scaffolds. Imparting adequate mechanical properties to biodegradable scaffolds for bone tissue engineering is an important challenge and extends from molecular to macroscale. This work focuses on the use of sodium montmorillonite (Na-MMT) to design polymer composite scaffolds having enhanced mechanical properties along with multiple interdependent properties. Materials design beginning at the molecular level was used in which Na-MMT clay was modified with three different unnatural amino acids and further characterized using Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD). Based on improved bicompatibility with human osteoblasts (bone cells) and intermediate increase in d-spacing of MMT clay (shown by XRD), 5-aminovaleric acid modified clay was further used to prepare biopolymer (chitosan-polygalacturonic acid complex) scaffolds. Osteoblast proliferation in biopolymer scaffolds containing 5-aminovaleric acid modified clay was similar to biopolymer scaffolds containing hydroxyapatite (HAP). A novel process based on biomineralization in bone was designed to prepare 5-aminovaleric acid modified clay capable of imparting multiple properties to the scaffolds. Bone-like apatite was mineralized in modified clay and a novel nanoclay-HAP hybrid (in situ HAPclay) was obtained. FTIR spectroscopy indicated a molecular level organic-inorganic association between the intercalated 5-aminovaleric acid and mineralized HAP. Osteoblasts formed clusters on biopolymer composite films prepared with different weight percent compositions of in situ HAPclay. Human MSCs formed mineralized nodules on composite films and mineralized extracellular matrix (ECM) in composite scaffolds without the use of osteogenic supplements. Polycaprolactone (PCL), a synthetic polymer, was

Computational Modeling in Tissue Engineering

CERN Document Server

2013-01-01

One of the major challenges in tissue engineering is the translation of biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of tissue engineering. This volume discusses computational modeling tools that allow studying the biological complexity in a more quantitative way. More specifically, computational tools can help in:  (i) quantifying and optimizing the tissue engineering product, e.g. by adapting scaffold design to optimize micro-environmental signals or by adapting selection criteria to improve homogeneity of the selected cell population; (ii) quantifying and optimizing the tissue engineering process, e.g. by adapting bioreactor design to improve quality and quantity of the final product; and (iii) assessing the influence of the in vivo environment on the behavior of the tissue engineering product, e.g. by investigating vascular ingrowth. The book presents examples of each...

Recent Advances in Biomaterials for 3D Printing and Tissue Engineering

OpenAIRE

Udayabhanu Jammalamadaka; Karthik Tappa

2018-01-01

Three-dimensional printing has significant potential as a fabrication method in creating scaffolds for tissue engineering. The applications of 3D printing in the field of regenerative medicine and tissue engineering are limited by the variety of biomaterials that can be used in this technology. Many researchers have developed novel biomaterials and compositions to enable their use in 3D printing methods. The advantages of fabricating scaffolds using 3D printing are numerous, including the abi...

Fabrication and in vitro evaluation of a sponge-like bioactive-glass/gelatin composite scaffold for bone tissue engineering

International Nuclear Information System (INIS)

Nadeem, Danish; Kiamehr, Mostafa; Yang, Xuebin; Su, Bo

2013-01-01

In this work a bioactive composite scaffold, comprised of bioactive-glass and gelatin, is introduced. Through direct foaming a sponge-like composite of a sol–gel derived bioactive-glass (70S30C; 70% SiO 2 , 30% CaO) and porcine gelatin was developed for use as a biodegradable scaffold for bone tissue engineering. The composite was developed to provide a suitable alternative to synthetic polymer based scaffolds, allowing directed regeneration of bone tissue. The fabricated scaffold was characterised through X-ray microtomography, scanning electron and light microscopy demonstrating a three dimensionally porous and interconnected structure, with an average pore size (170 μm) suitable for successful cell proliferation and tissue ingrowth. Acellular bioactivity was assessed through apatite formation during submersion in simulated body fluid (SBF) whereby the rate and onset of apatite nucleation was found to be comparable to that of bioactive-glass. Modification of dehydrothermal treatment parameters induced varying degrees of crosslinking, allowing the degradation of the composite to be tailored to suit specific applications and establishing its potential for a wide range of applications. Use of genipin to supplement crosslinking by dehydrothermal treatment provided further means of modifying degradability. Biocompatibility of the composite was qualified through successful cultures of human dental pulp stem cells (HDPSCs) on samples of the composite scaffold. Osteogenic differentiation of HDPSCs and extracellular matrix deposition were confirmed through positive alkaline phosphatase staining and immunohistochemistry. - Highlights: ► Optimised composition and fabrication produced sponge-like porosity (pore size ∼ 170 μm). ► Maximum aqueous stability via dehydrothermal treatment at 145 °C, for 48 h ► Biocompatibility and osteogenic potential confirmed via successful HDPSC cultures. ► Minimal toxicity exhibited in optimally crosslinked samples (10 m

Fabrication and in vitro evaluation of a sponge-like bioactive-glass/gelatin composite scaffold for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Nadeem, Danish [Biomaterials Engineering Group, School of Oral and Dental Sciences, University of Bristol, BS1 2LY (United Kingdom); Kiamehr, Mostafa [Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, LS2 9LU (United Kingdom); Yang, Xuebin [Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, LS2 9LU (United Kingdom); NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds LS7 4SA (United Kingdom); Su, Bo, E-mail: b.su@bristol.ac.uk [Biomaterials Engineering Group, School of Oral and Dental Sciences, University of Bristol, BS1 2LY (United Kingdom)

2013-07-01

In this work a bioactive composite scaffold, comprised of bioactive-glass and gelatin, is introduced. Through direct foaming a sponge-like composite of a sol–gel derived bioactive-glass (70S30C; 70% SiO{sub 2}, 30% CaO) and porcine gelatin was developed for use as a biodegradable scaffold for bone tissue engineering. The composite was developed to provide a suitable alternative to synthetic polymer based scaffolds, allowing directed regeneration of bone tissue. The fabricated scaffold was characterised through X-ray microtomography, scanning electron and light microscopy demonstrating a three dimensionally porous and interconnected structure, with an average pore size (170 μm) suitable for successful cell proliferation and tissue ingrowth. Acellular bioactivity was assessed through apatite formation during submersion in simulated body fluid (SBF) whereby the rate and onset of apatite nucleation was found to be comparable to that of bioactive-glass. Modification of dehydrothermal treatment parameters induced varying degrees of crosslinking, allowing the degradation of the composite to be tailored to suit specific applications and establishing its potential for a wide range of applications. Use of genipin to supplement crosslinking by dehydrothermal treatment provided further means of modifying degradability. Biocompatibility of the composite was qualified through successful cultures of human dental pulp stem cells (HDPSCs) on samples of the composite scaffold. Osteogenic differentiation of HDPSCs and extracellular matrix deposition were confirmed through positive alkaline phosphatase staining and immunohistochemistry. - Highlights: ► Optimised composition and fabrication produced sponge-like porosity (pore size ∼ 170 μm). ► Maximum aqueous stability via dehydrothermal treatment at 145 °C, for 48 h ► Biocompatibility and osteogenic potential confirmed via successful HDPSC cultures. ► Minimal toxicity exhibited in optimally crosslinked samples (10 m

Introduction to tissue engineering and application for cartilage engineering.

Science.gov (United States)

de Isla, N; Huseltein, C; Jessel, N; Pinzano, A; Decot, V; Magdalou, J; Bensoussan, D; Stoltz, J-F

2010-01-01

Tissue engineering is a multidisciplinary field that applies the principles of engineering, life sciences, cell and molecular biology toward the development of biological substitutes that restore, maintain, and improve tissue function. In Western Countries, tissues or cells management for clinical uses is a medical activity governed by different laws. Three general components are involved in tissue engineering: (1) reparative cells that can form a functional matrix; (2) an appropriate scaffold for transplantation and support; and (3) bioreactive molecules, such as cytokines and growth factors that will support and choreograph formation of the desired tissue. These three components may be used individually or in combination to regenerate organs or tissues. Thus the growing development of tissue engineering needs to solve four main problems: cells, engineering development, grafting and safety studies.

The combination of meltblown and electrospinning for bone tissue engineering

Czech Academy of Sciences Publication Activity Database

Erben, J.; Pilařová, K.; Sanetrník, F.; Chvojka, J.; Jenčová, V.; Blažková, L.; Havlíček, J.; Novák, O.; Mikeš, P.; Prosecká, Eva; Lukáš, D.; Kuželová Kostaková, E.

2015-01-01

Roč. 143, mar 15 (2015), s. 172-176 ISSN 0167-577X Institutional support: RVO:68378041 Keywords : meltblown * electrospinning * tissue engineering * polycaprolactone Subject RIV: JI - Composite Materials Impact factor: 2.437, year: 2015

Co-culture of Adult Mesenchymal Stem Cells and Nucleus Pulposus Cells in Bilaminar Pellets for Intervertebral Disc Regeneration.

Science.gov (United States)

Allon, Aliza A; Schneider, Richard A; Lotz, Jeffrey C

2009-01-01

Our goal is to optimize stem cell-based tissue engineering strategies in the context of the intervertebral disc environment. We explored the benefits of co-culturing nucleus pulposus cells (NPC) and adult mesenchymal stem cells (MSC) using a novel spherical bilaminar pellet culture system where one cell type is enclosed in a sphere of the other cell type. Our 3D system provides a structure that exploits embryonic processes such as tissue induction and condensation. We observed a unique phenomenon: the budding of co-culture pellets and the formation of satellite pellets that separate from the main pellet. MSC and NPC co-culture pellets were formed with three different structural organizations. The first had random organization. The other two had bilaminar organization with either MSC inside and NPC outside or NPC inside and MSC outside. By 14 days, all co-culture pellets exhibited budding and spontaneously generated satellite pellets. The satellite pellets were composed of both cell types and, surprisingly, all had the same bilaminar organization with MSC on the inside and NPC on the outside. This organization was independent of the structure of the main pellet that the satellites stemmed from. The main pellets generated satellite pellets that spontaneously organized into a bilaminar structure. This implies that structural organization occurs naturally in this cell culture system and may be inherently favorable for cell-based tissue engineering strategies. The occurrence of budding and the organization of satellite pellets may have important implications for the use of co-culture pellets in cell-based therapies for disc regeneration. From a therapeutic point of view, the generation of satellite pellets may be a beneficial feature that would serve to spread donor cells throughout the host matrix and restore normal matrix composition in a sustainable way, ultimately renewing tissue function.

Aligned poly(L-lactic-co-e-caprolactone) electrospun microfibers and knitted structure: a novel composite scaffold for ligament tissue engineering.

Science.gov (United States)

Vaquette, Cédryck; Kahn, Cyril; Frochot, Céline; Nouvel, Cécile; Six, Jean-Luc; De Isla, Natalia; Luo, Li-Hua; Cooper-White, Justin; Rahouadj, Rachid; Wang, Xiong

2010-09-15

We developed a novel technique involving knitting and electrospinning to fabricate a composite scaffold for ligament tissue engineering. Knitted structures were coated with poly(L-lactic-co-e-caprolactone) (PLCL) and then placed onto a rotating cylinder and a PLCL solution was electrospun onto the structure. Highly aligned 2-microm-diameter microfibers covered the space between the stitches and adhered to the knitted scaffolds. The stress-strain tensile curves exhibited an initial toe region similar to the tensile behavior of ligaments. Composite scaffolds had an elastic modulus (150 +/- 14 MPa) similar to the modulus of human ligaments. Biological evaluation showed that cells proliferated on the composite scaffolds and they spontaneously orientated along the direction of microfiber alignment. The microfiber architecture also induced a high level of extracellular matrix secretion, which was characterized by immunostaining. We found that cells produced collagen type I and type III, two main components found in ligaments. After 14 days of culture, collagen type III started to form a fibrous network. We fabricated a composite scaffold having the mechanical properties of the knitted structure and the morphological properties of the aligned microfibers. It is difficult to seed a highly macroporous structure with cells, however the technique we developed enabled an easy cell seeding due to presence of the microfiber layer. Therefore, these scaffolds presented attractive properties for a future use in bioreactors for ligament tissue engineering. (c) 2010 Wiley Periodicals, Inc.

In vitro evaluation of three-dimensional single-walled carbon nanotube composites for bone tissue engineering.

Science.gov (United States)

Gupta, Ashim; Main, Benjamin J; Taylor, Brittany L; Gupta, Manu; Whitworth, Craig A; Cady, Craig; Freeman, Joseph W; El-Amin, Saadiq F

2014-11-01

The purpose of this study was to develop three-dimensional single-walled carbon nanotube composites (SWCNT/PLAGA) using 10-mg single-walled carbon nanotubes (SWCNT) for bone regeneration and to determine the mechanical strength of the composites, and to evaluate the interaction of MC3T3-E1 cells via cell adhesion, growth, survival, proliferation, and gene expression. PLAGA (polylactic-co-glycolic acid) and SWCNT/PLAGA microspheres and composites were fabricated, characterized, and mechanical testing was performed. MC3T3-E1 cells were seeded and cell adhesion/morphology, growth/survival, proliferation, and gene expression analysis were performed to evaluate biocompatibility. Imaging studies demonstrated microspheres with uniform shape and smooth surfaces, and uniform incorporation of SWCNT into PLAGA matrix. The microspheres bonded in a random packing manner while maintaining spacing, thus resembling trabeculae of cancellous bone. Addition of SWCNT led to greater compressive modulus and ultimate compressive strength. Imaging studies revealed that MC3T3-E1 cells adhered, grew/survived, and exhibited normal, nonstressed morphology on the composites. SWCNT/PLAGA composites exhibited higher cell proliferation rate and gene expression compared with PLAGA. These results demonstrate the potential of SWCNT/PLAGA composites for musculoskeletal regeneration, for bone tissue engineering, and are promising for orthopedic applications as they possess the combined effect of increased mechanical strength, cell proliferation, and gene expression. © 2014 Wiley Periodicals, Inc.

Hard tissue compatibility of natural hydroxyapatite/chitosan composite

International Nuclear Information System (INIS)

Tang Xiaojun; Gui Lai; Lue Xiaoying

2008-01-01

The natural hydroxyapatite/chitosan (NHC) composite is a new synthesized material. The aim of this experiment was to assess the bone tissue compatibility of this NHC composite in vivo. Twenty-four healthy New Zealand rabbits were included in this study. Of those, 20 were used as the experimental group and four as the control group. In the experimental group, animals receive a cranium defect procedure and NHC composite repair. In the control group, animals underwent the cranium defect procedure without NHC composite repair. At 1, 4, 12, 24, and 40 weeks after surgery, the animals were sacrificed and samples were taken and assessed by gross observation, three-dimensional (3D) computerized tomographic (CT) reconstruction, histology and scanning electron microscope. Our results showed that at 1 week after repairing the bone defect with the NHC composite in the experimental group, new bone appeared around the composite and matured gradually. At 24 weeks after surgery, there were little collagenous tissues present between the material and surrounding bones. At 40 weeks after surgery, new bone had grown into the mature bone and total osseointegration had occurred. In the control group, however, no bone defect healing was observed at 40 weeks after surgery. All these results of the present in vivo work suggest that the NHC composite has a good hard tissue biocompatibility and an excellent osteoconductivity. It is suitable for artificial bone implants and frame materials of tissue engineering.

Hard tissue compatibility of natural hydroxyapatite/chitosan composite

Energy Technology Data Exchange (ETDEWEB)

Tang Xiaojun; Gui Lai [Department of Cranio-maxillofacial Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Ba-Da-Chu Road, Beijing, 100144 (China); Lue Xiaoying [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096 (China)], E-mail: laiguiplastic@tom.com, E-mail: luxy@seu.edu.cn

2008-12-15

The natural hydroxyapatite/chitosan (NHC) composite is a new synthesized material. The aim of this experiment was to assess the bone tissue compatibility of this NHC composite in vivo. Twenty-four healthy New Zealand rabbits were included in this study. Of those, 20 were used as the experimental group and four as the control group. In the experimental group, animals receive a cranium defect procedure and NHC composite repair. In the control group, animals underwent the cranium defect procedure without NHC composite repair. At 1, 4, 12, 24, and 40 weeks after surgery, the animals were sacrificed and samples were taken and assessed by gross observation, three-dimensional (3D) computerized tomographic (CT) reconstruction, histology and scanning electron microscope. Our results showed that at 1 week after repairing the bone defect with the NHC composite in the experimental group, new bone appeared around the composite and matured gradually. At 24 weeks after surgery, there were little collagenous tissues present between the material and surrounding bones. At 40 weeks after surgery, new bone had grown into the mature bone and total osseointegration had occurred. In the control group, however, no bone defect healing was observed at 40 weeks after surgery. All these results of the present in vivo work suggest that the NHC composite has a good hard tissue biocompatibility and an excellent osteoconductivity. It is suitable for artificial bone implants and frame materials of tissue engineering.

Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications.

Science.gov (United States)

Vedadghavami, Armin; Minooei, Farnaz; Mohammadi, Mohammad Hossein; Khetani, Sultan; Rezaei Kolahchi, Ahmad; Mashayekhan, Shohreh; Sanati-Nezhad, Amir

2017-10-15

Hydrogels have been recognized as crucial biomaterials in the field of tissue engineering, regenerative medicine, and drug delivery applications due to their specific characteristics. These biomaterials benefit from retaining a large amount of water, effective mass transfer, similarity to natural tissues and the ability to form different shapes. However, having relatively poor mechanical properties is a limiting factor associated with hydrogel biomaterials. Controlling the biomechanical properties of hydrogels is of paramount importance. In this work, firstly, mechanical characteristics of hydrogels and methods employed for characterizing these properties are explored. Subsequently, the most common approaches used for tuning mechanical properties of hydrogels including but are not limited to, interpenetrating polymer networks, nanocomposites, self-assembly techniques, and co-polymerization are discussed. The performance of different techniques used for tuning biomechanical properties of hydrogels is further compared. Such techniques involve lithography techniques for replication of tissues with complex mechanical profiles; microfluidic techniques applicable for generating gradients of mechanical properties in hydrogel biomaterials for engineering complex human tissues like intervertebral discs, osteochondral tissues, blood vessels and skin layers; and electrospinning techniques for synthesis of hybrid hydrogels and highly ordered fibers with tunable mechanical and biological properties. We finally discuss future perspectives and challenges for controlling biomimetic hydrogel materials possessing proper biomechanical properties. Hydrogels biomaterials are essential constituting components of engineered tissues with the applications in regenerative medicine and drug delivery. The mechanical properties of hydrogels play crucial roles in regulating the interactions between cells and extracellular matrix and directing the cells phenotype and genotype. Despite

Emerging bone tissue engineering via Polyhydroxyalkanoate (PHA)-based scaffolds.

Science.gov (United States)

Lim, Janice; You, Mingliang; Li, Jian; Li, Zibiao

2017-10-01

Polyhydroxyalkanoates (PHAs) are a class of biodegradable polymers derived from microorganisms. On top of their biodegradability and biocompatibility, different PHA types can contribute to varying mechanical and chemical properties. This has led to increasing attention to the use of PHAs in numerous biomedical applications over the past few decades. Bone tissue engineering refers to the regeneration of new bone through providing mechanical support while inducing cell growth on the PHA scaffolds having a porous structure for tissue regeneration. This review first introduces the various properties PHA scaffold that make them suitable for bone tissue engineering such as biocompatibility, biodegradability, mechanical properties as well as vascularization. The typical fabrication techniques of PHA scaffolds including electrospinning, salt-leaching and solution casting are further discussed, followed by the relatively new technology of using 3D printing in PHA scaffold fabrication. Finally, the recent progress of using different types of PHAs scaffold in bone tissue engineering applications are summarized in intrinsic PHA/blends forms or as composites with other polymeric or inorganic hybrid materials. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular, cellular, and tissue engineering

CERN Document Server

Bronzino, Joseph D

2015-01-01

Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering. Molecular, Cellular, and Tissue Engineering, the fourth volume of the handbook, presents material from respected scientists with diverse backgrounds in molecular biology, transport phenomena, physiological modeling, tissue engineering, stem cells, drug delivery systems, artificial organs, and personalized medicine. More than three dozen specific topics are examined, including DNA vaccines, biomimetic systems, cardiovascular dynamics, biomaterial scaffolds, cell mechanobiology, synthetic biomaterials, pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, nanobiomaterials for tissue engineering, biomedical imaging of engineered tissues, gene therapy, noninvasive targeted protein and peptide drug deliver...

A composite chitosan-gelatin bi-layered, biomimetic macroporous scaffold for blood vessel tissue engineering.

Science.gov (United States)

Badhe, Ravindra V; Bijukumar, Divya; Chejara, Dharmesh R; Mabrouk, Mostafa; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Kondiah, Pierre P D; Pillay, Viness

2017-02-10

A composite chitosan-gelatin macroporous hydrogel-based scaffold with bi-layered tubular architecture was engineered by solvent casting-co-particulate leaching. The scaffold constituted an inner macroporous layer concealed by a non-porous outer layer mimicking the 3D matrix of blood vessels with cellular adhesion and proliferation. The scaffold was evaluated for its morphological, physicochemical, physicomechanical and biodurability properties employing SEM, FTIR, DSC, XRD, porositometry, rheology and texture analysis. The fluid uptake and biodegradation in the presence of lysozymes was also investigated. Cellular attachment and proliferation was analysed using human dermal fibroblasts (HDF-a) seeded onto the scaffold and evaluated by MTT assay, SEM, and confocal microscopy. Results demonstrated that the scaffold had a desirable tensile strength=95.81±11kPa, elongation at break 112.5±13%, porosity 82% and pores between 100 and 230μm, 50% in vitro biodegradation at day 16 and proliferated fibroblasts over 20 days. These results demonstrate that scaffold may be an excellent tubular archetype for blood vessel tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of rabbit intervertebral disc physiology based on water metabolism. II. Changes in normal intervertebral discs under axial vibratory load

International Nuclear Information System (INIS)

Hirano, N.; Tsuji, H.; Ohshima, H.; Kitano, S.; Itoh, T.; Sano, A.

1988-01-01

Metabolic changes induced by axial vibratory load to the spine were investigated based on water metabolism in normal intervertebral discs of rabbits with or without pentobarbital anesthesia. Tritiated water concentration in the intervertebral discs of unanesthetized rabbits was reduced remarkably by axial vibration for 30 minutes using the vibration machine developed for this study. Repeated vibratory load for 18 and 42 hours duration showed the recovery of 3 H 2 O concentration of the intervertebral disc without anesthesia. Computer simulation suggested a reduction of blood flow surrounding the intervertebral disc following the vibration stress. However, no reduction of the 3 H 2 O concentration in the intervertebral disc was noted under anesthesia. Emotional stress cannot be excluded as a factor in water metabolism in the intervertebral disc

Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications.

Science.gov (United States)

Ain, Qurat Ul; Khan, Ahmad Nawaz; Nabavinia, Mahboubeh; Mujahid, Mohammad

2017-06-01

The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60±20nm. Various concentrations of HA ranging from 1 to 30wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA≤10wt% in TOPAS and at higher concentrations >10wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3MPa and 185% from 0.26 to 0.74MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Tissue bionics: examples in biomimetic tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail: Hindoostuart@googlemail.com

2008-09-01

Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

Tissue bionics: examples in biomimetic tissue engineering

International Nuclear Information System (INIS)

Green, David W

2008-01-01

Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic

Additive manufacturing techniques for the production of tissue engineering constructs.

Science.gov (United States)

Mota, Carlos; Puppi, Dario; Chiellini, Federica; Chiellini, Emo

2015-03-01

'Additive manufacturing' (AM) refers to a class of manufacturing processes based on the building of a solid object from three-dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue-engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue-engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt-extrusion-based techniques, solution/slurry extrusion-based techniques, and tissue and organ printing) employed for the development of tissue-engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions. Copyright © 2012 John Wiley & Sons, Ltd.

Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano-hydroxyapatite composite microsphere-based scaffolds for bone tissue engineering in rotating bioreactors.

Science.gov (United States)

Lv, Qing; Nair, Lakshmi; Laurencin, Cato T

2009-12-01

Dynamic flow culture bioreactor systems have been shown to enhance in vitro bone tissue formation by facilitating mass transfer and providing mechanical stimulation. Our laboratory has developed a biodegradable poly (lactic acid glycolic acid) (PLAGA) mixed scaffold consisting of lighter-than-water (LTW) and heavier-than-water (HTW) microspheres as potential matrices for engineering tissue using a high aspect ratio vessel (HARV) rotating bioreactor system. We have demonstrated enhanced osteoblast differentiation and mineralization on PLAGA scaffolds in the HARV rotating bioreactor system when compared with static culture. The objective of the present study is to improve the mechanical properties and bioactivity of polymeric scaffolds by designing LTW polymer/ceramic composite scaffolds suitable for dynamic culture using a HARV bioreactor. We employed a microsphere sintering method to fabricate three-dimensional PLAGA/nano-hydroxyapatite (n-HA) mixed scaffolds composed of LTW and HTW composite microspheres. The mechanical properties, pore size and porosity of the composite scaffolds were controlled by varying parameters, such as sintering temperature, sintering time, and PLAGA/n-HA ratio. The PLAGA/n-HA (4:1) scaffold sintered at 90 degrees C for 3 h demonstrated the highest mechanical properties and an appropriate pore structure for bone tissue engineering applications. Furthermore, evaluation human mesenchymal stem cells (HMSCs) response to PLAGA/n-HA scaffolds was performed. HMSCs on PLAGA/n-HA scaffolds demonstrated enhanced proliferation, differentiation, and mineralization when compared with those on PLAGA scaffolds. Therefore, PLAGA/n-HA mixed scaffolds are promising candidates for HARV bioreactor-based bone tissue engineering applications. Copyright 2008 Wiley Periodicals, Inc.

Composition-function relations of cartilaginous tissues engineered from chondrocytes and mesenchymal stem cells isolated from bone marrow and infrapatellar fat pad.

Science.gov (United States)

Vinardell, T; Buckley, C T; Thorpe, S D; Kelly, D J

2011-10-01

The objective of this study was to determine the functional properties of cartilaginous tissues generated by porcine MSCs isolated from different tissue sources, and to compare these properties to those derived from chondrocytes (CCs). MSCs were isolated from bone marrow (BM) and infrapatellar fat pad (FP), while CCs were harvested from the articular surface of the femoro-patellar joint. Culture-expanded CCs and MSCs were encapsulated in agarose hydrogels and cultured in the presence of TGFβ3. Samples were analysed biomechanically, biochemically and histologically at days 0, 21 and 42. After 42 days in free swelling culture, mean GAG content was 1.50% w/w in CC-seeded constructs, compared to 0.95% w/w in FP- and 0.43% w/w in BM-seeded constructs. Total collagen accumulation was highest in FP constructs. DNA content increased with time for all the groups. The mechanical functionality of cartilaginous tissues engineered using CCs was superior to that generated from either source of MSCs. Differences were also observed in the spatial distribution of matrix components in tissues engineered using CCs and MSCs, which appears to have a strong influence on the apparent mechanical properties of the constructs. Therefore, while functional cartilaginous tissues can be engineered using MSCs isolated from different sources, the spatial composition of these tissues is unlike that generated using chondrocytes, suggesting that MSCs and chondrocytes respond differently to the regulatory factors present within developing cartilaginous constructs. Copyright © 2010 John Wiley & Sons, Ltd.

