Department of Orthopaedics, Elisabeth Klinik GmbH, Olsberg, Germany.
Clin Hemorheol Microcirc. 2011;48(1):29-40. doi: 10.3233/CH-2011-1406.
Cost effective and safely to apply tissue engineered constructs of big volume bone transplants for the reconstruction of critical sized defects (CSD) are still not available. Key problems with synthetic scaffold materials are shrinkage and fast degradation of the scaffolds, a lack of blood supply and nutrition in the central scaffold volume and the absent or the scarce development of bone tissue along the scaffold to bridge the bone defect. The use of composite scaffolds made of biopolymers like polylactidglycolid acid (PLGA) coated and loaded with calcium phosphates (CaP) revealed promising therapeutical options for the regeneration of critical sized bone defects. In this study interconnectively macroporous PLGA scaffolds loaded with microporous and coated with nanoporous calcium phosphates were either seeded in fixed bed bioreactors with allogenic osteogenically induced mesenchymal stem cells and implanted or implanted unseeded into critical sized femoral bone defects. As CSD a 12 mm long segment of the chinchilla femur was excised where the proximal and distal parts of the femur were fixed and stabilized by the use of an eight-hole linear reconstruction plate and secured with three bicortical screws (2.7 mm diameter) on every side of the osteotomy. Aim of the study was if we could find a way to load and coat PLGA scaffolds with CaP so that shrinkage of scaffolds could be avoided, which would favour angiogenesis, blood supply and nutrition in the construct and thus avoid central necroses regularly observed so far in transplants not vascularized and which would be inhabited by cells of he bone lineage forming new bone and healing the defect. Four weeks, at least, a notable shrinkage of the scaffolds was avoided and scaffolds were practically not degraded. Both scaffolds, loaded and loaded and coated, revealed blood vessels in all parts of the implants after 4 weeks. Only in scaffolds seeded with allogenic mesenchymal stem cells the development of bridging bone constructs between proximal and distal edges of the femur was observed after four weeks without further supplementation of growth factors. In case of the implantation of non-seeded scaffolds no obvious scaffold bound bone development could be shown.
目前，仍然没有一种经济有效的方法可以将大体积的组织工程化骨移植物用于重建临界尺寸缺损（CSD）。合成支架材料的关键问题是支架的收缩和快速降解、支架中心体积缺乏血液供应和营养、以及沿着支架桥接骨缺损的骨组织缺失或稀少。使用由聚乳酸-聚乙醇酸（PLGA）等生物聚合物制成的复合支架，涂层并负载磷酸钙（CaP），为临界尺寸骨缺损的再生提供了有前途的治疗选择。在这项研究中，用微孔和纳米孔磷酸钙涂层的互穿大孔 PLGA 支架在固定床生物反应器中与同种异体成骨诱导间充质干细胞一起种植，并植入临界尺寸股骨缺损中，或未种植直接植入。在这项研究中，将一只沙兔股骨的 12mm 长段切除，近端和远端的股骨部分通过使用八孔线性重建板固定和稳定，并在每个截骨部位的每一侧使用三根双皮质螺钉（2.7mm 直径）固定。研究的目的是找到一种方法来负载和涂层 PLGA 支架，以避免支架收缩，这将有利于血管生成、构建中的血液供应和营养，从而避免迄今为止在未血管化的移植中观察到的中央坏死，并且将由形成新骨和修复缺损的骨系细胞栖息。至少四周，避免了支架的明显收缩，支架实际上没有降解。负载和负载涂层的支架在植入物的所有部位在 4 周后都显示出血管。只有在接种同种异体间充质干细胞的支架中，在 4 周后观察到了股骨近端和远端边缘之间的桥接骨构建的发育，而无需进一步补充生长因子。在未种植支架的情况下，没有明显的支架结合骨发育。
