Sticky bone-specific artificial extracellular matrix for stem cell-mediated rapid craniofacial bone therapy

Abstract Implantable scaffolds mimicking the different physicochemical attributes of the extracellular matrix (ECM) in native bone matrix have been developed for stem cell transplantation as a tailored microenvironment to direct the desired osteogenic responses. However, current approaches for the engineering of bone constructs fail to recapitulate the dynamic regulatory features of bone development and homeostatic maintenance, restricting their clinical outcomes especially in the repair of large craniofacial bone defects that involve a hostile ischemic environment. Here, a sticky bone-specific artificial ECM (aECM) was proposed as a bioengineered bone niche capable of regenerating fully functional bone tissue. The dual functionalization of two chimeric mussel adhesive proteins (MAPs) fused with the cell adhesive Alg-Gly-Asp (RGD) peptide or the osteoinductive bone morphogenetic protein-2 (BMP-2) peptide promoted in vitro cellular behaviors and osteogenic commitments of adipose-derived stem cells (ADSCs) through the synergistic effects of two bioactive peptides in a matrix-bound manner. The chimeric MAP-based aECM induced remarkably accelerated bone tissue formation and promoted the construction of functional vascular networks with bone marrow (BM)-like compartments on an ADSC-laden collagen sponge within a calvarial defect. Thus, our multicomposite bone-specific aECM could be a promising therapeutic platform for further driving the clinical translation of stem cell-mediated bone therapies.