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.

已开发出可模仿天然骨基质中细胞外基质（ECM）的不同理化特性的可植入支架，用于干细胞移植，作为定制的微环境来指导所需的成骨反应。然而，目前用于骨结构工程的方法不能概括骨骼发育和体内稳态维持的动态调节特征，从而限制了它们的临床结果，尤其是在修复涉及敌对缺血环境的大颅面骨缺损中。在此，提出了一种粘性骨特异性人工ECM（aECM）作为能够再生功能齐全的骨组织的生物工程骨生态位。通过两种生物活性肽的基质结合方式的协同作用，脂肪干细胞（ADSCs）的体外细胞行为和成骨作用。基于嵌合MAP的aECM可以显着加速骨骼组织的形成，并促进颅骨缺损内载有ADSC的胶原海绵上具有类似骨髓（BM）隔室的功能性血管网络的构建。因此，我们的多复合骨特异性aECM可能是一个有前途的治疗平台，可进一步推动干细胞介导的骨疗法的临床翻译。