Low-glucose culture environment can enhance the wound healing capability of diabetic adipose-derived stem cells.

BACKGROUND: Application of autologous adipose-derived stem cells (ASC) for diabetic chronic wounds has become an emerging treatment option. However, ASCs from diabetic individuals showed impaired cell function and suboptimal wound healing effects. We proposed that adopting a low-glucose level in the culture medium for diabetic ASCs may restore their pro-healing capabilities. METHODS: ASCs from diabetic humans and mice were retrieved and cultured in high-glucose (HG, 4.5 g/L) or low-glucose (LG, 1.0 g/L) conditions. Cell characteristics and functions were investigated in vitro. Moreover, we applied diabetic murine ASCs cultured in HG or LG condition to a wound healing model in diabetic mice to compare their healing capabilities in vivo. RESULTS: Human ASCs exhibited decreased cell proliferation and migration with enhanced senescence when cultured in HG condition in vitro. Similar findings were noted in ASCs derived from diabetic mice. The inferior cellular functions could be partially recovered when they were cultured in LG condition. In the animal study, wounds healed faster when treated with HG- or LG-cultured diabetic ASCs relative to the control group. Moreover, higher collagen density, more angiogenesis and cellular retention of applied ASCs were found in wound tissues treated with diabetic ASCs cultured in LG condition. CONCLUSIONS: In line with the literature, our study showed that a diabetic milieu exerts an adverse effect on ASCs. Adopting LG culture condition is a simple and effective approach to enhance the wound healing capabilities of diabetic ASCs, which is valuable for the clinical application of autologous ASCs from diabetic patients.

Gelatin Hydrogels Reinforced by Absorbable Nanoparticles and Fibrils Cured In Situ by Visible Light for Tissue Adhesive Applications.

Most gelatin hydrogels used in regenerative medicine applications today are fabricated by photocrosslinking due to the convenience and speed of this method. However, in most cases photoinitiators are used, which require UV light, which, in turn, can cause cell and tissue damage, or using functionalized gelatin. Recently, ruthenium (II) tris-bipyridyl chloride has been studied as an initiator that can induce dityrosine bond formation using visible light. In addition, continuous fibrils and small particles are often used to reinforce composite materials. Therefore, this study investigated the visible-light-induced photocrosslinking of native gelatin molecules via dityrosine bonds formation as well as gel reinforcement by collagen fibrils and mesoporous bioactive glass (MBG) particles. The results show that collagen and MBG exerted a synergistic effect on maintaining gel integrity with a dental LED curing light when the irradiation time was shortened to 30 s. Without the two reinforcing components, the gel could not form a geometric shape stable gel even when the exposure time was 120 s. The shear strength increased by 62% with the collagen and MBG compared with the blank control. Furthermore, our results demonstrate that the addition of collagen and MBG enhanced gel stability in an artificial saliva solution. These results demonstrate the considerable advantages of using tyrosine-containing biomolecules, and using a dental LED curing light for the crosslinking of hydrogels in terms of their suitability and feasibility for use as bioadhesives in confined clinical working space, such as the oral cavity, and in application as in situ-crosslinked injectable hydrogels.