Facilitating In Vivo Articular Cartilage Repair by Tissue-Engineered Cartilage Grafts Produced From Auricular Chondrocytes

2017 ◽  
Vol 46 (3) ◽  
pp. 713-727 ◽  
Author(s):  
Chin-Chean Wong ◽  
Chih-Hwa Chen ◽  
Li-Hsuan Chiu ◽  
Yang-Hwei Tsuang ◽  
Meng-Yi Bai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
3 Dimensional ◽  
Cell Conversion

Background: Insufficient cell numbers still present a challenge for articular cartilage repair. Converting heterotopic auricular chondrocytes by extracellular matrix may be the solution. Hypothesis: Specific extracellular matrix may convert the phenotype of auricular chondrocytes toward articular cartilage for repair. Study Design: Controlled laboratory study. Methods: For in vitro study, rabbit auricular chondrocytes were cultured in monolayer for several passages until reaching status of dedifferentiation. Later, they were transferred to chondrogenic type II collagen (Col II)–coated plates for further cell conversion. Articular chondrogenic profiles, such as glycosaminoglycan deposition, articular chondrogenic gene, and protein expression, were evaluated after 14-day cultivation. Furthermore, 3-dimensional constructs were fabricated using Col II hydrogel-associated auricular chondrocytes, and their histological and biomechanical properties were analyzed. For in vivo study, focal osteochondral defects were created in the rabbit knee joints, and auricular Col II constructs were implanted for repair. Results: The auricular chondrocytes converted by a 2-step protocol expressed specific profiles of chondrogenic molecules associated with articular chondrocytes. The histological and biomechanical features of converted auricular chondrocytes became similar to those of articular chondrocytes when cultivated with Col II 3-dimensional scaffolds. In an in vivo animal model of osteochondral defects, the treated group (auricular Col II) showed better cartilage repair than did the control groups (sham, auricular cells, and Col II). Histological analyses revealed that cartilage repair was achieved in the treated groups with abundant type II collagen and glycosaminoglycans syntheses rather than elastin expression. Conclusion: The study confirmed the feasibility of applying heterotopic chondrocytes for cartilage repair via extracellular matrix–induced cell conversion. Clinical Relevance: This study proposes a feasible methodology to convert heterotopic auricular chondrocytes for articular cartilage repair, which may serve as potential alternative sources for cartilage repair.

scholarly journals Comparative Effectiveness of Structural versus Regulatory Protein Gene Transfer on Articular Chondrocyte Matrix Gene Expression

Cartilage ◽  
2017 ◽  
Vol 10 (1) ◽  
pp. 102-110 ◽  
Author(s):  
Shuiliang Shi ◽  
Congrong Wang ◽  
Albert Chan ◽  
Kashif Kirmani ◽  
George J. Eckert ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Gene Transfer ◽  
Cartilage Repair ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Matrix Proteins ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
Regulatory Factors ◽  
Igf I

Objective The production of extracellular matrix is a necessary component of articular cartilage repair. Gene transfer is a promising method to improve matrix biosynthesis by articular chondrocytes. Gene transfer may employ transgenes encoding regulatory factors that stimulate the production of matrix proteins, or may employ transgenes that encode the proteins themselves. The objective of this study was to determine which of these 2 approaches would be the better choice for further development. We compared these 2 approaches using the transgenes encoding the structural matrix proteins, aggrecan or type II collagen, and the transgene encoding the anabolic factor, insulin-like growth factor I (IGF-I). Methods We transfected adult bovine articular chondrocytes with constructs encoding type II collagen, aggrecan, or IGF-I, and measured the expression of type II collagen ( COL2A1) and aggrecan ( ACAN) from their native genes and from their transgenes. Results IGF-I gene ( IGF1) transfer increased the expression of the native chondrocyte COL2A1 and ACAN genes 2.4 and 2.9 times control, respectively. COL2A1 gene transfer did not significantly increase COL2A1 transcripts, even when the transgene included the genomic COL2A1 regulatory sequences stimulated by chondrogenic growth factors. In contrast, ACAN gene transfer increased ACAN transcripts up to 3.4 times control levels. IGF1, but not ACAN, gene transfer increased aggrecan protein production. Conclusion Taken together, these results suggest that the type II collagen and aggrecan production required for articular cartilage repair will be more effectively achieved by genes that encode anabolic regulatory factors than by genes that encode the matrix molecules themselves.

