Glycoprotein Injectable Hydrogels Promote Accelerated Bone Regeneration through Angiogenesis and Innervation

Glycoproteins are gaining prominence as multifunctional biomaterials. The study reports development of glycoprotein mucin as biomaterial promoting bone regeneration. Mucin 1 deletion has resulted in stiffer femoral bones with scarce presence of osteoblasts in trabecular linings and its role has been established in determining bone mass and mineralization. Limited information about its structure limits its processability, exploration as biomaterial, which is discussed in this study. The role of mucin in ECM (extracellular cellular matrix) formation validated by RNA sequencing analysis of human bone marrow derived mesenchymal stem cells is reported. The structure and stability of mucins is dependent on the presence of glycans in its structure. A thermosensitive hydrogel acquired from thermosensitive Poly (N-isopropyl acrylamide)-(PNIPAM) modified mucin and collagen is developed. The hydrogel demonstrates porous structure and mechanical strength. Newly formed bone tissue is observed at 8 weeks post-implantation in the hydrogel treated groups. The formation of blood vessels, nerves, and bone is observed with upregulation of angiopoietin (ANG), neurofilament heavy chain (NF-H), and osteoadherin (OSAD) or osteocalcin (OCN) respectively in rat calvarial defects. The outcome demonstrates that the thermosensitive injectable hydrogel accelerates repair and healing in calvarial bone defects making it a promising biodegradable biomaterial capable of regenerating bone by promoting angiogenesis and innervation. Schematic representing the modification of mucin by conjugating PNIPAM and the formation of thermoreversible hydrogels with protein (collagen and mucin). The in vitro and in vivo experimental analysis is indicated in a snapshot.image