Human Nail Bed Extracellular Matrix Facilitates Bone Regeneration via JAK2/STAT3 Pathway Mediated Macrophage Polarization
Bone critical sized defect caused by trauma, tumor resection and serious infection represents one of the most challenging problems faced by orthopedic surgeons. However, construction of bone grafts with good osteointegration and osteoinductivity is a clinical challenge. It has been elaborated that the nail bed tissue is an essential element for digit tip regeneration, suggesting that the nail bed may provide a new material for bone regeneration. Human nail bed extracellular matrix derived from amputated patients stimulates macrophage polarization toward pro-healing phenotype and expression of BMP2 to facilitate the osteogenic differentiation of BMSCs in vitro. The in vivo osteogenic capacity of decellularized nail bed scaffolds has been confirmed by the rat critical-sized calvarial defect model. The in-depth analysis of immune responses to implanted scaffolds revealed that macrophage polarization toward pro-regenerative M2 phenotype directs the osteogenesis, as confirmed by macrophage depletion. The combination of proteomics analysis and RNA interference verifies that the JAK2/STAT3 pathway is the positive regulator of macrophage polarization initiated by decellularized nail bed during the promoted osteogenesis process. Thus, the decellularized human nail bed scaffold developed in this paper is a promising biomaterial for bone regeneration.