Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair

Abstract

While localized delivery of IGF-1 may be a promising repair strategy, further in vivo assessment is necessary, since fibrous tissue was commonly observed in the neo-surface of all treatment groups. More importantly, this study highlights the need to rigorously examine GF interactions in the wound healing environment and demonstrates that in vitro observations do not directly translate to the in vivo setting.

Oligo[poly(ethylene glycol)fumarate] Hydrogel Enhances Osteochondral Repair in Porcine Femoral Condyle Defects

“…OPF hydrogel is a polymer created through the synthesis of fumaric acid and PEG through ester bonds [26]. The ability of the ester bonds to undergo hydrolysis under acidic and basic conditions confers biodegradable characteristics, of which in vitro [19,21,26,42,54,55,58] and in vivo [13,17,18,57] degradation rates have been reported. It is also biocompatible, evident from in vitro [12, 42-44, 50, 55, 56, 58] and in vivo [13,17,18,57] assessments.…”

“…It is also biocompatible, evident from in vitro [12, 42-44, 50, 55, 56, 58] and in vivo [13,17,18,57] assessments. These characteristics have led to numerous in vitro [12, 20, 21, 27-30, 43-45, 56] and rabbit model studies [13,17,18,57]. A preclinical evaluation of the usage of this scaffold alone as a treatment strategy is lacking.…”

“…It possesses a higher water content than other hydrogels, such as poly(glycolic acid) and poly(L-lactic acid) polymer meshes. In addition, it is more biodegradable [19,21,26,42,54,55,58] and biocompatible [13,17,18,57] compared to natural scaffold materials, such as gelatin, collagen, and hyaluronic acid [20]. In a preclinical evaluation of this scaffold, we investigated the effects of freeze-dried OPF hydrogel scaffold in a porcine model, which is more clinically relevant due to greater physiologic and anatomic similarities to humans.…”

Polymers to direct cell fate by controlling the microenvironment

“…With respect to the latter, phage display has been a powerful technique for identifying ligands that can tightly control the kinetics of factor release [32]. Dual delivery of multiple growth factors and morphogens has been achieved in multiple systems including poly (lactide-co-glycolide) (PLG) [31], oligo(poly(ethylene glycol) fumarate) [33], and alginate [34] scaffolds. Multiple factors can be delivered sequentially, simultaneously, or both, and these techniques can be combined with DNA or RNAi delivery to enable long-standing protein expression [35] or abrogation of expression [36].…”

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

“…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].…”