Kanczler J M, Oreffo R O C
Bone & Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Developmental Origins of Health and Disease, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD,
Eur Cell Mater. 2008 May 2;15:100-14. doi: 10.22203/ecm.v015a08.
The repair of large bone defects remains a major clinical orthopaedic challenge. Bone is a highly vascularised tissue reliant on the close spatial and temporal connection between blood vessels and bone cells to maintain skeletal integrity. Angiogenesis thus plays a pivotal role in skeletal development and bone fracture repair. Current procedures to repair bone defects and to provide structural and mechanical support include the use of grafts (autologous, allogeneic) or implants (polymeric or metallic). These approaches face significant limitations due to insufficient supply, potential disease transmission, rejection, cost and the inability to integrate with the surrounding host tissue. The engineering of bone tissue offers new therapeutic strategies to aid musculoskeletal healing. Various scaffold constructs have been employed in the development of tissue-engineered bone; however, an active blood vessel network is an essential pre-requisite for these to survive and integrate with existing host tissue. Combination therapies of stem cells and polymeric growth factor release scaffolds tailored to promote angiogenesis and osteogenesis are under evaluation and development actively to stimulate bone regeneration. An understanding of the cellular and molecular interactions of blood vessels and bone cells will enhance and aid the successful development of future vascularised bone scaffold constructs, enabling survival and integration of bioengineered bone with the host tissue. The role of angiogenic and osteogenic factors in the adaptive response and interaction of osteoblasts and endothelial cells during the multi step process of bone development and repair will be highlighted in this review, with consideration of how some of these key mechanisms can be combined with new developments in tissue engineering to enable repair and growth of skeletal fractures. Elucidation of the processes of angiogenesis, osteogenesis and tissue engineering strategies offer exciting future therapeutic opportunities for skeletal repair and regeneration in orthopaedics.
大骨缺损的修复仍然是临床骨科面临的一项重大挑战。骨骼是一种血管高度丰富的组织，依赖于血管与骨细胞之间紧密的空间和时间联系来维持骨骼的完整性。因此，血管生成在骨骼发育和骨折修复中起着关键作用。目前修复骨缺损并提供结构和机械支撑的方法包括使用移植物（自体、异体）或植入物（聚合物或金属）。由于供应不足、潜在疾病传播风险、排斥反应、成本以及无法与周围宿主组织整合等问题，这些方法面临着重大局限性。骨组织工程提供了新的治疗策略来促进肌肉骨骼愈合。各种支架构建物已被用于组织工程骨的开发；然而，活跃的血管网络是这些构建物存活并与现有宿主组织整合的必要前提。干细胞与为促进血管生成和成骨而定制的聚合物生长因子释放支架的联合疗法正在积极评估和开发中，以刺激骨再生。了解血管与骨细胞之间的细胞和分子相互作用，将促进并有助于未来血管化骨支架构建物成功开发，使生物工程骨能够与宿主组织存活并整合。本综述将重点介绍血管生成和成骨因子在骨骼发育和修复多步骤过程中，成骨细胞和内皮细胞适应性反应及相互作用中的作用，并探讨如何将其中一些关键机制与组织工程的新进展相结合，以实现骨骼骨折的修复和生长。阐明血管生成、成骨过程以及组织工程策略，为骨科骨骼修复和再生提供了令人兴奋的未来治疗机会。