Chitin Scaffolds in Tissue Engineering

Science.gov (United States)

Jayakumar, Rangasamy; Chennazhi, Krishna Prasad; Srinivasan, Sowmya; Nair, Shantikumar V.; Furuike, Tetsuya; Tamura, Hiroshi

2011-01-01

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine. PMID:21673928

Ultrasound Imaging Techniques for Spatiotemporal Characterization of Composition, Microstructure, and Mechanical Properties in Tissue Engineering.

Science.gov (United States)

Deng, Cheri X; Hong, Xiaowei; Stegemann, Jan P

2016-08-01

Ultrasound techniques are increasingly being used to quantitatively characterize both native and engineered tissues. This review provides an overview and selected examples of the main techniques used in these applications. Grayscale imaging has been used to characterize extracellular matrix deposition, and quantitative ultrasound imaging based on the integrated backscatter coefficient has been applied to estimating cell concentrations and matrix morphology in tissue engineering. Spectral analysis has been employed to characterize the concentration and spatial distribution of mineral particles in a construct, as well as to monitor mineral deposition by cells over time. Ultrasound techniques have also been used to measure the mechanical properties of native and engineered tissues. Conventional ultrasound elasticity imaging and acoustic radiation force imaging have been applied to detect regions of altered stiffness within tissues. Sonorheometry and monitoring of steady-state excitation and recovery have been used to characterize viscoelastic properties of tissue using a single transducer to both deform and image the sample. Dual-mode ultrasound elastography uses separate ultrasound transducers to produce a more potent deformation force to microscale characterization of viscoelasticity of hydrogel constructs. These ultrasound-based techniques have high potential to impact the field of tissue engineering as they are further developed and their range of applications expands.

Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Ain, Qurat Ul [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan); Khan, Ahmad Nawaz, E-mail: ahmad.nawaz@scme.nust.edu.pk [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan); Nabavinia, Mahboubeh [Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA (United States); Mujahid, Mohammad [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan)

2017-06-01

The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60 ± 20 nm. Various concentrations of HA ranging from 1 to 30 wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA ≤ 10 wt% in TOPAS and at higher concentrations > 10 wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3 MPa and 185% from 0.26 to 0.74 MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1 day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. - Highlights: • TOPAS/HA hybrid composites exhibited enhanced mechanical properties owing to better dispersion and interaction of HA. • Without affecting the degradation rate, the

Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications

International Nuclear Information System (INIS)

Ain, Qurat Ul; Khan, Ahmad Nawaz; Nabavinia, Mahboubeh; Mujahid, Mohammad

2017-01-01

The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60 ± 20 nm. Various concentrations of HA ranging from 1 to 30 wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA ≤ 10 wt% in TOPAS and at higher concentrations > 10 wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3 MPa and 185% from 0.26 to 0.74 MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1 day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. - Highlights: • TOPAS/HA hybrid composites exhibited enhanced mechanical properties owing to better dispersion and interaction of HA. • Without affecting the degradation rate, the

Biomaterials for tissue engineering applications.

Science.gov (United States)

Keane, Timothy J; Badylak, Stephen F

2014-06-01

With advancements in biological and engineering sciences, the definition of an ideal biomaterial has evolved over the past 50 years from a substance that is inert to one that has select bioinductive properties and integrates well with adjacent host tissue. Biomaterials are a fundamental component of tissue engineering, which aims to replace diseased, damaged, or missing tissue with reconstructed functional tissue. Most biomaterials are less than satisfactory for pediatric patients because the scaffold must adapt to the growth and development of the surrounding tissues and organs over time. The pediatric community, therefore, provides a distinct challenge for the tissue engineering community. Copyright © 2014. Published by Elsevier Inc.

The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

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Marti-Figueroa, Carlos R; Ashton, Randolph S

2017-05-01

Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis

Cellularized cylindrical fiber/hydrogel composites for ligament tissue engineering.

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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.

Preparation of a biomimetic composite scaffold from gelatin/collagen and bioactive glass fibers for bone tissue engineering

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Sharifi, Esmaeel; Azami, Mahmoud [Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Kajbafzadeh, Abdol-Mohammad [Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Department of Pediatric Urology, Children' s Hospital Medical Center, Tehran, Iran (IRI) (Iran, Islamic Republic of); Moztarzadeh, Fatollah [Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Faridi-Majidi, Reza [Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Shamousi, Atefeh; Karimi, Roya [Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ai, Jafar, E-mail: jafar_ai@tums.ac.ir [Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Brain and Spinal Injury Research Center (BASIR), Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2016-02-01

Bone tissue is a composite material made of organic and inorganic components. Bone tissue engineering requires scaffolds that mimic bone nature in chemical and mechanical properties. This study proposes a novel method for preparing composite scaffolds that uses sub-micron bioglass fibers as the organic phase and gelatin/collagen as the inorganic phase. The scaffolds were constructed by using freeze drying and electro spinning methods and their mechanical properties were enhanced by using genipin crosslinking agent. Electron microscopy micrographs showed that the structure of composite scaffolds were porous with pore diameters of approximately 70–200 μm, this was again confirmed by mercury porosimetery. These pores are suitable for osteoblast growth. The diameters of the fibers were approximately 150–450 nm. Structural analysis confirmed the formation of desirable phases of sub-micron bioglass fibers. Cellular biocompatibility tests illustrated that scaffolds containing copper ion in the bioglass structure had more cell growth and osteoblast attachment in comparison to copper-free scaffolds. - Highlights: • Fabrication of 45S5 sub-micron bioglass fiber using electrospinning method. • Production of copper doped submicron bioglass fibers on 45S5 bioglass base by electrospinning sol gel route method. • Incorporation of bioglass/Cu-bioglass sub-micron fibers into gelatin/collagen matrix to form biomimetic composite scaffold which were non-cytotoxic according to MTT assay. • Discovering that copper can decrease the glass transition temperatures and enhance osteoblast cell adhesion and viability.

Preparation of a biomimetic composite scaffold from gelatin/collagen and bioactive glass fibers for bone tissue engineering

International Nuclear Information System (INIS)

Sharifi, Esmaeel; Azami, Mahmoud; Kajbafzadeh, Abdol-Mohammad; Moztarzadeh, Fatollah; Faridi-Majidi, Reza; Shamousi, Atefeh; Karimi, Roya; Ai, Jafar

2016-01-01

Bone tissue is a composite material made of organic and inorganic components. Bone tissue engineering requires scaffolds that mimic bone nature in chemical and mechanical properties. This study proposes a novel method for preparing composite scaffolds that uses sub-micron bioglass fibers as the organic phase and gelatin/collagen as the inorganic phase. The scaffolds were constructed by using freeze drying and electro spinning methods and their mechanical properties were enhanced by using genipin crosslinking agent. Electron microscopy micrographs showed that the structure of composite scaffolds were porous with pore diameters of approximately 70–200 μm, this was again confirmed by mercury porosimetery. These pores are suitable for osteoblast growth. The diameters of the fibers were approximately 150–450 nm. Structural analysis confirmed the formation of desirable phases of sub-micron bioglass fibers. Cellular biocompatibility tests illustrated that scaffolds containing copper ion in the bioglass structure had more cell growth and osteoblast attachment in comparison to copper-free scaffolds. - Highlights: • Fabrication of 45S5 sub-micron bioglass fiber using electrospinning method. • Production of copper doped submicron bioglass fibers on 45S5 bioglass base by electrospinning sol gel route method. • Incorporation of bioglass/Cu-bioglass sub-micron fibers into gelatin/collagen matrix to form biomimetic composite scaffold which were non-cytotoxic according to MTT assay. • Discovering that copper can decrease the glass transition temperatures and enhance osteoblast cell adhesion and viability.

Commercial considerations in tissue engineering.

Science.gov (United States)

Mansbridge, Jonathan

2006-10-01

Tissue engineering is a field with immense promise. Using the example of an early tissue-engineered skin implant, Dermagraft, factors involved in the successful commercial development of devices of this type are explored. Tissue engineering has to strike a balance between tissue culture, which is a resource-intensive activity, and business considerations that are concerned with minimizing cost and maximizing customer convenience. Bioreactor design takes place in a highly regulated environment, so factors to be incorporated into the concept include not only tissue culture considerations but also matters related to asepsis, scaleup, automation and ease of use by the final customer. Dermagraft is an allogeneic tissue. Stasis preservation, in this case cryopreservation, is essential in allogeneic tissue engineering, allowing sterility testing, inventory control and, in the case of Dermagraft, a cellular stress that may be important for hormesis following implantation. Although the use of allogeneic cells provides advantages in manufacturing under suitable conditions, it raises the spectre of immunological rejection. Such rejection has not been experienced with Dermagraft. Possible reasons for this and the vision of further application of allogeneic tissues are important considerations in future tissue-engineered cellular devices. This review illustrates approaches that indicate some of the criteria that may provide a basis for further developments. Marketing is a further requirement for success, which entails understanding of the mechanism of action of the procedure, and is illustrated for Dermagraft. The success of a tissue-engineered product is dependent on many interacting operations, some discussed here, each of which must be performed simultaneously and well.

Tissue Engineering of the Penis

Directory of Open Access Journals (Sweden)

Manish N. Patel

2011-01-01

Full Text Available Congenital disorders, cancer, trauma, or other conditions of the genitourinary tract can lead to significant organ damage or loss of function, necessitating eventual reconstruction or replacement of the damaged structures. However, current reconstructive techniques are limited by issues of tissue availability and compatibility. Physicians and scientists have begun to explore tissue engineering and regenerative medicine strategies for repair and reconstruction of the genitourinary tract. Tissue engineering allows the development of biological substitutes which could potentially restore normal function. Tissue engineering efforts designed to treat or replace most organs are currently being undertaken. Most of these efforts have occurred within the past decade. However, before these engineering techniques can be applied to humans, further studies are needed to ensure the safety and efficacy of these new materials. Recent progress suggests that engineered urologic tissues and cell therapy may soon have clinical applicability.

Silk fibroin as biomaterial for bone tissue engineering.

Science.gov (United States)

Melke, Johanna; Midha, Swati; Ghosh, Sourabh; Ito, Keita; Hofmann, Sandra

2016-02-01

Silk fibroin (SF) is a fibrous protein which is produced mainly by silkworms and spiders. Its unique mechanical properties, tunable biodegradation rate and the ability to support the differentiation of mesenchymal stem cells along the osteogenic lineage, have made SF a favorable scaffold material for bone tissue engineering. SF can be processed into various scaffold forms, combined synergistically with other biomaterials to form composites and chemically modified, which provides an impressive toolbox and allows SF scaffolds to be tailored to specific applications. This review discusses and summarizes recent advancements in processing SF, focusing on different fabrication and functionalization methods and their application to grow bone tissue in vitro and in vivo. Potential areas for future research, current challenges, uncertainties and gaps in knowledge are highlighted. Silk fibroin is a natural biomaterial with remarkable biomedical and mechanical properties which make it favorable for a broad range of bone tissue engineering applications. It can be processed into different scaffold forms, combined synergistically with other biomaterials to form composites and chemically modified which provides a unique toolbox and allows silk fibroin scaffolds to be tailored to specific applications. This review discusses and summarizes recent advancements in processing silk fibroin, focusing on different fabrication and functionalization methods and their application to grow bone tissue in vitro and in vivo. Potential areas for future research, current challenges, uncertainties and gaps in knowledge are highlighted. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The Crosstalk between Tissue Engineering and Pharmaceutical Biotechnology: Recent Advances and Future Directions.

Science.gov (United States)

Pacheco, Daniela P; Reis, Rui L; Correlo, Vítor M; Marques, Alexandra P

2015-01-01

Tissue-engineered constructs made of biotechnology-derived materials have been preferred due to their chemical and physical composition, which offers both high versatility and a support to enclose/ incorporate relevant signaling molecules and/or genes known to therapeutically induce tissue repair. Herein, a critical overview of the impact of different biotechnology-derived materials, scaffolds, and recombinant signaling molecules over the behavior of cells, another element of tissue engineered constructs, as well its regulatory role in tissue regeneration and disease progression is given. Additionally, these tissue-engineered constructs evolved to three-dimensional (3D) tissue-like models that, as an advancement of two-dimensional standard culture methods, are expected to be a valuable tool in the field of drug discovery and pharmaceutical research. Despite the improved design and conception of current proposed 3D tissue-like models, advanced control systems to enable and accelerate streamlining and automation of the numerous labor-intensive steps intrinsic to the development of tissue-engineered constructs are still to be achieved. In this sense, this review intends to present the biotechnology- derived materials that are being explored in the field of tissue engineering to generate 3D tissue-analogues and briefly highlight their foremost breakthroughs in tissue regeneration and drug discovery. It also aims to reinforce that the crosstalk between tissue engineering and pharmaceutical biotechnology has been fostering the outcomes of tissue engineering approaches through the use of biotechnology-derived signaling molecules. Gene delivery/therapy is also discussed as a forefront area that represents another cross point between tissue engineering and pharmaceutical biotechnology, in which nucleic acids can be considered a "super pharmaceutical" to drive biological responses, including tissue regeneration.

Chitosan based nanofibers in bone tissue engineering.

Science.gov (United States)

Balagangadharan, K; Dhivya, S; Selvamurugan, N

2017-11-01

Bone tissue engineering involves biomaterials, cells and regulatory factors to make biosynthetic bone grafts with efficient mineralization for regeneration of fractured or damaged bones. Out of all the techniques available for scaffold preparation, electrospinning is given priority as it can fabricate nanostructures. Also, electrospun nanofibers possess unique properties such as the high surface area to volume ratio, porosity, stability, permeability and morphological similarity to that of extra cellular matrix. Chitosan (CS) has a significant edge over other materials and as a graft material, CS can be used alone or in combination with other materials in the form of nanofibers to provide the structural and biochemical cues for acceleration of bone regeneration. Hence, this review was aimed to provide a detailed study available on CS and its composites prepared as nanofibers, and their associated properties found suitable for bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Tumor Engineering: The Other Face of Tissue Engineering

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Ghajar, Cyrus M; Bissell, Mina J

2010-03-09

cancer, the training grounds have largely consisted of small rodents, despite marked differences between human and mouse physiology, or plastic dishes, even though just like our tissues and organs most tumors exist within three-dimensional proteinacious milieus. One could argue that this is comparable to training for a desert war in the arctic. In this special issue of tissue engineering, Fischbach-Teschl and colleagues build a strong case for engineering complex cultures analogous to normal organs to tractably model aspects of the human tumor microenvironment that simply cannot be reproduced with traditional two-dimensional cell culture techniques and that cannot be studied in a controlled fashion in vivo. This idea has gained considerable traction of late as concepts presented and convincingly shown years ago have only now begun to be appreciated. Perhaps, then, it is time to organize those who wish to build complex tumor models to study cancer biology under a common umbrella. Accordingly, we propose that tumor engineering be defined as the construction of complex culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. Inherent in this definition is the collaboration that must occur between physical and life scientists to guide the design of patterning techniques, materials, and imaging modalities for the study of cancer from the subcellular to tissue level in physiologically relevant contexts. To date, the most successful tissue engineering approaches have employed methods that recapitulate the composition, architecture, and/or chemical presentation of native tissue. For instance, induction of blood vessel growth for therapeutic purposes has been achieved with sequential release of vascular endothelial growth factor (VEGF) and platelet derived growth factor to induce and stabilize blood vessels. This approach imitates that which occurs during physiological

Spectroscopic Parameters of Lumbar Intervertebral Disc Material

Science.gov (United States)

Terbetas, G.; Kozlovskaja, A.; Varanius, D.; Graziene, V.; Vaitkus, J.; Vaitkuviene, A.

2009-06-01

There are numerous methods of investigating intervertebral disc. Visualization methods are widely used in clinical practice. Histological, imunohistochemical and biochemical methods are more used in scientific research. We propose that a new spectroscopic investigation would be useful in determining intervertebral disc material, especially when no histological specimens are available. Purpose: to determine spectroscopic parameters of intervertebral disc material; to determine emission spectra common for all intervertebral discs; to create a background for further spectroscopic investigation where no histological specimen will be available. Material and Methods: 20 patients, 68 frozen sections of 20 μm thickness from operatively removed intervertebral disc hernia were excited by Nd:YAG microlaser STA-01-TH third harmonic 355 nm light throw 0, 1 mm fiber. Spectrophotometer OceanOptics USB2000 was used for spectra collection. Mathematical analysis of spectra was performed by ORIGIN multiple Gaussian peaks analysis. Results: In each specimen of disc hernia were found distinct maximal spectral peaks of 4 types supporting the histological evaluation of mixture content of the hernia. Fluorescence in the spectral regions 370-700 nm was detected in the disc hernias. The main spectral component was at 494 nm and the contribution of the components with the peak wavelength values at 388 nm, 412 nm and 435±5 nm were varying in the different groups of samples. In comparison to average spectrum of all cases, there are 4 groups of different spectral signatures in the region 400-500 nm in the patient groups, supporting a clinical data on different clinical features of the patients. Discussion and Conclusion: besides the classical open discectomy, new minimally invasive techniques of treating intervertebral disc emerge (PLDD). Intervertebral disc in these techniques is assessed by needle, no histological specimen is taken. Spectroscopic investigation via fiber optics through the

Manipulation of mechanical compliance of elastomeric PGS by incorporation of halloysite nanotubes for soft tissue engineering applications.

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Chen, Qi-Zhi; Liang, Shu-Ling; Wang, Jiang; Simon, George P

2011-11-01

Poly (glycerol sebacate) (PGS) is a promising elastomer for use in soft tissue engineering. However, it is difficult to achieve with PGS a satisfactory balance of mechanical compliance and degradation rate that meet the requirements of soft tissue engineering. In this work, we have synthesised a new PGS nanocomposite system filled with halloysite nanotubes, and mechanical properties, as well as related chemical characters, of the nanocomposites were investigated. It was found that the addition of nanotubular halloysite did not compromise the extensibility of material, compared with the pure PGS counterpart; instead the elongation at rupture was increased from 110 (in the pure PGS) to 225% (in the 20 wt% composite). Second, Young's modulus and resilience of 3-5 wt% composites were ∼0.8 MPa and >94% respectively, remaining close to the level of pure PGS which is desired for applications in soft tissue engineering. Third, an important feature of the 1-5 wt% composites was their stable mechanical properties over an extended period, which could allow the provision of reliable mechanical support to damaged tissues during the lag phase of the healing process. Finally, the in vitro study indicated that the addition of halloysite slowed down the degradation rate of the composites. In conclusion, the good compliance, enhanced stretchability, stable mechanical behavior over an extended period, and reduced degradation rates make the 3-5 wt% composites promising candidates for application in soft tissue engineering. Copyright © 2011 Elsevier Ltd. All rights reserved.

PHBV/PLLA-based composite scaffolds fabricated using an emulsion freezing/freeze-drying technique for bone tissue engineering: surface modification and in vitro biological evaluation

International Nuclear Information System (INIS)

Sultana, Naznin; Wang Min

2012-01-01

Tissue engineering combines living cells with biodegradable materials and/or bioactive components. Composite scaffolds containing biodegradable polymers and nanosized osteoconductive bioceramic with suitable properties are promising for bone tissue regeneration. In this paper, based on blending two biodegradable and biocompatible polymers, namely poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(l-lactic acid) (PLLA) with incorporated nano hydroxyapatite (HA), three-dimensional composite scaffolds with controlled microstructures and an interconnected porous structure, together with high porosity, were fabricated using an emulsion freezing/freeze-drying technique. The influence of various parameters involved in the emulsion freezing/freeze-drying technique was studied for the fabrication of good-quality polymer scaffolds based on PHBV polymers. The morphology, mechanical properties and crystallinity of PHBV/PLLA and HA in PHBV/PLLA composite scaffolds and PHBV polymer scaffolds were studied. The scaffolds were coated with collagen in order to improve wettability. During in vitro biological evaluation study, it was observed that SaOS-2 cells had high attachment on collagen-coated scaffolds. Significant improvement in cell proliferation and alkaline phosphatase activity for HA-incorporated composite scaffolds was observed due to the incorporation of HA. After 3 and 7 days of culture on all scaffolds, SaOS-2 cells also had normal morphology and growth. These results indicated that PHBV/PLLA-based scaffolds fabricated via an emulsion freezing/freeze-drying technique were favorable sites for osteoblastic cells and are promising for the applications of bone tissue engineering.

The growth of tissue engineering.

Science.gov (United States)

Lysaght, M J; Reyes, J

2001-10-01

This report draws upon data from a variety of sources to estimate the size, scope, and growth rate of the contemporary tissue engineering enterprise. At the beginning of 2001, tissue engineering research and development was being pursued by 3,300 scientists and support staff in more than 70 startup companies or business units with a combined annual expenditure of over $600 million. Spending by tissue engineering firms has been growing at a compound annual rate of 16%, and the aggregate investment since 1990 now exceeds $3.5 billion. At the beginning of 2001, the net capital value of the 16 publicly traded tissue engineering startups had reached $2.6 billion. Firms focusing on structural applications (skin, cartilage, bone, cardiac prosthesis, and the like) comprise the fastest growing segment. In contrast, efforts in biohybrid organs and other metabolic applications have contracted over the past few years. The number of companies involved in stem cells and regenerative medicine is rapidly increasing, and this area represents the most likely nidus of future growth for tissue engineering. A notable recent trend has been the emergence of a strong commercial activity in tissue engineering outside the United States, with at least 16 European or Australian companies (22% of total) now active.

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.

Biocompatibility of hydrogel-based scaffolds for tissue engineering applications.

Science.gov (United States)

Naahidi, Sheva; Jafari, Mousa; Logan, Megan; Wang, Yujie; Yuan, Yongfang; Bae, Hojae; Dixon, Brian; Chen, P

2017-09-01

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds. Copyright © 2017 Elsevier Inc. All rights reserved.

Extracellular matrix and tissue engineering applications

NARCIS (Netherlands)

Fernandes, H.A.M.; Moroni, Lorenzo; van Blitterswijk, Clemens; de Boer, Jan

2009-01-01

The extracellular matrix is a key component during regeneration and maintenance of tissues and organs, and it therefore plays a critical role in successful tissue engineering as well. Tissue engineers should recognise that engineering technology can be deduced from natural repair processes. Due to

Biomimetic multidirectional scaffolds for zonal osteochondral tissue engineering via a lyophilization bonding approach.

Science.gov (United States)

Clearfield, Drew; Nguyen, Andrew; Wei, Mei

2018-04-01

The zonal organization of osteochondral tissue underlies its long term function. Despite this, tissue engineering strategies targeted for osteochondral repair commonly rely on the use of isotropic biomaterials for tissue reconstruction. There exists a need for a new class of highly biomimetic, anisotropic scaffolds that may allow for the engineering of new tissue with zonal properties. To address this need, we report the facile production of monolithic multidirectional collagen-based scaffolds that recapitulate the zonal structure and composition of osteochondral tissue. First, superficial and osseous zone-mimicking scaffolds were fabricated by unidirectional freeze casting collagen-hyaluronic acid and collagen-hydroxyapatite-containing suspensions, respectively. Following their production, a lyophilization bonding process was used to conjoin these scaffolds with a distinct collagen-hyaluronic acid suspension mimicking the composition of the transition zone. Resulting matrices contained a thin, highly aligned superficial zone that interfaced with a cellular transition zone and vertically oriented calcified cartilage and osseous zones. Confocal microscopy confirmed a zone-specific localization of hyaluronic acid, reflecting the depth-dependent increase of glycosaminoglycans in the native tissue. Poorly crystalline, carbonated hydroxyapatite was localized to the calcified cartilage and osseous zones and bordered the transition zone. Compressive testing of hydrated scaffold zones confirmed an increase of stiffness with scaffold depth, where compressive moduli of chondral and osseous zones fell within or near ranges conducive for chondrogenesis or osteogenesis of mesenchymal stem cells. With the combination of these biomimetic architectural and compositional cues, these multidirectional scaffolds hold great promise for the engineering of zonal osteochondral tissue. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 948-958, 2018. © 2017 Wiley Periodicals

Role of chondroitin sulphate tethered silk scaffold in cartilaginous disc tissue regeneration.

Science.gov (United States)

Bhattacharjee, Maumita; Chawla, Shikha; Chameettachal, Shibu; Murab, Sumit; Bhavesh, Neel Sarovar; Ghosh, Sourabh

2016-04-12

Strategies for tissue engineering focus on scaffolds with tunable structure and morphology as well as optimum surface chemistry to simulate the anatomy and functionality of the target tissue. Silk fibroin has demonstrated its potential in supporting cartilaginous tissue formation both in vitro and in vivo. In this study, we investigate the role of controlled lamellar organization and chemical composition of biofunctionalized silk scaffolds in replicating the structural properties of the annulus region of an intervertebral disc using articular chondrocytes. Covalent attachment of chondroitin sulfate (CS) to silk is characterized. CS-conjugated silk constructs demonstrate enhanced cellular metabolic activity and chondrogenic redifferentiation potential with significantly improved mechanical properties over silk-only constructs. A matrix-assisted laser desorption ionization-time of flight analysis and protein-protein interaction studies help to generate insights into how CS conjugation can facilitate the production of disc associated matrix proteins, compared to a silk-only based construct. An in-depth understanding of the interplay between such extra cellular matrix associated proteins should help in designing more rational scaffolds for cartilaginous disc regeneration needs.

Role of chondroitin sulphate tethered silk scaffold in cartilaginous disc tissue regeneration

International Nuclear Information System (INIS)

Bhattacharjee, Maumita; Chawla, Shikha; Chameettachal, Shibu; Murab, Sumit; Ghosh, Sourabh; Bhavesh, Neel Sarovar

2016-01-01

Strategies for tissue engineering focus on scaffolds with tunable structure and morphology as well as optimum surface chemistry to simulate the anatomy and functionality of the target tissue. Silk fibroin has demonstrated its potential in supporting cartilaginous tissue formation both in vitro and in vivo. In this study, we investigate the role of controlled lamellar organization and chemical composition of biofunctionalized silk scaffolds in replicating the structural properties of the annulus region of an intervertebral disc using articular chondrocytes. Covalent attachment of chondroitin sulfate (CS) to silk is characterized. CS-conjugated silk constructs demonstrate enhanced cellular metabolic activity and chondrogenic redifferentiation potential with significantly improved mechanical properties over silk-only constructs. A matrix-assisted laser desorption ionization-time of flight analysis and protein–protein interaction studies help to generate insights into how CS conjugation can facilitate the production of disc associated matrix proteins, compared to a silk-only based construct. An in-depth understanding of the interplay between such extra cellular matrix associated proteins should help in designing more rational scaffolds for cartilaginous disc regeneration needs. (paper)

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice

Science.gov (United States)

Al-Himdani, Sarah; Jessop, Zita M.; Al-Sabah, Ayesha; Combellack, Emman; Ibrahim, Amel; Doak, Shareen H.; Hart, Andrew M.; Archer, Charles W.; Thornton, Catherine A.; Whitaker, Iain S.

