Novel injectable gel (system) as a vehicle for human articular chondrocytes in cartilage tissue regeneration

We developed a novel injectable carrageenan/fibrin/hyaluronic acid‐based hydrogel with in situ gelling properties to be seeded with chondrogenic cells and used for cartilage tissue engineering applications. We first analysed the distribution within the hydrogel construct and the phenotype of human articular chondrocytes (HACs) cultured for 3 weeks in vitro. We observed a statistically significant increase in the cell number during the first 2 weeks and maintenance of cell viability throughout the cell culture, together with the deposition/formation of a cartilage‐specific extracellular matrix (ECM). Taking advantage of a new in vivo model that allows the integration between newly formed and preexisting cartilage in immunodeficient mice to be investigated, we showed that injectable hydrogel seeded with human articular chondrocytes was able to regenerate and repair an experimentally made lesion in bovine articular cartilage, thus demonstrating the potential of this novel cell delivery system for cartilage tissue engineering. Copyright © 2009 John Wiley & Sons, Ltd.     

间充质干细胞在关节软骨组织工程中的应用

背景：组织工程技术的发展为关节软骨缺损修复和功能重建提供了新的方法和思路。目的：探讨以间充质干细胞作为种子细胞在关节软骨组织工程中的应用和研究进展。 方法：由第一作者检索 PubMed 数据库中2000-01-01/2014-09-30有关间充质干细胞和关节软骨组织工程的文献,检索词为“articular cartilage defects, cartilage tissue engineering, mesenchymal stem cel s”。共检索到70篇相关文献,对其中49篇文献进行综述。 结果与结论：关节软骨缺损自身修复能力很有限,目前的临床治疗手段无法达到满意修复,而组织工程的发展为解决这个问题提供了新思路。在种子细胞选择方面,软骨细胞去分化能力有限,胚胎干细胞受到伦理、法律等方面的制约,而间充质干细胞因其自体来源、易扩增、具有软骨分化潜能而受到广泛重视。但目前应用组织工程方法修复关节软骨缺损的效果存在一定的争议,主要是远期功能距离临床应用存在一定差距,在修复组织结构和生物力学方面还需要进一步研究。     

Efficacy of thermoresponsive,photocrosslinkable hydrogels derived from decellularized tendon and cartilage extracellular matrix for cartilage tissue engineering

Tissue engineering using adult mesenchymal stem cells (MSCs), a promising approach for cartilage repair, is highly dependent on the nature of the matrix scaffold. Thermoresponsive, photocrosslinkable hydrogels were fabricated by functionalizing pepsin‐soluble decellularized tendon and cartilage extracellular matrices (ECM) with methacrylate groups. Methacrylated gelatin hydrogels served as controls. When seeded with human bone marrow MSCs and cultured in chondrogenic medium, methacrylated ECM hydrogels experienced less cell‐mediated contraction, as compared against non‐methacrylated ECM hydrogels. However, methacrylation slowed or diminished chondrogenic differentiation of seeded MSCs, as determined through analyses of gene expression, biochemical composition and histology. In particular, methacrylated cartilage hydrogels supported minimal due to chondrogenesis over 42 weeks, as hydrogel disintegration beginning at day 14 presumably compromised cell–matrix interactions. As compared against methacrylated gelatin hydrogels, MSCs cultured in non‐methacrylated ECM hydrogels exhibited comparable expression of chondrogenic genes (Sox9, Aggrecan and collagen type II) but increased collagen type I expression. Non‐methacrylated cartilage hydrogels did not promote chondrogenesis to a greater extent than either non‐methacrylated or methacrylated tendon hydrogels. Whereas methacrylated gelatin hydrogels supported relatively homogeneous increases in proteoglycan and collagen type II deposition throughout the construct over 42 days, ECM hydrogels possessed greater heterogeneity of staining intensity and construct morphology. These results do not support the utility of pepsin‐solubilized cartilage and tendon hydrogels for cartilage tissue engineering over methacrylated gelatin hydrogels. Methacrylation of tendon and cartilage ECM hydrogels permits thermal‐ and light‐induced polymerization but compromises chondrogenic differentiation of seeded MSCs.     

Use of stem cells in the biological repair of articular cartilage

Importance of the field: Articular cartilage is avascular, aneural, and renowned for its poor capacity to repair after damage. For decades scientists and clinicians have deliberated over the potential to repair or regenerate articular cartilage and to date many techniques have been used in an attempt to create the best possible repair tissue.

