Nano hydrogel-based oxygen-releasing stem cell transplantation system for treating diabetic foot

Abstract

The employment of stem cells and hydrogel is widespread in contemporary clinical approaches to treating diabetic foot ulcers. However, the hypoxic conditions in the surrounding lesion tissue lead to a low stem cell survival rate following transplantation. This research introduces a novel hydrogel with superior oxygen permeability and biocompatibility, serving as a vehicle for developing a stem cell transplantation system incorporating oxygen-releasing microspheres and cardiosphere-derived stem cells (CDCs). By optimizing the peroxidase fixation quantity on the microsphere surface and the oxygen-releasing microsphere content within the transplantation system, intracellular oxygen levels were assessed using electron paramagnetic resonance (EPR) under simulated low-oxygen conditions in vitro. The expression of vascularization and repair-related indexes were evaluated via RT-PCR and ELISA. The microspheres were found to continuously release oxygen for three weeks within the transplantation system, promoting growth factor expression to maintain intracellular oxygen levels and support the survival and proliferation of CDCs. Moreover, the effect of this stem cell transplantation system on wound healing in a diabetic foot mice model was examined through an in vivo animal experiment. The oxygen-releasing microspheres within the transplantation system preserved the intracellular oxygen levels of CDCs in the hypoxic environment of injured tissues. By inhibiting the expression of inflammatory factors and stimulating the upregulation of pertinent growth factors, it improved the vascularization of ulcer tissue on the mice’s back and expedited the healing of the wound site. Overall, the stem cell transplantation system in this study, based on hydrogels containing CDCs and oxygen-releasing microspheres, offers a promising strategy for the clinical implementation of localized stem cell delivery to improve diabetic foot wound healing.

Recent advances of hydrogels as smart dressings for diabetic wounds

“…Chen and colleagues prepared a hydrogel-based temperature pH-sensitive water-soluble polymer matrix containing H 2 O 2 and catalase to continuously release O 2 for three weeks, promoting cell oxygenation, survival, and paracrine effects. 168 The use of smart hydrogels encapsulated with microorganisms is a popular strategy among researchers. 169 Chlorella vulgaris is an alga that can produce O 2 through photosynthesis, which researchers hope can be used as an exogenous O 2 release agent for diabetic wounds.…”

Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives

“…Traditional DF therapies have also been unsatisfactory. Moreover, standalone interventions or vascular bypass surgeries are inadequate to address the fundamental pathological mechanisms of widespread blood vessel constriction and blockage in DF as well as nerve and tissue impairments[ 6 ].…”

Efficacy of stem cell therapy for diabetic foot: Clinical evidence from meta‐analyses

“…2,3 However, current interventions or vascular bypass surgery are not sufficient to fundamentally address the pathological basis of extensive vasoconstriction and obstruction and nerve and tissue damage in DF. 4 Stem cell therapy has the advantage of being able to fully regulate tissue regeneration by improving the microenvironment, and is therefore considered a highly promising treatment for DF. 5 Traditional systematic review and meta-analysis (SR/MA) usually involve varying degrees of risk of bias in the production of evidence.…”

“… 2 , 3 However, current interventions or vascular bypass surgery are not sufficient to fundamentally address the pathological basis of extensive vasoconstriction and obstruction and nerve and tissue damage in DF. 4 …”