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A biomimetic collagen-bone granule-heparan sulfate combination scaffold for BMP2 delivery
Gene ( IF 3.5 ) Pub Date : 2020-10-09 , DOI: 10.1016/j.gene.2020.145217
Bach Quang Le , Tuan Chun Tan , Seong-baek Lee , Ju Woong Jang , Young Sik Kim , Jung Soo Lee , Jae Won Choi , Padmapriya Sathiyanathan , Victor Nurcombe , Simon M. Cool

Bone morphogenetic protein 2 (BMP2)-induced bone regeneration is most efficacious when a carrier can deliver the growth factor into the defect site while minimizing off-target effects. The control of BMP2 release by such carriers is proving one of the most critical aspects of BMP2 therapy. Thus, increasing numbers of biomaterials are being developed to satisfy the simultaneous need for sustained release, reduced rates of degradation and enhanced activity of the growth factor. Here we report on a biomimetic scaffold consisting of bovine collagen type I, bone granules (IntergraftTM), and heparan sulfate with increased affinity for BMP2 (HS3). The HS3 and collagen were complexed and then crosslinked via a simple dehydrothermal method. When loaded with a clinically relevant amount of BMP2 (1.25 mg/cc), the HS3-functionalised scaffolds were able to retain up to 58% of the initial amount of BMP2 over 27 days, approximately 3-times higher than scaffolds without HS3. The bioactivity of the retained BMP2 was confirmed by gene expression in myoblasts cells (C2C12) cultured on the scaffolds under osteogenic stimulation. Together these data demonstrate the efficacy of HS3 as a material to improve the performance collagen/bone granule-based scaffolds.



中文翻译:

仿生胶原-骨颗粒-硫酸乙酰肝素联合支架用于BMP2的递送

当载体可以将生长因子输送到缺损部位,同时将脱靶效应降至最低时,骨形态发生蛋白2(BMP2)诱导的骨再生最为有效。这种载体对BMP2释放的控制被证明是BMP2治疗的最关键方面之一。因此,正在开发越来越多的生物材料以满足同时释放,降低降解速率和增强生长因子活性的需求。在这里,我们报道了一种由I型牛胶原蛋白,骨颗粒(Intergraft TM)组成的仿生支架。)和对BMP2(HS3)具有更高亲和力的硫酸乙酰肝素。HS3和胶原蛋白络合,然后通过简单的脱氢方法交联。当装载有临床相关量的BMP2(1.25 mg / cc)时,HS3官能化的支架能够在27天之内保留高达BMP2初始量的58%,大约是不含HS3的支架的3倍。通过在成骨刺激下在支架上培养的成肌细胞(C2C12)中的基因表达,证实了保留的BMP2的生物活性。这些数据一起证明了HS3作为改善胶原/骨颗粒基支架性能的材料的功效。

更新日期:2020-10-11
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