2017-01-01

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering “holds the promise of revolutionizing patient care in the twenty-first century.” The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20–30 years from the start of basic science research to clinical utility

Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice.

Science.gov (United States)

Al-Himdani, Sarah; Jessop, Zita M; Al-Sabah, Ayesha; Combellack, Emman; Ibrahim, Amel; Doak, Shareen H; Hart, Andrew M; Archer, Charles W; Thornton, Catherine A; Whitaker, Iain S

2017-01-01

Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering "holds the promise of revolutionizing patient care in the twenty-first century." The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20-30 years from the start of basic science research to clinical utility

Current strategies in multiphasic scaffold design for osteochondral tissue engineering: A review.

Science.gov (United States)

Yousefi, Azizeh-Mitra; Hoque, Md Enamul; Prasad, Rangabhatala G S V; Uth, Nicholas

2015-07-01

The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article. © 2014 Wiley Periodicals, Inc.

A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering.

Science.gov (United States)

Zhang, Fan; Song, Qingxin; Huang, Xuan; Li, Fengning; Wang, Kun; Tang, Yixing; Hou, Canglong; Shen, Hongxing

2016-01-20

A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the material's mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Young's modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

The influence of construct scale on the composition and functional properties of cartilaginous tissues engineered using bone marrow-derived mesenchymal stem cells.

Science.gov (United States)

Buckley, Conor T; Meyer, Eric G; Kelly, Daniel J

2012-02-01

Engineering cartilaginous tissue of a scale necessary to treat defects observed clinically is a well-documented challenge in the field of cartilage tissue engineering. The objective of this study was to determine how the composition and mechanical properties of cartilaginous tissues that are engineered by using bone marrow-derived mesenchymal stem cells (MSCs) depend on the scale of the construct. Porcine bone marrow-derived MSCs were encapsulated in agarose hydrogels, and constructs of different cylindrical geometries (Ø4×1.5 mm; Ø5×3 mm; Ø6×4.5 mm; Ø8×4.5 mm) were fabricated and maintained in a chemically defined serum-free medium supplemented with transforming growth factor-β3 for 42 days. Total sulfated glycosaminoglycan (sGAG) accumulation by day 42 increased from 0.14% w/w to 0.88% w/w as the construct geometry increased from Ø4×1.5 to Ø8×4.5 mm, with collagen accumulation increasing from 0.31% w/w to 1.62% w/w. This led to an increase in the dynamic modulus from 90.81 to 327.51 kPa as the engineered tissue increased in scale from Ø4×1.5 to Ø8×4.5 mm. By decreasing the external oxygen tension from 20% to 5%, it was possible to achieve these higher levels of mechanical functionality in the smaller engineered tissues. Constructs were then sectioned into smaller subregions to quantify the spatial accumulation of extracellular matrix components, and a model of oxygen diffusion and consumption was used to predict spatial gradients in oxygen concentration throughout the construct. sGAG accumulation was always highest in regions where oxygen concentration was predicted to be lowest. In addition, as the size of the engineered construct increased, different regions of the construct preferentially supported either sGAG or collagen accumulation, thus suggesting that gradients in regulatory factors other than oxygen were playing a role in determining levels of collagen synthesis. The identification of such factors and the means to control their

Magnetic resonance imaging of intervertebral disc degeneration

International Nuclear Information System (INIS)

Maeda, Hiroshi; Noguchi, Masao; Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi.

1993-01-01

The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.)

Magnetic resonance imaging of intervertebral disc degeneration

Energy Technology Data Exchange (ETDEWEB)

Maeda, Hiroshi; Noguchi, Masao (Kitakyushu City Yahata Hospital, Fukuoka (Japan)); Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi

1993-02-01

The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.).

Regeneration of the anterior cruciate ligament: Current strategies in tissue engineering

Science.gov (United States)

Nau, Thomas; Teuschl, Andreas

2015-01-01

Recent advancements in the field of musculoskeletal tissue engineering have raised an increasing interest in the regeneration of the anterior cruciate ligament (ACL). It is the aim of this article to review the current research efforts and highlight promising tissue engineering strategies. The four main components of tissue engineering also apply in several ACL regeneration research efforts. Scaffolds from biological materials, biodegradable polymers and composite materials are used. The main cell sources are mesenchymal stem cells and ACL fibroblasts. In addition, growth factors and mechanical stimuli are applied. So far, the regenerated ACL constructs have been tested in a few animal studies and the results are encouraging. The different strategies, from in vitro ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration, are under constant development. We expect considerable progress in the near future that will result in a realistic option for ACL surgery soon. PMID:25621217

An update on the Application of Nanotechnology in Bone Tissue Engineering.

Science.gov (United States)

Griffin, M F; Kalaskar, D M; Seifalian, A; Butler, P E

2016-01-01

Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Future studies to improve the application of nanomaterials for bone tissue engineering are needed.

Microfluidic Bioprinting for Engineering Vascularized Tissues and Organoids.

Science.gov (United States)

Zhang, Yu Shrike; Pi, Qingmeng; van Genderen, Anne Metje

2017-08-11

Engineering vascularized tissue constructs and organoids has been historically challenging. Here we describe a novel method based on microfluidic bioprinting to generate a scaffold with multilayer interlacing hydrogel microfibers. To achieve smooth bioprinting, a core-sheath microfluidic printhead containing a composite bioink formulation extruded from the core flow and the crosslinking solution carried by the sheath flow, was designed and fitted onto the bioprinter. By blending gelatin methacryloyl (GelMA) with alginate, a polysaccharide that undergoes instantaneous ionic crosslinking in the presence of select divalent ions, followed by a secondary photocrosslinking of the GelMA component to achieve permanent stabilization, a microfibrous scaffold could be obtained using this bioprinting strategy. Importantly, the endothelial cells encapsulated inside the bioprinted microfibers can form the lumen-like structures resembling the vasculature over the course of culture for 16 days. The endothelialized microfibrous scaffold may be further used as a vascular bed to construct a vascularized tissue through subsequent seeding of the secondary cell type into the interstitial space of the microfibers. Microfluidic bioprinting provides a generalized strategy in convenient engineering of vascularized tissues at high fidelity.

Bovine annulus fibrosus cell lines isolated from intervertebral discs

Directory of Open Access Journals (Sweden)

Petra Kraus

2016-12-01

Full Text Available The adult bovine (Bos taurus intervertebral disc is primarily comprised of two major tissue types: The outer annulus fibrosus (AF and the central nucleus pulposus (NP. We isolated several primary cell lineages of passage (P 0 cells from the AF tissue omitting typically used enzymatic tissue digestion protocols. The cells grow past p10 without signs of senescence in DMEM + 10% FCS on 0.1% gelatin coated/uncoated surfaces of standard cell culture plates and survive freeze-thawing. Preliminary analysis of the AF derived cells for expression of the two structural genes Col1a1 and Col2a1 was performed by PISH recapitulating the expression observed in vivo.

Micro- and nanotechnology in cardiovascular tissue engineering

International Nuclear Information System (INIS)

Zhang Boyang; Xiao Yun; Hsieh, Anne; Thavandiran, Nimalan; Radisic, Milica

2011-01-01

While in nature the formation of complex tissues is gradually shaped by the long journey of development, in tissue engineering constructing complex tissues relies heavily on our ability to directly manipulate and control the micro-cellular environment in vitro. Not surprisingly, advancements in both microfabrication and nanofabrication have powered the field of tissue engineering in many aspects. Focusing on cardiac tissue engineering, this paper highlights the applications of fabrication techniques in various aspects of tissue engineering research: (1) cell responses to micro- and nanopatterned topographical cues, (2) cell responses to patterned biochemical cues, (3) controlled 3D scaffolds, (4) patterned tissue vascularization and (5) electromechanical regulation of tissue assembly and function.

FoxC2 Enhances BMP7-Mediated Anabolism in Nucleus Pulposus Cells of the Intervertebral Disc

OpenAIRE

Wang, Zheng; Fu, Changfeng; Chen, Yong; Xu, Feng; Wang, Zhenyu; Qu, Zhigang; Liu, Yi

2016-01-01

Bone-morphogenetic protein-7 (BMP-7) is a growth factor that plays a major role in mediating anabolism and anti-catabolism of the intervertebral disc matrix and cell homeostasis. In osteoblasts, Forkhead box protein C2 (FoxC2) is a downstream target of BMPs and promotes cell proliferation and differentiation. However, the role FoxC2 may play in degenerative human intervertebral disc tissue and the relationship between FoxC2 and BMP-7 in nucleus pulposus (NP) cells remain to be elucidated. Thi...

Development of an angiogenesis-promoting microvesicle-alginate-polycaprolactone composite graft for bone tissue engineering applications

Directory of Open Access Journals (Sweden)

Hui Xie

2016-05-01

Full Text Available One of the major challenges of bone tissue engineering applications is to construct a fully vascularized implant that can adapt to hypoxic environments in vivo. The incorporation of proangiogenic factors into scaffolds is a widely accepted method of achieving this goal. Recently, the proangiogenic potential of mesenchymal stem cell-derived microvesicles (MSC-MVs has been confirmed in several studies. In the present study, we incorporated MSC-MVs into alginate-polycaprolactone (PCL constructs that had previously been developed for bone tissue engineering applications, with the aim of promoting angiogenesis and bone regeneration. MSC-MVs were first isolated from the supernatant of rat bone marrow-derived MSCs and characterized by scanning electron microscopic, confocal microscopic, and flow cytometric analyses. The proangiogenic potential of MSC-MVs was demonstrated by the stimulation of tube formation of human umbilical vein endothelial cells in vitro. MSC-MVs and osteodifferentiated MSCs were then encapsulated with alginate and seeded onto porous three-dimensional printed PCL scaffolds. When combined with osteodifferentiated MSCs, the MV-alginate-PCL constructs enhanced vessel formation and tissue-engineered bone regeneration in a nude mouse subcutaneous bone formation model, as demonstrated by micro-computed tomographic, histological, and immunohistochemical analyses. This MV-alginate-PCL construct may offer a novel, proangiogenic, and cost-effective option for bone tissue engineering.

Vascular complications of prosthetic inter-vertebral discs

OpenAIRE

Daly, Kevin J.; Ross, E. Raymond S.; Norris, Heather; McCollum, Charles N.

2006-01-01

Five consecutive cases of prosthetic inter-vertebral disc displacement with severe vascular complications on revisional surgery are described. The objective of this case report is to warn spinal surgeons that major vascular complications are likely with anterior displacement of inter-vertebral discs. We have not been able to find a previous report on vascular complications associated with anterior displacement of prosthetic inter-vertebral discs. In all five patients the prosthetic disc had e...

Bone tissue engineering and regeneration: from discovery to the clinic--an overview.

Science.gov (United States)

O'Keefe, Regis J; Mao, Jeremy

2011-12-01

A National Institutes of Health sponsored workshop "Bone Tissue Engineering and Regeneration: From Discovery to the Clinic" gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. © Mary Ann Liebert, Inc.

Bone Tissue Engineering and Regeneration: From Discovery to the Clinic—An Overview

Science.gov (United States)

2011-01-01

A National Institutes of Health sponsored workshop “Bone Tissue Engineering and Regeneration: From Discovery to the Clinic” gathered thought leaders from medicine, science, and industry to determine the state of art in the field and to define the barriers to translating new technologies to novel therapies to treat bone defects. Tissue engineering holds enormous promise to improve human health through prevention of disease and the restoration of healthy tissue functions. Bone tissue engineering, similar to that for other tissues and organs, requires integration of multiple disciplines such as cell biology, stem cells, developmental and molecular biology, biomechanics, biomaterials science, and immunology and transplantation science. Although each of the research areas has undergone enormous advances in last decade, the translation to clinical care and the development of tissue engineering composites to replace human tissues has been limited. Bone, similar to other tissue and organs, has complex structure and functions and requires exquisite interactions between cells, matrices, biomechanical forces, and gene and protein regulatory factors for sustained function. The process of engineering bone, thus, requires a comprehensive approach with broad expertise. Although in vitro and preclinical animal studies have been pursued with a large and diverse collection of scaffolds, cells, and biomolecules, the field of bone tissue engineering remains fragmented up to the point that a clear translational roadmap has yet to emerge. Translation is particularly important for unmet clinical needs such as large segmental defects and medically compromised conditions such as tumor removal and infection sites. Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics. PMID:21902614

In vitro evaluation of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds for bone tissue engineering.

Science.gov (United States)

Jiang, Tao; Abdel-Fattah, Wafa I; Laurencin, Cato T

2006-10-01

A three-dimensional (3-D) scaffold is one of the major components in many tissue engineering approaches. We developed novel 3-D chitosan/poly(lactic acid-glycolic acid) (PLAGA) composite porous scaffolds by sintering together composite chitosan/PLAGA microspheres for bone tissue engineering applications. Pore sizes, pore volume, and mechanical properties of the scaffolds can be manipulated by controlling fabrication parameters, including sintering temperature and sintering time. The sintered microsphere scaffolds had a total pore volume between 28% and 37% with median pore size in the range 170-200microm. The compressive modulus and compressive strength of the scaffolds are in the range of trabecular bone making them suitable as scaffolds for load-bearing bone tissue engineering. In addition, MC3T3-E1 osteoblast-like cells proliferated well on the composite scaffolds as compared to PLAGA scaffolds. It was also shown that the presence of chitosan on microsphere surfaces increased the alkaline phosphatase activity of the cells cultured on the composite scaffolds and up-regulated gene expression of alkaline phosphatase, osteopontin, and bone sialoprotein.

Influence of degenerative changes of intervertebral disc

Directory of Open Access Journals (Sweden)

WANG Yi

2012-04-01

Full Text Available 【Abstract】Objective: To investigate the material properties of normal and degenerated intervertebral discs (IVDs and examine the effect of degenerative changes on IVD pathology. Methods: A computer-based online search was under-taken to identify English articles about material properties of IVDs published from January 1950 to 2011 in PubMed database. The retrieved keywords included material properties, intervertebral disc and degeneration. Based on the principles of reliability, advancement and efficiency, the obtained data were primarily examined, and the original source was retrieved to read the full-text. Repetitive articles were excluded. The data of material properties of normal and degenerated IVDs were summarized and analyzed by meta-analysis. Results: The data of Young's modulus, Poisson's ratio, shear modulus, hydraulic permeability and intradiscal pres-sure of normal and degenerated IVDs were obtained. Com-pared with normal IVDs, the Young's modulus and shear modulus of annulus fibrosus and nucleus pulposus were higher in degenerated IVDs, the Poisson's ratio was lower while the hydraulic permeability and intradiscal pressure were higher. Besides, the degeneration-related alterations in IVDs had an influence both on itself and other spinal structures, leading to diseases such as bulging disc, discogenic pain and spinal stenosis. Meanwhile, the heavy mechanical loading and injury indicated important pathways to IVD degeneration. Conclusions: To a certain extent, the degenerative changes of IVD influence its material properties. And the degeneration-related alterations of composition can cause structural failure of IVDs, leading to injuries and diseases. Key words: Intervertebral disc; Mechanical phenomena; Degeneration; Elastic modulus; Permeability; Pathology

Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering

Science.gov (United States)

Lu, Helen H.; Thomopoulos, Stavros

2014-01-01

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions. PMID:23642244

Biomechanics and mechanobiology in functional tissue engineering

Science.gov (United States)

Guilak, Farshid; Butler, David L.; Goldstein, Steven A.; Baaijens, Frank P.T.

2014-01-01

The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of “functional tissue engineering” has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements. PMID:24818797

Biological aspects of tissue-engineered cartilage.

Science.gov (United States)

Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

2018-04-01

Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

Synthetic biology meets tissue engineering.

Science.gov (United States)

Davies, Jamie A; Cachat, Elise

2016-06-15

Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. © 2016 Authors; published by Portland Press Limited.

Biofunctional Ionic-Doped Calcium Phosphates: Silk Fibroin Composites for Bone Tissue Engineering Scaffolding.

Science.gov (United States)

Pina, S; Canadas, R F; Jiménez, G; Perán, M; Marchal, J A; Reis, R L; Oliveira, J M

2017-01-01

The treatment and regeneration of bone defects caused by traumatism or diseases have not been completely addressed by current therapies. Lately, advanced tools and technologies have been successfully developed for bone tissue regeneration. Functional scaffolding materials such as biopolymers and bioresorbable fillers have gained particular attention, owing to their ability to promote cell adhesion, proliferation, and extracellular matrix production, which promote new bone growth. Here, we present novel biofunctional scaffolds for bone regeneration composed of silk fibroin (SF) and β-tricalcium phosphate (β-TCP) and incorporating Sr, Zn, and Mn, which were successfully developed using salt-leaching followed by a freeze-drying technique. The scaffolds presented a suitable pore size, porosity, and high interconnectivity, adequate for promoting cell attachment and proliferation. The degradation behavior and compressive mechanical strengths showed that SF/ionic-doped TCP scaffolds exhibit improved characteristics for bone tissue engineering when compared with SF scaffolds alone. The in vitro bioactivity assays using a simulated body fluid showed the growth of an apatite layer. Furthermore, in vitro assays using human adipose-derived stem cells presented different effects on cell proliferation/differentiation when varying the doping agents in the biofunctional scaffolds. The incorporation of Zn into the scaffolds led to improved proliferation, while the Sr- and Mn-doped scaffolds presented higher osteogenic potential as demonstrated by DNA quantification and alkaline phosphatase activity. The combination of Sr with Zn led to an influence on cell proliferation and osteogenesis when compared with single ions. Our results indicate that biofunctional ionic-doped composite scaffolds are good candidates for further in vivo studies on bone tissue regeneration. © 2017 S. Karger AG, Basel.

Proteomic differences between native and tissue-engineered tendon and ligament.

Science.gov (United States)

Kharaz, Yalda A; Tew, Simon R; Peffers, Mandy; Canty-Laird, Elizabeth G; Comerford, Eithne

2016-05-01

Tendons and ligaments (T/Ls) play key roles in the musculoskeletal system, but they are susceptible to traumatic or age-related rupture, leading to severe morbidity as well as increased susceptibility to degenerative joint diseases such as osteoarthritis. Tissue engineering represents an attractive therapeutic approach to treating T/L injury but it is hampered by our poor understanding of the defining characteristics of the two tissues. The present study aimed to determine differences in the proteomic profile between native T/Ls and tissue engineered (TE) T/L constructs. The canine long digital extensor tendon and anterior cruciate ligament were analyzed along with 3D TE fibrin-based constructs created from their cells. Native tendon and ligament differed in their content of key structural proteins, with the ligament being more abundant in fibrocartilaginous proteins. 3D T/L TE constructs contained less extracellular matrix (ECM) proteins and had a greater proportion of cellular-associated proteins than native tissue, corresponding to their low collagen and high DNA content. Constructs were able to recapitulate native T/L tissue characteristics particularly with regard to ECM proteins. However, 3D T/L TE constructs had similar ECM and cellular protein compositions indicating that cell source may not be an important factor for T/L tissue engineering. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Silk-fibrin/hyaluronic acid composite gels for nucleus pulposus tissue regeneration.

Science.gov (United States)

Park, Sang-Hyug; Cho, Hongsik; Gil, Eun Seok; Mandal, Biman B; Min, Byoung-Hyun; Kaplan, David L

2011-12-01

Scaffold designs are critical for in vitro culture of tissue-engineered cartilage in three-dimensional environments to enhance cellular differentiation for tissue engineering and regenerative medicine. In the present study we demonstrated silk and fibrin/hyaluronic acid (HA) composite gels as scaffolds for nucleus pulposus (NP) cartilage formation, providing both biochemical support for NP outcomes as well as fostering the retention of size of the scaffold during culture due to the combined features of the two proteins. Passage two (P2) human chondrocytes cultured in 10% serum were encapsulated within silk-fibrin/HA gels. Five study groups with fibrin/HA gel culture (F/H) along with varying silk concentrations (2% silk gel only, fibrin/HA gel culture with 1% silk [F/H+1S], 1.5% silk [F/H+1.5S], and 2% silk [F/H+2S]) were cultured in serum-free chondrogenic defined media (CDM) for 4 weeks. Histological examination with alcian blue showed a defined chondrogenic area at 1 week in all groups that widened homogenously until 4 weeks. In particular, chondrogenic differentiation observed in the F/H+1.5S had no reduction in size throughout the culture period. The results of biochemical and molecular biological evaluations supported observations made during histological examination. Mechanical strength measurements showed that the silk mixed gels provided stronger mechanical properties for NP tissue than fibrin/HA composite gels in CDM. This effect could potentially be useful in the study of in vitro NP tissue engineering as well as for clinical implications for NP tissue regeneration.

Molecular signaling in intervertebral disk development.

Science.gov (United States)

DiPaola, Christian P; Farmer, James C; Manova, Katia; Niswander, Lee A

2005-09-01

The purpose of this investigation is to identify and study the expression pattern of pertinent molecular factors involved in the differentiation of the intervertebral disk (IVD). It is likely that hedgehog genes and the BMP inhibitors are key factors involved in spinal joint formation. Radioactive in situ hybridization with mRNA probes for pax-1, SHH, IHH and Noggin gene was performed on mouse embryo and adult tissue. Immunohistochemistry was performed to localize hedgehog receptor, "patched" (ptc). From 14.5 dpc until birth pax-1 mRNA was expressed in the developing anulus fibrosus (AF). During the same developmental period Noggin mRNA is highly expressed throughout the spine, in the developing AF, while ptc protein and SHH mRNA were expressed in the developing nucleus pulposus (NP). IHH mRNA was expressed by condensing chondrocytes of the vertebral bodies and later becomes confined to the vertebral endplate. We show for the first time that pax-1 is expressed in the adult intervertebral disk. Ptc expression in the NP is an indicator of hedgehog protein signaling in the developing IVD. The expression pattern of the BMP inhibitor Noggin appears to be important for the normal formation of the IVD and may prove to play a role in its segmental pattern formation.

Investigation of particle-functionalized tissue engineering scaffolds using X-ray tomographic microscopy

DEFF Research Database (Denmark)

Nygaard, J V; Andersen, M Ø; Howard, K A

2008-01-01

A low-density, porous chitosan/poly-(dl-lactide-co-glycolide) (PLGA) microparticle composite scaffold was produced by thermally induced phase separation followed by lyophilization, to provide a bicontinuous microstructure potentially suitable for tissue engineering and locally controlled drug...

Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application.

Science.gov (United States)

Wang, L; Lazebnik, M; Detamore, M S

2009-03-01

To compare temporomandibular joint (TMJ) condylar cartilage cells in vitro to hyaline cartilage cells cultured in a three-dimensional (3D) environment for tissue engineering of mandibular condylar cartilage. Mandibular condylar cartilage and hyaline cartilage cells were harvested from pigs and cultured for 6 weeks in polyglycolic acid (PGA) scaffolds. Both types of cells were treated with glucosamine sulfate (0.4 mM), insulin-like growth factor-I (IGF-I) (100 ng/ml) and their combination. At weeks 0 and 6, cell number, glycosaminoglycan (GAG) and collagen content were determined, types I and II collagen were visualized by immunohistochemistry and GAGs were visualized by histology. Hyaline cartilage cells produced from half an order to a full order of magnitude more GAGs and collagen than mandibular condylar cartilage cells in 3D culture. IGF-I was a highly effective signal for biosynthesis with hyaline cartilage cells, while glucosamine sulfate decreased cell proliferation and biosynthesis with both types of cells. In vitro culture of TMJ condylar cartilage cells produced a fibrous tissue with predominantly type I collagen, while hyaline cartilage cells formed a fibrocartilage-like tissue with types I and II collagen. The combination of IGF and glucosamine had a synergistic effect on maintaining the phenotype of TMJ condylar cells to generate both types I and II collagen. Given the superior biosynthetic activity by hyaline cartilage cells and the practical surgical limitations of harvesting cells from the TMJ of a patient requiring TMJ reconstruction, cartilage cells from elsewhere in the body may be a potentially better alternative to cells harvested from the TMJ for TMJ tissue engineering. This finding may also apply to other fibrocartilages such as the intervertebral disc and knee meniscus in applications where a mature cartilage cell source is desired.

Using radionuclide imaging for monitoring repairment of bone defect with tissue-engineered bone graft in rabbits

International Nuclear Information System (INIS)

Xia Changsuo; Ye Fagang; Zou Yunwen; Ji Shixiang; Wang Dengchun

2004-01-01

Objective: To observe the effect of tissue-engineered bone grafts in repairing bone defect in rabbits, and assess the value of radionuclide for monitoring the therapeutic effect of this approach. Methods: Bilateral radial defects of 15 mm in length in 24 rabbits were made. The tissue-engineered bone grafts (composite graft) contained bone marrow stromal cells (BMSCs) of rabbits and calcium phosphate cement (CPC) were grafted in left side defects, CPC only grafts (artificial bone graft) in right defects. After the operation, radionuclide was used to monitor the therapeutic effects at 4, 8 and 12 weeks. Results: 99 Tc m -methylene diphosphonic acid (MDP) radionuclide bone imaging indicated that there was more radionuclide accumulation in grafting region of composite than that of CPC. There was significant difference between 99 Tc m -MDP uptake of the region of interest (ROI) and scintillant counts of composite bone and the artificial bone (P<0.01). Conclusion: Tissue-engineered bone grafts is eligible for repairing radial bone defects, and radionuclide imaging may accurately monitor the revascularization and bone regeneration after the bone graft implantation. (authors)

Angiogenesis in the degeneration of the lumbar intervertebral disc

OpenAIRE

David, Gh; Ciurea, AV; Iencean, SM; Mohan, A

2010-01-01

The goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth ...

Laser-assisted cold-sprayed hydroxyapatite/titanium composites: evaluation for tissues engineering applications

CSIR Research Space (South Africa)

Tlotleng, Monnamme

2013-08-01

Full Text Available This research work seeks to establish titanium alloys (Ti-6Al-4V), in the field of tissue engineering, as material of interest for bone replacement with a particular focus on hip implants replacement. The aim of this study was to produce a surface...

Heterogeneity of Scaffold Biomaterials in Tissue Engineering

Directory of Open Access Journals (Sweden)

Lauren Edgar

2016-05-01

Full Text Available Tissue engineering (TE offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal.

Reverse engineering development: Crosstalk opportunities between developmental biology and tissue engineering.

