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 <i>in vitro</i> and <i>in vivo</i> 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 <i>in vivo</i> cartilage repair ability of the hydrogels was confirmed following <i>in situ</i> 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. <i>In vitro</i> 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.