Hoffman Michael D, Benoit Danielle S W
University of Rochester, Department of Biomedical Engineering, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA; University of Rochester Medical Center, Center for Musculoskeletal Research, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA.
University of Rochester, Department of Biomedical Engineering, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA; University of Rochester Medical Center, Center for Musculoskeletal Research, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA; University of Rochester, Department of Chemical Engineering, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA; University of Rochester Medical Center, Department of Orthopaedics, 207 Robert B. Goergen Hall, Box 270168, Rochester, NY 14627-0168, USA.
Biomaterials. 2015 Jun;52:426-40. doi: 10.1016/j.biomaterials.2015.02.064. Epub 2015 Mar 18.
Emulating autograft healing within the context of decellularized bone allografts has immediate clinical applications in the treatment of critical-sized bone defects. The periosteum, a thin, osteogenic tissue that surrounds bone, houses a heterogenous population of stem cells and osteoprogenitors. There is evidence that periosteum-cell derived paracrine factors, specifically vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), orchestrate autograft healing through host cell recruitment and subsequent tissue elaboration. In previous work, we demonstrated that the use of poly(ethylene glycol) (PEG) hydrogels as a tissue engineered (T.E.) periosteum to localize mesenchymal stem cells (MSCs) to the surface of decellularized bone enhances allograft healing and integration. Herein, we utilize a mixed population of 50:50 MSCs and osteoprogenitor cells to better mimic native periosteum cell population and paracrine factor production to further promote allograft healing. This mixed cell population was localized to the surface of decellularized allografts within degradable hydrogels and shown to expedite allograft healing. Specifically, bone callus formation and biomechanical graft-host integration are increased as compared to unmodified allografts. These results demonstrate the dual importance of periosteum-mediated paracrine factors orchestrating host cell recruitment as well as new bone formation while developing clinically translatable strategies for allograft healing and integration.
在脱细胞骨同种异体移植的背景下模拟自体移植愈合在治疗临界尺寸骨缺损方面具有直接的临床应用价值。骨膜是一种围绕骨骼的薄的成骨组织，其中含有异质性的干细胞和骨祖细胞群体。有证据表明，骨膜细胞衍生的旁分泌因子，特别是血管内皮生长因子（VEGF）和骨形态发生蛋白2（BMP2），通过宿主细胞募集和随后的组织形成来协调自体移植愈合。在之前的工作中，我们证明了使用聚乙二醇（PEG）水凝胶作为组织工程（T.E.）骨膜将间充质干细胞（MSCs）定位到脱细胞骨表面可增强同种异体移植的愈合和整合。在此，我们利用50:50的间充质干细胞和骨祖细胞混合群体来更好地模拟天然骨膜细胞群体和旁分泌因子的产生，以进一步促进同种异体移植愈合。这种混合细胞群体被定位到可降解水凝胶内的脱细胞同种异体移植表面，并显示出可加速同种异体移植愈合。具体而言，与未修饰的同种异体移植相比，骨痂形成和生物力学上的移植-宿主整合有所增加。这些结果证明了骨膜介导的旁分泌因子在协调宿主细胞募集以及新骨形成方面的双重重要性，同时也为同种异体移植愈合和整合开发了具有临床可转化性的策略。
