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Adipose-Derived Stem Cells (ADSCs) Loaded Gelatin-Sericin-Laminin Cryogels for Tissue Regeneration in Diabetic Wounds
journal contribution
posted on 2019-12-11, 01:29 authored by Suhela Tyeb, Parvaiz A. Shiekh, Vivek Verma, Ashok KumarHealing 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.