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Preclinical biological and physicochemical evaluation of two-photon engineered 3D biomimetic copolymer scaffolds for bone healing.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-01-27 , DOI: 10.1039/c9bm01827a
Carina Kampleitner 1 , Katayoon Changi 2 , Reda M Felfel 3 , Colin A Scotchford 3 , Virginie Sottile 4 , Rainer Kluger 5 , Oskar Hoffmann 1 , David M Grant 3 , Michelle M Epstein 2
Affiliation  

A major challenge in orthopedics is the repair of large non-union bone fractures. A promising therapy for this indication is the use of biodegradable bioinspired biomaterials that stabilize the fracture site, relieve pain and initiate bone formation and healing. This study uses a multidisciplinary evaluation strategy to assess immunogenicity, allergenicity, bone responses and physicochemical properties of a novel biomaterial scaffold. Two-photon stereolithography generated personalized custom-built scaffolds with a repeating 3D structure of Schwarz Primitive minimal surface unit cell with a specific pore size of ∼400 μm from three different methacrylated poly(d,l-lactide-co-ε-caprolactone) copolymers with lactide to caprolactone monomer ratios of 16 : 4, 18 : 2 and 9 : 1. Using in vitro and in vivo assays for bone responses, immunological reactions and degradation dynamics, we found that copolymer composition influenced the scaffold physicochemical and biological properties. The scaffolds with the fastest degradation rate correlated with adverse cellular effects and mechanical stiffness correlated with in vitro osteoblast mineralization. The physicochemical properties also correlated with in vivo bone healing and immune responses. Overall these observations provide compelling support for these scaffolds for bone repair and illustrate the effectiveness of a promising multidisciplinary strategy with great potential for the preclinical evaluation of biomaterials.

中文翻译:

对两个光子工程改造的3D仿生共聚物支架进行骨愈合的临床前生物学和理化评估。

骨科的主要挑战是修复大的不愈合骨骨折。针对这种适应症的一种有前途的疗法是使用可生物降解的生物启发性生物材料,该材料可稳定骨折部位,减轻疼痛并启动骨形成和愈合。这项研究使用多学科评估策略来评估新型生物材料支架的免疫原性,变应原性,骨反应和理化特性。双光子立体光刻技术可从三种不同的甲基丙烯酸酯化聚(d,l-丙交酯-co-ε-己内酯)共聚物中生成具有重复Schwarz Primitive最小表面晶胞3D结构的个性化定制支架,其特定孔径为〜400μm丙交酯与己内酯单体之比为16:4、18:2和9:1。使用体外和体内的骨反应检测方法,免疫反应和降解动力学,我们发现共聚物组成影响支架的理化和生物学特性。具有最快降解速率的支架与不利的细胞作用有关,而机械刚度与体外成骨细胞矿化有关。物理化学性质还与体内骨骼愈合和免疫反应有关。总的来说,这些观察为这些支架的骨修复提供了令人信服的支持,并说明了一种有前途的多学科策略的有效性,该策略在生物材料的临床前评估中具有巨大潜力。具有最快降解速率的支架与不利的细胞作用有关,而机械刚度与体外成骨细胞矿化有关。物理化学性质还与体内骨骼愈合和免疫反应有关。总的来说,这些观察为这些支架的骨修复提供了令人信服的支持,并说明了一种有前途的多学科策略的有效性,该策略在生物材料的临床前评估中具有巨大潜力。具有最快降解速率的支架与不利的细胞作用有关,而机械刚度与体外成骨细胞矿化有关。物理化学性质还与体内骨骼愈合和免疫反应有关。总体而言,这些观察结果为这些支架的骨修复提供了令人信服的支持,并说明了一种有前途的多学科策略的有效性,该策略对于生物材料的临床前评估具有巨大潜力。
更新日期:2020-03-19
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