Transforming growth factor-beta 1 release from oligo(poly(ethylene glycol) fumarate) hydrogels in conditions that model the cartilage wound healing environment

Abstract

This research demonstrates that controlled material degradation and transforming growth factor-beta1 (TGF-beta1) release can be achieved by encapsulation of TGF-beta1-loaded gelatin microparticles within the biodegradable polymer oligo(poly(ethylene glycol) fumarate) (OPF), so that these microparticles function as both a digestible porogen and a delivery vehicle. Release studies performed with non-encapsulated microparticles confirmed that at normal physiological pH, TGF-beta1 complexes with acidic gelatin, resulting in slow release rates. At pH 4.0, this complexation no longer persists, and TGF-beta1 release is enhanced. However, by encapsulating TGF-beta1-loaded microparticles in a network of OPF, release at either pH can be diffusionally controlled. For instance, after 28 days of incubation at pH 4.0, final cumulative release from non-encapsulated microparticles crosslinked in 10 and 40 mM glutaraldehyde (GA) was 75.4+/-1.6% and 76.6+/-1.1%, respectively. However, when either microparticle formulation was encapsulated in an OPF hydrogel (noted as OPF-10 mM and OPF-40 mM, respectively), these values were reduced to 44.7+/-14.6% and 47.4+/-4.7%. More interestingly, release studies, in conditions that model the expected collagenase concentration of injured cartilage, demonstrated that by altering the microparticle crosslinking extent and loading within OPF hydrogels, TGF-beta1 release, composite swelling, and polymer loss could be systematically altered. Composites encapsulating less crosslinked microparticles (OPF-10 mM) exhibited 100% release after only 18 days and were completely degraded by day 24 in collagenase-containing phosphate-buffered saline (PBS). Hydrogels encapsulating 40 mM GA microparticles did not exhibit 100% release or polymer loss until day 28. Hydrogels with no microparticle component demonstrated only 79.3+/-9.2% release and 89.2+/-3.4% polymer loss after 28 days in enzyme-containing PBS. Accordingly, these studies confirm that the rate of TGF-beta1 release and material degradation can be controlled by altering key parameters of these novel, in situ crosslinkable biomaterials, so that TGF-beta1 release and scaffold degradation may be tailored to optimize cartilage repair.