Department of Materials Science and Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
Department of Plastic and Reconstructive Surgery, Seoul National University Boramae Medical Center, Seoul, 07061, Republic of Korea.
Sci Rep. 2020 Oct 8;10(1):16811. doi: 10.1038/s41598-020-74004-0.
Patients with diabetes experience delayed wound healing because of the uncontrolled glucose level in their bloodstream, which leads to impaired function of white blood cells, poor circulation, decreased production and repair of new blood vessels. Treatment using polydeoxyribonucleotide (PDRN), which is a DNA extracted from the sperm cells of salmon, has been introduced to accelerate the healing process of diabetic wounds. To accelerate the wound-healing process, sustained delivery of PDRN is critical. In this study, taking advantage of the non-invasive gelation property of alginate, PDRN was loaded inside the hydrogel (Alg-PDRN). The release behavior of PDRN was altered by controlling the crosslinking density of the Alg hydrogel. The amount of PDRN was the greatest inside the hydrogel with the highest crosslinking density because of the decreased diffusion. However, there was an optimal degree of crosslinking for the effective release of PDRN. In vitro studies using human dermal fibroblasts and diabetes mellitus fibroblasts and an in ovo chorioallantoic membrane assay confirmed that the Alg-PDRN hydrogel effectively induced cell proliferation and expression of angiogenic growth factors and promoted new blood vessel formation. Its effectiveness for accelerated diabetic wound healing was also confirmed in an in-vivo animal experiment using a diabetic mouse model.
糖尿病患者由于血液中葡萄糖水平不受控制,导致白细胞功能受损、血液循环不良、新血管生成和修复减少,从而出现伤口愈合延迟的情况。使用聚脱氧核糖核苷酸(PDRN)治疗已被引入以加速糖尿病伤口的愈合过程。为了加速伤口愈合过程,PDRN 的持续输送至关重要。在这项研究中,利用海藻酸钠的非侵入性凝胶特性,将 PDRN 装载到水凝胶(Alg-PDRN)内部。通过控制 Alg 水凝胶的交联密度来改变 PDRN 的释放行为。由于扩散减少,交联密度最高的水凝胶内部的 PDRN 量最大。然而,对于 PDRN 的有效释放,存在最佳的交联程度。使用人真皮成纤维细胞和糖尿病成纤维细胞进行的体外研究以及鸡胚绒毛尿囊膜分析证实,Alg-PDRN 水凝胶可有效诱导细胞增殖和血管生成生长因子的表达,并促进新血管形成。在使用糖尿病小鼠模型的体内动物实验中,也证实了其在加速糖尿病伤口愈合方面的有效性。