Hyaluronic acid hydrogels with controlled degradation properties for oriented bone regeneration

Abstract

Non-healing fractures can result from trauma, disease, or age-related bone loss. While many treatments focus on restoring bone volume, few try to recapitulate bone organization. However, the native architecture of bone is optimized to provide its necessary mechanical properties. Hyaluronic acid (HA) hydrogel scaffold systems with tunable degradation properties were developed for the controlled delivery of osteoinductive and angiogenic growth factors, thus affecting the quantity and quality of regenerated tissue. HA hydrogels were designed to degrade at fast, intermediate, and slow rates due to hydrolysis and further provided controlled release of cationic proteins due to electrostatic interactions. Scaffolds delivering bone morphogenetic protein-2 (BMP-2) were evaluated in a rat calvarial bone critical size defect model. BMP-2 delivery from the HA hydrogels had a clear osteoinductive effect in vivo and, for all hydrogel types, BMP-2 delivery resulted in significant mineralization compared to control hydrogels. The temporal progression of this effect could be modulated by altering the degradation rate of the scaffold. All three degradation rates tested resulted in similar amounts of mineral formation at the latest (six week) time point examined. Interestingly, however, the fastest and slowest degrading scaffolds seemed to result in more organized bone than the intermediate degrading scaffold, which was designed to degrade in 6-8 weeks to match the healing time. Additionally, healing could be enhanced by co-delivery of vascular endothelial growth factor along with BMP-2.

Diels−Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering

“…Indeed, in a reaction with 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCI), the yield of immobilization of furfurylamine on HA was much lower than that using DMTMM (Figure 9 and Figure S3). The structure and degree of substitution were HA-PEG hydrogels were synthesized by mixing solutions of HA-furan an included in HA hydrogels to vary the mechanical properties and pore size of the scaffolds [65][66][67][68] By controlling the chain length of the PEG cross-linker, one can control these properties.…”

Evaluation of Alginate and Hyaluronic Acid for Their Use in Bone Tissue Engineering

“…Moreover, when containing bFGF, HA hydrogels enhance calcium deposition, osteopontin and BSP expression and decrease alkaline phosphatase in rat bone marrow stromal cells [26]. In vivo, HA hydrogels containing BMP-2 showed increased bone formation [19,27].…”

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

“…Hybrid materials, including various polymer/calcium phosphate composites, have been explored with tunable degradation properties. Extracellular matrix-based materials, such as collagen-glycosaminoglycan scaffolds and hyaluronic acid hydrogels, have also been explored with cells that are seeded before grafting (9,10). Softer materials, including hydrogel-based delivery systems, can effectively present biological cues, such as growth factors at low doses (11,12).…”