Science.gov (United States)

Marcucio, Ralph S; Qin, Ling; Alsberg, Eben; Boerckel, Joel D

2017-11-01

The fields of developmental biology and tissue engineering have been revolutionized in recent years by technological advancements, expanded understanding, and biomaterials design, leading to the emerging paradigm of "developmental" or "biomimetic" tissue engineering. While developmental biology and tissue engineering have long overlapping histories, the fields have largely diverged in recent years at the same time that crosstalk opportunities for mutual benefit are more salient than ever. In this perspective article, we will use musculoskeletal development and tissue engineering as a platform on which to discuss these emerging crosstalk opportunities and will present our opinions on the bright future of these overlapping spheres of influence. The multicellular programs that control musculoskeletal development are rapidly becoming clarified, represented by shifting paradigms in our understanding of cellular function, identity, and lineage specification during development. Simultaneously, advancements in bioartificial matrices that replicate the biochemical, microstructural, and mechanical properties of developing tissues present new tools and approaches for recapitulating development in tissue engineering. Here, we introduce concepts and experimental approaches in musculoskeletal developmental biology and biomaterials design and discuss applications in tissue engineering as well as opportunities for tissue engineering approaches to inform our understanding of fundamental biology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2356-2368, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Cell-Based Strategies for Meniscus Tissue Engineering

Science.gov (United States)

Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

2016-01-01

Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

Magnetic nanoparticle-loaded electrospun polymeric nanofibers for tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Zhang, Heng [Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000 (China); Xia, JiYi [Department of Science and Technology, Southwest Medical University, Luzhou 646000 (China); Pang, XianLun [Health Management Center, The Affiliated Hospital (TCM) of Southwest Medical University, Luzhou 646000 (China); Zhao, Ming; Wang, BiQiong; Yang, LingLin [Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000 (China); Wan, HaiSu [Experiment Center of Basic Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000 (China); Wu, JingBo, E-mail: wjb6147@163.com [Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000 (China); Fu, ShaoZhi, E-mail: shaozhifu513@163.com [Department of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou 646000 (China)

2017-04-01

Magnetic nanoparticles have been one of the most attractive nanomaterials for various biomedical applications including magnetic resonance imaging (MRI), diagnostic contrast enhancement, magnetic cell separation, and targeted drug delivery. Three-dimensional (3-D) fibrous scaffolds have broad application prospects in the biomedical field, such as drug delivery and tissue engineering. In this work, a novel three-dimensional composite membrane composed of the tri-block copolymer poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) and magnetic iron oxide nanoparticles (Fe{sub 3}O{sub 4} NPs) were fabricated using electrospinning technology. The physico-chemical properties of the PCEC/Fe{sub 3}O{sub 4} membranes were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Morphological observation using scanning electron microscopy (SEM) showed that the composite fibers containing 5% Fe{sub 3}O{sub 4} nanoparticles had a diameter of 250 nm. In vitro cell culture of NIH 3T3 cells on the PCEC/Fe{sub 3}O{sub 4} membranes showed that the PCEC/Fe{sub 3}O{sub 4} fibers might be a suitable scaffold for cell adhesion. Moreover, MTT analysis also demonstrated that the membranes possessed lower cytotoxicity. Therefore, this study revealed that the magnetic PCEC/Fe{sub 3}O{sub 4} fibers might have great potential for using in skin tissue engineering. - Graphical abstract: In this study, we prepared a kind of magnetic three-dimensional scaffolds (PCEC/Fe{sub 3}O{sub 4}) using iron oxide nanoparticles (Fe{sub 3}O{sub 4} NPs) and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) copolymer through electrospinning technique. Their crystallization property, thermal property, in vitro degradation, and morphology were investigated. Furthermore, the cell compatibility and toxicity were also evaluated using NIH 3T3 cells. The results showed that the Fe{sub 3}O

Aloe Vera for Tissue Engineering Applications

Directory of Open Access Journals (Sweden)

Shekh Rahman

2017-02-01

Full Text Available Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers.

Aloe Vera for Tissue Engineering Applications.

Science.gov (United States)

Rahman, Shekh; Carter, Princeton; Bhattarai, Narayan

2017-02-14

Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers.

The development of the collagen fibre network in tissue-engineered cartilage constructs in vivo. Engineered cartilage reorganises fibre network

Directory of Open Access Journals (Sweden)

H Paetzold

2012-04-01

Full Text Available For long term durability of tissue-engineered cartilage implanted in vivo, the development of the collagen fibre network orientation is essential as well as the distribution of collagen, since expanded chondrocytes are known to synthesise collagen type I. Typically, these properties differ strongly between native and tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study with implanted tissue-engineered cartilage in pigs were surprisingly good. The purpose of this study was therefore to analyse if the structure and composition of the artificial cartilage tissue changes in the first 52 weeks after implantation. Thus, collagen network orientation and collagen type distribution in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of Göttinger minipigs for 2, 26 or 52 weeks have been further investigated by processing digitised microscopy images of histological sections. The comparison to native cartilage demonstrated that fibre orientation over the cartilage depth has a clear tendency towards native cartilage with increasing time of implantation. After 2 weeks, the collagen fibres of the superficial zone were oriented parallel to the articular surface with little anisotropy present in the middle and deep zones. Overall, fibre orientation and collagen distribution within the implants were less homogenous than in native cartilage tissue. Despite a relatively low number of specimens, the consistent observation of a continuous approximation to native tissue is very promising and suggests that it may not be necessary to engineer the perfect tissue for implantation but rather to provide an intermediate solution to help the body to heal itself.

Tissue-engineered matrices as functional delivery systems: adsorption and release of bioactive proteins from degradable composite scaffolds.

Science.gov (United States)

Cushnie, Emily K; Khan, Yusuf M; Laurencin, Cato T

2010-08-01

A tissue-engineered bone graft should imitate the ideal autograft in both form and function. However, biomaterials that have appropriate chemical and mechanical properties for grafting applications often lack biological components that may enhance regeneration. The concept of adding proteins such as growth factors to scaffolds has therefore emerged as a possible solution to improve overall graft design. In this study, we investigated this concept by loading porous hydroxyapatite-poly(lactide-co-glycolide) (HA-PLAGA) scaffolds with a model protein, cytochrome c, and then studying its release in a phosphate-buffered saline solution. The HA-PLAGA scaffold has previously been shown to be bioactive, osteoconductive, and to have appropriate physical properties for tissue engineering applications. The loading experiments demonstrated that the HA-PLAGA scaffold could also function effectively as a substrate for protein adsorption and release. Scaffold protein adsorptive loading (as opposed to physical entrapment within the matrix) was directly related to levels of scaffold HA-content. The HA phase of the scaffold facilitated protein retention in the matrix following incubation in aqueous buffer for periods up to 8 weeks. Greater levels of protein retention time may improve the protein's effective activity by increasing the probability for protein-cell interactions. The ability to control protein loading and delivery simply via composition of the HA-PLAGA scaffold offers the potential of forming robust functionalized bone grafts. (c) 2010 Wiley Periodicals, Inc.

Treatment of the degenerated intervertebral disc; closure, repair and regeneration of the annulus fibrosus

NARCIS (Netherlands)

Sharifi, Shahriar; Bulstra, S.K.; Grijpma, Dirk W.; Kuijer, R.

2015-01-01

Degeneration of the intervertebral disc (IVD) and disc herniation are two causes of low back pain. The aetiology of these disorders is unknown, but tissue weakening, which primarily occurs due to inherited genetic factors, ageing, nutritional compromise and loading history, is the basic factor

Design Approaches to Myocardial and Vascular Tissue Engineering.

Science.gov (United States)

Akintewe, Olukemi O; Roberts, Erin G; Rim, Nae-Gyune; Ferguson, Michael A H; Wong, Joyce Y

2017-06-21

Engineered tissues represent an increasingly promising therapeutic approach for correcting structural defects and promoting tissue regeneration in cardiovascular diseases. One of the challenges associated with this approach has been the necessity for the replacement tissue to promote sufficient vascularization to maintain functionality after implantation. This review highlights a number of promising prevascularization design approaches for introducing vasculature into engineered tissues. Although we focus on encouraging blood vessel formation within myocardial implants, we also discuss techniques developed for other tissues that could eventually become relevant to engineered cardiac tissues. Because the ultimate solution to engineered tissue vascularization will require collaboration between wide-ranging disciplines such as developmental biology, tissue engineering, and computational modeling, we explore contributions from each field.

Scientific and industrial status of tissue engineering ...

African Journals Online (AJOL)

Tissue engineering is a newly emerging field targeting many unresolved health problems. So far, the achievements of this technology in the production of different tissue engineered substitutes were promising. This review is intended to describe, briefly and in a simple language, what tissue engineering is, what the ...

Biomaterials for tissue engineering: summary

Science.gov (United States)

Christenson, L.; Mikos, A. G.; Gibbons, D. F.; Picciolo, G. L.; McIntire, L. V. (Principal Investigator)

1997-01-01

This article summarizes presentations and discussion at the workshop "Enabling Biomaterial Technology for Tissue Engineering," which was held during the Fifth World Biomaterials Congress in May 1996. Presentations covered the areas of material substrate architecture, barrier effects, and cellular response, including analysis of biomaterials challenges involved in producing specific tissue-engineered products.

Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs.

Science.gov (United States)

Choi, Kyung-Suk; Lee, Chanmi; Harfe, Brian D

2012-01-01

The intervertebral discs, located between adjacent vertebrae, are required for stability of the spine and distributing mechanical load throughout the vertebral column. All cell types located in the middle regions of the discs, called nuclei pulposi, are derived from the embryonic notochord. Recently, it was shown that the hedgehog signaling pathway plays an essential role during formation of nuclei pulposi. However, during the time that nuclei pulposi are forming, Shh is expressed in both the notochord and the nearby floor plate. To determine the source of SHH protein sufficient for formation of nuclei pulposi we removed Shh from either the floor plate or the notochord using tamoxifen-inducible Cre alleles. Removal of Shh from the floor plate resulted in phenotypically normal intervertebral discs, indicating that Shh expression in this tissue is not required for disc patterning. In addition, embryos that lacked Shh in the floor plate had normal vertebral columns, demonstrating that Shh expression in the notochord is sufficient for pattering the entire vertebral column. Removal of Shh from the notochord resulted in the absence of Shh in the floor plate, loss of intervertebral discs and vertebral structures. These data indicate that Shh expression in the notochord is sufficient for patterning of the intervertebral discs and the vertebral column. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Microgel Technology to Advance Modular Tissue Engineering

NARCIS (Netherlands)

Kamperman, Tom

2018-01-01

The field of tissue engineering aims to restore the function of damaged or missing tissues by combining cells and/or a supportive biomaterial scaffold into an engineered tissue construct. The construct’s design requirements are typically set by native tissues – the gold standard for tissue

Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.

Science.gov (United States)

McCann, Matthew R; Tamplin, Owen J; Rossant, Janet; Séguin, Cheryle A

2012-01-01

Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.

CT-guided intradiscal ozone injection combined with intervertebral facet joint steroid injection for lumbar disk herniation accompanied with intervertebral arthritis

International Nuclear Information System (INIS)

Zhang Li; Chen Zhaohui; Sun Xijun; Liu Jianping; Li Jiakai

2009-01-01

Objective: To compare the clinical effectiveness of ozone (O 3 ) nucleus pulposus ablation only with that of O 3 nucleus pulposus ablation combined with intervertebral facet joint injection of compound Betamethasome in treating lumbar disk herniation accompanied with intervertebral facet arthritis. Methods: Eighty patients with lumbar disk herniation and intervertebral facet arthritis were equally and randomly divided into two groups. Under CT guidance, O 3 nucleus pulposus ablation was performed in patients of group A(n=40), while O 3 nucleus pulposus ablation combined with intervertebral facet joint injection of compound Betamethasome (0.5-1 ml) was carried out in patients of group B(n=40). Using double blind method the therapeutic effectiveness was evaluated before and 1 week,3,6-months after the procedure by an Oswestry Low Back Pain Disability Questionnaire. Results: One week after the procedure the effective rate of group A and group B was 65% and 82.5% respectively. Three and six months after the treatment, the effective rate was 75% and 70% respectively for group A, while it was 90% and 92.5% respectively for group B. The difference between two groups was significant (P 3 combined with intervertebral facet joint injection of compound Betamethasome is an effective and safe treatment for lumbar disk herniation accompanied with intervertebral facet arthritis.It is worth popularizing this technique in clinical practice. (authors)

Tissue Engineering in Regenerative Dental Therapy

Directory of Open Access Journals (Sweden)

Hiral Jhaveri-Desai

2011-01-01

Full Text Available Tissue engineering is amongst the latest exciting technologies having impacted the field of dentistry. Initially considered as a futuristic approach, tissue engineering is now being successfully applied in regenerative surgery. This article reviews the important determinants of tissue engineering and how they contribute to the improvement of wound healing and surgical outcomes in the oral region. Furthermore, we shall address the clinical applications of engineering involving oral and maxillofacial surgical and periodontal procedures along with other concepts that are still in experimental phase of development. This knowledge will aid the surgical and engineering researchers to comprehend the collaboration between these fields leading to extounding dental applications and to ever-continuing man-made miracles in the field of human science.

Stem cells in bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Seong, Jeong Min [Department of Preventive and Social Dentistry and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik [Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Mantalaris, Anathathios, E-mail: yshwang@khu.ac.k [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom)

2010-12-15

Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

Stem cells in bone tissue engineering

International Nuclear Information System (INIS)

Seong, Jeong Min; Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik; Mantalaris, Anathathios

2010-01-01

Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

Imaging in cellular and tissue engineering

CERN Document Server

Yu, Hanry

2013-01-01

Details on specific imaging modalities for different cellular and tissue engineering applications are scattered throughout articles and chapters in the literature. Gathering this information into a single reference, Imaging in Cellular and Tissue Engineering presents both the fundamentals and state of the art in imaging methods, approaches, and applications in regenerative medicine. The book underscores the broadening scope of imaging applications in cellular and tissue engineering. It covers a wide range of optical and biological applications, including the repair or replacement of whole tiss

Recent Progress of Fabrication of Cell Scaffold by Electrospinning Technique for Articular Cartilage Tissue Engineering

Directory of Open Access Journals (Sweden)

Yingge Zhou

2018-01-01

Full Text Available As a versatile nanofiber manufacturing technique, electrospinning has been widely employed for the fabrication of tissue engineering scaffolds. Since the structure of natural extracellular matrices varies substantially in different tissues, there has been growing awareness of the fact that the hierarchical 3D structure of scaffolds may affect intercellular interactions, material transportation, fluid flow, environmental stimulation, and so forth. Physical blending of the synthetic and natural polymers to form composite materials better mimics the composition and mechanical properties of natural tissues. Scaffolds with element gradient, such as growth factor gradient, have demonstrated good potentials to promote heterogeneous cell growth and differentiation. Compared to 2D scaffolds with limited thicknesses, 3D scaffolds have superior cell differentiation and development rate. The objective of this review paper is to review and discuss the recent trends of electrospinning strategies for cartilage tissue engineering, particularly the biomimetic, gradient, and 3D scaffolds, along with future prospects of potential clinical applications.

Membrane supported scaffold architectures for tissue engineering

NARCIS (Netherlands)

Bettahalli Narasimha, M.S.

2011-01-01

Tissue engineering aims at restoring or regenerating a damaged tissue. Often the tissue recreation occurs by combining cells, derived from a patient biopsy, onto a 3D porous matrix, functioning as a scaffold. One of the current limitations of tissue engineering is the inability to provide sufficient

Antibacterial glass and glass-biodegradable matrix composites for bone tissue engineering

OpenAIRE

Fernandes, João Pedro Silva

2017-01-01

Multiple joint and bone diseases affect millions of people worldwide. In fact the Bone and Joint Decade’s association predicted that the percentage of people over 50 years of age affected by bone diseases will double by 2020. Bone diseases commonly require the need for surgical intervention, often involving partial or total bone substitution. Therefore biodegradable biomaterials designed as bone tissue engineered (BTE) devices to be implanted into the human body, function as a ...

Nanomaterials for Craniofacial and Dental Tissue Engineering.

Science.gov (United States)

Li, G; Zhou, T; Lin, S; Shi, S; Lin, Y

2017-07-01

Tissue engineering shows great potential as a future treatment for the craniofacial and dental defects caused by trauma, tumor, and other diseases. Due to the biomimetic features and excellent physiochemical properties, nanomaterials are of vital importance in promoting cell growth and stimulating tissue regeneration in tissue engineering. For craniofacial and dental tissue engineering, the frequently used nanomaterials include nanoparticles, nanofibers, nanotubes, and nanosheets. Nanofibers are attractive for cell invasion and proliferation because of their resemblance to extracellular matrix and the presence of large pores, and they have been used as scaffolds in bone, cartilage, and tooth regeneration. Nanotubes and nanoparticles improve the mechanical and chemical properties of scaffold, increase cell attachment and migration, and facilitate tissue regeneration. In addition, nanofibers and nanoparticles are also used as a delivery system to carry the bioactive agent in bone and tooth regeneration, have better control of the release speed of agent upon degradation of the matrix, and promote tissue regeneration. Although applications of nanomaterials in tissue engineering remain in their infancy with numerous challenges to face, the current results indicate that nanomaterials have massive potential in craniofacial and dental tissue engineering.

Fibre-reinforced hydrogels for tissue engineering

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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).

Micro- and nanotechnology in cardiovascular tissue engineering.

Science.gov (United States)

Zhang, Boyang; Xiao, Yun; Hsieh, Anne; Thavandiran, Nimalan; Radisic, Milica

2011-12-09

While in nature the formation of complex tissues is gradually shaped by the long journey of development, in tissue engineering constructing complex tissues relies heavily on our ability to directly manipulate and control the micro-cellular environment in vitro. Not surprisingly, advancements in both microfabrication and nanofabrication have powered the field of tissue engineering in many aspects. Focusing on cardiac tissue engineering, this paper highlights the applications of fabrication techniques in various aspects of tissue engineering research: (1) cell responses to micro- and nanopatterned topographical cues, (2) cell responses to patterned biochemical cues, (3) controlled 3D scaffolds, (4) patterned tissue vascularization and (5) electromechanical regulation of tissue assembly and function.

Tissue engineering: state of the art in oral rehabilitation.

Science.gov (United States)

Scheller, E L; Krebsbach, P H; Kohn, D H

2009-05-01

More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering.

Gene therapy for cartilage and bone tissue engineering

CERN Document Server

Hu, Yu-Chen

2014-01-01

"Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

The collagen structure of bovine intervertebral disc studied using polarization-sensitive optical coherence tomography

Energy Technology Data Exchange (ETDEWEB)

Matcher, Stephen J; Winlove, C Peter; Gangnus, Sergei V [Present address: JSC ' Saratovneftegeophysics' , Saratov (Russian Federation)

2004-04-07

Polarization-sensitive optical coherence tomography (PS-OCT) is used to measure the birefringence properties of bovine intervertebral disc and equine flexor tendon. For equine tendon the birefringence {delta}n is (6.0 {+-} 0.2) x 10{sup -3} at a wavelength of 1.3 {mu}m. This is somewhat larger than the values reported for bovine tendon. The surface region of the annulus fibrosus of a freshly excised intact bovine intervertebral disc displays an identical value of birefringence, {delta}n = (6.0 {+-} 0.6) x 10{sup -3} at 1.3 {mu}m. The nucleus pulposus does not display birefringence, the measured apparent value of {delta}n = (0.39 {+-} 0.01) x 10{sup -3} being indistinguishable from the effects of depolarization due to multiple scattering. A clear difference is found between the depth-resolved retardance of equine tendon and that of bovine intervertebral disc. This apparently relates to the lamellar structure of the latter tissue, in which the collagen fibre orientation alternates between successive lamellae. A semi-empirical model based on Jones calculus shows that the measurements are in reasonable agreement with previous optical and x-ray data. These results imply that PS-OCT could be a useful tool to study collagen organization within the intervertebral disc in vitro and possibly in vivo and its variation with applied load and disease.

The collagen structure of bovine intervertebral disc studied using polarization-sensitive optical coherence tomography

International Nuclear Information System (INIS)

Matcher, Stephen J; Winlove, C Peter; Gangnus, Sergei V

2004-01-01

Polarization-sensitive optical coherence tomography (PS-OCT) is used to measure the birefringence properties of bovine intervertebral disc and equine flexor tendon. For equine tendon the birefringence Δn is (6.0 ± 0.2) x 10 -3 at a wavelength of 1.3 μm. This is somewhat larger than the values reported for bovine tendon. The surface region of the annulus fibrosus of a freshly excised intact bovine intervertebral disc displays an identical value of birefringence, Δn = (6.0 ± 0.6) x 10 -3 at 1.3 μm. The nucleus pulposus does not display birefringence, the measured apparent value of Δn = (0.39 ± 0.01) x 10 -3 being indistinguishable from the effects of depolarization due to multiple scattering. A clear difference is found between the depth-resolved retardance of equine tendon and that of bovine intervertebral disc. This apparently relates to the lamellar structure of the latter tissue, in which the collagen fibre orientation alternates between successive lamellae. A semi-empirical model based on Jones calculus shows that the measurements are in reasonable agreement with previous optical and x-ray data. These results imply that PS-OCT could be a useful tool to study collagen organization within the intervertebral disc in vitro and possibly in vivo and its variation with applied load and disease

Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

Science.gov (United States)

Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

Nanocarbons in Electrospun Polymeric Nanomats for Tissue Engineering: A Review

Directory of Open Access Journals (Sweden)

Roberto Scaffaro

2017-02-01

Full Text Available Electrospinning is a versatile process technology, exploited for the production of fibers with varying diameters, ranging from nano- to micro-scale, particularly useful for a wide range of applications. Among these, tissue engineering is particularly relevant to this technology since electrospun fibers offer topological structure features similar to the native extracellular matrix, thus providing an excellent environment for the growth of cells and tissues. Recently, nanocarbons have been emerging as promising fillers for biopolymeric nanofibrous scaffolds. In fact, they offer interesting physicochemical properties due to their small size, large surface area, high electrical conductivity and ability to interface/interact with the cells/tissues. Nevertheless, their biocompatibility is currently under debate and strictly correlated to their surface characteristics, in terms of chemical composition, hydrophilicity and roughness. Among the several nanofibrous scaffolds prepared by electrospinning, biopolymer/nanocarbons systems exhibit huge potential applications, since they combine the features of the matrix with those determined by the nanocarbons, such as conductivity and improved bioactivity. Furthermore, combining nanocarbons and electrospinning allows designing structures with engineered patterns at both nano- and microscale level. This article presents a comprehensive review of various types of electrospun polymer-nanocarbon currently used for tissue engineering applications. Furthermore, the differences among graphene, carbon nanotubes, nanodiamonds and fullerenes and their effect on the ultimate properties of the polymer-based nanofibrous scaffolds is elucidated and critically reviewed.

Porous titanium bases for osteochondral tissue engineering

Science.gov (United States)

Nover, Adam B.; Lee, Stephanie L.; Georgescu, Maria S.; Howard, Daniel R.; Saunders, Reuben A.; Yu, William T.; Klein, Robert W.; Napolitano, Anthony P.; Ateshian, Gerard A.

2015-01-01

Tissue engineering of osteochondral grafts may offer a cell-based alternative to native allografts, which are in short supply. Previous studies promote the fabrication of grafts consisting of a viable cell-seeded hydrogel integrated atop a porous, bone-like metal. Advantages of the manufacturing process have led to the evaluation of porous titanium as the bone-like base material. Here, porous titanium was shown to support the growth of cartilage to produce native levels of Young’s modulus, using a clinically relevant cell source. Mechanical and biochemical properties were similar or higher for the osteochondral constructs compared to chondral-only controls. Further investigation into the mechanical influence of the base on the composite material suggests that underlying pores may decrease interstitial fluid pressurization and applied strains, which may be overcome by alterations to the base structure. Future studies aim to optimize titanium-based tissue engineered osteochondral constructs to best match the structural architecture and strength of native grafts. Statement of Significance The studies described in this manuscript follow up on previous studies from our lab pertaining to the fabrication of osteochondral grafts that consist of a bone-like porous metal and a chondrocyte-seeded hydrogel. Here, tissue engineered osteochondral grafts were cultured to native stiffness using adult chondrocytes, a clinically relevant cell source, and a porous titanium base, a material currently used in clinical implants. This porous titanium is manufactured via selective laser melting, offering the advantages of precise control over shape, pore size, and orientation. Additionally, this manuscript describes the mechanical influence of the porous base, which may have applicability to porous bases derived from other materials. PMID:26320541

Potential applications of three-dimensional structure of silk fibroin/poly(ester-urethane) urea nanofibrous scaffold in heart valve tissue engineering

Science.gov (United States)

Du, Juan; Zhu, Tonghe; Yu, Haiyan; Zhu, Jingjing; Sun, Changbing; Wang, Jincheng; Chen, Sihao; Wang, Jihu; Guo, Xuran

2018-07-01

Tissue engineering heart valves (TEHV) are thought to have many advantages in low immunogenicity, good histocompatibility, excellent mechanical properties. In this paper, we reported the fabrication and characterization of a novel composite nanofibrous scaffold consisting of silk fibroin (SF) and poly(ester-urethane) urea (LDI-PEUU) by using electrospinning. Chemical and physical properties of scaffolds were evaluated using scanning electron microscopy, attenuated total reflectance Fourier transform infrared, X-ray diffraction, contact angle measurement, thermogravimetric analysis, biodegradation test and tensile strength analysis. We determined that the composite scaffolds supported the growth of human umbilical vein endothelial cell (HUVEC). The results of cell proliferation and cell morphology indicate that SF/LDI-PEUU nanofibers promoted cell viability, which supporting the application in tissue engineering. All results clarified that SF/LDI-PEUU (40:60) nanofibrous scaffolds meet the required specifications for tissue engineering and could be used as a promising construct for heart valve tissue engineering.

Degradation and biocompatibility of porous nano-hydroxyapatite/polyurethane composite scaffold for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Dong Zhihong [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064 (China); Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050 (China); Li Yubao, E-mail: nic7504@scu.edu.cn [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064 (China); Zou Qin [Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064 (China)

2009-04-01

Porous scaffold containing 30 wt% nano-hydroxyapatite (n-HA) and 70 wt% polyurethane (PU) from castor oil was prepared by a foaming method and investigated by X-ray diffraction (XRD), Fourier transform infrared absorption (FTIR), scanning electron microscopy (SEM) techniques. The results show that n-HA particles disperse homogeneously in the PU matrix. The porous scaffold has not only macropores of 100-800 {mu}m in size but also a lot of micropores on the walls of macropores. The porosity and compressive strength of scaffold are 80% and 271 kPa, respectively. After soaking in simulated body fluid (SBF), hydrolysis and deposition partly occur on the scaffold. The biological evaluation in vitro and in vivo shows that the n-HA/PU scaffold is non-cytotoxic and degradable. The porous structure provides a good microenvironment for cell adherence, growth and proliferation. The n-HA/PU composite scaffold can be satisfied with the basic requirement for tissue engineering, and has the potential to be applied in repair and substitute of human menisci of the knee-joint and articular cartilage.

Piezoelectric polymers as biomaterials for tissue engineering applications.

Science.gov (United States)

Ribeiro, Clarisse; Sencadas, Vítor; Correia, Daniela M; Lanceros-Méndez, Senentxu

2015-12-01

Tissue engineering often rely on scaffolds for supporting cell differentiation and growth. Novel paradigms for tissue engineering include the need of active or smart scaffolds in order to properly regenerate specific tissues. In particular, as electrical and electromechanical clues are among the most relevant ones in determining tissue functionality in tissues such as muscle and bone, among others, electroactive materials and, in particular, piezoelectric ones, show strong potential for novel tissue engineering strategies, in particular taking also into account the existence of these phenomena within some specific tissues, indicating their requirement also during tissue regeneration. This referee reports on piezoelectric materials used for tissue engineering applications. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and a start point for novel research pathways in the most relevant and challenging open questions. Copyright © 2015 Elsevier B.V. All rights reserved.