Areas covered in this review: This review article summarises surgical interventions that have been developed since the late 1940's; covering conservative strategies, invasive techniques and touching upon latest advancements involving stem cells and tissue engineering.

What will the reader gain: The reader will gain a sound understanding into the history and background of strategies that have developed in attempts to reverse clinical symptoms of damaged or diseased articular cartilage. The article provides an insight into the plethora of potential repair mechanisms, and reviews future developments involving stem cells and biomaterials.

Take home message: Although work is still in its infancy, the use of stem cells in the biological repair of articular cartilage provides a promising outlook onto future developments; advancing from strategies and techniques that are already in use.     

Characterization of costal cartilage and its suitability as a cell source for articular cartilage tissue engineering

Costal cartilage is a promising donor source of chondrocytes to alleviate cell scarcity in articular cartilage tissue engineering. Limited knowledge exists, however, on costal cartilage characteristics. This study describes the characterization of costal cartilage and articular cartilage properties and compares neocartilage engineered with costal chondrocytes to native articular cartilage, all within a sheep model. Specifically, we (a) quantitatively characterized the properties of costal cartilage in comparison to patellofemoral articular cartilage, and (b) evaluated the quality of neocartilage derived from costal chondrocytes for potential use in articular cartilage regeneration. Ovine costal and articular cartilages from various topographical locations were characterized mechanically, biochemically, and histologically. Costal cartilage was stiffer in compression but softer and weaker in tension than articular cartilage. These differences were attributed to high amounts of glycosaminoglycans and mineralization and a low amount of collagen in costal cartilage. Compared to articular cartilage, costal cartilage was more densely populated with chondrocytes, rendering it an excellent chondrocyte source. In terms of tissue engineering, using the self‐assembling process, costal chondrocytes formed articular cartilage‐like neocartilage. Quantitatively compared via a functionality index, neocartilage achieved 55% of the medial condyle cartilage mechanical and biochemical properties. This characterization study highlighted the differences between costal and articular cartilages in native forms and demonstrated that costal cartilage is a valuable source of chondrocytes suitable for articular cartilage regeneration strategies.     

组织工程技术修复损伤关节软骨的研究与应用

背景：软骨是一种无血管的组织,软骨损伤后自身修复能力有限。当前用于治疗关节软骨损伤的方法从保守治疗到手术治疗多种多样。随着组织工程技术的发展,关节软骨的修复又进入了新的高度。目的：综述组织工程方法修复软骨损伤的新进展。方法：由第一作者在2013年5月应用计算机检索2000至2013年PubMed 数据库及CNKI 数据库,英文以“cartilage tissue engineering,cartilage defect;stem cel ,scaffold;growth factor”为关键词,中文以“软骨组织工程,软骨缺损,干细胞,支架,生长因子”为关键词,选择内容与软骨组织工程、软骨损伤修复相关的文章,同一领域文献则选择近期发表或发表在权威杂志文章,共纳入64篇文献。结果与结论：软骨组织工程三大要素--种子细胞、支架和细胞因子,三者必须协调发展和互利。现阶段组织工程方法修复关节软骨损伤的研究虽已取得很大进展,但大多停留于实验探索阶段,尚未应用于临床。随着新材料的不断研发,新的组织工程软骨修复材料将兼顾材料学和生物科学的需要,使其更接近机体自身组织生物学特性。在新的技术支持下,动物实验研究也将向临床试验转变,使关节软骨损伤的治疗取得突破性进展。     

兔膝关节软骨缺损对关节退变的影响

目的:探讨软骨损伤与关节退变之间的关系,以及持续被动运动治疗在其中的作用.方法:新西兰大白兔15只共30个膝关节随机分为3组,采用在关节软骨上钻孔的方法建立软骨损伤模型,术后按照不同的处理分为假手术组、对照组和持续被动运动(CPM)组,各组采取相应的处理方法.术后12周处死实验兔并进行关节软骨大体评分、HE染色评分和MMP-3免疫组化染色.结果:A组软骨表现正常.B组软骨在肉眼观察、病理学表现和MMP-3阳性细胞分数改变上均显示有明显退变.C组的各项指标均与A组接近而与B组差异有显著性意义(P＜0.05).结论:人为造成兔膝关节软骨缺损,可以进展成为骨关节炎(OA).软骨缺损后早期给予CPM治疗8h/d,连续4周,在12周后可有效减缓OA的发生.     

