Abstract
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.
Highlights
Construction of periosteum-like tissue (PT) in vivo harbored a higher fraction of periosteum-like tissue-derived cells (PTDCs) than those in the BMP group
The fraction of PTDCs in the PBS group had the highest fraction of PTDCs to regulate the osteogenic capacity of bone morphogenetic protein-2 (BMP-2) in bone defect repair.[35,36]
To confirm the induction of PTs via a among all three groups, which indicated that the migrated PTDCs in the PBS group remained undifferentiated and did not undergo osteogenic and chondrogenic processes (Fig. 2e)
Summary
The periosteum serves as an attachment surface for skeletal muscles and ligaments and covers almost the entire bone surface.[1,2] the periosteum harbors multiple cell types, including osteogenic cells and fibroblastic cells, blood vessels, and nerve endings, which play a central role in bone fracture and defect repair.[3,4,5,6,7] As a thin membrane covers the bone, the periosteum consists of multiple extracellular matrices (ECMs), such as collagens and glycosaminoglycans.[8,9] Periosteum-derived cells (PDCs) or periosteum-derived multipotent mesenchymal stromal cells (MSCs), as a crucial component of the periosteum, are heterogeneous and may contain different subpopulations of multipotent stem cells.[10,11]PDCs are deeply involved in the generation of bone, cartilage, and hematopoietic marrow.[5,7] A recent study identified a multipotent and self-renewing type of periosteal stem cell that emerges in the periosteum.[12]. To further evaluate the fate of PTDCs derived from PTs during explanted from the Lepr-cre; tdTomato mice among the PBS, BMP, bone reconstruction, we traced the transplanted PTDCs via and BMP/CS groups, we conducted flow cytometry, CFU-F assays, lineage-tracing technology and in vivo imaging in allogenic and qPCR assays (Fig. 2a).
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