The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

International Nuclear Information System (INIS)

Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick; Jackson, David

2009-01-01

Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

Using Polymeric Scaffolds for Vascular Tissue Engineering

Directory of Open Access Journals (Sweden)

Alida Abruzzo

2014-01-01

Full Text Available With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for small-diameter (<6 mm inner diameter vascular graft that can provide long-term patency. Despite the technological improvements, restenosis and graft thrombosis continue to hamper the success of the implants. Vascular tissue engineering is a new field that has undergone enormous growth over the last decade and has proposed valid solutions for blood vessels repair. The goal of vascular tissue engineering is to produce neovessels and neoorgan tissue from autologous cells using a biodegradable polymer as a scaffold. The most important advantage of tissue-engineered implants is that these tissues can grow, remodel, rebuild, and respond to injury. This review describes the development of polymeric materials over the years and current tissue engineering strategies for the improvement of vascular conduits.

A high throughput mechanical screening device for cartilage tissue engineering.

Science.gov (United States)

Mohanraj, Bhavana; Hou, Chieh; Meloni, Gregory R; Cosgrove, Brian D; Dodge, George R; Mauck, Robert L

2014-06-27

Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome, given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying 'hits', or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput. © 2013 Published by Elsevier Ltd.

Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering

Directory of Open Access Journals (Sweden)

Chengdong Xiong

2009-07-01

Full Text Available Abstract In this study, we report the physico-chemical and biological properties of a novel biodegradable composite scaffold made of nano-hydroxyapatite and natural derived polymers of chitosan and carboxymethyl cellulose, namely, n-HA/CS/CMC, which was prepared by freeze-drying method. The physico-chemical properties of n-HA/CS/CMC scaffold were tested by infrared absorption spectra (IR, transmission electron microscope(TEM, scanning electron microscope(SEM, universal material testing machine and phosphate buffer solution (PBS soaking experiment. Besides, the biological properties were evaluated by MG63 cells and Mesenchymal stem cells (MSCs culture experiment in vitro and a short period implantation study in vivo. The results show that the composite scaffold is mainly formed through the ionic crossing-linking of the two polyions between CS and CMC, and n-HA is incorporated into the polyelectrolyte matrix of CS-CMC without agglomeration, which endows the scaffold with good physico-chemical properties such as highly interconnected porous structure, high compressive strength and good structural stability and degradation. More important, the results of cells attached, proliferated on the scaffold indicate that the scaffold is non-toxic and has good cell biocompatibility, and the results of implantation experiment in vivo further confirm that the scaffold has good tissue biocompatibility. All the above results suggest that the novel degradable n-HA/CS/CMC composite scaffold has a great potential to be used as bone tissue engineering material.

Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering

Science.gov (United States)

Liuyun, Jiang; Yubao, Li; Chengdong, Xiong

2009-01-01

In this study, we report the physico-chemical and biological properties of a novel biodegradable composite scaffold made of nano-hydroxyapatite and natural derived polymers of chitosan and carboxymethyl cellulose, namely, n-HA/CS/CMC, which was prepared by freeze-drying method. The physico-chemical properties of n-HA/CS/CMC scaffold were tested by infrared absorption spectra (IR), transmission electron microscope(TEM), scanning electron microscope(SEM), universal material testing machine and phosphate buffer solution (PBS) soaking experiment. Besides, the biological properties were evaluated by MG63 cells and Mesenchymal stem cells (MSCs) culture experiment in vitro and a short period implantation study in vivo. The results show that the composite scaffold is mainly formed through the ionic crossing-linking of the two polyions between CS and CMC, and n-HA is incorporated into the polyelectrolyte matrix of CS-CMC without agglomeration, which endows the scaffold with good physico-chemical properties such as highly interconnected porous structure, high compressive strength and good structural stability and degradation. More important, the results of cells attached, proliferated on the scaffold indicate that the scaffold is non-toxic and has good cell biocompatibility, and the results of implantation experiment in vivo further confirm that the scaffold has good tissue biocompatibility. All the above results suggest that the novel degradable n-HA/CS/CMC composite scaffold has a great potential to be used as bone tissue engineering material. PMID:19594953

Modeling collagen remodeling in tissue engineered cardiovascular tissues

NARCIS (Netherlands)

Soares, A.L.F.

2012-01-01

Commonly, heart valve replacements consist of non-living materials lacking the ability to grow, repair and remodel. Tissue engineering (TE) offers a promising alternative to these replacement strategies since it can overcome its disadvantages. The technique aims to create an autologous living tissue

Fabrication of Nanohydroxyapatite/Poly(caprolactone Composite Microfibers Using Electrospinning Technique for Tissue Engineering Applications

Directory of Open Access Journals (Sweden)

Mohd Izzat Hassan

2014-01-01

Full Text Available Tissue engineering fibrous scaffolds serve as three-dimensional (3D environmental framework by mimicking the extracellular matrix (ECM for cells to grow. Biodegradable polycaprolactone (PCL microfibers were fabricated to mimic the ECM as a scaffold with 7.5% (w/v and 12.5% (w/v concentrations. Lower PCL concentration of 7.5% (w/v resulted in microfibers with bead defects. The average diameter of fibers increased at higher voltage and the distance of tip to collector. Further investigation was performed by the incorporation of nanosized hydroxyapatite (nHA into microfibers. The incorporation of 10% (w/w nHA with 7.5% (w/v PCL solution produced submicron sized beadless fibers. The microfibrous scaffolds were evaluated using various techniques. Biodegradable PCL and nHA/PCL could be promising for tissue engineering scaffold application.

Oligoaniline-based conductive biomaterials for tissue engineering.

Science.gov (United States)

Zarrintaj, Payam; Bakhshandeh, Behnaz; Saeb, Mohammad Reza; Sefat, Farshid; Rezaeian, Iraj; Ganjali, Mohammad Reza; Ramakrishna, Seeram; Mozafari, Masoud

2018-05-01

The science and engineering of biomaterials have improved the human life expectancy. Tissue engineering is one of the nascent strategies with an aim to fulfill this target. Tissue engineering scaffolds are one of the most significant aspects of the recent tissue repair strategies; hence, it is imperative to design biomimetic substrates with suitable features. Conductive substrates can ameliorate the cellular activity through enhancement of cellular signaling. Biocompatible polymers with conductivity can mimic the cells' niche in an appropriate manner. Bioconductive polymers based on aniline oligomers can potentially actualize this purpose because of their unique and tailoring properties. The aniline oligomers can be positioned within the molecular structure of other polymers, thus painter acting with the side groups of the main polymer or acting as a comonomer in their backbone. The conductivity of oligoaniline-based conductive biomaterials can be tailored to mimic the electrical and mechanical properties of targeted tissues/organs. These bioconductive substrates can be designed with high mechanical strength for hard tissues such as the bone and with high elasticity to be used for the cardiac tissue or can be synthesized in the form of injectable hydrogels, particles, and nanofibers for noninvasive implantation; these structures can be used for applications such as drug/gene delivery and extracellular biomimetic structures. It is expected that with progress in the fields of biomaterials and tissue engineering, more innovative constructs will be proposed in the near future. This review discusses the recent advancements in the use of oligoaniline-based conductive biomaterials for tissue engineering and regenerative medicine applications. The tissue engineering applications of aniline oligomers and their derivatives have recently attracted an increasing interest due to their electroactive and biodegradable properties. However, no reports have systematically reviewed

Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular Matrix.

Science.gov (United States)

Piotrowski-Daspit, Alexandra S; Nelson, Celeste M

2016-07-10

The architecture of branched organs such as the lungs, kidneys, and mammary glands arises through the developmental process of branching morphogenesis, which is regulated by a variety of soluble and physical signals in the microenvironment. Described here is a method created to study the process of branching morphogenesis by forming engineered three-dimensional (3D) epithelial tissues of defined shape and size that are completely embedded within an extracellular matrix (ECM). This method enables the formation of arrays of identical tissues and enables the control of a variety of environmental factors, including tissue geometry, spacing, and ECM composition. This method can also be combined with widely used techniques such as traction force microscopy (TFM) to gain more information about the interactions between cells and their surrounding ECM. The protocol can be used to investigate a variety of cell and tissue processes beyond branching morphogenesis, including cancer invasion.

Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Pon-On, Weeraphat, E-mail: fsciwpp@ku.ac.th [Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University (Thailand); Department of Physiology, Faculty of Science, Mahidol University (Thailand); Tang, I-Ming [ThEP Center, Commission of Higher Education, 328 Si Ayutthaya Rd. (Thailand); Department of Materials Science, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand)

2014-05-01

In the present study, composite scaffolds made with different weight ratios (0.5:1, 1:1 and 2:1) of bioactive glass (15Ca:80Si:5P) (BG)/polyvinyl alcohol (PVA) (PVABG) and chitosan (Chi)/collagen (Col) (ChiCol) were prepared by three mechanical freeze–thaw followed by freeze-drying to obtain the porous scaffolds. The mechanical properties and the in vitro biocompatibility of the composite scaffolds to simulated body fluid (SBF) and to rat osteoblast-like UMR-106 cells were investigated. The results from the studies indicated that the porosity and compressive strength were controlled by the weight ratio of PVABG:ChiCol. The highest compressive modulus of the composites made was 214.64 MPa which was for the 1:1 weight ratio PVABG:ChiCol. Mineralization study in SBF showed the formation of apatite crystals on the PVABG:ChiCol surface after 7 days of incubation. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the PVABG:ChiCol surface. MTT and ALP tests on the 1:1 weight ratio PVABG:ChiCol composite indicated that the UMR-106 cells were viable. Alkaline phosphatase activity was found to increase with increasing culturing time. In addition, we showed the potential of PVABG:ChiCol drug delivery through PBS solution studies. 81.14% of BSA loading had been achieved and controlled release for over four weeks was observed. Our results indicated that the PVABG:ChiCol composites, especially the 1:1 weight ratio composite exhibited significantly improved mechanical, mineral deposition, biological properties and controlled release. This made them potential candidates for bone tissue engineering applications. - Graphical abstract: Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications. - Highlights: • Preparation of PVABG:ChiCol hybrid composites and their bioactivities • Mechanical

Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications

International Nuclear Information System (INIS)

Pon-On, Weeraphat; Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Tang, I-Ming

2014-01-01

In the present study, composite scaffolds made with different weight ratios (0.5:1, 1:1 and 2:1) of bioactive glass (15Ca:80Si:5P) (BG)/polyvinyl alcohol (PVA) (PVABG) and chitosan (Chi)/collagen (Col) (ChiCol) were prepared by three mechanical freeze–thaw followed by freeze-drying to obtain the porous scaffolds. The mechanical properties and the in vitro biocompatibility of the composite scaffolds to simulated body fluid (SBF) and to rat osteoblast-like UMR-106 cells were investigated. The results from the studies indicated that the porosity and compressive strength were controlled by the weight ratio of PVABG:ChiCol. The highest compressive modulus of the composites made was 214.64 MPa which was for the 1:1 weight ratio PVABG:ChiCol. Mineralization study in SBF showed the formation of apatite crystals on the PVABG:ChiCol surface after 7 days of incubation. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the PVABG:ChiCol surface. MTT and ALP tests on the 1:1 weight ratio PVABG:ChiCol composite indicated that the UMR-106 cells were viable. Alkaline phosphatase activity was found to increase with increasing culturing time. In addition, we showed the potential of PVABG:ChiCol drug delivery through PBS solution studies. 81.14% of BSA loading had been achieved and controlled release for over four weeks was observed. Our results indicated that the PVABG:ChiCol composites, especially the 1:1 weight ratio composite exhibited significantly improved mechanical, mineral deposition, biological properties and controlled release. This made them potential candidates for bone tissue engineering applications. - Graphical abstract: Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications. - Highlights: • Preparation of PVABG:ChiCol hybrid composites and their bioactivities • Mechanical

Evaluating protein incorporation and release in electrospun composite scaffolds for bone tissue engineering applications.

Science.gov (United States)

Briggs, Tonye; Matos, Jeffrey; Collins, George; Arinzeh, Treena Livingston

2015-10-01

Electrospun polymer/ceramic composites have gained interest for use as scaffolds for bone tissue engineering applications. In this study, we investigated methods to incorporate Platelet Derived Growth Factor-BB (PDGF-BB) in electrospun polycaprolactone (PCL) or PCL prepared with polyethylene oxide (PEO), where both contained varying levels (up to 30 wt %) of ceramic composed of biphasic calcium phosphates, hydroxyapatite (HA)/β-tricalcium phosphate (TCP). Using a model protein, lysozyme, we compared two methods of protein incorporation, adsorption and emulsion electrospinning. Adsorption of lysozyme on scaffolds with ceramic resulted in minimal release of lysozyme over time. Using emulsion electrospinning, lysozyme released from scaffolds containing a high concentration of ceramic where the majority of the release occurred at later time points. We investigated the effect of reducing the electrostatic interaction between the protein and the ceramic on protein release with the addition of the cationic surfactant, cetyl trimethylammonium bromide (CTAB). In vitro release studies demonstrated that electrospun scaffolds prepared with CTAB released more lysozyme or PDGF-BB compared with scaffolds without the cationic surfactant. Human mesenchymal stem cells (MSCs) on composite scaffolds containing PDGF-BB incorporated through emulsion electrospinning expressed higher levels of osteogenic markers compared to scaffolds without PDGF-BB, indicating that the bioactivity of the growth factor was maintained. This study revealed methods for incorporating growth factors in polymer/ceramic scaffolds to promote osteoinduction and thereby facilitate bone regeneration. © 2015 Wiley Periodicals, Inc.

Silk fibroin in tissue engineering.

Science.gov (United States)

Kasoju, Naresh; Bora, Utpal

2012-07-01

Tissue engineering (TE) is a multidisciplinary field that aims at the in vitro engineering of tissues and organs by integrating science and technology of cells, materials and biochemical factors. Mimicking the natural extracellular matrix is one of the critical and challenging technological barriers, for which scaffold engineering has become a prime focus of research within the field of TE. Amongst the variety of materials tested, silk fibroin (SF) is increasingly being recognized as a promising material for scaffold fabrication. Ease of processing, excellent biocompatibility, remarkable mechanical properties and tailorable degradability of SF has been explored for fabrication of various articles such as films, porous matrices, hydrogels, nonwoven mats, etc., and has been investigated for use in various TE applications, including bone, tendon, ligament, cartilage, skin, liver, trachea, nerve, cornea, eardrum, dental, bladder, etc. The current review extensively covers the progress made in the SF-based in vitro engineering and regeneration of various human tissues and identifies opportunities for further development of this field. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanoparticles for bone tissue engineering.

Science.gov (United States)

Vieira, Sílvia; Vial, Stephanie; Reis, Rui L; Oliveira, J Miguel

2017-05-01

Tissue engineering (TE) envisions the creation of functional substitutes for damaged tissues through integrated solutions, where medical, biological, and engineering principles are combined. Bone regeneration is one of the areas in which designing a model that mimics all tissue properties is still a challenge. The hierarchical structure and high vascularization of bone hampers a TE approach, especially in large bone defects. Nanotechnology can open up a new era for TE, allowing the creation of nanostructures that are comparable in size to those appearing in natural bone. Therefore, nanoengineered systems are now able to more closely mimic the structures observed in naturally occurring systems, and it is also possible to combine several approaches - such as drug delivery and cell labeling - within a single system. This review aims to cover the most recent developments on the use of different nanoparticles for bone TE, with emphasis on their application for scaffolds improvement; drug and gene delivery carriers, and labeling techniques. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:590-611, 2017. © 2017 American Institute of Chemical Engineers.

Vascular complications of prosthetic inter-vertebral discs.

Science.gov (United States)

Daly, Kevin J; Ross, E Raymond S; Norris, Heather; McCollum, Charles N

2006-10-01

Five consecutive cases of prosthetic inter-vertebral disc displacement with severe vascular complications on revisional surgery are described. The objective of this case report is to warn spinal surgeons that major vascular complications are likely with anterior displacement of inter-vertebral discs. We have not been able to find a previous report on vascular complications associated with anterior displacement of prosthetic inter-vertebral discs. In all five patients the prosthetic disc had eroded into the bifurcation of the inferior vena cava and the left common iliac vein. In three cases the aortic bifurcation was also involved. The fibrosis was so severe that dissecting out the arteries and veins to provide access to the relevant disc proved impossible. Formal division of the left common iliac vein and artery with subsequent repair was our solution. Anterior inter-vertebral disc displacement was associated with severe vascular injury. Preventing anterior disc displacement is essential in disc design. In the event of anterior displacement, disc removal should be planned with a Vascular Surgeon.

Oxidative stress participates in age-related changes in rat lumbar intervertebral discs.

Science.gov (United States)

Hou, Gang; Lu, Huading; Chen, Mingjuan; Yao, Hui; Zhao, Huiqing

2014-01-01

Aging is a major factor associated with lumber intervertebral disc degeneration, and oxidative stress is known to play an essential role in the pathogenesis of many age-related diseases. In this study, we investigated oxidative stress in intervertebral discs of Wistar rats in three different age groups: youth, adult, and geriatric. Age-related intervertebral disc changes were examined by histological analysis. In addition, oxidative stress was evaluated by assessing nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPPs). Intervertebral disc, but not serum, NO concentrations significantly differed between the three groups. Serum and intervertebral disc SOD activity gradually decreased with age. Furthermore, both serum and intervertebral disc MDA and AOPP levels gradually increased with age. Our studies suggest that oxidative stress is associated with age-related intervertebral disc changes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Functional characterization of detergent-decellularized equine tendon extracellular matrix for tissue engineering applications.

Directory of Open Access Journals (Sweden)

Daniel W Youngstrom

Full Text Available Natural extracellular matrix provides a number of distinct advantages for engineering replacement orthopedic tissue due to its intrinsic functional properties. The goal of this study was to optimize a biologically derived scaffold for tendon tissue engineering using equine flexor digitorum superficialis tendons. We investigated changes in scaffold composition and ultrastructure in response to several mechanical, detergent and enzymatic decellularization protocols using microscopic techniques and a panel of biochemical assays to evaluate total protein, collagen, glycosaminoglycan, and deoxyribonucleic acid content. Biocompatibility was also assessed with static mesenchymal stem cell (MSC culture. Implementation of a combination of freeze/thaw cycles, incubation in 2% sodium dodecyl sulfate (SDS, trypsinization, treatment with DNase-I, and ethanol sterilization produced a non-cytotoxic biomaterial free of appreciable residual cellular debris with no significant modification of biomechanical properties. These decellularized tendon scaffolds (DTS are suitable for complex tissue engineering applications, as they provide a clean slate for cell culture while maintaining native three-dimensional architecture.

MR imaging of spondylolytic spondylolisthesis: changes of intervertebral foramen and nerve root compression

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Hyung [Ajou Univ. College of Medicine, Seoul (Korea, Republic of); Chung, Tae Sub; Kim, Young Soo [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

1999-08-01

To evaluate the factors affecting intervertebral foramen stenosis and nerve root compression in spondylolytic spondylolisthesis. We investigated 120 intervertebral foramina of 60 patients with spondylolytic spondylolisthesis who had undergone lumbar MRI. A retrospective review of their MR images revealed the degree of intervertebral foramen stenosis and causes of nerve root compression. The relationship between disk height diminution following spondylolysis and degree of intervertebral foramen stenosis was also evaluated. Forty eight of 60 patients showed a similar degree of intervertebral foramen stenosis, and in 12 patients the degree of stenosis was different. In 110 intervertebral foramina, stenosis of both the superior and inferior compartments of intervertebral foramina was demonstrated. In 37 of 120 cases (30.8%), stenosis was mild ; in 44 of 120 (36.7%) it was modcrate, and in 29 of 120 (24.2%) it was severe. Stenosis of the inferior compartment was demonstrated in ten of 120 intervertebral foramina (8.3%). Nerve root compression was caused by posterior bulging of the intervertebral disk (65/120), descent of the pedicle (51/120), an isthmic bony segment above the site of spondylolytic (44/120), a bony spur formed at a spondylolytic site (11/120), and fibrocartilaginous callus at a spondylolytic site (5/48). In all cases there was degenerative change of the intervertebral disk at the affected level. There was no relationship between degree of disk height diminution and degree of intervertebral foramen stenosis (p > 0.05). The degree of intervertebral foramen stenosis and causes of nerve root compression in spondylolytic spondylolisthesis are variable, and MRI demonstrates them precisely. There was no positive relationship between degree of nerve root compression at an intervertebral foramen and degree of spondylolysis and degeneration of an intervertebral foramen. The degree of nerve root compression is believed to be another criterion for describing

MR imaging of spondylolytic spondylolisthesis: changes of intervertebral foramen and nerve root compression

International Nuclear Information System (INIS)

Kim, Ji Hyung; Chung, Tae Sub; Kim, Young Soo

1999-01-01

To evaluate the factors affecting intervertebral foramen stenosis and nerve root compression in spondylolytic spondylolisthesis. We investigated 120 intervertebral foramina of 60 patients with spondylolytic spondylolisthesis who had undergone lumbar MRI. A retrospective review of their MR images revealed the degree of intervertebral foramen stenosis and causes of nerve root compression. The relationship between disk height diminution following spondylolysis and degree of intervertebral foramen stenosis was also evaluated. Forty eight of 60 patients showed a similar degree of intervertebral foramen stenosis, and in 12 patients the degree of stenosis was different. In 110 intervertebral foramina, stenosis of both the superior and inferior compartments of intervertebral foramina was demonstrated. In 37 of 120 cases (30.8%), stenosis was mild ; in 44 of 120 (36.7%) it was modcrate, and in 29 of 120 (24.2%) it was severe. Stenosis of the inferior compartment was demonstrated in ten of 120 intervertebral foramina (8.3%). Nerve root compression was caused by posterior bulging of the intervertebral disk (65/120), descent of the pedicle (51/120), an isthmic bony segment above the site of spondylolytic (44/120), a bony spur formed at a spondylolytic site (11/120), and fibrocartilaginous callus at a spondylolytic site (5/48). In all cases there was degenerative change of the intervertebral disk at the affected level. There was no relationship between degree of disk height diminution and degree of intervertebral foramen stenosis (p > 0.05). The degree of intervertebral foramen stenosis and causes of nerve root compression in spondylolytic spondylolisthesis are variable, and MRI demonstrates them precisely. There was no positive relationship between degree of nerve root compression at an intervertebral foramen and degree of spondylolysis and degeneration of an intervertebral foramen. The degree of nerve root compression is believed to be another criterion for describing

Injectable biomaterials for adipose tissue engineering

International Nuclear Information System (INIS)

Young, D A; Christman, K L

2012-01-01

Adipose tissue engineering has recently gained significant attention from materials scientists as a result of the exponential growth of soft tissue filler procedures being performed within the clinic. While several injectable materials are currently being marketed for filling subcutaneous voids, they often face limited longevity due to rapid resorption. Their inability to encourage natural adipose formation or ingrowth necessitates repeated injections for a prolonged effect and thus classifies them as temporary fillers. As a result, a significant need for injectable materials that not only act as fillers but also promote in vivo adipogenesis is beginning to be realized. This paper will discuss the advantages and disadvantages of commercially available soft tissue fillers. It will then summarize the current state of research using injectable synthetic materials, biopolymers and extracellular matrix-derived materials for adipose tissue engineering. Furthermore, the successful attributes observed across each of these materials will be outlined along with a discussion of the current difficulties and future directions for adipose tissue engineering. (paper)

Extracellular matrix fragmentation in young, healthy cartilaginous tissues.

Science.gov (United States)

Craddock, R J; Hodson, N W; Ozols, M; Shearer, T; Hoyland, J A; Sherratt, M J

2018-02-09

Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC) and the nucleus pulposus (NP) of the intervertebral disc (IVD). Whilst structural heterogeneity of intact aggrecan ( containing three globular domains) is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months), bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 %) were fragmented (lacking one or more globular domains). Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa) comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis). As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2) as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2), it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally) and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

Bladder tissue engineering through nanotechnology.

Science.gov (United States)

Harrington, Daniel A; Sharma, Arun K; Erickson, Bradley A; Cheng, Earl Y

2008-08-01

The field of tissue engineering has developed in phases: initially researchers searched for "inert" biomaterials to act solely as replacement structures in the body. Then, they explored biodegradable scaffolds--both naturally derived and synthetic--for the temporary support of growing tissues. Now, a third phase of tissue engineering has developed, through the subcategory of "regenerative medicine." This renewed focus toward control over tissue morphology and cell phenotype requires proportional advances in scaffold design. Discoveries in nanotechnology have driven both our understanding of cell-substrate interactions, and our ability to influence them. By operating at the size regime of proteins themselves, nanotechnology gives us the opportunity to directly speak the language of cells, through reliable, repeatable creation of nanoscale features. Understanding the synthesis of nanoscale materials, via "top-down" and "bottom-up" strategies, allows researchers to assess the capabilities and limits inherent in both techniques. Urology research as a whole, and bladder regeneration in particular, are well-positioned to benefit from such advances, since our present technology has yet to reach the end goal of functional bladder restoration. In this article, we discuss the current applications of nanoscale materials to bladder tissue engineering, and encourage researchers to explore these interdisciplinary technologies now, or risk playing catch-up in the future.

Trends in Tissue Engineering for Blood Vessels

Directory of Open Access Journals (Sweden)

Judee Grace Nemeno-Guanzon

2012-01-01

Full Text Available Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient’s conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.

Development of Novel Biodegradable Amino Acid Ester Based Polyphosphazene-Hydroxyapatite Composites for Bone Tissue Engineering

National Research Council Canada - National Science Library

Sethuraman, Swaminathan; Nair, Lakshmi S; Singh, Anurima; Bender, Jared D; Greish, Yaser E; Brown, Paul W; Allcock, H. R; Laurencin, Cato T

2005-01-01

.... CPCs are attractive candidates for the development of scaffolds for bone tissue engineering, since they are moldable, resorbable, set at physiological temperature without the use of toxic chemicals...

Biodegradable Polymer-Based Scaffolds for Bone Tissue Engineering

CERN Document Server

Sultana, Naznin

2013-01-01

This book addresses the principles, methods and applications of biodegradable polymer based scaffolds for bone tissue engineering. The general principle of bone tissue engineering is reviewed and the traditional and novel scaffolding materials, their properties and scaffold fabrication techniques are explored. By acting as temporary synthetic extracellular matrices for cell accommodation, proliferation, and differentiation, scaffolds play a pivotal role in tissue engineering. This book does not only provide the comprehensive summary of the current trends in scaffolding design but also presents the new trends and directions for scaffold development for the ever expanding tissue engineering applications.

A review of evolution of electrospun tissue engineering scaffold: From two dimensions to three dimensions.

