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Combinatorial delivery of bioactive molecules by a nanoparticle-decorated and functionalized biodegradable scaffold†
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-06-14 00:00:00 , DOI: 10.1039/c8tb00474a
Ewa M. Czekanska 1, 2, 3, 4, 5 , Jin Geng 6, 7, 8, 9 , Michael Glinka 1, 2, 3, 4, 5 , Kate White 1, 2, 3, 4, 5 , Janos Kanczler 1, 2, 3, 4, 5 , Nicholas D Evans 1, 2, 3, 4, 5 , Richard O. C. Oreffo 1, 2, 3, 4, 5 , Mark Bradley 6, 7, 8, 9
Affiliation  

The combination of supportive biomaterials and bioactive factors to stimulate endogenous progenitor cells is of key interest for the treatment of conditions in which intrinsic bone healing capacities are compromised. To address this need a “scaffold-decoration platform” was developed in which a biocompatible, biotin-functionalised 3D structural polymer network was generated through a solvent blending process, and used to recruit avidin modified nanoparticles within its 3D structure through biotin–avidin conjugation. This was enabled via the generation of a suite of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, encapsulating two bioactive factors, vascular endothelial growth factor (VEGF) and L-ascorbic acid 2-phosphate (AA2P) and conjugated to streptavidin to allow attachment to the bone generating scaffold. The levels of encapsulated and released VEGF and AA2P were tailored to fall within the desired range to promote biological activity as confirmed by an increase in endothelial cell tubule formation and collagen production by osteoblast cells in response to nanoparticle release of VEGF and AA2P, respectively. The release of VEGF from the scaffolds produced a significant effect on vasculature development within the chick chorioallantoic membrane (CAM) angiogenic assay. Similarly, the scaffolds showed strong biological effects in ex vivo assays indicating the potential of this platform for localised delivery of bioactive molecules with applications in both hard and soft tissue engineering.

中文翻译:

纳米粒子修饰和功能化的可生物降解支架可组合递送生物活性分子

支持性生物材料和生物活性因子的组合刺激内源性祖细胞对于治疗固有骨愈合能力受到损害的疾病至关重要。为了满足这一需求,开发了“支架装饰平台”,其中通过溶剂共混过程生成了生物相容性,生物素官能化的3D结构聚合物网络,并用于通过生物素-亲和素偶联在其3D结构内募集抗生物素蛋白修饰的纳米粒子。这是使通过产生一套聚(乳酸-的-glycolic乙酸)(PLGA)纳米粒子,包封两种生物活性因子,血管内皮生长因子(VEGF)和大号-抗坏血酸2-磷酸酯(AA2P),并与抗生蛋白链菌素结合,以使其附着在产生骨骼的支架上。将包封和释放的VEGF和AA2P的水平调整到所需的范围内,以促进生物学活性,这分别由内皮细胞小管形成的增加和成骨细胞分别响应VEGF和AA2P纳米颗粒释放的胶原蛋白生成所证实。从支架释放的VEGF对鸡绒膜尿囊膜(CAM)血管生成测定法中的脉管系统发育产生了显着影响。类似地,支架在离体试验中显示出强大的生物学效应,表明该平台在生物组织分子的硬和软化应用中用于局部递送生物活性分子的潜力。
更新日期:2018-06-14
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