Domingues Margarida F, Carvalho Marta S, Sanjuan-Alberte Paola, Silva João C
Department of Bioengineering and iBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa Av. Rovisco Pais Lisboa 1049-001 Portugal
Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa Av. Rovisco Pais Lisboa 1049-001 Portugal.
RSC Adv. 2025 Sep 4;15(38):31812-31829. doi: 10.1039/d5ra02106e. eCollection 2025 Aug 29.
Bone-related injuries represent a major global challenge, particularly for the aging population. While bone has self-healing capabilities, large defects and non-union fractures often fail to completely regenerate, leading to long-term disability and the need for surgical intervention. Autologous bone grafts remain the gold standard for such procedures, but challenges such as limited donor availability and donor site comorbidity persist. Bone tissue engineering (BTE) presents an alternative approach for bone regeneration, using biomaterials, cells and growth factors that mimic the natural composition and structure of bone. Cell-derived decellularized extracellular matrix (dECM), particularly from mesenchymal stem/stromal cell (MSCs), is among the most promising biomaterials for BTE, as it closely mimics the composition of native bone ECM and provides immunomodulatory and trophic molecules that support bone regeneration. However, dECM's mechanical properties are often insufficient, requiring its combination with synthetic polymers to improve scaffold strength and structural integrity, critical to support hard tissues such as bone. This review explores the potential of MSC-dECM composite scaffolds developed for BTE, including 3D printed constructs, electrospun fibrous matrices, hydrogels and metallic scaffolds. It describes how the incorporation of MSC-dECM enhances the osteoconductive and osteoinductive properties of these scaffolds, leading to increased expression of osteogenic markers and calcium deposition , as well as enhanced bone formation . Finally, the review addresses the current challenges and future directions in advancing the application of MSC-dECM-enriched scaffolds towards clinically effective bone repair strategies, including the need to scale up MSC-dECM production, further elucidate its regenerative mechanisms, and integrate it into precise patient-tailored approaches.
骨相关损伤是一项重大的全球挑战，对老龄人口而言尤为如此。虽然骨骼具有自我修复能力，但大的骨缺损和骨不连骨折往往无法完全再生，导致长期残疾并需要手术干预。自体骨移植仍然是此类手术的金标准，但供体可用性有限和供体部位合并症等挑战依然存在。骨组织工程（BTE）为骨再生提供了一种替代方法，它使用模仿骨自然组成和结构的生物材料、细胞和生长因子。细胞衍生的脱细胞细胞外基质（dECM），特别是来自间充质干/基质细胞（MSC）的dECM，是BTE最有前景的生物材料之一，因为它紧密模仿天然骨ECM的组成，并提供支持骨再生的免疫调节和营养分子。然而，dECM的机械性能往往不足，需要与合成聚合物结合以提高支架强度和结构完整性，这对于支撑骨骼等硬组织至关重要。本综述探讨了为BTE开发的MSC-dECM复合支架的潜力，包括3D打印构建体、电纺纤维基质、水凝胶和金属支架。它描述了MSC-dECM的加入如何增强这些支架的骨传导性和骨诱导性，导致成骨标志物表达增加和钙沉积增加，以及骨形成增强。最后，本综述阐述了在推进富含MSC-dECM的支架应用于临床有效的骨修复策略方面当前面临的挑战和未来方向，包括扩大MSC-dECM生产规模的必要性、进一步阐明其再生机制，以及将其整合到精确的个性化患者治疗方法中。
