Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair

Abstract

The present work investigated the use of biodegradable hydrogel composite scaffolds, based on the macromer oligo(poly(ethylene glycol) fumarate) (OPF), to deliver growth factors for the repair of osteochondral tissue in a rabbit model. In particular, bilayered OPF composites were used to mimic the structural layers of the osteochondral unit, and insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) were loaded into gelatin microparticles and embedded within the OPF hydrogel matrix in a spatially controlled manner. Three different scaffold formations were implanted in a medial femoral condyle osteochondral defect: 1) IGF-1 in the chondral layer, 2) BMP-2 in the subchondral layer, and 3) IGF-1 and BMP-2 in their respective separate layers. The quantity and quality of osteochondral repair was evaluated at 6 and 12 weeks with histological scoring and micro-computed tomography (micro-CT). While histological scoring results at 6 weeks showed no differences between experimental groups, micro-CT analysis revealed that the delivery of BMP-2 alone increased the number of bony trabecular islets formed, an indication of early bone formation, over that of IGF-1 delivery alone. At 12 weeks post-implantation, minimal differences were detected between the three groups for cartilage repair. However, the dual delivery of IGF-1 and BMP-2 had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface than the single delivery of IGF-1. These results suggest that the delivery of BMP-2 enhances subchondral bone formation and that, while the dual delivery of IGF-1 and BMP-2 in separate layers does not improve cartilage repair under the conditions studied, they may synergistically enhance the degree of subchondral bone formation. Overall, bilayered OPF hydrogel composites demonstrate potential as spatially-guided, multiple growth factor release vehicles for osteochondral tissue repair.

New scaffolds encapsulating TGF-β3/BMP-7 combinations driving strong chondrogenic differentiation

“…Overall, our results support the strategy of activating scaffolds for the co-delivery of rationally selected GFs, as observed elsewhere [4,5,7,41]. We have also made a strong case for combining TGF-β3 with BMP-7 in a suitable delivery system for cartilage repair.…”

“…For instance, the group of Mikos tried to improve cartilage repair using TGF-β1 and Insulin-like Growth Factor-1 (IGF-1) loaded into a hydrogel. While histological scoring showed minimal differences between the co-delivery and the single delivery, the dual delivery group had a higher proportion of subchondral bone repair, greater bone growth at the defect margins, and lower bone specific surface [4,5]. Du et al developed a dual-release hydrogel system of basic Fibroblast Growth Factor (bFGF) and TGF-β to enhance human mesenchymal stem cell (hMSC) differentiation [6].…”

Extracellular Calcium Modulates Chondrogenic and Osteogenic Differentiation of Human Adipose-Derived Stem Cells: A Novel Approach for Osteochondral Tissue Engineering Using a Single Stem Cell Source

“…A more recent approach to develop a full osteochondral construct used a dual growth factor delivery approach, for a spatially guided formation of osteochondral tissue. 53 Although most of these studies have successfully formed bone, cartilage, or both, the transitional interphase between the cartilage and subchondral bone that mimics both mechanically and biochemically the interphase of osteochondral tissue, remains a challenge.…”

A Review on Biodegradable Polymeric Materials Striving Towards the Attainment of Green Environment

“…Steven Lu et al (2014) [60] demonstrated the preparation of OPF based biodegradable hydrogel composite scaffolds. The authors investigated growth factor for the repair of osteochondral tissue in a rabbit model.…”