Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model.
Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model.
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DOI：
10.22203/ecm.v023a31
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发表时间：
2012-06-05
影响因子：
3.1
通讯作者：
Christman KL
中科院分区：
文献类型：
--
作者：
DeQuach JA;Lin JE;Cam C;Hu D;Salvatore MA;Sheikh F;Christman KL
外周动脉疾病（PAD）目前影响着欧洲和北美约2700万患者，如果不治疗，可能进展到严重肢体缺血（CLI）阶段，这可能导致截肢和潜在死亡。不幸的是，很少有治疗缺血性骨骼肌在这些条件下存在。生物材料已被用于增加细胞移植存活率以及提供生长因子治疗肢体缺血;然而，现有的材料不模仿他们打算治疗的天然骨骼肌微环境。此外，没有涉及单独的生物材料的治疗方法已被检查。本研究的目的是开发一种来自脱细胞骨骼肌细胞外基质的临床相关可注射水凝胶，并通过研究大鼠后肢缺血模型中的材料来检查其作为独立疗法治疗PAD的潜力。我们使用体外试验测试了支架降解产物的促有丝分裂活性，并测量了与胶原相比平滑肌细胞和骨骼肌成肌细胞的增殖率增加。在大鼠后肢缺血模型中，结扎并切除股动脉，然后在损伤后1周注射150 μl骨骼肌基质或胶原。我们证明，骨骼肌基质增加小动脉和毛细血管密度，以及招募更多的结蛋白阳性和MyoD阳性细胞相比，胶原蛋白。我们的研究结果表明，这种组织特异性可注射水凝胶可能是治疗与PAD相关的缺血的潜在疗法，并且对恢复通常在CLI中丢失的肌肉质量具有潜在的有益作用。
Peripheral artery disease (PAD) currently affects approximately 27 million patients in Europe and North America, and if untreated, may progress to the stage of critical limb ischemia (CLI), which has implications for amputation and potential mortality. Unfortunately, few therapies exist for treating the ischemic skeletal muscle in these conditions. Biomaterials have been used to increase cell transplant survival as well as deliver growth factors to treat limb ischemia; however, existing materials do not mimic the native skeletal muscle microenvironment they are intended to treat. Furthermore, no therapies involving biomaterials alone have been examined. The goal of this study was to develop a clinically relevant injectable hydrogel derived from decellularized skeletal muscle extracellular matrix and examine its potential for treating PAD as a stand-alone therapy by studying the material in a rat hindlimb ischemia model. We tested the mitogenic activity of the scaffold’s degradation products using an in vitro assay and measured increased proliferation rates of smooth muscle cells and skeletal myoblasts compared to collagen. In a rat hindlimb ischemia model, the femoral artery was ligated and resected, followed by injection of 150 μl of skeletal muscle matrix or collagen one week post-injury. We demonstrate that the skeletal muscle matrix increased arteriole and capillary density, as well as recruited more desmin-positive and MyoD-positive cells compared to collagen. Our results indicate that this tissue specific injectable hydrogel may be a potential therapy for treating ischemia related to PAD, as well as have potential beneficial effects on restoring muscle mass that is typically lost in CLI.