3D ingrowth of bovine articular chondrocytes in biodegradable cryogel scaffolds for cartilage tissue engineering

A feasibility study was undertaken to examine the potential of biodegradable HEMA-lactate-dextran (HEMA-LLA-D)-based cryogels as scaffolds for cartilage tissue engineering. This was a preliminary in vitro study giving essential information on the biocompatibility of cryogels with cartilage cells. HEMA-lactate (HEMA-LLA) and HEMA-LLA-D were synthesized and characterized by different techniques. Cryogel scaffolds with supermacroporous structures were produced by cryogenic treatment of these macromers. Chondrocytes obtained from bovine articular cartilage were seeded onto cylindrical cryogels and cultured. The samples were examined by several microcopical techniques for cell viability and morphological analyses were performed at two culture points. Histological study of the constructs revealed the cells' growth on the surface and within the scaffolds. Confocal microscopical images demonstrated that the majority of live vs. dead cells had been attached to and integrated with the pores of the scaffold. SEM analysis showed round to oval-shaped chondrocytic cells interconnected with each other by communicating junctions. The chondrocytes rapidly proliferated in the cryogels, manifesting that they fully covered the scaffold surface after 9 days and almost filled the spaces in the pores of the scaffold after 15 days of culture. Chondrocytes secreted significant amount of extracellular matrix in the scaffolds and exhibited highly interconnective morphology. Light and transmission electron microscopy revealed groups of active cartilage cells closely apposed to the cryogel. We concluded that cryogel scaffolds could be excellent candidates for cartilage tissue regeneration with their extraordinary properties, including soft, elastic nature, highly open interconnected pore structure and very rapid, controllable swellability.     

组织工程软骨与柚皮苷联合修复兔膝关节软骨缺损的组织学证实

背景：目前临床上虽有多种方法用于治疗软骨缺损,但没有从根本上解决关节软骨缺损修复问题。目的：通过组织学研究进一步评价柚皮苷结合组织工程软骨修复兔关节软骨缺损的效果。方法：取兔骨髓间充质干细胞体外增殖后,复合于改建后的脱细胞真皮基质载体上,制成组织工程软骨,植入到兔膝关节软骨缺损,并以柚皮苷汤灌胃,于4,8周后分别对修复组织进行苏木精-伊红、Masson三色染色、甲苯胺蓝染色、Ⅱ型胶原染色、Ⅹ型胶原染色等组织学检查。结果与结论：术后8周,柚皮苷结合干细胞复合体组缺损处修复组织变成乳白色,半透明光滑组织,缺损修复组织与周围正常软骨已基本难区分,表面光滑。组织学检查发现修复缺损处基本为新生软骨填充。结果证实,柚皮苷结合组织工程软骨能提高家兔膝关节软骨缺损的修复质量。     

兔关节内积血对关节软骨影响的实验研究

目的：探讨短期关节内积血对关节软骨基础研究的影响。方法：新西兰大白兔36只随机分为2组。A组：右后膝关节内注入自体静脉血4ml，左后膝关节作为空白对照，在第3天重复一次，剂量同前。B组：右后膝关节内注入自体静脉血4ml，左后膝关节2ml，其余步骤与A组完全相同。分别于第1周、4周、8周取材．测定水、胶原含量的改变，同时进行大体及光镜观察。结果：①受出血影响，第1、4周含水率都明显增加（均为P〈0．05），第8周时与对照组比较无明显差异（P〉0．05）。胶原含量在第1周低于对照组（P〈0．05），4ml组低于2ml组（P〈0．05）。第4、8周与对照组比较均无明显差异（P〉0．05）。②HE染色结果：实验侧软骨表面不光滑，细胞排列欠整齐，潮线变模糊。4ml侧比2ml侧变化明显。结论：不同量的关节内出血对关节软骨的影响不同，量大者对含水率、蛋白多糖、胶原的影响大于量小者。     