Science.gov (United States)

Ngadiman, Nor Hasrul Akhmal; Noordin, M Y; Idris, Ani; Kurniawan, Denni

2017-07-01

The potential of electrospinning process to fabricate ultrafine fibers as building blocks for tissue engineering scaffolds is well recognized. The scaffold construct produced by electrospinning process depends on the quality of the fibers. In electrospinning, material selection and parameter setting are among many factors that contribute to the quality of the ultrafine fibers, which eventually determine the performance of the tissue engineering scaffolds. The major challenge of conventional electrospun scaffolds is the nature of electrospinning process which can only produce two-dimensional electrospun mats, hence limiting their applications. Researchers have started to focus on overcoming this limitation by combining electrospinning with other techniques to fabricate three-dimensional scaffold constructs. This article reviews various polymeric materials and their composites/blends that have been successfully electrospun for tissue engineering scaffolds, their mechanical properties, and the various parameters settings that influence the fiber morphology. This review also highlights the secondary processes to electrospinning that have been used to develop three-dimensional tissue engineering scaffolds as well as the steps undertaken to overcome electrospinning limitations.

Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering.

Science.gov (United States)

Chen, Zhuoyue; Song, Yue; Zhang, Jing; Liu, Wei; Cui, Jihong; Li, Hongmin; Chen, Fulin

2017-03-01

Electrospinning is an effective means to generate nano- to micro-scale polymer fibers resembling native extracellular matrix for tissue engineering. However, a major problem of electrospun materials is that limited pore size and porosity may prevent adequate cellular infiltration and tissue ingrowth. In this study, we first prepared thin layers of hydroxyapatite nanoparticle (nHA)/poly-hydroxybutyrate (PHB) via electrospinning. We then laminated the nHA/PHB thin layers to obtain a scaffold for cell seeding and bone tissue engineering. The results demonstrated that the laminated scaffold possessed optimized cell-loading capacity. Bone marrow mesenchymal stem cells (MSCs) exhibited better adherence, proliferation and osteogenic phenotypes on nHA/PHB scaffolds than on PHB scaffolds. Thereafter, we seeded MSCs onto nHA/PHB scaffolds to fabricate bone grafts. Histological observation showed osteoid tissue formation throughout the scaffold, with most of the scaffold absorbed in the specimens 2months after implantation, and blood vessels ingrowth into the graft could be observed in the graft. We concluded that electrospun and laminated nanoscaled biocomposite scaffolds hold great therapeutic potential for bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces

Science.gov (United States)

Boys, Alexander J.; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J.; Estroff, Lara A.

2017-01-01

Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors. PMID:29333332

Fundamentals of bladder tissue engineering | Mahfouz | African ...

African Journals Online (AJOL)

Fundamentals of bladder tissue engineering. ... could affect the bladder and lead to eventual loss of its integrity, with the need for replacement or repair. ... Tissue engineering relies upon three essential pillars; the scaffold, the cells seeded on ...

Perfusion decellularization of a human limb: A novel platform for composite tissue engineering and reconstructive surgery.

Directory of Open Access Journals (Sweden)

Mattia Francesco Maria Gerli

Full Text Available Muscle and fasciocutaneous flaps taken from autologous donor sites are currently the most utilized approach for trauma repair, accounting annually for 4.5 million procedures in the US alone. However, the donor tissue size is limited and the complications related to these surgical techniques lead to morbidities, often involving the donor sites. Alternatively, recent reports indicated that extracellular matrix (ECM scaffolds boost the regenerative potential of the injured site, as shown in a small cohort of volumetric muscle loss patients. Perfusion decellularization is a bioengineering technology that allows the generation of clinical-scale ECM scaffolds with preserved complex architecture and with an intact vascular template, from a variety of donor organs and tissues. We recently reported that this technology is amenable to generate full composite tissue scaffolds from rat and non-human primate limbs. Translating this platform to human extremities could substantially benefit soft tissue and volumetric muscle loss patients providing tissue- and species-specific grafts. In this proof-of-concept study, we show the successful generation a large-scale, acellular composite tissue scaffold from a full cadaveric human upper extremity. This construct retained its morphological architecture and perfusable vascular conduits. Histological and biochemical validation confirmed the successful removal of nuclear and cellular components, and highlighted the preservation of the native extracellular matrix components. Our results indicate that perfusion decellularization can be applied to produce human composite tissue acellular scaffolds. With its preserved structure and vascular template, these biocompatible constructs, could have significant advantages over the currently implanted matrices by means of nutrient distribution, size-scalability and immunological response.

Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

DEFF Research Database (Denmark)

Chen, Muwan; Le, Dang Q S; Hein, San

2012-01-01

Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone......, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount...... of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug....

A multi-scale controlled tissue engineering scaffold prepared by 3D printing and NFES technology

Directory of Open Access Journals (Sweden)

Feifei Yan

2014-03-01

Full Text Available The current focus in the field of life science is the use of tissue engineering scaffolds to repair human organs, which has shown great potential in clinical applications. Extracellular matrix morphology and the performance and internal structure of natural organs are required to meet certain requirements. Therefore, integrating multiple processes can effectively overcome the limitations of the individual processes and can take into account the needs of scaffolds for the material, structure, mechanical properties and many other aspects. This study combined the biological 3D printing technology and the near-field electro-spinning (NFES process to prepare a multi-scale controlled tissue engineering scaffold. While using 3D printing technology to directly prepare the macro-scaffold, the compositing NFES process to build tissue micro-morphology ultimately formed a tissue engineering scaffold which has the specific extracellular matrix structure. This scaffold not only takes into account the material, structure, performance and many other requirements, but also focuses on resolving the controllability problems in macro- and micro-forming which further aim to induce cell directed differentiation, reproduction and, ultimately, the formation of target tissue organs. It has in-depth immeasurable significance to build ideal scaffolds and further promote the application of tissue engineering.

Growing tissues in real and simulated microgravity: new methods for tissue engineering.

Science.gov (United States)

Grimm, Daniela; Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Ulbrich, Claudia; Magnusson, Nils E; Infanger, Manfred; Bauer, Johann

2014-12-01

Tissue engineering in simulated (s-) and real microgravity (r-μg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-μg in Space or to s-μg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals.

Cell–scaffold interaction within engineered tissue

Energy Technology Data Exchange (ETDEWEB)

Chen, Haiping; Liu, Yuanyuan, E-mail: Yuanyuan_liu@shu.edu.cn; Jiang, Zhenglong; Chen, Weihua; Yu, Yongzhe; Hu, Qingxi

2014-05-01

The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted large amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.

Development of multilayer constructs for tissue engineering

NARCIS (Netherlands)

Bettahalli, N. M. S.; Groen, N.; Steg, H.; Unadkat, H.; de Boer, J.; van Blitterswijk, C. A.; Wessling, M.; Stamatialis, D.

The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

Development of multilayer constructs for tissue engineering

NARCIS (Netherlands)

Bettahalli Narasimha, M.S.; Groen, N.; Steg, H.; Unadkat, H.V.; de Boer, Jan; van Blitterswijk, Clemens; Wessling, Matthias; Stamatialis, Dimitrios

2014-01-01

The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

Engineering flesh : towards professional responsibility for 'lived bodies' in tissue engineering

NARCIS (Netherlands)

Derksen, M.H.G.

2008-01-01

Engineering Flesh. Towards professional responsibility for ‘lived bodies’ in Tissue Engineering This study analyses the work of biomedical engineers as normative work that affects people’s daily lives as bodies. In biomedical engineering, engineers study bodies as machine-like objects and develop

3D bioprinting and the current applications in tissue engineering.

Science.gov (United States)

Huang, Ying; Zhang, Xiao-Fei; Gao, Guifang; Yonezawa, Tomo; Cui, Xiaofeng

2017-08-01

Bioprinting as an enabling technology for tissue engineering possesses the promises to fabricate highly mimicked tissue or organs with digital control. As one of the biofabrication approaches, bioprinting has the advantages of high throughput and precise control of both scaffold and cells. Therefore, this technology is not only ideal for translational medicine but also for basic research applications. Bioprinting has already been widely applied to construct functional tissues such as vasculature, muscle, cartilage, and bone. In this review, the authors introduce the most popular techniques currently applied in bioprinting, as well as the various bioprinting processes. In addition, the composition of bioink including scaffolds and cells are described. Furthermore, the most current applications in organ and tissue bioprinting are introduced. The authors also discuss the challenges we are currently facing and the great potential of bioprinting. This technology has the capacity not only in complex tissue structure fabrication based on the converted medical images, but also as an efficient tool for drug discovery and preclinical testing. One of the most promising future advances of bioprinting is to develop a standard medical device with the capacity of treating patients directly on the repairing site, which requires the development of automation and robotic technology, as well as our further understanding of biomaterials and stem cell biology to integrate various printing mechanisms for multi-phasic tissue engineering. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Science.gov (United States)

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.

Pericyte-targeting drug delivery and tissue engineering

Directory of Open Access Journals (Sweden)

Kang E

2016-05-01

Full Text Available Eunah Kang,1 Jong Wook Shin2 1School of Chemical Engineering and Material Science, 2Division of Allergic and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, Chung-Ang University, Dongjak-Gu, Seoul, South Korea Abstract: Pericytes are contractile mural cells that wrap around the endothelial cells of capillaries and venules. Depending on the triggers by cellular signals, pericytes have specific functionality in tumor microenvironments, properties of potent stem cells, and plasticity in cellular pathology. These features of pericytes can be activated for the promotion or reduction of angiogenesis. Frontier studies have exploited pericyte-targeting drug delivery, using pericyte-specific peptides, small molecules, and DNA in tumor therapy. Moreover, the communication between pericytes and endothelial cells has been applied to the induction of vessel neoformation in tissue engineering. Pericytes may prove to be a novel target for tumor therapy and tissue engineering. The present paper specifically reviews pericyte-specific drug delivery and tissue engineering, allowing insight into the emerging research targeting pericytes. Keywords: pericytes, pericyte-targeting drug delivery, tissue engineering, platelet-derived growth factor, angiogenesis, vascular remodeling

ZnO Nanostructures for Tissue Engineering Applications

Directory of Open Access Journals (Sweden)

Marco Laurenti

2017-11-01

Full Text Available This review focuses on the most recent applications of zinc oxide (ZnO nanostructures for tissue engineering. ZnO is one of the most investigated metal oxides, thanks to its multifunctional properties coupled with the ease of preparing various morphologies, such as nanowires, nanorods, and nanoparticles. Most ZnO applications are based on its semiconducting, catalytic and piezoelectric properties. However, several works have highlighted that ZnO nanostructures may successfully promote the growth, proliferation and differentiation of several cell lines, in combination with the rise of promising antibacterial activities. In particular, osteogenesis and angiogenesis have been effectively demonstrated in numerous cases. Such peculiarities have been observed both for pure nanostructured ZnO scaffolds as well as for three-dimensional ZnO-based hybrid composite scaffolds, fabricated by additive manufacturing technologies. Therefore, all these findings suggest that ZnO nanostructures represent a powerful tool in promoting the acceleration of diverse biological processes, finally leading to the formation of new living tissue useful for organ repair.

Tissue engineering of ligaments for reconstructive surgery.

Science.gov (United States)

Hogan, MaCalus V; Kawakami, Yohei; Murawski, Christopher D; Fu, Freddie H

2015-05-01

The use of musculoskeletal bioengineering and regenerative medicine applications in orthopaedic surgery has continued to evolve. The aim of this systematic review was to address tissue-engineering strategies for knee ligament reconstruction. A systematic review of PubMed/Medline using the terms "knee AND ligament" AND "tissue engineering" OR "regenerative medicine" was performed. Two authors performed the search, independently assessed the studies for inclusion, and extracted the data for inclusion in the review. Both preclinical and clinical studies were reviewed, and the articles deemed most relevant were included in this article to provide relevant basic science and recent clinical translational knowledge concerning "tissue-engineering" strategies currently used in knee ligament reconstruction. A total of 224 articles were reviewed in our initial PubMed search. Non-English-language studies were excluded. Clinical and preclinical studies were identified, and those with a focus on knee ligament tissue-engineering strategies including stem cell-based therapies, growth factor administration, hybrid biomaterial, and scaffold development, as well as mechanical stimulation modalities, were reviewed. The body of knowledge surrounding tissue-engineering strategies for ligament reconstruction continues to expand. Presently, various tissue-engineering techniques have some potential advantages, including faster recovery, better ligamentization, and possibly, a reduction of recurrence. Preclinical research of these novel therapies continues to provide promising results. There remains a need for well-designed, high-powered comparative clinical studies to serve as a foundation for successful translation into the clinical setting going forward. Level IV, systematic review of Level IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Self-assembled composite matrix in a hierarchical 3-D scaffold for bone tissue engineering

DEFF Research Database (Denmark)

Chen, Muwan; Le, Dang Quang Svend; Baatrup, Anette

2011-01-01

It is of high clinical relevance in bone tissue engineering that scaffolds promote a high seeding efficiency of cells capable of osteogenic differentiation, such as human bone marrow-derived mesenchymal stem cells (hMSCs). We evaluated the effects of a novel polycaprolactone (PCL) scaffold on h...

Cardiac tissue engineering

Directory of Open Access Journals (Sweden)

MILICA RADISIC

2005-03-01

Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid

NARCIS (Netherlands)

Sivan, S.-S.; Wachtel, E.; Tsitron, E.; Sakkee, N.; Ham, F. van der; Groot, J.de; Roberts, S.; Maroudas, A.

2008-01-01

Knowledge of rates of protein turnover is important for a quantitative understanding of tissue synthesis and catabolism. In this work, we have used the racemization of aspartic acid as a marker for the turnover of collagen obtained from healthy and pathological human intervertebral disc matrices. We

Engineering Parameters in Bioreactor's Design: A Critical Aspect in Tissue Engineering

Science.gov (United States)

Amoabediny, Ghassem; Pouran, Behdad; Tabesh, Hadi; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Khatibi, Nahid; Mottaghy, Khosrow; Zandieh-Doulabi, Behrouz

2013-01-01

Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors. PMID:24000327

Engineering parameters in bioreactor's design: a critical aspect in tissue engineering.

Science.gov (United States)

Salehi-Nik, Nasim; Amoabediny, Ghassem; Pouran, Behdad; Tabesh, Hadi; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Khatibi, Nahid; Anisi, Fatemeh; Mottaghy, Khosrow; Zandieh-Doulabi, Behrouz

2013-01-01

Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue.

Science.gov (United States)

Kowalski, William J; Yuan, Fangping; Nakane, Takeichiro; Masumoto, Hidetoshi; Dwenger, Marc; Ye, Fei; Tinney, Joseph P; Keller, Bradley B

2017-08-01

Biological tissues have complex, three-dimensional (3D) organizations of cells and matrix factors that provide the architecture necessary to meet morphogenic and functional demands. Disordered cell alignment is associated with congenital heart disease, cardiomyopathy, and neurodegenerative diseases and repairing or replacing these tissues using engineered constructs may improve regenerative capacity. However, optimizing cell alignment within engineered tissues requires quantitative 3D data on cell orientations and both efficient and validated processing algorithms. We developed an automated method to measure local 3D orientations based on structure tensor analysis and incorporated an adaptive subregion size to account for multiple scales. Our method calculates the statistical concentration parameter, κ, to quantify alignment, as well as the traditional orientational order parameter. We validated our method using synthetic images and accurately measured principal axis and concentration. We then applied our method to confocal stacks of cleared, whole-mount engineered cardiac tissues generated from human-induced pluripotent stem cells or embryonic chick cardiac cells and quantified cardiomyocyte alignment. We found significant differences in alignment based on cellular composition and tissue geometry. These results from our synthetic images and confocal data demonstrate the efficiency and accuracy of our method to measure alignment in 3D tissues.

Engineered Muscle Actuators: Cells and Tissues

National Research Council Canada - National Science Library

Dennis, Robert G; Herr, Hugh; Parker, Kevin K; Larkin, Lisa; Arruda, Ellen; Baar, Keith

2007-01-01

.... Our primary objectives were to engineer living skeletal muscle actuators in culture using integrated bioreactors to guide tissue development and to maintain tissue contractility, to achieve 50...

An Overview of Recent Patents on Musculoskeletal Interface Tissue Engineering

Science.gov (United States)

Rao, Rohit T.; Browe, Daniel P.; Lowe, Christopher J.; Freeman, Joseph W.

2018-01-01

Interface tissue engineering involves the development of engineered grafts that promote integration between multiple tissue types. Musculoskeletal tissue interfaces are critical to the safe and efficient transmission of mechanical forces between multiple musculoskeletal tissues e.g. between ligament and bone tissue. However, these interfaces often do not physiologically regenerate upon injury, resulting in impaired tissue function. Therefore, interface tissue engineering approaches are considered to be particularly relevant for the structural restoration of musculoskeletal tissues interfaces. In this article we provide an overview of the various strategies used for engineering musculoskeletal tissue interfaces with a specific focus on the recent important patents that have been issued for inventions that were specifically designed for engineering musculoskeletal interfaces as well as those that show promise to be adapted for this purpose. PMID:26577344

Tissue Engineering: Toward a New Era of Medicine.

Science.gov (United States)

Shafiee, Ashkan; Atala, Anthony

2017-01-14

The goal of tissue engineering is to mitigate the critical shortage of donor organs via in vitro fabrication of functional biological structures. Tissue engineering is one of the most prominent examples of interdisciplinary fields, where scientists with different backgrounds work together to boost the quality of life by addressing critical health issues. Many different fields, such as developmental and molecular biology, as well as technologies, such as micro- and nanotechnologies and additive manufacturing, have been integral for advancing the field of tissue engineering. Over the past 20 years, spectacular advancements have been achieved to harness nature's ability to cure diseased tissues and organs. Patients have received laboratory-grown tissues and organs made out of their own cells, thus eliminating the risk of rejection. However, challenges remain when addressing more complex solid organs such as the heart, liver, and kidney. Herein, we review recent accomplishments as well as challenges that must be addressed in the field of tissue engineering and provide a perspective regarding strategies in further development.

Bioreactors in tissue engineering - principles, applications and commercial constraints.

Science.gov (United States)

Hansmann, Jan; Groeber, Florian; Kahlig, Alexander; Kleinhans, Claudia; Walles, Heike

2013-03-01

Bioreactor technology is vital for tissue engineering. Usually, bioreactors are used to provide a tissue-specific physiological in vitro environment during tissue maturation. In addition to this most obvious application, bioreactors have the potential to improve the efficiency of the overall tissue-engineering concept. To date, a variety of bioreactor systems for tissue-specific applications have been developed. Of these, some systems are already commercially available. With bioreactor technology, various functional tissues of different types were generated and cultured in vitro. Nevertheless, these efforts and achievements alone have not yet led to many clinically successful tissue-engineered implants. We review possible applications for bioreactor systems within a tissue-engineering process and present basic principles and requirements for bioreactor development. Moreover, the use of bioreactor systems for the expansion of clinically relevant cell types is addressed. In contrast to cell expansion, for the generation of functional three-dimensional tissue equivalents, additional physical cues must be provided. Therefore, bioreactors for musculoskeletal tissue engineering are discussed. Finally, bioreactor technology is reviewed in the context of commercial constraints. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biofabrication of soft tissue templates for engineering the bone-ligament interface.

Science.gov (United States)

Harris, Ella; Liu, Yurong; Cunniffe, Grainne; Morrissey, David; Carroll, Simon; Mulhall, Kevin; Kelly, Daniel J

2017-10-01

Regenerating damaged tissue interfaces remains a significant clinical challenge, requiring recapitulation of the structure, composition, and function of the native enthesis. In the ligament-to-bone interface, this region transitions from ligament to fibrocartilage, to calcified cartilage and then to bone. This gradation in tissue types facilitates the transfer of load between soft and hard structures while minimizing stress concentrations at the interface. Previous attempts to engineer the ligament-bone interface have utilized various scaffold materials with an array of various cell types and/or biological cues. The primary goal of this study was to engineer a multiphased construct mimicking the ligament-bone interface by driving differentiation of a single population of mesenchymal stem cells (MSCs), seeded within blended fibrin-alginate hydrogels, down an endochondral, fibrocartilaginous, or ligamentous pathway through spatial presentation of growth factors along the length of the construct within a custom-developed, dual-chamber culture system. MSCs within these engineered constructs demonstrated spatially distinct regions of differentiation, adopting either a cartilaginous or ligamentous phenotype depending on their local environment. Furthermore, there was also evidence of spatially defined progression toward an endochondral phenotype when chondrogenically primed MSCs within this construct were additionally exposed to hypertrophic cues. The study demonstrates the feasibility of engineering spatially complex soft tissues within a single MSC laden hydrogel through the defined presentation of biochemical cues. This novel approach represents a new strategy for engineering the ligament-bone interface. Biotechnol. Bioeng. 2017;114: 2400-2411. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Radiation synthesis of gelatin/CM-chitosan/{beta}-tricalcium phosphate composite scaffold for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Zhou Ying [College of Engineering, Peking University, Beijing 100871 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Xu Ling, E-mail: lingxu@pku.edu.cn [College of Engineering, Peking University, Beijing 100871 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Zhang Xiangmei; Zhao Yinghui [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Wei Shicheng, E-mail: sc-wei@pku.edu.cn [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Zhai Maolin [Beijing National Laboratory for Molecular Sciences, Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China)

2012-05-01

A series of biodegradable composite scaffolds was fabricated from an aqueous solution of gelatin, carboxymethyl chitosan (CM-chitosan) and {beta}-tricalcium phosphate ({beta}-TCP) by radiation-induced crosslinking at ambient temperature. Ultrasonic treatment on the polymer solutions significantly influenced the distribution of {beta}-TCP particles. An ultrasonic time of 20 min, followed by 30 kGy irradiation induced a crosslinked scaffold with homogeneous distribution of {beta}-TCP particles, interconnected porous structure, sound swelling capacity and mechanical strength. Fourier Transform Infrared Spectroscopy and X-ray Diffraction analysis indicated that {beta}-TCP successfully incorporated with the network of gelatin and CM-chitosan. In vivo implantation of the scaffold into the mandible of beagle dog revealed that the scaffolds had excellent biocompatibility and the presence of {beta}-TCP can accelerate bone regeneration. The comprehensive results of this study paved way for the application of gelatin/CM-chitosan/{beta}-TCP composite scaffolds as candidate of bone tissue engineering material. - Highlights: Black-Right-Pointing-Pointer Radiation induced a crosslinked scaffold with interconnected porous structure. Black-Right-Pointing-Pointer Ultrasonic time of 20 min led to homogenerously distribution of {beta}-TCP. Black-Right-Pointing-Pointer Increasing amount of {beta}-TCP would restrict the swelling properties. Black-Right-Pointing-Pointer Proper fraction of {beta}-TCP will promote the mechanical properties of the scaffolds. Black-Right-Pointing-Pointer Hybrid of {beta}-TCP promoted the bone regeneration of the mandibles of beagle dogs.

Engineering a multi-biofunctional composite using poly(ethylenimine) decorated graphene oxide for bone tissue regeneration

Science.gov (United States)

Kumar, Sachin; Raj, Shammy; Sarkar, Kishor; Chatterjee, Kaushik

2016-03-01

Toward preparing strong multi-biofunctional materials, poly(ethylenimine) (PEI) conjugated graphene oxide (GO_PEI) was synthesized using poly(acrylic acid) (PAA) as a spacer and incorporated in poly(ε-caprolactone) (PCL) at different fractions. GO_PEI significantly promoted the proliferation and formation of focal adhesions in human mesenchymal stem cells (hMSCs) on PCL. GO_PEI was highly potent in inducing stem cell osteogenesis leading to near doubling of alkaline phosphatase expression and mineralization over neat PCL with 5% filler content and was ~50% better than GO. Remarkably, 5% GO_PEI was as potent as soluble osteoinductive factors. Increased adsorption of osteogenic factors due to the amine and oxygen containing functional groups on GO_PEI augment stem cell differentiation. GO_PEI was also highly efficient in imparting bactericidal activity with 85% reduction in counts of E. coli colonies compared to neat PCL at 5% filler content and was more than twice as efficient as GO. This may be attributed to the synergistic effect of the sharp edges of the particles along with the presence of the different chemical moieties. Thus, GO_PEI based polymer composites can be utilized to prepare bioactive resorbable biomaterials as an alternative to using labile biomolecules for fabricating orthopedic devices for fracture fixation and tissue engineering.Toward preparing strong multi-biofunctional materials, poly(ethylenimine) (PEI) conjugated graphene oxide (GO_PEI) was synthesized using poly(acrylic acid) (PAA) as a spacer and incorporated in poly(ε-caprolactone) (PCL) at different fractions. GO_PEI significantly promoted the proliferation and formation of focal adhesions in human mesenchymal stem cells (hMSCs) on PCL. GO_PEI was highly potent in inducing stem cell osteogenesis leading to near doubling of alkaline phosphatase expression and mineralization over neat PCL with 5% filler content and was ~50% better than GO. Remarkably, 5% GO_PEI was as potent as soluble

Functional tissue engineering : ten more years of progress

NARCIS (Netherlands)

Guilak, F.; Baaijens, F.P.T.

2014-01-01

"Functional tissue engineering" is a subset of the field of tissue engineering that was proposed by the United States National Committee on Biomechanics over a decade ago in order to place more emphasis on the roles of biomechanics and mechanobiology in tissue repair and regeneration. Over the past

Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications.

Science.gov (United States)

Tay, Chor Yong; Irvine, Scott Alexander; Boey, Freddy Y C; Tan, Lay Poh; Venkatraman, Subbu

2011-05-23

The development of biomedical devices and reconstruction of functional ex vivo tissues often requires the need to fabricate biomimetic surfaces with features of sub-micrometer precision. This can be achieved with the advancements in micro-/nano-engineering techniques, allowing researchers to manipulate a plethora of cellular behaviors at the cell-biomaterial interface. Systematic studies conducted on these 2D engineered surfaces have unraveled numerous novel findings that can potentially be integrated as part of the design consideration for future 2D and 3D biomaterials and will no doubt greatly benefit tissue engineering. In this review, recent developments detailing the use of micro-/nano-engineering techniques to direct cellular orientation and function pertinent to soft tissue engineering will be highlighted. Particularly, this article aims to provide valuable insights into distinctive cell interactions and reactions to controlled surfaces, which can be exploited to understand the mechanisms of cell growth on micro-/nano-engineered interfaces, and to harness this knowledge to optimize the performance of 3D artificial soft tissue grafts and biomedical applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biomaterials in myocardial tissue engineering

Science.gov (United States)

Reis, Lewis A.; Chiu, Loraine L. Y.; Feric, Nicole; Fu, Lara; Radisic, Milica

2016-01-01

Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternate sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augment injured or impaired myocardium with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds—composed of natural or synthetic biomaterials, or decellularized extracellular matrix—that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue, and finally injectable biomaterials (hydrogels)designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. PMID:25066525

Application of polarization OCT in tissue engineering

Science.gov (United States)

Yang, Ying; Ahearne, Mark; Bagnaninchi, Pierre O.; Hu, Bin; Hampson, Karen; El Haj, Alicia J.

