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 β3 (TGF-β3). 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-β3 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.

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

“…Methacrylation successfully slowed cell‐mediated contraction, with methacrylated hydrogels at 6 weeks measuring approximately 70% of the initial area, whereas non‐methacrylated hydrogels measured less than 20% of the initial area. These results agree with a recent study by Beck et al () in which methacrylate groups were added to a pepsin‐soluble devitalized cartilage paste. Despite an improved maintenance of initial construct size, the methacrylation process compromised the long‐term stability of CartilageMA constructs, which demonstrated fibrillation and subsequent disintegration beginning at day 14 and extending through to day 42.…”

Cartilage extracellular matrix as a biomaterial for cartilage regeneration

“…Given that GAGs contribute to the compressive stiffness of cartilage matrix via the electrostatic interactions between GAG chains and water, the mechanical performance of the scaffolds can be reduced in comparison to native articular cartilage after decellularization. In recent work, we demonstrated that inclusion of DVC particles eliminated scaffold contraction in vitro …”

“…While press‐fit scaffolds may be appropriate for regularly shaped cartilage defects, it may not be suitable for irregularly shaped defects. Our research group has introduced paste‐like cartilage matrix–based materials that are intended to fill irregularly shaped cartilage defects, where the paste can be crosslinked after placement to stay in place . Investigating and expanding the different forms of cartilage matrix–based products are needed to encompass various patient‐specific applications.…”

Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration

“…In a different study, Beck et al . investigated the regenerative potential of photocrosslinked hydrogel pastes containing DVC or DCC particles, which were placed surgically into cartilage defects [183]. The study highlighted the in vitro stem cell recruitment’s ability of these chondroinductive formulations, which hold potential as platforms for the regeneration of critical-sized bone defects by EC ossification of intermediate cartilage tissue.…”