The aim of this study was to develop novel hydroxyapatite (HAP)-based bioactive bone replacement materials for segmental osteotomy reconstruction. Customized three-dimensional (3D) bone construct was manufactured from nanohydroxyapatite (nHAP) with poly(lactide-co-glycolide) (PLGA) coating using 3D models derived from the computed tomography (CT) scanning of the rabbit’s ulna and gradient 3D printing of the bone substitute mimicking the anatomical shape of the natural bone defect. Engineered construct revealed adequate micro-architectural design for successful bone regeneration having a total porosity of 64% and an average pore size of 256 μm. Radiography and micro-CT analysis depicted new bone apposition through the whole length of the reconstructed ulna with a small area of non-resorbed construct in the central area of defect. Histological analysis revealed new bone formation with both endochondral and endesmal type of ossification. Immunohistochemistry analysis depicted the presence of bone formation indicators – bone morphogenetic protein (BMP), osteocalcin (OCN) and osteopontin (OPN) within newly formed bone. Manufactured personalized construct acts as a “smart” responsive biomaterial capable of modulating the functionality and potential for the personalized bone reconstruction on a clinically relevant length scale.

中文翻译：

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开发用于超临界尺寸缺陷重建的新型可吸收性羟基磷灰石骨替代物：在节段兔尺骨重建中的物理化学和生物学表征和概念证明。

本研究的目的是开发用于节段截骨重建的新型羟基磷灰石（HAP）基生物活性骨替代材料。定制的 3D (3D) 骨骼结构由纳米羟基磷灰石 (nHAP) 和聚（丙交酯-乙交酯） (PLGA) 涂层制成，使用源自兔子尺骨的计算机断层扫描 (CT) 扫描和梯度 3D 打印的 3D 模型模仿自然骨缺损的解剖形状的骨替代物。工程构造揭示了用于成功骨再生的足够微结构设计，总孔隙率为 64%，平均孔径为 256 μm。射线照相术和显微 CT 分析描绘了通过重建尺骨的整个长度的新骨附着，在缺损的中心区域有一小块未吸收的结构。组织学分析显示新骨形成具有软骨内和内皮型骨化。免疫组织化学分析描述了骨形成指标——骨形态发生蛋白 (BMP)、骨钙素 (OCN) 和骨桥蛋白 (OPN) 在新形成的骨中的存在。制造的个性化构造充当“智能”响应生物材料，能够在临床相关长度尺度上调节个性化骨重建的功能和潜力。