PDF(Pubmed)
Abstract：
The regeneration of large bone defects is still demanding, requiring biocompatible scaffolds, with osteoconductive and osteoinductive properties. This study aimed to assess the pre-clinical efficacy of a nano-hydroxyapatite (nano-HA)/PGLA/dextran-based scaffold loaded with Polylevolysine (PLL) and fibronectin (FN), intended for bone regeneration of a critical-size tibial defect, using an ovine model. After physicochemical characterization, the scaffolds were implanted in vivo, producing two monocortical defects on both tibiae of ten adult sheep, randomly divided into two groups to be euthanized at three and six months after surgery. The proximal left and right defects were filled, respectively, with the test scaffold (nano-HA/PGLA/dextran-based scaffold loaded with PLL and FN) and the control scaffold (nano-HA/PGLA/dextran-based scaffold not loaded with PLL and FN); the distal defects were considered negative control sites, not receiving any scaffold. Histological and histomorphometric analyses were performed to quantify the bone ingrowth and residual material 3 and 6 months after surgery. In both scaffolds, the morphological analyses, at the SEM, revealed the presence of submicrometric crystals on the surfaces and within the scaffolds, while optical microscopy showed a macroscopic 3D porous architecture. XRD confirmed the presence of nano-HA with a high level of crystallinity degree. At the histological and histomorphometric evaluation, new bone formation and residual biomaterial were detectable inside the defects 3 months after intervention, without differences between the scaffolds. At 6 months, the regenerated bone was significantly higher in the defects filled with the test scaffold (loaded with PLL and FN) than in those filled with the control scaffold, while the residual material was higher in correspondence to the control scaffold. Nano-HA/PGLA/dextran-based scaffolds loaded with PLL and FN appear promising in promoting bone regeneration in critical-size defects, showing balanced regenerative and resorbable properties to support new bone deposition.
摘要：
大型骨缺损的再生仍有要求,需要生物相容性支架，具有骨传导和骨诱导特性。这项研究旨在评估纳米羟基磷灰石（nano-HA）/PGLA/葡聚糖基支架的临床前功效，该支架负载有聚左旋赖氨酸（PLL）和纤连蛋白（FN），用于临界尺寸胫骨缺损的骨再生，用绵羊模型.经过物理化学表征，支架被植入体内，在十只成年绵羊的两个胫骨上产生两个单皮质缺陷，随机分为两组，分别于术后3个月和6个月实施安乐死。近端左右缺损被填补，分别,试验支架(纳米HA/PGLA/葡聚糖基支架负载PLL和FN)和对照支架(纳米HA/PGLA/葡聚糖基支架未负载PLL和FN);远端缺陷被认为是阴性对照位点,没有接收任何脚手架。在手术后3个月和6个月进行组织学和组织形态学分析以量化骨向内生长和残余材料。在两个脚手架中，形态学分析，在SEM上，揭示了表面和支架内的亚微米晶体的存在，而光学显微镜显示出宏观的3D多孔结构。XRD证实了具有高结晶度的纳米HA的存在。在组织学和组织形态学评估中，干预后3个月，在缺损内可检测到新骨形成和残留的生物材料，没有脚手架之间的差异。6个月时,在填充有测试支架（负载有PLL和FN）的缺损中，再生骨明显高于填充有对照支架的缺损，而与对照支架相对应的残余材料较高。载有PLL和FN的纳米HA/PGLA/葡聚糖基支架在促进临界尺寸缺陷的骨再生方面似乎很有希望，显示出平衡的再生和可吸收特性，以支持新骨沉积。
