Functionalized Collagen/elastin-like Polypeptide Hydrogels for Craniofacial Bone Regeneration.

Critical-sized cranial bone defects fail to re-ossify and require a surgical intervention of cranioplasty. To achieve superior bone healing in such cases, we developed a hydrogel consisting of an interpenetrating network of collagen and elastin-like polypeptide to encapsulate BMP-2, doxycycline, and 45S5 Bioglass. This hydrogel had an appropriate elastic modulus of 39 ± 2.2 kPa to allow proper handling during implantation. The hydrogel promoted human adipose-derived stem attachment, proliferation, and differentiation toward the osteogenic lineage, including deposition of hydroxyapatite particles embedded within a collagenous fibrillar structure after 21 days of in vitro culture. After eight weeks of implantation of the acellular hydrogel in a critical-sized rat cranial defect model, we noticed only small quantity of various pro-inflammatory (< 20 pg/mg) and anti-inflammatory (< 10 pg/mg) factors in the adjacent cranial tissue, indicating the overall biocompatibility of the hydrogel. Scanning electron microscopy evidenced presence of new fibrous extracellular matrix and mineral aggregates at the defect site, with Ca/P ratio of 0.5 and 2.0 by eight and twelve weeks, respectively. Micro-CT and histological analysis showed formation of mature mineralized tissue that bridged with the surrounding bone. Taken together, the acellular composite hydrogel shows great promise for superior bone healing after cranioplasty. This article is protected by copyright. All rights reserved.