2008-02-01

For tissue engineering of load-bearing tissues, such as bone, tendon, cartilage, and cornea, it is critical to generate a highly organized extracellular matrix. The major component of the matrix in these tissues is collagen, which usually forms a highly hierarchical structure with increasing scale from fibril to fiber bundles. These bundles are ordered into a 3D network to withstand forces such as tensile, compressive or shear. To induce the formation of organized matrix and create a mimic body environment for tissue engineering, in particular, tendon tissue engineering, we have fabricated scaffolds with features to support the formation of uniaxially orientated collagen bundles. In addition, mechanical stimuli were applied to stimulate tissue formation and matrix organization. In parallel, we seek a nondestructive tool to monitor the changes within the constructs in response to these external stimulations. Polarizationsensitive optical coherence tomography (PSOCT) is a non-destructive technique that provides functional imaging, and possesses the ability to assess in depth the organization of tissue. In this way, an engineered tissue construct can be monitored on-line, and correlated with the application of different stimuli by PSOCT. We have constructed a PSOCT using a superluminescent diode (FWHM 52nm) in this study and produced two types of tendon constructs. The matrix structural evolution under different mechanical stimulation has been evaluated by the PSOCT. The results in this study demonstrate that PSOCT was a powerful tool enabling us to monitor non-destructively and real time the progressive changes in matrix organization and assess the impact of various stimuli on tissue orientation and growth.

Challenges and opportunities for tissue-engineering polarized epithelium.

Science.gov (United States)

Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

2014-02-01

The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

Engineering vascular development for tissue regeneration

NARCIS (Netherlands)

Rivron, N.C.

2010-01-01

Tissue engineering and regenerative medicine aim at restoring a damaged tissue by recreating in vitro or promoting its regeneratin in vovo. The vasculature is central to these therapies for the irrigation of the defective tissue (oxygen, nutrients or circulating regenerative cells) and as an

Engineering spinal fusion: evaluating ceramic materials for cell based tissue engineered approaches

NARCIS (Netherlands)

Wilson, C.E.

2011-01-01

The principal aim of this thesis was to advance the development of tissue engineered posterolateral spinal fusion by investigating the potential of calcium phosphate ceramic materials to support cell based tissue engineered bone formation. This was accomplished by developing several novel model

Controlled drug release for tissue engineering.

Science.gov (United States)

Rambhia, Kunal J; Ma, Peter X

2015-12-10

Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Developing 3D microstructures for tissue engineering

DEFF Research Database (Denmark)

Mohanty, Soumyaranjan

casting process to generate various large scale tissue engineering constructs with single pore geometry with the desired mechanical stiffness and porosity. In addition, a new technique was developed to fa bricate dual-pore scaffolds for various tissue-engineering applications where 3D printing...... materials have been developed and tested for enhancing the differentiation of hiPSC-derived hepatocytes and fabricating biodegradable scaffolds for in-vivo tissue engineering applications. Along with various scaffolds fabrication methods we finally presented an optimized study of hepatic differentiation...... of hiPSC-derived DE cells cultured for 25 days in a 3D perfusion bioreactor system with an array of 16 small-scale tissue-bioreactors with integrated dual-pore pore scaffolds and flow rates. Hepatic differentiation and functionality of hiPSC-derived hepatocytes were successfully assessed and compared...

Extracellular matrix fragmentation in young, healthy cartilaginous tissues

Directory of Open Access Journals (Sweden)

RJ Craddock

2018-02-01

Full Text Available Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC and the nucleus pulposus (NP of the intervertebral disc (IVD. Whilst structural heterogeneity of intact aggrecan ( containing three globular domains is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months, bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 % were fragmented (lacking one or more globular domains. Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p < 0.0001. In contrast, fibrillar collagen appeared structurally intact and tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis. As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2 as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2, it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

3D conductive nanocomposite scaffold for bone tissue engineering

Directory of Open Access Journals (Sweden)

Shahini A

2013-12-01

Full Text Available Aref Shahini,1 Mostafa Yazdimamaghani,2 Kenneth J Walker,2 Margaret A Eastman,3 Hamed Hatami-Marbini,4 Brenda J Smith,5 John L Ricci,6 Sundar V Madihally,2 Daryoosh Vashaee,1 Lobat Tayebi2,7 1School of Electrical and Computer Engineering, Helmerich Advanced Technology Research Center, 2School of Chemical Engineering, 3Department of Chemistry, 4School of Mechanical and Aerospace Engineering, 5Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA; 6Department of Biomaterials and Biomimetics, New York University, New York, NY; 7School of Material Science and Engineering, Helmerich Advanced Technology Research Center, Oklahoma State University, Tulsa, OK, USA Abstract: Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene poly(4-styrene sulfonate (PEDOT:PSS, in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent

Preparation of collagen/polyurethane/knitted silk as a composite scaffold for tendon tissue engineering.

Science.gov (United States)

Sharifi-Aghdam, Maryam; Faridi-Majidi, Reza; Derakhshan, Mohammad Ali; Chegeni, Arash; Azami, Mahmoud

2017-07-01

The main objective of this study was to prepare a hybrid three-dimensional scaffold that mimics natural tendon tissues. It has been found that a knitted silk shows good mechanical strength; however, cell growth on the bare silk is not desirable. Hence, electrospun collagen/polyurethane combination was used to cover knitted silk. A series of collagen and polyurethane solutions (4%-7% w/v) in aqueous acetic acid were prepared and electrospun. According to obtained scanning electron microscopy images from pure collagen and polyurethane nanofibers, concentration was set constant at 5% (w/v) for blend solutions of collagen/polyurethane. Afterward, blend solutions with the weight ratios of 75/25, 50/50 and 25/75 were electrospun. Scanning electron microscopy images demonstrated the smooth and uniform morphology for the optimized nanofibers. The least fibers diameter among three weight ratios was found for collagen/polyurethane (25/75) which was 100.86 ± 40 nm and therefore was selected to be electrospun on the knitted silk. Attenuated total reflectance-Fourier transform infrared spectra confirmed the chemical composition of obtained electrospun nanofibers on the knitted silk. Tensile test of the specimens including blend nanofiber, knitted silk and commercial tendon substitute examined and indicated that collagen/polyurethane-coated knitted silk has appropriate mechanical properties as a scaffold for tendon tissue engineering. Then, Alamar Blue assay of the L929 fibroblast cell line seeded on the prepared scaffolds demonstrated appropriate viability of the cells with a significant proliferation on the scaffold containing more collagen content. The results illustrate that the designed structure would be promising for being used as a temporary substitute for tendon repair.

The role of mechanical loading in ligament tissue engineering.

Science.gov (United States)

Benhardt, Hugh A; Cosgriff-Hernandez, Elizabeth M

2009-12-01

Tissue-engineered ligaments have received growing interest as a promising alternative for ligament reconstruction when traditional transplants are unavailable or fail. Mechanical stimulation was recently identified as a critical component in engineering load-bearing tissues. It is well established that living tissue responds to altered loads through endogenous changes in cellular behavior, tissue organization, and bulk mechanical properties. Without the appropriate biomechanical cues, new tissue formation lacks the necessary collagenous organization and alignment for sufficient load-bearing capacity. Therefore, tissue engineers utilize mechanical conditioning to guide tissue remodeling and improve the performance of ligament grafts. This review provides a comparative analysis of the response of ligament and tendon fibroblasts to mechanical loading in current bioreactor studies. The differential effect of mechanical stimulation on cellular processes such as protease production, matrix protein synthesis, and cell proliferation is examined in the context of tissue engineering design.

MicroRNAs in skin tissue engineering.

Science.gov (United States)

Miller, Kyle J; Brown, David A; Ibrahim, Mohamed M; Ramchal, Talisha D; Levinson, Howard

2015-07-01

35.2 million annual cases in the U.S. require clinical intervention for major skin loss. To meet this demand, the field of skin tissue engineering has grown rapidly over the past 40 years. Traditionally, skin tissue engineering relies on the "cell-scaffold-signal" approach, whereby isolated cells are formulated into a three-dimensional substrate matrix, or scaffold, and exposed to the proper molecular, physical, and/or electrical signals to encourage growth and differentiation. However, clinically available bioengineered skin equivalents (BSEs) suffer from a number of drawbacks, including time required to generate autologous BSEs, poor allogeneic BSE survival, and physical limitations such as mass transfer issues. Additionally, different types of skin wounds require different BSE designs. MicroRNA has recently emerged as a new and exciting field of RNA interference that can overcome the barriers of BSE design. MicroRNA can regulate cellular behavior, change the bioactive milieu of the skin, and be delivered to skin tissue in a number of ways. While it is still in its infancy, the use of microRNAs in skin tissue engineering offers the opportunity to both enhance and expand a field for which there is still a vast unmet clinical need. Here we give a review of skin tissue engineering, focusing on the important cellular processes, bioactive mediators, and scaffolds. We further discuss potential microRNA targets for each individual component, and we conclude with possible future applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules.

Science.gov (United States)

Zhang, Wujie; Choi, Jung K; He, Xiaoming

2017-02-01

Construction of vascularized tissues is one of the major challenges of tissue engineering. The goal of this study was to engineer 3D microvascular tissues by incorporating the HUVEC-CS cells with a collagen/alginate-chitosan (AC) microcapsule scaffold. In the presence of AC microcapsules, a 3D vascular-like network was clearly observable. The results indicated the importance of AC microcapsules in engineering microvascular tissues -- providing support and guiding alignment of HUVEC-CS cells. This approach provides an alternative and promising method for constructing vascularized tissues.

Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules

OpenAIRE

Zhang, Wujie; Choi, Jung K.; He, Xiaoming

2017-01-01

Construction of vascularized tissues is one of the major challenges of tissue engineering. The goal of this study was to engineer 3D microvascular tissues by incorporating the HUVEC-CS cells with a collagen/alginate-chitosan (AC) microcapsule scaffold. In the presence of AC microcapsules, a 3D vascular-like network was clearly observable. The results indicated the importance of AC microcapsules in engineering microvascular tissues -- providing support and guiding alignment of HUVEC-CS cells. ...

3D Photo-Fabrication for Tissue Engineering and Drug Delivery

Directory of Open Access Journals (Sweden)

Rúben F. Pereira

2015-03-01

Full Text Available The most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing milieu present in human tissues, and that stimulate tissue repair and regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native extracellular matrix (ECM on a cellular and subcellular scale. Photo-fabrication techniques have already been used to generate 3D environments with precise architectures and heterogeneous composition, through a multi-layer procedure involving the selective photocrosslinking reaction of a light-sensitive prepolymer. Cells and therapeutic molecules can be included in the initial hydrogel precursor solution, and processed into 3D constructs. Recently, photo-fabrication has also been explored to dynamically modulate hydrogel features in real time, providing enhanced control of cell fate and delivery of bioactive compounds. This paper focuses on the use of 3D photo-fabrication techniques to produce advanced constructs for tissue regeneration and drug delivery applications. State-of-the-art photo-fabrication techniques are described, with emphasis on the operating principles and biofabrication strategies to create spatially controlled patterns of cells and bioactive factors. Considering its fast processing, spatiotemporal control, high resolution, and accuracy, photo-fabrication is assuming a critical role in the design of sophisticated 3D constructs. This technology is capable of providing appropriate environments for tissue regeneration, and regulating the spatiotemporal delivery of therapeutics.

Imaging of degenerative lumbar intervertebral discs; linking anatomy, pathology and imaging.

Science.gov (United States)

Adams, Ashok; Roche, Oran; Mazumder, Asif; Davagnanam, Indran; Mankad, Kshitij

2014-09-01

Low back pain is a common medical condition that has significant implications for healthcare providers and the UK economy. Low back pain can be classified as 'specific' in which an underlying pathophysiological mechanism is identified (eg, herniated intervertebral disc). Advanced imaging should be performed in this situation and in those patients in whom systemic disease is strongly suspected. In the majority (approximately 90%), low back pain in 'non specific' and there is a weak correlation with imaging abnormalities. This is an area of ongoing research and remains controversial in terms of imaging approach and treatment (eg, theory of discogenic pain, interpretation and treatment of endplate changes). With regards Modic endplate changes, current research suggests that an infective component may be involved that may identify novel potential treatments in patients with chronic low back pain refractory to other treatment modalities. MRI is the imaging modality of choice for the assessment of degenerative changes in intervertebral discs. MRI has superior soft tissue contrast resolution when compared to other imaging modalities (eg, plain radiography, CT). An understanding of normal anatomy and MR appearances of intervertebral discs, particularly with regards to how these appearances change with advancing age, is required to aid image interpretation. Knowledge of the spectrum of degenerative processes that may occur in the intervertebral discs is required in order to identify and explain abnormal MRI appearances. As the communication of MRI findings may guide therapeutic decision making and surgical intervention, the terminology used by radiologists must be accurate and consistent. Therefore, description of degenerative disc changes in the current paper is based on the most up-to-date recommendations, the aim being to aid reporting by radiologists and interpretation of reports by referring clinicians. Published by the BMJ Publishing Group Limited. For permission to

Silk fibroin based biomimetic artificial extracellular matrix for hepatic tissue engineering applications

International Nuclear Information System (INIS)

Kasoju, Naresh; Bora, Utpal

2012-01-01

Hepatic tissue engineering, which aims to construct artificial liver tissues, requires a suitable extracellular matrix (ECM) for growth and proliferation of metabolically active hepatocytes. The current paper describes the development of a biomimetic artificial ECM, for hepatic tissue engineering applications, by mimicking the architectural features and biochemical composition of native ECM. Electrospinning was chosen as the fabrication technique of choice, while regenerated silk fibroin (RSF) and galactosylated chitosan (GalCS) were chosen as materials of choice. Poly(ethylene oxide) was used as a processing aid. Methodical optimization studies were performed to obtain smooth and continuous nanofibers with homogenous size distribution. Extensive characterization studies were performed to determine its morphological, physical, chemical/structural, thermal and cytotoxicity properties. Subsequently, detailed in vitro hepatocyte compatibility studies were performed using HepG2 cell line. Remarkably, the studies revealed that the growth, viability, metabolic activity and proliferation of hepatocytes were relatively superior on RSF–GalCS scaffold than on pure RSF and pure GalCS. In summary, the electrospun nanofibrous RSF–GalCS scaffold tries to mimic both architectural and biochemical features of native ECM, and hence could be an appropriate scaffold for in vitro engineering of hepatic tissue. However, additional experiments are needed to confirm the superiority in characteristic functionality of hepatocytes growing on RSF–GalCS scaffold in relation to RSF and GalCS scaffolds, and to test its behavior in vivo. (paper)

Expediting the transition from replacement medicine to tissue engineering.

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Coury, Arthur J

2016-06-01

In this article, an expansive interpretation of "Tissue Engineering" is proposed which is in congruence with classical and recent published definitions. I further simplify the definition of tissue engineering as: "Exerting systematic control of the body's cells, matrices and fluids." As a consequence, many medical therapies not commonly considered tissue engineering are placed in this category because of their effect on the body's responses. While the progress of tissue engineering strategies is inexorable and generally positive, it has been subject to setbacks as have many important medical therapies. Medical practice is currently undergoing a transition on several fronts (academics, start-up companies, going concerns) from the era of "replacement medicine" where body parts and functions are replaced by mechanical, electrical or chemical therapies to the era of tissue engineering where health is restored by regeneration generation or limitation of the body's tissues and functions by exploiting our expanding knowledge of the body's biological processes to produce natural, healthy outcomes.

Fibrin promotes proliferation and matrix production of intervertebral disc cells cultured in three-dimensional poly(lactic-co-glycolic acid) scaffold.

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Sha'ban, Munirah; Yoon, Sun Jung; Ko, Youn Kyung; Ha, Hyun Jung; Kim, Soon Hee; So, Jung Won; Idrus, Ruszymah Bt Hj; Khang, Gilson

2008-01-01

Previously, we have proven that fibrin and poly(lactic-co-glycolic acid) (PLGA) scaffolds facilitate cell proliferation, matrix production and early chondrogenesis of rabbit articular chondrocytes in in vitro and in vivo experiments. In this study, we evaluated the potential of fibrin/PLGA scaffold for intervertebral disc (IVD) tissue engineering using annulus fibrosus (AF) and nucleus pulposus (NP) cells in relation to potential clinical application. PLGA scaffolds were soaked in cells-fibrin suspension and polymerized by dropping thrombin-sodium chloride (CaCl(2)) solution. A PLGA-cell complex without fibrin was used as control. Higher cellular proliferation activity was observed in fibrin/PLGA-seeded AF and NP cells at each time point of 3, 7, 14 and 7 days using the MTT assay. After 3 weeks in vitro incubation, fibrin/PLGA exhibited a firmer gross morphology than PLGA groups. A significant cartilaginous tissue formation was observed in fibrin/PLGA, as proven by the development of cells cluster of various sizes and three-dimensional (3D) cartilaginous histoarchitecture and the presence of proteoglycan-rich matrix and glycosaminoglycan (GAG). The sGAG production measured by 1,9-dimethylmethylene blue (DMMB) assay revealed greater sGAG production in fibrin/PLGA than PLGA group. Immunohistochemical analyses showed expressions of collagen type II, aggrecan core protein and collagen type I genes throughout in vitro culture in both fibrin/PLGA and PLGA. In conclusion, fibrin promotes cell proliferation, stable in vitro tissue morphology, superior cartilaginous tissue formation and sGAG production of AF and NP cells cultured in PLGA scaffold. The 3D porous PLGA scaffold-cell complexes using fibrin can provide a vehicle for delivery of cells to regenerate tissue-engineered IVD tissue.

Microfluidic systems for stem cell-based neural tissue engineering.

Science.gov (United States)

Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

2016-07-05

Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

Tissue engineering and surgery: from translational studies to human trials

Directory of Open Access Journals (Sweden)

Vranckx Jan Jeroen

2017-06-01

Full Text Available Tissue engineering was introduced as an innovative and promising field in the mid-1980s. The capacity of cells to migrate and proliferate in growth-inducing medium induced great expectancies on generating custom-shaped bioconstructs for tissue regeneration. Tissue engineering represents a unique multidisciplinary translational forum where the principles of biomaterial engineering, the molecular biology of cells and genes, and the clinical sciences of reconstruction would interact intensively through the combined efforts of scientists, engineers, and clinicians. The anticipated possibilities of cell engineering, matrix development, and growth factor therapies are extensive and would largely expand our clinical reconstructive armamentarium. Application of proangiogenic proteins may stimulate wound repair, restore avascular wound beds, or reverse hypoxia in flaps. Autologous cells procured from biopsies may generate an ‘autologous’ dermal and epidermal laminated cover on extensive burn wounds. Three-dimensional printing may generate ‘custom-made’ preshaped scaffolds – shaped as a nose, an ear, or a mandible – in which these cells can be seeded. The paucity of optimal donor tissues may be solved with off-the-shelf tissues using tissue engineering strategies. However, despite the expectations, the speed of translation of in vitro tissue engineering sciences into clinical reality is very slow due to the intrinsic complexity of human tissues. This review focuses on the transition from translational protocols towards current clinical applications of tissue engineering strategies in surgery.

Co-culture systems-based strategies for articular cartilage tissue engineering.

Science.gov (United States)

Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

2018-03-01

Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

The self-assembling process and applications in tissue engineering

Science.gov (United States)

Lee, Jennifer K.; Link, Jarrett M.; Hu, Jerry C. Y.; Athanasiou, Kyriacos A.

2018-01-01

Tissue engineering strives to create neotissues capable of restoring function. Scaffold-free technologies have emerged that can recapitulate native tissue function without the use of an exogenous scaffold. This chapter will survey, in particular, the self-assembling and self-organization processes as scaffold-free techniques. Characteristics and benefits of each process are described, and key examples of tissues created using these scaffold-free processes are examined to provide guidance for future tissue engineering developments. This chapter aims to explore the potential of self-assembly and self-organization scaffold-free approaches, detailing the recent progress in the in vitro tissue engineering of biomimetic tissues with these methods, toward generating functional tissue replacements. PMID:28348174

Generalized deep-tissue hyperalgesia in patients with chronic low-back pain

DEFF Research Database (Denmark)

O'Neill, Søren; Manniche, Claus; Graven-Nielsen, Thomas

2007-01-01

be demonstrated in a group of patients with chronic low-back pain with intervertebral disc herniation. Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12 age and sex matched controls were included. Subjects were exposed to quantitative nociceptive stimuli to the infraspinatus...... in the anterior tibialis muscle compared to controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in chronic low-back pain patients with radiating pain and MRI confirmed intervertebral disc herniation, suggesting that this central sensitization should also be addressed in the pain......Some chronic painful conditions including e.g. fibromyalgia, whiplash associated disorders, endometriosis, and irritable bowel syndrome are associated with generalized musculoskeletal hyperalgesia. The aim of the present study was to determine whether generalized deep-tissue hyperalgesia could...

Recombinant protein scaffolds for tissue engineering

International Nuclear Information System (INIS)

Werkmeister, Jerome A; Ramshaw, John A M

2012-01-01

New biological materials for tissue engineering are now being developed using common genetic engineering capabilities to clone and express a variety of genetic elements that allow cost-effective purification and scaffold fabrication from these recombinant proteins, peptides or from chimeric combinations of these. The field is limitless as long as the gene sequences are known. The utility is dependent on the ease, product yield and adaptability of these protein products to the biomedical field. The development of recombinant proteins as scaffolds, while still an emerging technology with respect to commercial products, is scientifically superior to current use of natural materials or synthetic polymer scaffolds, in terms of designing specific structures with desired degrees of biological complexities and motifs. In the field of tissue engineering, next generation scaffolds will be the key to directing appropriate tissue regeneration. The initial period of biodegradable synthetic scaffolds that provided shape and mechanical integrity, but no biological information, is phasing out. The era of protein scaffolds offers distinct advantages, particularly with the combination of powerful tools of molecular biology. These include, for example, the production of human proteins of uniform quality that are free of infectious agents and the ability to make suitable quantities of proteins that are found in low quantity or are hard to isolate from tissue. For the particular needs of tissue engineering scaffolds, fibrous proteins like collagens, elastin, silks and combinations of these offer further advantages of natural well-defined structural scaffolds as well as endless possibilities of controlling functionality by genetic manipulation. (topical review)

Cryopreservation of tissue engineered constructs for bone.

Science.gov (United States)

Kofron, Michelle D; Opsitnick, Natalie C; Attawia, Mohamed A; Laurencin, Cato T

2003-11-01

The large-scale clinical use of tissue engineered constructs will require provisions for its mass availability and accessibility. Therefore, it is imperative to understand the effects of low temperature (-196 degrees C) on the tissue engineered biological system. Initial studies used samples of the osteoblast-like cell line (SaOS-2) adhered to a two-dimensional poly(lactide-co-glycolide) thin film (2D-PLAGA) or a three-dimensional poly(lactide-co-glycolide) sintered microsphere matrix (3D-PLAGA) designed for bone tissue engineering. Experimental samples were tested for their ability to maintain cell viability, following low temperature banking for one week, in solutions of the penetrating cryoprotective agents, dimethylsulfoxide (DMSO), ethylene glycol, and glycerol. Results indicated the DMSO solution yielded the greatest percent cell survival for SaOS-2 cells adhered to both the 2D- and 3D-PLAGA scaffolds; therefore, DMSO was used to cryopreserve mineralizing primary rabbit osteoblasts cells adhered to 2D-PLAGA matrices for 35 days. Results indicated retention of the extracellular matrix architecture as no statistically significant difference in the pre- and post-thaw mineralized structures was measured. Percent cell viability of the mineralized constructs following low temperature storage was approximately 50%. These are the first studies to address the issue of preservation techniques for tissue engineered constructs. The ability to successfully cryopreserve mineralized tissue engineered matrices for bone may offer an unlimited and readily available source of bone-like materials for orthopaedic applications.

Engineering Parameters in Bioreactor’s Design: A Critical Aspect in Tissue Engineering

Directory of Open Access Journals (Sweden)

Nasim Salehi-Nik

2013-01-01

Full Text Available Bioreactors are important inevitable part of any tissue engineering (TE strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

Collagen-chitosan scaffold - Lauric acid plasticizer for skin tissue engineering on burn cases

Science.gov (United States)

Widiyanti, Prihartini; Setyadi, Ewing Dian; Rudyardjo, Djony Izak

2017-02-01

The prevalence of burns in the world is more than 800 cases per one million people each year and this is the second highest cause of death due to trauma after traffic accident. Many studies are turning to skin substitute methods of tissue engineering. The purpose of this study is to determine the composition of the collagen, chitosan, and lauric acid scaffold, as well as knowing the results of the characterization of the scaffold. The synthesis of chitosan collagen lauric acid scaffold as a skin tissue was engineered using freeze dried method. Results from making of collagen chitosan lauric acid scaffold was characterized physically, biologically and mechanically by SEM, cytotoxicity, biodegradation, and tensile strength. From the morphology test, the result obtained is that pore diameter size ranges from 94.11 to 140.1 µm for samples A,B,C,D, which are in the range of normal pore size 63-150 µm, while sample E has value below the standard which is about 37.87 to 47.36 µm. From cytotoxicity assay, the result obtained is the percentage value of living cells between 20.11 to 21.51%. This value is below 50% the standard value of living cells. Incompatibility is made possible because of human error mainly the replication of washing process over the standard. Degradation testing obtained values of 19.44% - 40% by weight which are degraded during the 7 days of observation. Tensile test results obtained a range of values of 0.192 - 3.53 MPa. Only sample A (3.53 MPa) and B (1.935 MPa) meet the standard values of skin tissue scaffold that is 1-24 MPa. Based on the results of the characteristics of this study, composite chitosan collagen scaffold with lauric acid plasticizer has a potential candidate for skin tissue engineering for skin burns cases.

Bioactive glass-based scaffolds for bone tissue engineering

NARCIS (Netherlands)

Will, J.; Gerhardt, L.C.; Boccaccini, A.R.

