Cai Chenhui, Zuo Rui, Zhang Zaoqing, Li Haoke, Liu Zhongyi, Zhao Xu, El-Newehy Mohamed, Abdulhameed Meera Moydeen, Yuan Zhengchao, Mo Xiumei, Chu Tongwei, Zhang Chao
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing 400037, China.
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Acta Biomater. 2025 Jul 10. doi: 10.1016/j.actbio.2025.07.023.
Addressing bone injury repair remains a significant challenge in clinical settings, as effective regeneration of healthy bone tissue requires simultaneous promotion of both osteogenesis and angiogenesis. Costal cartilage, being the most abundant cartilage tissue in the human body, shares structural similarities and prolonged cartilaginous properties with long bone growth plates. Its potential as a seed cell source for bone repair, however, remains unexplored. Vascular endothelial growth factor (VEGF), a key factor in bone regeneration, suffers from a short half-life and limited retention at the bone defect area, restricting its therapeutic use. In this study, a collagen hydrogel embedded with costal-cartilage-derived stem cells (CDSCs) and prominin-1-derived peptide (PR1P) was engineered to enhance endogenous VEGF recruitment. CDSCs demonstrate a strong proliferation capacity within bone defect environments, showing significant potential for bone repair. The sustained release of PR1P facilitates in situ VEGF recruitment to enhance angiogenesis and create an optimal osteogenic microenvironment for CDSCs but also demonstrates a modulatory inhibitory effect on osteoclast differentiation. In vivo application of this CDSC-laden PR1P hydrogel significantly accelerated femoral defect healing through synergistic enhancement of osteogenesis, angiogenesis, and suppression of osteoclast activity. Collectively, the study presents a promising approach to bone defect repair, underscoring the potential of CDSCs-based tissue engineering for clinical translation. STATEMENT OF SIGNIFICANCE: Costal cartilage is the richest cartilage tissue in the human body. Our previous research isolated costal-cartilage-derived stem cells (CDSCs) and confirmed their potential for multilineage differentiation and in situ regeneration. This study further demonstrated CDSCs' significant potential for bone repair. A collagen hydrogel embedded with CDSCs and prominin-1-derived peptide (PR1P) was engineered. CDSCs demonstrate self-renewal capacity within bone defect environments. The sustained release of PR1P facilitates in situ VEGF recruitment, enhancing angiogenesis and creating an optimal osteogenic microenvironment. Additionally, the composite hydrogel has an inhibitory effect on osteoclastogenesis. Transplantation of this composite hydrogel enhanced femoral defect healing in mice by promoting both bone formation and vascular regeneration and suppressing osteoclastogenesis, presenting a promising strategy for bone defect repair.
在临床环境中，解决骨损伤修复问题仍然是一项重大挑战，因为健康骨组织的有效再生需要同时促进成骨和血管生成。肋软骨是人体中最丰富的软骨组织，与长骨生长板具有结构相似性和较长的软骨特性。然而，其作为骨修复种子细胞来源的潜力尚未得到探索。血管内皮生长因子（VEGF）是骨再生的关键因子，但其半衰期短且在骨缺损区域的保留有限，限制了其治疗用途。在本研究中，设计了一种嵌入肋软骨来源干细胞（CDSCs）和prominin-1衍生肽（PR1P）的胶原水凝胶，以增强内源性VEGF募集。CDSCs在骨缺损环境中表现出强大的增殖能力，显示出显著的骨修复潜力。PR1P的持续释放有助于原位募集VEGF，以增强血管生成并为CDSCs创造最佳的成骨微环境，同时还对破骨细胞分化具有调节抑制作用。这种负载CDSC的PR1P水凝胶的体内应用通过协同增强成骨、血管生成和抑制破骨细胞活性，显著加速了股骨缺损的愈合。总体而言，该研究提出了一种有前景的骨缺损修复方法，强调了基于CDSCs的组织工程在临床转化中的潜力。
肋软骨是人体中最丰富的软骨组织。我们之前的研究分离出了肋软骨来源干细胞（CDSCs），并证实了它们的多谱系分化和原位再生潜力。本研究进一步证明了CDSCs在骨修复方面的显著潜力。设计了一种嵌入CDSCs和prominin-1衍生肽（PR1P）的胶原水凝胶。CDSCs在骨缺损环境中表现出自我更新能力。PR1P的持续释放有助于原位募集VEGF，增强血管生成并创造最佳的成骨微环境。此外，复合水凝胶对破骨细胞生成具有抑制作用。这种复合水凝胶的移植通过促进骨形成和血管再生以及抑制破骨细胞生成，增强了小鼠股骨缺损的愈合，为骨缺损修复提供了一种有前景的策略。
