Adipose-derived stem cell spheroid-laden microbial transglutaminase cross-linked gelatin hydrogel for treating diabetic periodontal wounds and craniofacial defects

Abstract

Background Diabetes mellitus deteriorates the destruction and impairs the healing of periodontal wounds and craniofacial defects. This study is to evaluate the potential of self-assembled adipose-derived stem cell spheroids (ADsp) in microbial transglutaminase cross-linked gelatin hydrogel (mTG) for treating diabetic periodontal wounds and craniofacial defects. Methods Human adipose-derived stem cells (ADSCs) were isolated by lipoaspiration, pluripotent genes and trilineage differentiation were examined, and the maintenance of ADsp properties in mTG was verified. Oral mucosal wounds and calvarial osseous defects were created in diabetic rats. Gross observation, histologic evaluation, and immunohistochemistry for proliferating cells and keratinization were conducted in the mucosal wounds within 4–28 days. Micro-CT imaging, histologic evaluation, and immunohistochemistry for proliferating cells and osteogenic differentiation were conducted in the osseous defects at 7 and 28 days. Results ADSCs expressed pluripotent genes and were capable of trilineage differentiation. ADsp retained morphology and stemness in mTG. In diabetic mucosal wounds, wound closure, epithelization, and keratinization were accelerated in those with ADsp and ADsp-mTG. In diabetic osseous defects, osteogenic differentiation markers were evidently expressed, cell proliferation was promoted from day 7, and bone formation was significantly promoted at day 28 in those with osteogenically pretreated ADsp-mTG. Conclusions ADsp-mTG accelerated diabetic oral mucosal wound healing, and osteogenically pretreated ADsp-mTG promoted diabetic osseous defect regeneration, proving that ADsp-mTG facilitated diabetic periodontal wound healing and craniofacial osseous defect regeneration.

Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review

“…Lee injected ADSCs intramuscularly into bone defects and found increased Runx2 expression and significantly improved bone formation compared to the control group ( Lee et al, 2010 ). The scaffold structure can direct the differentiation of ADSCs towards an osteogenic pathway rather than the more conventional adipogenic differentiation, ultimately leading to a more favorable outcome in bone repair ( Fang et al, 2021 ; Tu et al, 2023 ). Sándor reported 13 cases of continuous craniofacial hard tissue defects repaired with the aid of ADCSs.…”

Factors Defining Human Adipose Stem/Stromal Cell Immunomodulation in Vitro

“…Thus, cultivation of MSCs in three-dimensional (3D) systems, such as low attachment surfaces, hydrogels, or scaffolds, to resemble the in vivo spatial organization with increased cell–cell and cell–matrix interactions, have gained attention [ 171 , 179 ]. The methods to generate 3D MSC spheroids, including ASC ones, and the limitation and challenges of different MSC spheroid generation platforms have been recently reviewed [ 171 , 180 ].Enhanced therapeutic and anti-inflammatory mechanisms have been reported in different preclinical models treated with human ASCs cultured by a 3D strategy [ 86 , 100 , 178 , 181 – 190 ].…”

Highly Hydrophobic Gelatin Nanocomposite Film Assisted by Nano-ZnO/(3-Aminopropyl) Triethoxysilane/Stearic Acid Coating for Liquid Food Packaging

“…3 In this way, modification of G is necessary. Transglutaminase, 4 dialdehyde carboxymethyl cellulose, 5 polyhedral oligomeric silsesquioxane, 6 etc., are proved good candidates for the enhancement of mechanical properties of G films. Hydrophobic modification 7 and incorporation of hydrophobic substrate 8 are common approaches to make G films proof of water and humid environment.…”