Injectable and degradable calcium phosphate/silanized hyaluronic acid composite foam for bone defect repair: A study in a Rabbit model

Calcium phosphate cements (CPCs) are widely used as bone substitutes due to their injectability, which makes them well-suited for minimally invasive surgeries. However, their biomaterial-induced biological response often falls short in promoting osteogenesis, primarily due to their limited interconnected macroporosity and inadequate biodegradation rate, which impede cell migration and vascularization. Recent advancements have introduced a dual syringe-mixing technique to create injectable composite foam pastes that result into macroporous composite foams. These foams consist of a mineral cementitious precursor (leading to the formation of a calcium deficient hydroxyapatite cement CDHA), combined with different organic matrices such as silanized hydroxypropyl methylcellulose (SiHPMC), gelatin (GEL), or silanized hyaluronic acid (SiHYA). Although the physico-chemical features of these hybrid (organo-mineral) composite foams are comparable, their respective in vivo performances vary significantly. In the present study involving femoral defects in rabbits, all formulations demonstrated high levels of osteointegration and bone formation after six weeks of implantation. However, their biodegradation rates, influenced by the organic matrix, differed markedly, with CDHA/SiHPMC exhibiting minimal degradation and CDHA/GEL showing near-complete biomaterial resorption. Notably, the CDHA/SiHYA composite foam presented an optimal balance between biodegradation and bone formation, suggesting its potential for effective clinical application in bone defect treatment. We have shown herein that, as in the case of industrial composites, these composites for regenerative medicine, that are the result of a combination in a single mass of materials that differ in terms of their chemical nature, achieve a summation of performance depending of their organic phase, in terms of biological reactivity. • Design of injectable composite foams for bone tissue engineering • This design allows an in vivo macroporous interconnected hybride composite cement. • The influence of the hydrogels that compose composite foams is studied. • Biodegradation and bone formation (in rabbit model) of composite foams cements are described. • For these 3 different hydrogels, 3 different biological answers were obtained.