The periosteum, a highly vascularized thin tissue, has excellent osteogenic and bone regenerative abilities. The generation of periosteum-mimicking tissue has become a novel strategy for bone defect repair and regeneration, especially in critical-sized bone defects caused by trauma and bone tumor resection. Here, we utilized a bone morphogenetic protein-2 (BMP-2)-loaded scaffold to create periosteum-like tissue (PT) in vivo, mimicking the mesenchymal condensation during native long bone development. We found that BMP-2-induced endochondral ossification plays an indispensable role in the construction of PTs. Moreover, we confirmed that BMP-2-induced PTs exhibit a similar architecture to the periosteum and harbor abundant functional periosteum-like tissue-derived cells (PTDCs), blood vessels, and osteochondral progenitor cells. Interestingly, we found that the addition of chondroitin sulfate (CS), an essential component of the extracellular matrix (ECM), could further increase the abundance and enhance the function of recruited PTDCs from the PTs and finally increase the regenerative capacity of the PTs in autologous transplantation assays, even in old mice. This novel biomimetic strategy for generating PT through in vivo endochondral ossification deserves further clinical translation.

骨膜是一种高度血管化的薄组织，具有优良的成骨和骨再生能力。骨膜模拟组织的生成已成为骨缺损修复和再生的一种新策略，特别是在创伤和骨肿瘤切除引起的临界大小的骨缺损中。在这里，我们利用加载骨形态发生蛋白 2 (BMP-2) 的支架在体内创建骨膜样组织 (PT)，模拟天然长骨发育过程中的间充质浓缩。我们发现 BMP-2 诱导的软骨内骨化在 PT 的构建中起着不可或缺的作用。此外，我们证实 BMP-2 诱导的 PT 表现出与骨膜相似的结构，并含有丰富的功能性骨膜样组织衍生细胞 (PTDC)、血管和骨软骨祖细胞。有趣的是，我们发现添加硫酸软骨素 (CS) 是细胞外基质 (ECM) 的重要组成部分，可以进一步增加从 PT 募集的 PTDCs 的丰度和功能，最终提高 PTs 在自体移植中的再生能力试验，即使在老老鼠身上。这种通过体内软骨内骨化产生 PT 的新型仿生策略值得进一步临床转化。