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Chondroinductive Hydrogel Pastes Composed of Naturally Derived Devitalized Cartilage.

ABSTRACT: Hydrogel precursors are liquid solutions that are prone to leaking from the defect site once implanted in vivo. Therefore, the objective of the current study was to create a hydrogel precursor that exhibited a yield stress. Additionally, devitalized cartilage extracellular matrix (DVC) was mixed with DVC that had been solubilized and methacrylated (MeSDVC) to create hydrogels that were chondroinductive. Precursors composed of 10% MeSDVC or 10% MeSDVC with 10% DVC were first evaluated rheologically, where non-Newtonian behavior was observed in all hydrogel precursors. Rat bone marrow stem cells (rBMSCs) were mixed in the precursor solutions, and the solutions were then crosslinked and cultured in vitro for 6 weeks with and without exposure to human transforming growth factor ?3 (TGF-?3). The compressive modulus, gene expression, biochemical content, swelling, and histology of the gels were analyzed. The DVC-containing gels consistently outperformed the MeSDVC-only group in chondrogenic gene expression, especially at 6 weeks, where the relative collagen II expression of the DVC-containing groups with and without TGF-?3 exposure was 40- and 78-fold higher, respectively, than that of MeSDVC alone. Future work will test for chondrogenesis in vivo and overall, these two cartilage-derived components are promising materials for cartilage tissue engineering applications.

SUBMITTER: Beck EC

PROVIDER: S-EPMC5209355 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Chondroinductive Hydrogel Pastes Composed of Naturally Derived Devitalized Cartilage.

Beck Emily C EC Barragan Marilyn M Tadros Madeleine H MH Kiyotake Emi A EA Acosta Francisca M FM Kieweg Sarah L SL Detamore Michael S MS

Annals of biomedical engineering 20160107 6

Hydrogel precursors are liquid solutions that are prone to leaking from the defect site once implanted in vivo. Therefore, the objective of the current study was to create a hydrogel precursor that exhibited a yield stress. Additionally, devitalized cartilage extracellular matrix (DVC) was mixed with DVC that had been solubilized and methacrylated (MeSDVC) to create hydrogels that were chondroinductive. Precursors composed of 10% MeSDVC or 10% MeSDVC with 10% DVC were first evaluated rheological ...[more]

PMID: 26744243

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Project description:Background Traumatic impacts to the articular joint surface are known to lead to cartilage degeneration, as in post-traumatic osteoarthritis (PTOA). Limited progress in the development of disease-modifying OA drugs (DMOADs) may be due to insufficient mechanistic understanding of human disease onset/progression and insufficient in vitro models for disease and therapeutic modeling. In this study, biomimetic hydrogels laden with adult human mesenchymal stromal cells (MSC) are used to examine the effects of traumatic impacts as a model of PTOA. We hypothesize that MSC-based, engineered cartilage models will respond to traumatic impacts in a manner congruent with early PTOA pathogenesis observed in animal models. Methods Engineered cartilage constructs were fabricated by encapsulating adult human bone marrow-derived mesenchymal stem cells in a photocross-linkable, biomimetic hydrogel of 15% methacrylated gelatin and promoting chondrogenic differentiation for 28 days in a defined medium and TGF-β3. Constructs were subjected to traumatic impacts with different strains or 10 ng/ml IL-1β, as a common comparative method of modeling OA. Cell viability and metabolism, elastic modulus, gene expression, matrix protein production and activation of catabolic enzymes were assessed. Results Cell viability staining showed that traumatic impacts of 30% strain caused an appropriate level of cell death in engineered cartilage constructs. Gene expression and histo/immunohistochemical analyses revealed an acute decrease in anabolic activities, such as COL2 and ACAN expression, and a rapid increase in catabolic enzyme expression, e.g., MMP13, and inflammatory modulators, e.g., COX2. Safranin O staining and GAG assays together revealed a transient decrease in matrix production 24 h after trauma that recovered within 7 days. The decrease in elastic modulus of engineered cartilage constructs was coincident with GAG loss and mediated by the encapsulated cells. The acute and transient changes observed after traumatic impacts contrasted with progressive changes observed using continual IL-1β treatment. Conclusions Traumatic impacts delivered to engineered cartilage constructs induced PTOA-like changes in the encapsulated cells. While IL-1b may be appropriate in modeling OA pathogenesis, the results of this study indicate it may not be appropriate in understanding the etiology of PTOA. The development of a more physiological in vitro PTOA model may contribute to the more rapid development of DMOADs. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03022-8.

Project description:Many attempts have been made to repair articular cartilage defects, including mesenchymal stem cell (MSC)-based tissue engineering strategies. Although this approach shows promise, optimizing MSC sources and their delivery is challenging. This study was designed to test the feasibility of using MSCs found in the human arthroscopic flushing fluid (AFF) for cartilage regeneration, by incorporating them into a newly developed one-step rapid cross-linking hyper-branched polyPEGDA/HA hydrogel. AFF-MSCs were isolated from the original intra-articular flushing fluid of 10 patients prior to arthroscopic procedures. The hydrogel was fabricated with hyper-branched polyPEGDA and thiolated hyaluronic acid (HA). In vitro assays demonstrated that AFF-MSCs possessed the typical MSC morphology and phenotype, and maintained chondrogenic differentiation properties when encapsulated within the hydrogel. The AFF-MSC/hydrogel composite could significantly repair full-thickness cartilage defects generated in a rat model after 8 weeks of implantation; smooth cartilage was formed with evidence of hyaline cartilage formation. These data suggest that human AFF-MSCs are a novel and abundant MSC source that have high therapeutic value for cartilage regeneration.Statement of significanceMany attempts have been made to repair the defects of articular cartilage, including mesenchymal stem cell (MSC)-based tissue engineering strategies. Optimizing MSC sources and their delivery approaches still remain clinically challenging. Recent studies determined that MSCs derived from synovium and synovial fluid exhibited superior chondrogenic potential. However, no feasible methods to harvest these human tissues and cells have been impeding them for clinical application. Hereby, we explored a simple and easy accessible approach to obtain a new stem cell source from arthroscopic flushing fluid (AFF-MSCs), which probably contains plenty of MSCs from synovium and synovial fluid. Further experiments demonstrated that encapsulation of these stem cells with one-step rapid cross-linked polyPEGDA/HA hydrogel held very encouraging potential for cartilage regeneration.

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Chondroinductive Hydrogel Pastes Composed of Naturally Derived Devitalized Cartilage.

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Chondroinductive Hydrogel Pastes Composed of Naturally Derived Devitalized Cartilage.

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