A Comparison of Self-Assembly and Hydrogel Encapsulation as a Means to Engineer Functional Cartilaginous Grafts Using Culture Expanded Chondrocytes

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

doi:10.1089/ten.tec.2013.0118

Cited by 27 publications

(33 citation statements)

References 53 publications

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“…Adult human bone marrow-derived stem cells (hMSCs) were expanded to passage 2 and seeded into 6.5 mm diameter transwell inserts (3.0 lm pore polycarbonate membrane, Corning) at a density of 4 Â 10^6 cells per insert [29,30]. Constructs were cultured in either chondrogenic medium (consisting of hgDMEM GlutaMAX supplemented with 100 U/mL penicillin/streptomycin (both Gibco), 100 lg/mL sodium pyruvate, 40 lg/mL L-proline, 50 lg/mL L-ascorbic acid-2-phosphate, 4.7 lg/mL linoleic acid, 1.5 mg/mL bovine serum albumin, 1Â insulin-transferrin-sele nium, 100 nM dexamethasone (all from Sigma-Aldrich), 2.5 lg/mL amphotericin B, and 10 ng/mL of human transforming growth factor-b3 (TGF-b3; Prospec-Tany TechnoGene Ltd)) for 6 weeks at 5% O 2 or cultured in chondrogenic medium for the first 4 weeks and switched to hypertrophic medium (consisting of hgDMEM GlutaMAX supplemented with 100 U/mL penicillin/streptomycin, 100 lg/mL sodium pyruvate, 40 lg/mL L-proline, 50 lg/mL L-ascorbic acid-2-phosphate, 4.7 lg/mL linoleic acid, 1.5 mg/mL bovine serum albumin, 1Â insulin-transferrin-se lenium, 1 nM dexamethasone, 2.5 lg/mL amphotericin B, 1 nM L-thyroxine, and 10 mM b-Glycerophosphate (both SigmaAldrich)) at 20% O 2 for the final 2 weeks to induce deposition of a hypertrophic cartilage ECM (Fig.…”

Section: Generating Scaffolds For Subcutaneous Implantationmentioning

confidence: 99%

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing

et al. 2015

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Clinical translation of tissue engineered therapeutics is hampered by the significant logistical and regulatory challenges associated with such products, prompting increased interest in the use of decellularized extracellular matrix (ECM) to enhance endogenous regeneration. Most bones develop and heal by endochondral ossification, the replacement of a hypertrophic cartilaginous intermediary with bone. The hypothesis of this study is that a porous scaffold derived from decellularized tissue engineered hypertrophic cartilage will retain the necessary signals to instruct host cells to accelerate endogenous bone regeneration. Cartilage tissue (CT) and hypertrophic cartilage tissue (HT) were engineered using human bone marrow derived mesenchymal stem cells, decellularized and the remaining ECM was freeze-dried to generate porous scaffolds. When implanted subcutaneously in nude mice, only the decellularized HT-derived scaffolds were found to induce vascularization and de novo mineral accumulation. Furthermore, when implanted into critically-sized femoral defects, full bridging was observed in half of the defects treated with HT scaffolds, while no evidence of such bridging was found in empty controls. Host cells which had migrated throughout the scaffold were capable of producing new bone tissue, in contrast to fibrous tissue formation within empty controls. These results demonstrate the capacity of decellularized engineered tissues as 'off-the-shelf' implants to promote tissue regeneration.

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Section: Generating Scaffolds For Subcutaneous Implantationmentioning

confidence: 99%

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing

et al. 2015

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“…The final published version may differ from this proof. biomechanical characteristics similar to native cartilage [14][15][16][17][18]. These self-assembled constructs have been tested extensively in vitro to assess ideal cellular concentration [19] and culture time [15].…”

Section: Introductionmentioning

confidence: 99%

Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels

Meppelink

Zhao

Griffin

et al. 2016

Tissue Engineering Part A

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Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

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“…38 In contrast, scaffold-free or self-assembly approaches have been shown to result in superior chondrogenesis of BM-derived MSCs compared to pellet culture. 39 Furthermore, this method has been used to engineer cartilaginous grafts from multiple different cell sources [39][40][41][42][43][44][45] and to engineer tissues of scale with healthy chondrocytes. 46,47 It is therefore also hypothesized that diseased FPSCs can be used to engineer cartilaginous grafts of clinically relevant dimensions ( > 2 cm) for the osteoarthritic patient population using such a scaffold-free or self-assembly approach.…”

Section: Introductionmentioning

confidence: 99%

Infrapatellar Fat Pad-Derived Stem Cells Maintain Their Chondrogenic Capacity in Disease and Can be Used to Engineer Cartilaginous Grafts of Clinically Relevant Dimensions

Liu

Buckley

Almeida

et al. 2014

Tissue Engineering Part A

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A Comparison of Self-Assembly and Hydrogel Encapsulation as a Means to Engineer Functional Cartilaginous Grafts Using Culture Expanded Chondrocytes

Cited by 27 publications

References 53 publications

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing

Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels

Infrapatellar Fat Pad-Derived Stem Cells Maintain Their Chondrogenic Capacity in Disease and Can be Used to Engineer Cartilaginous Grafts of Clinically Relevant Dimensions

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