微骨折与自体骨髓间充质干细胞外基质支架修复猪膝关节软骨缺损

背景：微骨折术方法简单,操作方便,是治疗关节软骨缺损有效的方法之一,但仍然存在再生软骨为纤维软骨、再生软骨退化等问题。现在学者们主要致力于使用各种方法改良微骨折修复软骨缺损的效果。 目的：探索微骨折处理软骨缺损区域后植入自体骨髓间充质干细胞外基质支架治疗猪膝关节软骨缺损的疗效。 方法：分离并原代培养猪骨髓间充质干细胞,收集其分泌的细胞外基质膜,采用交联、冻干技术将收集的基质膜制备成三维多孔支架。选取小型成年猪,制备双膝股骨髁、股骨滑车部全层软骨缺损模型,深2 mm,直径6 mm;采用自体左右对照模式,右膝作为对照组,使用单纯微骨折治疗软骨缺损,左膝作为实验组,采用微骨折处理软骨缺损区域后,植入预先制备的支架。术后6个月使用番红固绿染色、Masson 染色等评价软骨再生情况,使用Wakitani评分整体评估再生软骨,并测定再生组织糖胺聚糖、DNA含量。 结果与结论：术后6个月,实验组股骨滑车和股骨髁处均可见软骨修复,表面光滑,对照组股骨滑车修复组织表面较平整,股骨髁未见明显修复。实验组股骨滑车和股骨髁再生软骨经番红固绿染色、Masson染色均显示软骨层基质含量丰富,软骨下骨骨小梁密集,对照组软骨层染色不明显,软骨下骨修复欠佳。实验组Wakitani评分、糖胺聚糖含量高于对照组,DNA含量低于对照组（P＆lt;0.05）。结果可见微骨折结合自体骨髓间充质干细胞外基质支架修复软骨效果良好,股骨滑车和股骨髁治疗效果无显著差异。     

聚乙烯醇水凝胶弹性体复合物修复关节软骨缺损的实验研究

目的：研究应用聚乙烯醇水凝胶弹性体复合物作为关节软骨替代物修复成年犬的关节软骨缺损。方法：取8只成年犬随机均分为A、B两组，每组4只。在犬双后肢膝关节股骨内髁负重面制造软骨缺损区，在缺损区植入同等大小的聚乙烯醇水凝胶弹性体复合物。手术后8周和24周分别将A、B两组实验动物处死取材。在肉眼和光镜下观察植入物周围的软骨和软骨下骨，对应的半月板和胫骨面的软骨组织。结果：大体观察，实验动物术后关节功能良好，植入物在8周和24周均未见松动和脱落，与软骨下骨牢固结合。植入物周围软骨和对应部位的半月板和胫骨面软骨未见退变表现。光镜下观察8周和24周植入物周围未见软骨组织退变表现；软骨下骨组织长入钛纤维网孔隙中，形成生物力学固定；植入物周围无淋巴细胞浸润。结论：聚乙烯醇水凝胶弹性体具有与关节软骨类似的物理特性和良好的生物相容性，能作为关节软骨替代物修复关节软骨的缺损，恢复关节面的完整，维持关节功能。     

Sequential hydrophile and lipophile solubilization as an efficient method for decellularization of porcine aortic valve leaflets: Structure,mechanical property and biocompatibility study

Antigenicity of xenogeneic tissues is the major obstacle to increased use of these materials in clinical medicine. Residual xenoantigens in decellularized tissue elicit the immune response after implantation, causing graft failure. With this in mind, the potential use is proposed of three protein solubilization‐based protocols for porcine aortic valve leaflets decellularization. It was demonstrated that hydrophile solubilization alone achieved incomplete decellularization; lipophile solubilization alone (LSA) completely removed all cells and two most critical xenoantigens – galactose‐α(1,3)‐galactose (α‐Gal) and major histocompatibility complex I (MHC I) – but caused severe alterations of the structure and mechanical properties; sequential hydrophile and lipophile solubilization (SHLS) resulted in a complete removal of cells, α‐Gal and MHC I, and good preservation of the structure and mechanical properties. In contrast, a previously reported method using Triton X‐100, sodium deoxycholate and IGEPAL CA‐630 resulted in a complete removal of all cells and MHC I, but with remaining α‐Gal epitope. LSA‐ and SHLS‐treated leaflets showed significantly reduced leucocyte activation (polymorphonuclear elastase) upon interaction with human blood in vitro. When implanted subdermally in rats for 6 weeks, LSA‐ or SHLS‐treated leaflets were presented with more biocompatible implants and all four decellularized leaflets were highly resistant to calcification. These findings illustrate that the SHLS protocol could be considered as a promising decellularization method for the decellularization of xenogeneic tissues in tissue engineering and regenerative medicine. Copyright © 2016 John Wiley & Sons, Ltd.     