2012-01-01

Originally developed to fill and restore bone defects, bioactive glasses are currently also being intensively investigated for bone tissue engineering applications. In this chapter, we review and discuss current knowledge on porous bone tissue engineering scaffolds made from bioactive silicate

Rabbit model of intervertebral disc degeneration by external compression device characterized by X-ray, MRI, histology, and cell viability

Directory of Open Access Journals (Sweden)

Ismail Ismail

2006-12-01

Full Text Available Appropriate experimental animal models, which mimic the degenerative process occurring in human intervertebral disc (IVD breakdown and can be used for new treatment studies such as tissue engineering or disc distraction are lacking. We studied the external compression device that used by Kroeber et al to create intervertebral disc degeneration in rabbit model characterized by X-ray, MRI, Histology, and Cell Viability. Ten NZW rabbit were randomly assigned to one of five groups. Intervertebral disc VL4-L5 are compressed using an external loading device, 1.9 MPa. First group rabbit are loaded for 14 days, second loaded for 28 days, thirth group are loaded for 14 days, and unloaded for 14 days, fourth group loaded for 28 days and unloaded for 28 days. The fifth group, rabbits underwent a sham operation. Additional, rabbits were used as sample for cell viability study. In disc height : sample in group one have biggest decreasing of disc height, that is 23.9 unit. In MRI assessment, the worst grade is grade 3. In histological score, the worst group is group three (58.69, and the best is group 4 (45.69. Group one have the largest dead cell, that are 403.5, and the smallest is group four (124.75. Trypan blue staining showed that group four have better viable cell (91.1 compare than group three (86.4. The study conclude disc degeneration can be created by external axial loading for 14 days in rabbit intervertebral disc. Duration of 28 days unloading gave better result for cells to recover. (Med J Indones 2006; 15:199-207  Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Keywords: Rabbit model –intervertebral disc degeneration- external compression device-X-ray, MRI, Histology, and Cell viabilty /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso

Matrix Remodeling During Intervertebral Disc Growth and Degeneration Detected by Multichromatic FAST Staining

Science.gov (United States)

Leung, Victor Y.L.; Chan, Wilson C.W.; Hung, Siu-Chun; Cheung, Kenneth M.C.; Chan, Danny

2009-01-01

Various imaging techniques have been used to assess degeneration of the intervertebral disc, including many histological methods, but cartilage-oriented histological stains do not clearly show the comparatively complex structures of the disc. In addition, there is no integrated method to assess efficiently both the compartmental organization and matrix composition in disc samples. In this study, a novel histological method, termed FAST staining, has been developed to investigate disc growth and degeneration by sequential staining with fast green, Alcian blue, Safranin-O, and tartrazine to generate multichromatic histological profiles (FAST profiles). This identifies the major compartments of the vertebra-disc region, including the cartilaginous endplate and multiple zones of the annulus fibrosus, by specific FAST profile patterns. A disc degeneration model in rabbit established using a previously described puncture method showed gradual but profound alteration of the FAST profile during disc degeneration, supporting continual alteration of glycosaminoglycan. Changes of the FAST profile pattern in the nucleus pulposus and annulus fibrosus of the postnatal mouse spine suggested matrix remodeling activity during the growth of intervertebral discs. In summary, we developed an effective staining method capable of defining intervertebral disc compartments in detail and showing matrix remodeling events within the disc. The FAST staining method may be used to develop a histopathological grading system to evaluate disc degeneration or malformation. (J Histochem Cytochem 57:249–256, 2009) PMID:19001641

STEM CELL ORIGIN DIFFERENTLY AFFECTS BONE TISSUE ENGINEERING STRATEGIES.

Directory of Open Access Journals (Sweden)

Monica eMattioli-Belmonte

2015-09-01

Full Text Available Bone tissue engineering is a promising research area for the improvement of traditional bone grafting procedure drawbacks. Thanks to the capability of self-renewal and multi-lineage differentiation, stem cells are one of the major actors in tissue engineering approaches, and adult mesenchymal stem cells (MSCs are considered to be appropriate for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs are the earliest- discovered and well-known stem cell population used in bone tissue engineering. However, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The successful identification and combination of tissue engineering, scaffold, progenitor cells, and physiologic signalling molecules enabled the surgeon to design, recreate the missing tissue in its near natural form. On the basis of these considerations, we analysed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e. periodontal ligament, maxillary periosteum as well as adipose-derived stem cells, in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, considering their peculiar features, they may alternatively represent interesting cell sources in different stem cell-based bone/periodontal tissue regeneration approaches.

From stem to roots: Tissue engineering in endodontics

Science.gov (United States)

Kala, M.; Banthia, Priyank; Banthia, Ruchi

2012-01-01

The vitality of dentin-pulp complex is fundamental to the life of tooth and is a priority for targeting clinical management strategies. Loss of the tooth, jawbone or both, due to periodontal disease, dental caries, trauma or some genetic disorders, affects not only basic mouth functions but aesthetic appearance and quality of life. One novel approach to restore tooth structure is based on biology: regenerative endodontic procedure by application of tissue engineering. Regenerative endodontics is an exciting new concept that seeks to apply the advances in tissue engineering to the regeneration of the pulp-dentin complex. The basic logic behind this approach is that patient-specific tissue-derived cell populations can be used to functionally replace integral tooth tissues. The development of such ‘test tube teeth’ requires precise regulation of the regenerative events in order to achieve proper tooth size and shape, as well as the development of new technologies to facilitate these processes. This article provides an extensive review of literature on the concept of tissue engineering and its application in endodontics, providing an insight into the new developmental approaches on the horizon. Key words:Regenerative, tissue engineering, stem cells, scaffold. PMID:24558528

Textile Technologies and Tissue Engineering: A Path Towards Organ Weaving

Science.gov (United States)

Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein

2016-01-01

Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, pore size and mechanical properties of the fabrics play important role in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted. PMID:26924450

Nanoscale biomaterial interface modification for advanced tissue engineering applications

International Nuclear Information System (INIS)

Safonov, V; Zykova, A; Smolik, J; Rogovska, R; Donkov, N; Goltsev, A; Dubrava, T; Rassokha, I; Georgieva, V

2012-01-01

Recently, various stem cells, including mesenchymal stem cells (MSCs), have been found to have considerable potential for application in tissue engineering and future advanced therapies due to their biological capability to differentiate into specific lineages. Modified surface properties, such as composition, nano-roughness and wettability, affect the most important processes at the biomaterial interface. The aim of the present is work is to study the stem cells' (MSCs) adhesive potential, morphology, phenotypical characteristics in in vitro tests, and to distinguish betwen the different factors influencing the cell/biomaterial interaction, such as nano-topography, surface chemistry and surface free energy.

Fabrication and evaluation of biomimetic scaffolds by using collagen-alginate fibrillar gels for potential tissue engineering applications

International Nuclear Information System (INIS)

Sang Lin; Luo Dongmei; Xu Songmei; Wang Xiaoliang; Li Xudong

2011-01-01

Pore architecture and its stable functionality under cell culturing of three dimensional (3D) scaffolds are of great importance for tissue engineering purposes. In this study, alginate was incorporated with collagen to fabricate collagen-alginate composite scaffolds with different collagen/alginate ratios by lyophilizing the respective composite gels formed via collagen fibrillogenesis in vitro and then chemically crosslinking. The effects of alginate amount and crosslinking treatment on pore architecture, swelling behavior, enzymatic degradation and tensile property of composite scaffolds were systematically investigated. The relevant results indicated that the present strategy was simple but efficient to fabricate highly interconnected strong biomimetic 3D scaffolds with nanofibrous surface. NIH3T3 cells were used as a model cell to evaluate the cytocompatibility, attachment to the nanofibrous surface and porous architectural stability in terms of cell proliferation and infiltration within the crosslinked scaffolds. Compared with the mechanically weakest crosslinked collagen sponges, the cell-cultured composite scaffolds presented a good porous architecture, thus permitting cell proliferation on the top surface as well as infiltration into the inner part of 3D composite scaffolds. These composite scaffolds with pore size ranging from 150 to 300 μm, over 90% porosity, tuned biodegradability and water-uptake capability are promising for tissue engineering applications.

Biological augmentation and tissue engineering approaches in meniscus surgery.

Science.gov (United States)

Moran, Cathal J; Busilacchi, Alberto; Lee, Cassandra A; Athanasiou, Kyriacos A; Verdonk, Peter C

2015-05-01

The purpose of this review was to evaluate the role of biological augmentation and tissue engineering strategies in meniscus surgery. Although clinical (human), preclinical (animal), and in vitro tissue engineering studies are included here, we have placed additional focus on addressing preclinical and clinical studies reported during the 5-year period used in this review in a systematic fashion while also providing a summary review of some important in vitro tissue engineering findings in the field over the past decade. A search was performed on PubMed for original works published from 2009 to March 31, 2014 using the term "meniscus" with all the following terms: "scaffolds," "constructs," "cells," "growth factors," "implant," "tissue engineering," and "regenerative medicine." Inclusion criteria were the following: English-language articles and original clinical, preclinical (in vivo), and in vitro studies of tissue engineering and regenerative medicine application in knee meniscus lesions published from 2009 to March 31, 2014. Three clinical studies and 18 preclinical studies were identified along with 68 tissue engineering in vitro studies. These reports show the increasing promise of biological augmentation and tissue engineering strategies in meniscus surgery. The role of stem cell and growth factor therapy appears to be particularly useful. A review of in vitro tissue engineering studies found a large number of scaffold types to be of promise for meniscus replacement. Limitations include a relatively low number of clinical or preclinical in vivo studies, in addition to the fact there is as yet no report in the literature of a tissue-engineered meniscus construct used clinically. Neither does the literature provide clarity on the optimal meniscus scaffold type or biological augmentation with which meniscus repair or replacement would be best addressed in the future. There is increasing focus on the role of mechanobiology and biomechanical and

Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue

Science.gov (United States)

Goh, Kheng Lim; Holmes, David F.

2017-01-01

composites to a wide variety of collagen reinforcing (non-mutable) connective tissue, has allowed us to draw general conclusions concerning the mechanical response of the MCT at specific mechanical states, namely the stiff and complaint states. The intent of this review is to provide the latest insights, as well as identify technical challenges and opportunities, that may be useful for developing methods for effective mechanical support when adapting decellularised connective tissues from the sea urchin for tissue engineering or for the design of a synthetic analogue. PMID:28441344

Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue.

Science.gov (United States)

Goh, Kheng Lim; Holmes, David F

2017-04-25

composites to a wide variety of collagen reinforcing (non-mutable) connective tissue, has allowed us to draw general conclusions concerning the mechanical response of the MCT at specific mechanical states, namely the stiff and complaint states. The intent of this review is to provide the latest insights, as well as identify technical challenges and opportunities, that may be useful for developing methods for effective mechanical support when adapting decellularised connective tissues from the sea urchin for tissue engineering or for the design of a synthetic analogue.

Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue

Directory of Open Access Journals (Sweden)

Kheng Lim Goh

2017-04-01

reinforced composites to a wide variety of collagen reinforcing (non-mutable connective tissue, has allowed us to draw general conclusions concerning the mechanical response of the MCT at specific mechanical states, namely the stiff and complaint states. The intent of this review is to provide the latest insights, as well as identify technical challenges and opportunities, that may be useful for developing methods for effective mechanical support when adapting decellularised connective tissues from the sea urchin for tissue engineering or for the design of a synthetic analogue.

Critical review on the physical and mechanical factors involved in tissue engineering of cartilage.

Science.gov (United States)

Gaut, Carrie; Sugaya, Kiminobu

2015-01-01

Articular cartilage defects often progress to osteoarthritis, which negatively impacts quality of life for millions of people worldwide and leads to high healthcare expenditures. Tissue engineering approaches to osteoarthritis have concentrated on proliferation and differentiation of stem cells by activation and suppression of signaling pathways, and by using a variety of scaffolding techniques. Recent studies indicate a key role of environmental factors in the differentiation of mesenchymal stem cells to mature cartilage-producing chondrocytes. Therapeutic approaches that consider environmental regulation could optimize chondrogenesis protocols for regeneration of articular cartilage. This review focuses on the effect of scaffold structure and composition, mechanical stress and hypoxia in modulating mesenchymal stem cell fate and the current use of these environmental factors in tissue engineering research.

The Application of Tissue Engineering Procedures to Repair the Larynx

Science.gov (United States)

Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

2006-01-01

The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

Tissue engineering and regenerative medicine: manufacturing challenges.

Science.gov (United States)

Williams, D J; Sebastine, I M

2005-12-01

Tissue engineering and regenerative medicine are interdisciplinary fields that apply principles of engineering and life sciences to develop biological substitutes, typically composed of biological and synthetic components, that restore, maintain or improve tissue function. Many tissue engineering technologies are still at a laboratory or pre-commercial scale. The short review paper describes the most significant manufacturing and bio-process challenges inherent in the commercialisation and exploitation of the exciting results emerging from the biological and clinical laboratories exploring tissue engineering and regenerative medicine. A three-generation road map of the industry has been used to structure a view of these challenges and to define where the manufacturing community can contribute to the commercial success of the products from these emerging fields. The first-generation industry is characterised by its demonstrated clinical applications and products in the marketplace, the second is characterised by emerging clinical applications, and the third generation is characterised by aspirational clinical applications. The paper focuses on the cost reduction requirement of the first generation of the industry to allow more market penetration and consequent patient impact. It indicates the technological requirements, for instance the creation of three-dimensional tissue structures, and value chain issues in the second generation of the industry. The third-generation industry challenges lie in fundamental biological and clinical science. The paper sets out a road map of these generations to identify areas for research.

Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving.

Science.gov (United States)

Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein; Khademhosseini, Ali

2016-04-06

Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization

NARCIS (Netherlands)

Mazza, G. (Giuseppe); Al-Akkad, W. (Walid); Telese, A. (Andrea); Longato, L. (Lisa); Urbani, L. (Luca); Robinson, B. (Benjamin); Hall, A. (Andrew); Kong, K. (Kenny); Frenguelli, L. (Luca); Marrone, G. (Giusi); Willacy, O. (Oliver); Shaeri, M. (Mohsen); A.J. Burns (Alan); Malago, M. (Massimo); Gilbertson, J. (Janet); Rendell, N. (Nigel); Moore, K. (Kevin); Hughes, D. (David); Notingher, I. (Ioan); Jell, G. (Gavin); Del Rio Hernandez, A. (Armando); P. de Coppi (Paolo); Rombouts, K. (Krista); Pinzani, M. (Massimo)

2017-01-01

textabstractThe development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of

3D printing of composite tissue with complex shape applied to ear regeneration

International Nuclear Information System (INIS)

Lee, Jung-Seob; Hong, Jung Min; Jung, Jin Woo; Shim, Jin-Hyung; Cho, Dong-Woo; Oh, Jeong-Hoon

2014-01-01

In the ear reconstruction field, tissue engineering enabling the regeneration of the ear's own tissue has been considered to be a promising technology. However, the ear is known to be difficult to regenerate using traditional methods due to its complex shape and composition. In this study, we used three-dimensional (3D) printing technology including a sacrificial layer process to regenerate both the auricular cartilage and fat tissue. The main part was printed with poly-caprolactone (PCL) and cell-laden hydrogel. At the same time, poly-ethylene-glycol (PEG) was also deposited as a sacrificial layer to support the main structure. After complete fabrication, PEG can be easily removed in aqueous solutions, and the procedure for removing PEG has no effect on the cell viability. For fabricating composite tissue, chondrocytes and adipocytes differentiated from adipose-derived stromal cells were encapsulated in hydrogel to dispense into the cartilage and fat regions, respectively, of ear-shaped structures. Finally, we fabricated the composite structure for feasibility testing, satisfying expectations for both the geometry and anatomy of the native ear. We also carried out in vitro assays for evaluating the chondrogenesis and adipogenesis of the cell-printed structure. As a result, the possibility of ear regeneration using 3D printing technology which allowed tissue formation from the separately printed chondrocytes and adipocytes was demonstrated. (paper)

Stem cell homing-based tissue engineering using bioactive materials

Science.gov (United States)

Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

2017-06-01

Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

Adhesive protein interactions with chitosan: consequences for valve endothelial cell growth on tissue-engineering materials.

Science.gov (United States)

Cuy, Janet L; Beckstead, Benjamin L; Brown, Chad D; Hoffman, Allan S; Giachelli, Cecilia M

2003-11-01

Stable endothelialization of a tissue-engineered heart valve is essential for proper valve function, although adhesive characteristics of the native valve endothelial cell (VEC) have rarely been explored. This research evaluated VEC adhesive qualities and attempted to enhance VEC growth on the biopolymer chitosan, a novel tissue-engineering scaffold material with promising biological and chemical properties. Aortic VEC cultures were isolated and found to preferentially adhere to fibronectin, collagen types IV and I over laminin and osteopontin in a dose-dependent manner. Seeding of VEC onto comparison substrates revealed VEC growth and morphology to be preferential in the order: tissue culture polystyrene > gelatin, poly(DL-lactide-co-glycolide), chitosan > poly(hydroxy alkanoate). Adhesive protein precoating of chitosan did not significantly enhance VEC growth, despite equivalent protein adsorption as to polystyrene. Initial cell adhesion to protein-precoated chitosan, however, was higher than for polystyrene. Composite chitosan/collagen type IV films were investigated as an alternative to simple protein precoatings, and were shown to improve VEC growth and morphology over chitosan alone. These findings suggest potential manipulation of chitosan properties to improve amenability to valve tissue-engineering applications. Copyright 2003 Wiley Periodicals, Inc.

Fabricating a pearl/PLGA composite scaffold by the low-temperature deposition manufacturing technique for bone tissue engineering

International Nuclear Information System (INIS)

Xu Mingen; Li Yanlei; Suo Hairui; Wang Qiujun; Ge Yakun; Xu Ying; Yan Yongnian; Liu Li

2010-01-01

Here we developed a composite scaffold of pearl/poly(lactic-co-glycolic acid) (pearl/PLGA) utilizing the low-temperature deposition manufacturing (LDM). LDM makes it possible to fabricate scaffolds with designed microstructure and macrostructure, while keeping the bioactivity of biomaterials by working at a low temperature. Process optimization was carried out to fabricate a mixture of pearl powder, PLGA and 1,4-dioxane with the designed hierarchical structures, and freeze-dried at a temperature of -40 deg. C. Scaffolds with square and designated bone shape were fabricated by following the 3D model. Marrow stem cells (MSCs) were seeded on the pearl/PLGA scaffold and then cultured in a rotating cell culture system. The adhesion, proliferation and differentiation of MSCs into osteoblasts were determined using scanning electronic microscopy, WST-1 assay, alkaline phosphatase activity assay, immunofluorescence staining and real-time reverse transcription polymerase chain reaction. The results showed that the composite scaffold had high porosity (81.98 ± 3.75%), proper pore size (micropores: <10 μm; macropore: 495 ± 54 μm) and mechanical property (compressive strength: 0.81 ± 0.04 MPa; elastic modulus: 23.14 ± 0.75 MPa). The pearl/PLGA scaffolds exhibited better biocompatibility and osteoconductivity compared with the tricalcium phosphate/PLGA scaffold. All these results indicate that the pearl/PLGA scaffolds fulfill the basic requirements of bone tissue engineering scaffold.

Traction force microscopy of engineered cardiac tissues.

Science.gov (United States)

Pasqualini, Francesco Silvio; Agarwal, Ashutosh; O'Connor, Blakely Bussie; Liu, Qihan; Sheehy, Sean P; Parker, Kevin Kit

2018-01-01

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.

Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc.

Science.gov (United States)

Takada, Toru; Nishida, Kotaro; Doita, Minoru; Kurosaka, Masahiro

2002-07-15

Rat and human intervertebral disc specimens were examined immunohistochemically. Reverse transcription polymerase chain reaction (RT-PCR) analysis was also performed on rat disc tissue to demonstrate the existence of Fas ligand. To clarify the existence of Fas ligand on intact intervertebral disc cells. The nucleus pulposus has been reported to be an immune-privileged site. The immune-privileged characteristic in other tissues such as the retina and testis has been attributed to the local expression of Fas ligand, which acts by inducing apoptosis of invading Fas-positive T-cells. The existence of Fas ligand in normal disc cells has not yet been addressed. Skeletally mature SD male rats were killed, and the coccygeal discs were harvested. Human disc specimens were obtained from idiopathic scoliosis patients during surgical procedures. Immunohistochemical staining for Fas ligand was performed for cross-sections of the discs by standard procedures. Reverse transcription polymerase chain reaction analysis was also carried out to demonstrate Fas ligand mRNA expression on rat intervertebral discs. Testes of the rats were used for positive controls, and muscles were used for negative controls. The sections were observed by light microscopy. The nucleus pulposus cells exhibited intense positive immune staining for Fas ligand. The outer anulus fibrosus cells and notochordal cells exhibited little immunopositivity. The positive controls exhibited positive immune staining, and the negative control showed no immunopositivity. The result of RT-PCR confirmed the existence of Fas ligand in disc cells. The human nucleus pulposus cells showed a similar predilection to rat disc cells. We demonstrated the existence of Fas ligand on disc cells, which should play a key role in the potential molecular mechanism to maintain immune privilege of the disc. Immune privilege and Fas ligand expression of the intervertebral disc may provide a new insight for basic science research as well as

Integrated approaches to spatiotemporally directing angiogenesis in host and engineered tissues.

Science.gov (United States)

Kant, Rajeev J; Coulombe, Kareen L K

2018-03-15

The field of tissue engineering has turned towards biomimicry to solve the problem of tissue oxygenation and nutrient/waste exchange through the development of vasculature. Induction of angiogenesis and subsequent development of a vascular bed in engineered tissues is actively being pursued through combinations of physical and chemical cues, notably through the presentation of topographies and growth factors. Presenting angiogenic signals in a spatiotemporal fashion is beginning to generate improved vascular networks, which will allow for the creation of large and dense engineered tissues. This review provides a brief background on the cells, mechanisms, and molecules driving vascular development (including angiogenesis), followed by how biomaterials and growth factors can be used to direct vessel formation and maturation. Techniques to accomplish spatiotemporal control of vascularization include incorporation or encapsulation of growth factors, topographical engineering, and 3D bioprinting. The vascularization of engineered tissues and their application in angiogenic therapy in vivo is reviewed herein with an emphasis on the most densely vascularized tissue of the human body - the heart. Vascularization is vital to wound healing and tissue regeneration, and development of hierarchical networks enables efficient nutrient transfer. In tissue engineering, vascularization is necessary to support physiologically dense engineered tissues, and thus the field seeks to induce vascular formation using biomaterials and chemical signals to provide appropriate, pro-angiogenic signals for cells. This review critically examines the materials and techniques used to generate scaffolds with spatiotemporal cues to direct vascularization in engineered and host tissues in vitro and in vivo. Assessment of the field's progress is intended to inspire vascular applications across all forms of tissue engineering with a specific focus on highlighting the nuances of cardiac tissue

Fabrication of scaffolds in tissue engineering: A review

Science.gov (United States)

Zhao, Peng; Gu, Haibing; Mi, Haoyang; Rao, Chengchen; Fu, Jianzhong; Turng, Lih-sheng

2018-03-01

Tissue engineering (TE) is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

A method for quantitative measurement of lumbar intervertebral disc structures

DEFF Research Database (Denmark)

Tunset, Andreas; Kjær, Per; Samir Chreiteh, Shadi

2013-01-01

There is a shortage of agreement studies relevant for measuring changes over time in lumbar intervertebral disc structures. The objectives of this study were: 1) to develop a method for measurement of intervertebral disc height, anterior and posterior disc material and dural sac diameter using MR...

Non-crystalline composite tissue engineering scaffolds using boron-containing bioactive glass and poly(d,l-lactic acid) coatings

International Nuclear Information System (INIS)

Mantsos, T; Chatzistavrou, X; Roether, J A; Boccaccini, A R; Hupa, L; Arstila, H

2009-01-01

The aim of this study was the fabrication of three-dimensional, highly porous, bioactive scaffolds using a recently developed bioactive glass powder, denominated '0106', with nominal composition (in wt%): 50 SiO 2 , 22.6 CaO, 5.9 Na 2 O, 4 P 2 O 5 , 12 K 2 O, 5.3 MgO and 0.2 B 2 O 3 . The optimum sintering conditions for the fabrication of scaffolds by the foam-replica method were identified (sintering temperature: 670 deg, C and dwell time: 5 h). Composite samples were also fabricated by applying a biopolymer coating of poly( D,L -lactic acid) (PDLLA) using a dip coating process. The average compressive strength values were 0.4 MPa for uncoated and 0.6 MPa for coated scaffolds. In vitro bioactivity studies in simulated body fluid (SBF) showed that a carbonate hydroxyapatite (HCAp) layer was deposited on uncoated and coated scaffolds after only 4 days of immersion in SBF, demonstrating the high in vitro bioactivity of the scaffolds. It was also confirmed that the scaffold structure remained amorphous (no crystallization) after the specific heat treatment used, with scaffolds exhibiting mechanical properties and bioactivity suitable for use in bone tissue engineering applications.

Non-crystalline composite tissue engineering scaffolds using boron-containing bioactive glass and poly(d,l-lactic acid) coatings

Energy Technology Data Exchange (ETDEWEB)

Mantsos, T; Chatzistavrou, X; Roether, J A; Boccaccini, A R [Department of Materials, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom); Hupa, L; Arstila, H, E-mail: a.boccaccini@imperial.ac.u [Process Chemistry Centre, Abo Akademi University, Piispankatu 8, FI-20500 Turku (Finland)

2009-10-15

The aim of this study was the fabrication of three-dimensional, highly porous, bioactive scaffolds using a recently developed bioactive glass powder, denominated '0106', with nominal composition (in wt%): 50 SiO{sub 2}, 22.6 CaO, 5.9 Na{sub 2}O, 4 P{sub 2}O{sub 5}, 12 K{sub 2}O, 5.3 MgO and 0.2 B{sub 2}O{sub 3}. The optimum sintering conditions for the fabrication of scaffolds by the foam-replica method were identified (sintering temperature: 670 deg, C and dwell time: 5 h). Composite samples were also fabricated by applying a biopolymer coating of poly({sub D,L}-lactic acid) (PDLLA) using a dip coating process. The average compressive strength values were 0.4 MPa for uncoated and 0.6 MPa for coated scaffolds. In vitro bioactivity studies in simulated body fluid (SBF) showed that a carbonate hydroxyapatite (HCAp) layer was deposited on uncoated and coated scaffolds after only 4 days of immersion in SBF, demonstrating the high in vitro bioactivity of the scaffolds. It was also confirmed that the scaffold structure remained amorphous (no crystallization) after the specific heat treatment used, with scaffolds exhibiting mechanical properties and bioactivity suitable for use in bone tissue engineering applications.

Esophageal tissue engineering: Current status and perspectives.

Science.gov (United States)

Poghosyan, T; Catry, J; Luong-Nguyen, M; Bruneval, P; Domet, T; Arakelian, L; Sfeir, R; Michaud, L; Vanneaux, V; Gottrand, F; Larghero, J; Cattan, P

2016-02-01

Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Engineering a concept: the creation of tissue engineering.

Science.gov (United States)

Williams, D

1997-12-01

Tissue engineering is a fashionable phrase and a new concept. This article analyses what is meant by this term and discusses some of the products that may emerge from the translation of this concept into clinical reality.

Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs.

Science.gov (United States)

Choi, Kyung-Suk; Harfe, Brian D

2011-06-07

The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a "wrapper" around the notochord to constrain these cells along the vertebral column.

The impact of the artificial intervertebral disc on functioning the lumbar spine

Directory of Open Access Journals (Sweden)

Mańsko M.

2015-12-01

Full Text Available In the hereby thesis the anatomy of the lumbar vertebra and intervertebral disc were presented. Functioning and kinematics of the spine and intervertebral forces were described.Full three – dimensional model of the lumbar vertebrae L2 – L4 was created. On the basis of it model of artificial intervertebral disc was constructed (between L2 and L3. The simplified model of vertebra L2 was formulated via finite elements method. Processed model has been used for biomechanical analysis.Strength calculations were made and appropriate conclusions were drawn. Presented results show behavior influenced of three – dimensional model of the lumbar vertebra with artificial intervertebral disc by operation of loads.

Mechanostimulation Protocols for Cardiac Tissue Engineering

Directory of Open Access Journals (Sweden)