多功能植入物在糖尿病模型中诱导骨形成。,Advanced Healthcare Materials

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多功能植入物在糖尿病模型中诱导骨形成。
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-08-19 , DOI: 10.1002/adhm.202000770
Behnoush Khorsand ₁ , Timothy M Acri ₁ , Anh-Vu Do ₁ , John E Femino ₂ , Emily Petersen ₂ , Douglas C Fredericks ₂ , Aliasger K Salem ₁

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糖尿病（DM）患者的骨折愈合不良。先前显示，质粒DNA（pDNA）的非病毒基因传递独立编码骨形态发生蛋白-2（BMP-2）和成纤维细胞生长因子2（FGF-2），协同作用以促进DM动物模型中的骨再生。此外，胰岛素（INS）和维生素D3的激素活性形式1α，25-二羟基维生素D3（1α，25（OH）₂ D ₃）（VD3）已被独立显示在DM患者调节骨折愈合中起关键作用。然而，这些单独的疗法不能充分刺激骨再生，这说明需要对糖尿病患者的骨折进行新颖的治疗。在这里，研究了INS和VD3以及BMP-2和FGF-2基因的局部递送以促进异型2型糖尿病大鼠骨形成的能力。一种复合组成VD3和INS的开发，它包含聚（乳酸-共-glycolic酸）的微粒（MPS）嵌入在由胶原基质包围的纤维蛋白凝胶渗透着聚乙烯亚胺（PEI） - （pBMP-2 + pFGF- 2）纳米复合物。使用亚肌肉骨诱导模型，表明与其他治疗方法相比，局部递送INS，VD3和PEI-（pBMP-2 + pFGF-2）可以显着改善骨生成，因此暗示该方法可作为促进DM中骨再生的方法骨折患者。

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A Multi-Functional Implant Induces Bone Formation in a Diabetic Model.

Patients with diabetes mellitus (DM) have defective healing of bone fractures. It was previously shown that nonviral gene delivery of plasmid DNA (pDNA) that independently encodes bone morphogenetic protein‐2 (BMP‐2) and fibroblast growth factor‐2 (FGF‐2), acts synergistically to promote bone regeneration in a DM animal model. Additionally, both insulin (INS) and the hormonally active form of vitamin D3, 1α,25‐dihydroxyvitamin D3 (1α,25(OH)₂D₃) (VD3) have independently been shown to play key roles in regulating bone fracture healing in DM patients. However, these individual therapies fail to adequately stimulate bone regeneration, illustrating a need for novel treatment of bone fractures in diabetic patients. Here, the ability of local delivery of INS and VD3 along with BMP‐2 and FGF‐2 genes is investigated to promote bone formation ectopically in Type‐2 diabetic rats. A composite consisting of VD3 and INS is developed that contains poly(lactic‐co‐glycolic acid) microparticles (MPs) embedded in a fibrin gel surrounded by a collagen matrix that is permeated with polyethylenimine (PEI)‐(pBMP‐2+pFGF‐2) nanoplexes. Using a submuscular osteoinduction model, it is demonstrated that local delivery of INS, VD3, and PEI‐(pBMP‐2+pFGF‐2) significantly improves bone generation compared to other treatments, thusimplicating this approach as a method to promote bone regeneration in DM patients with bone fractures.

更新日期：2020-09-23

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