Adipose-Derived Stem Cells (ADSCs) Loaded Gelatin-Sericin-Laminin Cryogels for Tissue Regeneration in Diabetic Wounds

Abstract

Healing in wounds like pressure ulcers, diabetic ulcers, venous ulcers, and arterial insufficiency ulcers is immensely hampered and causes both an economic burden and morbidity to patients. These wounds face a plethora of hostile conditions like elevated reactive oxygen species (ROS), impaired angiogenesis, senescent fibroblasts, and deficient stem cells that significantly diminish the probability of self-healing in these wounds. Adipose-derived stem cell therapy (ADSC) presents a promising approach to achieve efficient healing in such cases. To address the complex scenario of chronic wounds, we propose a combinatorial approach of delivering ADSCs on antioxidant gelatin-sericin (GS) scaffolds coated with laminin (GSL), an endothelial basement protein to improve angiogenesis. The synthesized GS scaffolds showed values of compression modulus, pore size, porosity, and the swelling ratio in the range of 65 kPa, 158 ± 48.8 μm, 91.1% ± 1.25, and 28 ± 2.5, respectively. A DPPH assay revealed GS scaffolds exhibit around 20% more scavenging as against gelatin (G) scaffolds and better protection against free radical assault, thus enhancing cell viability and the metabolic index of fibroblast cells. Different cells, namely, fibroblasts, keratinocytes, and ADSCs, cultured on GS scaffolds had better metabolic activity as compared with G scaffolds. Laminin coating onto the scaffolds leads to improved attachment and tube formation of endothelial cells as depicted in scanning electron microscopy images. Finally, we validated the applicability of the ADSCs loaded laminin-coated GS scaffolds in a diabetic ulcer rat model. Hematoxylin and eosin, Masson’s trichrome, and picrosirius red staining showed better regeneration and collagen remodeling in ADSCs loaded GSL scaffolds. Immunostaining of CD31 staining demonstrates enhanced angiogenesis in GSL-ADSC as compared with other groups.

An Overview on Collagen and Gelatin-Based Cryogels: Fabrication, Classification, Properties and Biomedical Applications

“…Tyeb et al designed a novel composite cryogels made of gelatin, sericin and laminin with applicability for the culture of fibroblasts, keratinocytes, ADSCs, and HUVEC cells [ 92 ]. Additionally, when the composite cryogels loaded with ADSCs were implanted in diabetic rats, these scaffolds showed enhanced wound healing capacity and mild inflammation [ 92 ]. Recently, GBCs have been investigated to imitate the microenvironment of different skin layers.…”

Extracellular matrix-based biomaterials as adipose-derived stem cell delivery vehicles in wound healing: a comparative study between a collagen scaffold and two xenografts

“…It is worth noting that angiogenesis was particularly enhanced when hADSCs were delivered through the BM side of XenoMEM™. Again, we believe that compositional differences may be responsible for this, considering that previous studies have shown improved angiogenetic capacity of scaffolds loaded with basement membrane components [59,60].…”

Exosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 axisExosomes Derived from miR-183-Overexpressing Human Adipose-Derived Stem Cells Alleviate Hepatic Ischemia-Reperfusion (I/R) Injury through miR-183/ALOX5 Axis

“…ADSCs are a type of pluripotent stem cells with high self-renewal ability with adipogenic, osteogenic, chondrogenic and myoblast differentiation [8]. Researches have proved that ADSCs have the ability to differentiate into hepatocytes with hepatocyte functions, such as glycogen synthesis, urea formation, expression of hepatocellular speci c genes, and cytochrome P450 enzyme activity, etc [9,10]. Current researches have testi ed that ADSCs can be applied to treat liver diseases such as hepatitis, liver brosis and liver failure [11][12][13].…”