scholarly journals Natural Type II Collagen Hydrogel, Fibrin Sealant, and Adipose-Derived Stem Cells as a Promising Combination for Articular Cartilage Repair

Cartilage ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 439-443 ◽  
Author(s):  
Mariana Lazarini ◽  
Pedro Bordeaux-Rego ◽  
Renata Giardini-Rosa ◽  
Adriana S. S. Duarte ◽  
Mariana Ozello Baratti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Fibrin Sealant ◽  
Type Ii Collagen ◽  
Adipose Derived Stem Cells ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
Collagen Hydrogel

Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.

Articular cartilage repair with recombinant human type II collagen/polylactide scaffold in a preliminary porcine study

2015 ◽  
Vol 34 (5) ◽  
pp. 745-753 ◽  
Author(s):  
Virpi Muhonen ◽  
Eve Salonius ◽  
Anne-Marie Haaparanta ◽  
Elina Järvinen ◽  
Teemu Paatela ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cartilage Repair ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Articular Cartilage Repair ◽  
Human Type

scholarly journals Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1571
Author(s):  
Matilde Tschon ◽  
Francesca Salamanna ◽  
Lucia Martini ◽  
Gianluca Giavaresi ◽  
Luca Lorenzini ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Pain Sensitivity ◽  
Type Ii Collagen ◽  
Male Rats ◽  
In Vivo Model ◽  
Type Ii ◽  
Chemical Induction ◽  
Local Pain ◽  
Gait Parameters

The purpose of this study was to verify the efficacy of a single intra-articular (i.a.) injection of a hyaluronic acid-chitlac (HY-CTL) enriched with two low dosages of triamcinolone acetonide (TA, 2.0 mg/mL and 4.5 mg/mL), in comparison with HY-CTL alone, with a clinical control (TA 40 mg/mL) and with saline solution (NaCl) in an in vivo osteoarthritis (OA) model. Seven days after chemical induction of OA, 80 Sprague Dawley male rats were grouped into five arms (n = 16) and received a single i.a. injection of: 40 mg/mL TA, HY-CTL alone, HY-CTL with 2.0 mg/mL TA (RV2), HY-CTL with 4.5 mg/mL TA (RV4.5) and 0.9% NaCl. Pain sensitivity and Catwalk were performed at baseline and at 7, 14 and 21 days after the i.a. treatments. The histopathology of the joint, meniscus and synovial reaction, type II collagen expression and aggrecan expression were assessed 21 days after treatments. RV4.5 improved the local pain sensitivity in comparison with TA and NaCl. RV4.5 and TA exerted similar beneficial effects in all gait parameters. Histopathological analyses, measured by Osteoarthritis Research Society International (OARSI) and Kumar scores and by immunohistochemistry, evidenced that RV4.5 and TA reduced OA features in the same manner and showed a stronger type II collagen and aggrecan expression; both treatments reduced synovitis, as measured by Krenn score and, at the meniscus level, RV4.5 improved degenerative signs as evaluated by Pauli score. TA or RV4.5 treatments limited the local articular cartilage deterioration in knee OA with an improvement of the physical structure of articular cartilage, gait parameters, the sensitivity to local pain and a reduction of the synovial inflammation.

Cell-derived decellularized extracellular matrix scaffolds for articular cartilage repair

2020 ◽  
pp. 039139882095386
Author(s):  
Wenrun Zhu ◽  
Lu Cao ◽  
Chunfeng Song ◽  
Zhiying Pang ◽  
Haochen Jiang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cell Attachment ◽  
Tissue Growth ◽  
Bioactive Molecules ◽  
Cartilage Tissue ◽  
Articular Cartilage Repair ◽  
Decellularized Extracellular Matrix

