In Vivo Analysis of the Biocompatibility and Immune Response of Jellyfish Collagen Scaffolds and its Suitability for Bone Regeneration
In Vivo Analysis of the Biocompatibility and Immune Response of Jellyfish Collagen Scaffolds and its Suitability for Bone Regeneration
复制标题
DOI：
10.3390/ijms21124518
复制
发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Barbeck, Mike
中科院分区：
文献类型：
--
作者：
Flaig, Iris;Radenkovic, Milena;Barbeck, Mike
水母胶原蛋白，由于其与哺乳动物I、II、III、V和IX型的同质性及其批次间一致的生产率，可被定义为“0型胶原蛋白”，作为哺乳动物胶原蛋白基生物材料的替代品，对于与（骨）组织再生相关的不同医学应用具有特殊意义。然而，迄今为止，尚未进行关于M1-和M2-巨噬细胞的诱导及其时间依赖性比率以及水母胶原支架的骨再生能力的分析的体内研究。因此，本研究的目的是确定水母胶原蛋白支架的免疫反应的性质及其骨愈合能力。两项使用已建立的植入模型的体内研究，即，建立Wistar大鼠皮下埋植模型和卵巢埋植模型。此外，还使用了专门的组织学、组织病理学和组织形态计量学方法。作为对照生物材料，皮下研究使用了来源于猪心包膜的胶原蛋白支架，该支架已被声明具有生物相容性。本研究的结果表明，水母胶原支架几乎完全吸收，直到60天植入后逐步整合在皮下结缔组织主要由巨噬细胞和单个多核巨细胞介导。有趣的是，降解过程在血管丰富的结缔组织中结束，这被认为是组织再生的最佳基础。研究结果表明，与猪心包基质相比，水母胶原蛋白诱导的免疫应答总体较弱，诱导的巨噬细胞数量显著减少，M1-和M2-巨噬细胞的出现更为平衡。然而，两种基于胶原的生物材料诱导了两种巨噬细胞亚型的平衡数量，这支持了其良好的生物相容性。此外，颅骨植入水母支架的组织形态测量结果显示，第60天平均有46.20%的从头骨形成，与对照组相比显着更高。因此，水母胶原支架在骨植入床内也诱导了显著更高数量的抗炎巨噬细胞。总之，结果表明，水母胶原支架允许定向整合行为，这被认为是根据引导骨再生（GBR）的概念。此外，水母胶原支架诱导了长期的抗炎巨噬细胞反应和最佳的血管化模式，在其植入床，从而显示出良好的生物相容性和（骨）组织愈合性能。
Jellyfish collagen, which can be defined as "collagen type 0" due to its homogeneity to the mammalian types I, II, III, V, and IX and its batch-to-batch consistent producibility, is of special interest for different medical applications related to (bone) tissue regeneration as an alternative to mammalian collagen-based biomaterials. However, no in vivo studies regarding the induction of M1- and M2-macrophages and their time-dependent ration as well as the analysis of the bone regeneration capacity of jellyfish collagen scaffolds have been conducted until now. Thus, the goal of this study was to determine the nature of the immune response to jellyfish collagen scaffolds and their bone healing capacities. Two in vivo studies using established implantation models, i.e., the subcutaneous and the calvarian implantation model in Wistar rats, were conducted. Furthermore, specialized histological, histopathological, and histomorphometrical methods have been used. As a control biomaterial, a collagen scaffold, originating from porcine pericardium, which has already been stated as biocompatible, was used for the subcutaneous study. The results of the present study show that jellyfish collagen scaffolds are nearly completely resorbed until day 60 post implantation by stepwise integration within the subcutaneous connective tissue mediated mainly by macrophages and single multinucleated giant cells. Interestingly, the degradation process ended in a vessel rich connective tissue that is understood to be an optimal basis for tissue regeneration. The study results showed an overall weaker immune response to jellyfish collagen than to porcine pericardium matrices by the induction of significantly lower numbers of macrophages together with a more balanced occurrence of M1- and M2-macrophages. However, both collagen-based biomaterials induced balanced numbers of both macrophage subtypes, which supports their good biocompatibility. Moreover, the histomorphometrical results for the calvarial implantation of the jellyfish scaffolds revealed an average of 46.20% de novo bone formation at day 60, which was significantly higher compared to the control group. Thereby, the jellyfish collagen scaffolds induced also significantly higher numbers of anti-inflammatory macrophages within the bony implantation beds. Altogether, the results show that the jellyfish collagen scaffolds allowed for a directed integration behavior, which is assumed to be in accordance with the concept of Guided Bone Regeneration (GBR). Furthermore, the jellyfish collagen scaffolds induced a long-term anti-inflammatory macrophage response and an optimal vascularization pattern within their implant beds, thus showing excellent biocompatibility and (bone) tissue healing properties.