Burdette Alexander J, Guda Teja, Thompson Michelle E, Banas Richard, Sheppard Forest
Department of Expeditionary and Trauma, Naval Medical Research Unit San Antonio, Medicine, JBSA-Fort Sam Houston.
Department of Biomedical Engineering, University of Texas San Antonio, San Antonio.
J Craniofac Surg. 2018 Jan;29(1):116-123. doi: 10.1097/SCS.0000000000004103.
Severe traumatic injuries often result in critical size bone defects, which are unable to heal without treatment. Autologous grafting is the standard of care but requires additional surgeries for graft procurement. Amnion-derived multipotent progenitor cells release a secretome of biomolecules identified as integral to the process of bone regeneration and angiogenesis. This secretome is currently under development as a biotherapeutic. The efficacy of this secretome biotherapeutic was evaluated in vitro on the proliferation and migration of mesenchymal stem cells and osteoprogenitor cells as well as in vivo using a critical size rat calvarial defect model. The secretome biotherapeutic was loaded onto a collagen scaffold and placed into the defect, which was allowed to heal for 4 and 12 weeks. The secretome biotherapeutic enhanced the proliferation and migration of mesenchymal stem cells and proliferation of osteoprogenitor cells. Further, the secretome biotherapeutic improved new bone volume and connectivity by 12 weeks and significantly improved angiogenesis at 4 weeks and bone density at 4 and 12 weeks with no deleterious effects. The improvement in new bone volume, connectivity, and angiogenesis suggests that the secretome biotherapeutic has beneficial effects for bone healing and a higher dose of the secretome biotherapeutic may further improve regeneration.
严重创伤性损伤常导致临界尺寸的骨缺损，未经治疗无法愈合。自体移植是标准治疗方法，但需要额外的手术来获取移植物。羊膜来源的多能祖细胞释放出一组生物分子分泌产物，这些产物被确定为骨再生和血管生成过程所必需。这种分泌产物目前正作为一种生物治疗剂进行研发。在体外评估了这种分泌产物生物治疗剂对间充质干细胞和骨祖细胞增殖及迁移的作用，并在体内使用临界尺寸的大鼠颅骨缺损模型进行了评估。将分泌产物生物治疗剂加载到胶原支架上并置于缺损处，让其愈合4周和12周。分泌产物生物治疗剂增强了间充质干细胞的增殖和迁移以及骨祖细胞的增殖。此外，分泌产物生物治疗剂在12周时改善了新骨体积和连通性，在4周时显著改善了血管生成，在4周和12周时改善了骨密度，且无有害影响。新骨体积、连通性和血管生成的改善表明，分泌产物生物治疗剂对骨愈合具有有益作用，更高剂量的分泌产物生物治疗剂可能会进一步改善再生。