Processed xenogenic cartilage as innovative biomatrix for cartilage tissue engineering: effects on chondrocyte differentiation and function

One key point in the development of new bioimplant matrices for the reconstruction and replacement of cartilage defects is to provide an adequate microenvironment to ensure chondrocyte migration and de novo synthesis of cartilage‐specific extracellular matrix (ECM). A recently developed decellularization and sterilization process maintains the three‐dimensional (3D) collagen structure of native septal cartilage while increasing matrix porosity, which is considered to be crucial for cartilage tissue engineering. Human primary nasal septal chondrocytes were amplified in monolayer culture and 3D‐cultured on processed porcine nasal septal cartilage scaffolds. The influence of chondrogenic growth factors on neosynthesis of ECM proteins was examined at the protein and gene expression levels. Seeding experiments demonstrated that processed xenogenic cartilage matrices provide excellent environmental properties for human nasal septal chondrocytes with respect to cell adhesion, migration into the matrix and neosynthesis of cartilage‐specific ECM proteins, such as collagen type II and aggrecan. Matrix biomechanical stability indicated that the constructs retrieve full stability and function during 3D culture for up to 42 days, proportional to collagen type II and GAG production. Thus, processed xenogenic cartilage offers a suitable environment for human nasal chondrocytes and has promising potential for cartilage tissue engineering in the head and neck region. Copyright © 2012 John Wiley & Sons, Ltd.     

Glycogen storage in tissue-engineered cartilage

Recent focus in cartilage tissue engineering has been to develop functional tissue that can survive after implantation. One such determinant is the ability of the engineered tissue to be able to sustain its metabolic activity post-implantation. In vivo, chondrocytes contain stores of intracellular glycogen to support metabolism and it is unknown whether these cells can store glycogen during tissue growth in vitro. Thus, the purpose of this study was to determine the appropriate nutrient conditions to elicit glycogen storage in tissue-engineered cartilage. Isolated bovine articular chondrocytes were seeded in scaffold-free, 3D culture and grown under different nutrient conditions (glucose concentrations and media volumes) for 4 weeks. Intracellular glycogen storage, glucose utilization and extracellular matrix (ECM) accumulation of the engineered tissues were then evaluated. Glucose concentration (5-10 mM) and media volume (1-4 ml) had no apparent effect on cartilaginous tissue formation. However, glucose consumption by the cells increased in proportion to the volume of medium provided. Lactate production was similarly affected but in direct proportion to the glucose consumed, indicating a change in glucose utilization. Similarly, under elevated medium volume, engineered tissues stained positive for intracellular glycogen, which was also confirmed biochemically (1 ml, 1 +/- 2; 2 ml, 13 +/- 4; 4 ml, 13 +/- 3 microg/construct). The storage of intracellular glycogen in engineered cartilage can be elicited by culturing the constructs in elevated volumes of medium (>or=1 ml medium/million cells), which might help to ensure appropriate metabolic function after implantation.     

Enhanced treatment of articular cartilage defect of the knee by intra‐articular injection of Bcl‐xL‐engineered mesenchymal stem cells in rabbit model

Direct intra‐articular injection of mesenchymal stem cells (MSCs) has been proposed as a potential cell therapy for cartilage defects. This cell therapy relies on the survival of the implanted MSCs. However, the arduous local environment may limit cell viability after implantation, which would restrict the cells' regenerative capacity. Thus, it is necessary to reinforce the implanted cells against the unfavourable microenvironment in order to improve the efficacy of cell therapy. We examined whether the transduction of an anti‐apoptotic protein, Bcl‐xL, into MSCs could prevent cell death and improve the implantation efficiency of MSCs in a rabbit model. Our current findings demonstrate that the group treated with Bcl‐xL‐engineered MSCs could improve cartilage healing both morphologically and histologically when compared with the controls. These results suggest that intra‐articular injection of Bcl‐xL‐engineered MSCs is a potential non‐invasive therapeutic method for effectively treating cartilage defects of the knee. Copyright © 2009 John Wiley & Sons, Ltd.     

