Biodegradable PHBVHHx-PEG/Collagen Hydrogel Scaffolds for Cartilage Repair

Abstract

Recently, there has been increased attention on the treatment of cartilage repair. Overall, we constructed PHBVHHx-COL, a composite hydrogel of PHBVHHx-co-PEG and collagen, and evaluated its cartilage repair efficacy through in vitro and in vivo studies using hydrogel loaded with peripheral blood-derived mesenchymal stem cells (PBMSCs). Rheological properties and compressive mechanical properties of the hydrogels were systematically evaluated. The cytocompatibility of the hydrogels was evaluated using the Cell Counting Kit-8 test, live/dead staining, scratch test, and transwell test. The effect of chondrogenic differentiation of PBMSCs on hydrogels was evaluated using immunofluorescence staining and reverse transcription-polymerase chain reaction. Furthermore, the in vivo cartilage repair ability of the hydrogels was confirmed following in situ injections in rabbit chondral defect models. Finally, the induced polarization of the hydrogel scaffold on macrophages was explored by the expression of CD86 and CD206. In vitro experimental results confirmed that PHBVHHx-COL-gel led to better cell migration, proliferation, and chondrogenic differentiation than PHBVHHx-PEG and COL hydrogels. Hematoxylin and eosin staining indicated that the tissue of the repaired area in the PHBVHHx-COL group was nearly in fusion with the surrounding normal tissue and the reconstruction of subchondral bone was good. Safranin-O staining and COL-2 immunohistochemistry indicated that the tissue of the repaired area in the PHBVHHx-COL group had more cartilage-specific matrix secretion. The PHBVHHx-COL group exhibited more M2 macrophage infiltration and less M1 macrophage presentation than the other groups. This study demonstrated that PHBVHHx-COL scaffolds loaded with PBMSCs significantly promoted the repair of cartilage injury through immune regulation by M2 polarization and could be potential candidates for cartilage tissue engineering.

Impact Statement

In our study, for the first time, porous scaffolds of PHBVHHx were utilized for cartilage repair. We found that injectable PHBVHHx-COL gel possesses good compressive mechanical properties and biocompatibility as a tissue engineering scaffold. When loaded with PBMSCs, PHBVHHx-COL gel demonstrated a significant cartilage repair effect. After 12 weeks, the repaired cartilage tissue closely resembled normal cartilage tissue.