A Multi-Functional Implant Induces Bone Formation in a Diabetic Model
A Multi-Functional Implant Induces Bone Formation in a Diabetic Model
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多功能植入物在糖尿病模型中诱导骨形成
DOI：
10.1002/adhm.202000770
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发表时间：
2020-08-19
影响因子：
10
通讯作者：
Salem, Aliasger K.
中科院分区：
文献类型：
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作者：
Khorsand, Behnoush;Acri, Timothy M.;Salem, Aliasger K.
糖尿病(DM)患者骨折愈合不良。已有研究表明，非病毒基因载体DNA(PDNA)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)，在糖尿病动物模型中具有协同促进骨再生的作用。此外，胰岛素(INS)和具有激素活性的维生素D3，1α，25-二羟基维生素D3(1α，25(OH)(2)D-3)(VD3)已被证明在调节糖尿病患者骨折愈合方面发挥关键作用。然而，这些个体化治疗方法不能充分刺激骨再生，说明糖尿病患者的骨折需要新的治疗方法。在这里，我们研究了局部注射INS和VD3以及BMP-2和FGF2基因促进2型糖尿病大鼠异位成骨的能力。开发了一种由VD3和INS组成的复合材料，该复合材料含有嵌入在纤维蛋白凝胶中的聚乳酸-乙醇酸共聚微粒(MPS)，该凝胶周围包裹着渗透着聚乙烯亚胺(PEI)-(pBMP-2+pFGF-2)纳米网络的胶原基质。使用肌下骨诱导模型显示，与其他治疗方法相比，局部注射INS、VD3和PEI-(pBMP-2+pFGF-2)可显著促进骨生成，从而简化了该方法，使其成为促进糖尿病合并骨折患者骨再生的一种方法。
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, 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)(2)D-3) (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 withBMP-2andFGF-2genes 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.