Articular cartilage repair remains a great clinical challenge. Tissue engineering approaches based on decellularized extracellular matrix (dECM) scaffolds show promise for facilitating articular cartilage repair. Traditional regenerative approaches currently used in clinical practice, such as microfracture, mosaicplasty, and autologous chondrocyte implantation, can improve cartilage repair and show therapeutic effect to some degree; however, the long-term curative effect is suboptimal. As dECM prepared by proper decellularization procedures is a biodegradable material, which provides space for regeneration tissue growth, possesses low immunogenicity, and retains most of its bioactive molecules that maintain tissue homeostasis and facilitate tissue repair, dECM scaffolds may provide a biomimetic microenvironment promoting cell attachment, proliferation, and chondrogenic differentiation. Currently, cell-derived dECM scaffolds have become a research hotspot in the field of cartilage tissue engineering, as ECM derived from cells cultured in vitro has many advantages compared with native cartilage ECM. This review describes cell types used to secrete ECM, methods of inducing cells to secrete cartilage-like ECM and decellularization methods to prepare cell-derived dECM. The potential mechanism of dECM scaffolds on cartilage repair, methods for improving the mechanical strength of cell-derived dECM scaffolds, and future perspectives on cell-derived dECM scaffolds are also discussed in this review.

Stress Relaxation of Cartilage Under Simple Shear and Compression: Experiments and Finite Element Analyses

2012 ◽  
Author(s):  
Chen-Yuan Chung ◽  
Mostafa Motavalli ◽  
Joseph M. Mansour
Keyword(s):  
Extracellular Matrix ◽  
Finite Element ◽  
Articular Cartilage ◽  
Simple Shear ◽  
Type Ii Collagen ◽  
Biomechanical Properties ◽  
Type Ii ◽  
Finite Element Analyses ◽  
Stress And Deformation ◽  
Engineered Cartilage

Articular cartilage is a hydrated connective tissue consisting of a relatively small number of chondrocytes surrounded by a saturated extracellular matrix comprised mainly of type-II collagen fibrils and proteoglycans. As a deformable fluid saturated material, cartilage is most often modeled using biphasic or poroelastic theories [1,2]. The ultimate goal of this work is to evaluate biomechanical properties of native and tissue engineered cartilage under combined compression and shear. The purpose of this investigation was to determine stress and deformation fields in cartilage under compression and simple shear and relate these to measured results.

A Novel in Vitro Model to Investigate Behavior of Articular Chondrocytes in Osteoarthritis

2009 ◽  
Vol 37 (2) ◽  
pp. 426-431 ◽  
Author(s):  
KENNETH S. RANKIN ◽  
RACHEL L. LAKEY ◽  
CRAIG H. GERRAND ◽  
ANDREW P. SPROWSON ◽  
ANDREW W. McCASKIE ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Articular Chondrocytes ◽  
Type Ii Collagen ◽  
Type Ii ◽  
Transcriptional Expression ◽  
Matrix Metalloproteinase 1 ◽  
Standard Culture ◽  
Cells Cultured

Objective. To investigate in vivo simulation of the microenvironment in which osteoarthritis (OA) chondrocytes are cultured in vitro.Methods. Human articular chondrocytes were cultured under normoxic and hypoxic conditions. Cells were cultured on standard culture plastic or a porous polyHEMA surface that closely resembles the in vivo cartilage microarchitecture. Morphological changes to the cells were demonstrated by fluorescent staining with DAPI and vinculin. Proteoglycan and type II collagen protein levels were assessed using established techniques. Matrix metalloproteinase-1 (MMP-1) production was assessed by ELISA. The gene expression of type II collagen and SOX9 was measured using real-time polymerase chain reaction.Results. Cells grown on culture plastic were seen to be flat and hexagonal. Cells cultured on the porous polyHEMA surface exhibited morphology in keeping with the in vivo microenvironment. Glycosaminoglycan release in hypoxia was high from cells cultured on standard culture plastic. Transcriptional expression of type II collagen was upregulated in hypoxia and by culture on the polyHEMA surface. Transcriptional expression of SOX9 in hypoxia was upregulated compared to normoxia; no significant effect was seen by varying the culture surface. Translational expression of type II collagen was upregulated at 20% oxygen on the polyHEMA surface compared to culture plastic and this was related to MMP-1 expression.Conclusion. Culture of chondrocytes in hypoxia and on a porous surface simulates the in vivo microenvironment and illustrates the molecular mechanisms of OA.

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