Segmental bone defects caused by trauma and disease represent a major clinical problem worldwide. Current treatment options are limited and often associated with poor outcomes and severe complications. Bone engineering is a promising alternative solution, but a number of technical challenges must be addressed to allow for effective and reproducible construction of segmental grafts that meet the size and geometrical requirements needed for individual patients and routine clinical applications. It is important to devise engineering strategies and standard operating procedures that make it possible to scale up the size of bone-engineered grafts, minimize process and product variability, and facilitate technology transfer and implementation. To address these issues, we have combined traditional and modular tissue engineering approaches in a strategy referred to as Segmental Additive Tissue Engineering (SATE). To demonstrate this approach, a digital reconstruction of a rabbit femoral defect was partitioned transversally to the longitudinal axis into segments (modules) with discoidal geometry and defined thickness to enable protocol standardization and effective tissue formation in vitro. Bone grafts corresponding to each segment were then engineered using biomimetic scaffolds seeded with human induced pluripotent stem cell-derived mesodermal progenitors (iPSC-MPs) and a novel perfusion bioreactor with universal design. The SATE strategy enables the effective and reproducible engineering of segmental bone grafts for personalized skeletal reconstruction, and will facilitate technology transfer and implementation of a tissue engineering approach to segmental bone defect therapy.

中文翻译：

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节段性添加剂组织工程。

由创伤和疾病引起的节段性骨缺损代表了世界范围内的主要临床问题。当前的治疗选择是有限的，并且通常与不良的预后和严重的并发症有关。骨工程学是一种有前途的替代解决方案，但是必须解决许多技术难题，才能有效且可重复地构建分段移植物，以满足个体患者和常规临床应用所需的尺寸和几何要求。重要的是要设计工程策略和标准操作程序，以使其能够扩大骨工程植入物的尺寸，最大程度地减少工艺和产品的变异性，并促进技术转让和实施。为了解决这些问题，我们将传统和模块化组织工程方法结合在一起，称为“分段添加组织工程（SATE）”策略。为了证明这种方法，将兔股骨缺损的数字重建横向于纵轴划分为具有盘状几何形状和定义厚度的段（模块），以实现协议标准化和体外有效的组织形成。然后使用仿生支架工程化对应于每个节段的骨移植物，所述仿生支架上植入人诱导的多能干细胞衍生的中胚层祖细胞（iPSC-MPs）和具有通用设计的新型灌注生物反应器。SATE策略可对段式骨移植进行有效且可重复的工程设计，以实现个性化的骨骼重建，