Pilot study of a novel vacuum‐assisted method for decellularization of tracheae for clinical tissue engineering applications

Tissue engineered tracheae have been successfully implanted to treat a small number of patients on compassionate grounds. The treatment has not become mainstream due to the time taken to produce the scaffold and the resultant financial costs. We have developed a method for decellularization (DC) based on vacuum technology, which when combined with an enzyme/detergent protocol significantly reduces the time required to create clinically suitable scaffolds. We have applied this technology to prepare porcine tracheal scaffolds and compared the results to scaffolds produced under normal atmospheric pressures. The principal outcome measures were the reduction in time (9 days to prepare the scaffold) followed by a reduction in residual DNA levels (DC no‐vac: 137.8±48.82 ng/mg vs. DC vac 36.83±18.45 ng/mg, p<0.05.). Our approach did not impact on the collagen or glycosaminoglycan content or on the biomechanical properties of the scaffolds. We applied the vacuum technology to human tracheae, which, when implanted in vivo showed no significant adverse immunological response. The addition of a vacuum to a conventional decellularization protocol significantly reduces production time, whilst providing a suitable scaffold. This increases clinical utility and lowers production costs. To our knowledge this is the first time that vacuum assisted decellularization has been explored. Copyright © 2015 John Wiley & Sons, Ltd.     

A dynamic distention protocol for whole‐organ bladder decellularization: histological and biomechanical characterization of the acellular matrix

A combined physical–chemical protocol for whole full‐thickness bladder decellularization is proposed, based on organ cyclic distention through repeated infusion/withdrawal of the decellularization agents through the urethra. The dynamic decellularization was intended to enhance cell removal efficiency, facilitating the delivery of detergents within the inner layers of the tissue and the removal of cell debris. The use of mild chemical detergents (hypotonic solution and non‐ionic detergent) was employed to limit adverse effects upon matrix 3D ultrastructure. Inspection of the presence of residual DNA and RNA was carried out on decellularized matrices to verify effective cell removal. Histological investigation was focused on assessing the retention of adequate structural and functional components that regulate the biomechanical behaviour of the acellular tissue. Biomechanical properties were evaluated through uniaxial tensile loading tests of tissue strips and through ex vivo filling cystometry to evaluate the whole‐organ mechanical response to a physiological‐like loading state. According to our results, a dynamic decellularization protocol of 17 h duration with a 5 ml/min detergent infusion flow rate revealed higher DNA removal efficiency than standard static decellularization, resulting in residual DNA content < 50 ng/mg dry tissue weight. Furthermore, the collagen network and elastic fibres distribution were preserved in the acellular ECM, which exhibited suitable biomechanical properties in the perspective of its future use as an implant for bladder augmentation. Copyright © 2013 John Wiley & Sons, Ltd.     

ERK activation is required for hydrostatic pressure‐induced tensile changes in engineered articular cartilage

The objective of this study was to identify ERK 1/2 involvement in the changes in compressive and tensile mechanical properties associated with hydrostatic pressure treatment of self‐assembled cartilage constructs. In study 1, ERK 1/2 phosphorylation was detected by immunoblot, following application of hydrostatic pressure (1 h of static 10 MPa) applied at days 10–14 of self‐assembly culture. In study 2, ERK 1/2 activation was blocked during hydrostatic pressure application on days 10–14. With pharmacological inhibition of the ERK pathway by the MEK1/ERK inhibitor U0126 during hydrostatic pressure application on days 10–14, the increase in Young's modulus induced by hydrostatic pressure was blocked. Furthermore, this reduction in Young's modulus with U0126 treatment during hydrostatic pressure application corresponded to a decrease in total collagen expression. However, U0126 did not inhibit the increase in aggregate modulus or GAG induced by hydrostatic pressure. These findings demonstrate a link between hydrostatic pressure application, ERK signalling and changes in the biomechanical properties of a tissue‐engineered construct. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of visco‐elastic silk–chitosan microcomposite scaffolds on matrix deposition and biomechanical functionality for cartilage tissue engineering

Commonly used polymer‐based scaffolds often lack visco‐elastic properties to serve as a replacement for cartilage tissue. This study explores the effect of reinforcement of silk matrix with chitosan microparticles to create a visco‐elastic matrix that could support the redifferentiation of expanded chondrocytes. Goat chondrocytes produced collagen type II and glycosaminoglycan (GAG)‐enriched matrix on all the scaffolds (silk:chitosan 1:1, 1:2 and 2:1). The control group of silk‐only constructs suffered from leaching out of GAG molecules into the medium. Chitosan‐reinforced scaffolds retained a statistically significant (p < 0.02) higher amount of GAG, which in turn significantly increased (p < 0.005) the aggregate modulus (as compared to silk‐only controls) of the construct akin to that of native tissue. Furthermore, the microcomposite constructs demonstrated highly pronounced hysteresis at 4% strain up to 400 cycles, mimicking the visco‐elastic properties of native cartilage tissue. These results demonstrated a step towards optimizing the design of biomaterial scaffolds used for cartilage tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.