Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing

Abstract

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.

Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering

“…The wound healing properties of Ok-PDRN have also been assessed using several cell lines [ 8 , 26 , 27 , 28 ]. Ok-PDRN significantly increased the cell migration ability on all cell lines, including osteosarcoma cells, CDD-686sk, normal and diabetic human dermal fibroblasts (HDFs), and human umbilical vein endothelial cells (HUVEC).…”

“…A total of nine studies have evaluated the wound healing activity of Ok- (six studies) and Om-PDRNs (three studies) [ 4 , 8 , 9 , 27 , 28 , 45 , 46 , 47 ]. In the case of Ok-PDRN, one study has evaluated the effective range of Ok-PDRN for wound healing as a function of molecular weight distributions (under 50 kDa, between 50 and 1500 kDa, over 1500 kDa) [ 27 ].…”

“…Histological evaluation revealed that PDRN quickly reduced diabetic wound depth and width, thickened the epidermis with re-epithelialization, and promoted epithelialization of the epidermis around the wound. Another study also reported the regenerative effects of Ok-PDRN on diabetic wounds using a diabetic mouse model with a punch biopsy tool [ 8 ]. The authors of this study developed an Ok-PDRN-loaded alginate hydrogel (Alg-PDRN hydrogel) and evaluated its wound-healing effect on the full-thickness wound model.…”

“…Additionally, PDRN stimulates nucleic acid synthesis by serving as a source of pyrimidines and purines [ 5 ]. Further, PDRN possesses several therapeutic properties, including angiogenesis-promoting, anti-apoptotic, anti-inflammatory, anti-ischemic, and tissue repair activities [ 6 , 7 , 8 , 9 ].…”

Preparation of Foam Dressings Based on Gelatin, Hyaluronic Acid, and Carboxymethyl Chitosan Containing Fibroblast Growth Factor-7 for Dermal Regeneration

“…The dehydrated tissues were embedded in paraffin and sectioned at 4 µm. For evaluating histopathological changes and collagen formation, the slides were stained with H&E (ab ab245880, Abcam, Cambridge, UK) and MT (TRM-2, ScyTek, West Logan, UT, USA) according to manufacturer’s guidelines, respectively [ 23 ]. There were twenty-four wounds per mouse per condition because twelve mice per each group with four wounds on its back per each mouse were used.…”