Jakob M, Saxer F, Scotti C, Schreiner S, Studer P, Scherberich A, Heberer M, Martin I
Department of Surgery, University Hospital Basel, Basel, Switzerland.
Eur Surg Res. 2012;49(1):1-7. doi: 10.1159/000338362. Epub 2012 Jul 11.
Despite the compelling clinical needs in enhancing bone regeneration and the potential offered by the field of tissue engineering, the adoption of cell-based bone graft substitutes in clinical practice is limited to date. In fact, no study has yet convincingly demonstrated reproducible clinical performance of tissue-engineered implants and at least equivalent cost-effectiveness compared to the current treatment standards. Here, we propose and discuss how tissue engineering strategies could be evolved towards more efficient solutions, depicting three different experimental paradigms: (i) bioreactor-based production; (ii) intraoperative manufacturing, and (iii) developmental engineering. The described approaches reflect the need to streamline graft manufacturing processes while maintaining the potency of osteoprogenitors and recapitulating the sequence of biological steps occurring during bone development, including vascularization. The need to combine the assessment of efficacy of the different strategies with the understanding of their mechanisms of action in the target regenerative processes is highlighted. This will be crucial to identify the necessary and sufficient set of signals that need to be delivered at the injury or defect site and should thus form the basis to define release criteria for reproducibly effective engineered bone graft substitutes.
尽管在增强骨再生方面存在迫切的临床需求，且组织工程领域也提供了相应潜力，但迄今为止，基于细胞的骨移植替代物在临床实践中的应用仍然有限。事实上，尚无研究能令人信服地证明组织工程植入物具有可重复的临床性能，以及与当前治疗标准相比至少相当的成本效益。在此，我们提出并讨论组织工程策略如何朝着更有效的解决方案发展，描述了三种不同的实验范式：（i）基于生物反应器的生产；（ii）术中制造，以及（iii）发育工程。所描述的方法反映了简化移植物制造过程的需求，同时保持骨祖细胞的活性，并重现骨发育过程中发生的生物步骤序列，包括血管生成。强调了将不同策略的疗效评估与其在目标再生过程中的作用机制理解相结合的必要性。这对于确定在损伤或缺损部位需要传递的必要且充分的信号集至关重要，因此应构成定义可重复有效工程化骨移植替代物释放标准的基础。
