Citrate-based biodegradable injectable hydrogel composites for orthopedic applications

Previous studies have confirmed that natural bone apatite crystals are bound with citrate-rich molecules. Citrates on apatite crystals impact bone development and its load-bearing function. However, such understanding has never been translated into bone biomaterials design. Herein, a first citrate-based injectable composite material for orthopedic applications is developed based on our recently developed biodegradable poly(ethylene glycol) maleate citrate (PEGMC) and hydroxyapatite (HA). PEGMC contains rich carboxylic groups that could chelate with calcium-containing HA thus facilitating polymer/HA interactions, similar to natural citrate-bound apatite crystal. The crosslinking of poly(ethylene glycol) diacrylate (PEGDA) with PEGMC/HA composites allows an addition control over degradation and mechanical properties of the crosslinked PEGMC/HA (CPEGMC/HA) composites. CPEGMC/HA composite can serve as an ideal injectable cell carrier as confirmed by the enhanced DNA content, ALP activity, and calcium production through a human fetal osteoblast encapsulation study. Ex vivo study on porcine femoral head demonstrated that PEGMC/HA is a potentially promising injectable biodegradable bone material for the treatment of osteonecrosis of the femoral head. Development of biodegradable citrate-based injectable PEGMC/HA composite is an initial step for the development of the next generation of bone tissue engineering and orthopedic biomaterials.