Hydrogel scaffold with substrate elasticity mimicking physiological-niche promotes proliferation of functional keratinocytes.
Pankaj MoghaAnkita SrivastavaSushant KumarSreya DasSanjay KureelAlka DwivediAtharva KarulkarNikita JainAbhijeet SawantChitra NayakAbhijit MajumderRahul PurwarPublished in: RSC advances (2019)
High numbers of autologous human primary keratinocytes (HPKs) are required for patients with burns, wounds and for gene therapy of skin disorders. Although freshly isolated HPKs exhibit a robust regenerative capacity, traditional methodology fails to provide a sufficient number of cells. Here we demonstrated a well characterized, non-cytotoxic and inert hydrogel as a substrate that mimics skin elasticity, which can accelerate proliferation and generate higher numbers of HPKs compared to existing tissue culture plastic (TCP) dishes. More importantly, this novel method was independent of feeder layer or any exogenous pharmaceutical drug. The HPKs from the hydrogel-substrate were functional as demonstrated by wound-healing assay, and the expression of IFN-γ-responsive genes (CXCL10, HLADR). Importantly, gene delivery efficiency by a lentiviral based delivery system was significantly higher in HPKs cultured on hydrogels compared with TCP. In conclusion, our study provides the first evidence that cell-material mechanical interaction is enough to provide a rapid expansion of functional keratinocytes that might be used as autologous grafts for skin disorders.
Keyphrases
- wound healing
- gene therapy
- cell therapy
- endothelial cells
- signaling pathway
- stem cells
- tissue engineering
- induced apoptosis
- bone marrow
- poor prognosis
- drug delivery
- immune response
- single cell
- high throughput
- cell cycle arrest
- platelet rich plasma
- structural basis
- cell death
- emergency department
- amino acid
- genome wide
- oxidative stress
- binding protein
- endoplasmic reticulum stress
- adverse drug