Abstract
IntroductionCell therapy using adipose-derived stem cells has been reported to improve chronic wounds via differentiation and paracrine effects. One such strategy is to deliver stem cells in hydrogels, which are studied increasingly as cell delivery vehicles for therapeutic healing and inducing tissue regeneration. This study aimed to determine the behaviour of encapsulated adipose-derived stem cells and identify the secretion profile of suitable growth factors for wound healing in a newly developed thermoresponsive PEG–hyaluronic acid (HA) hybrid hydrogel to provide a novel living dressing system.MethodsIn this study, human adipose-derived stem cells (hADSCs) were encapsulated in situ in a water-soluble, thermoresponsive hyperbranched PEG-based copolymer (PEGMEMA–MEO2MA–PEGDA) with multiple acrylate functional groups in combination with thiolated HA, which was developed via deactivated enhanced atom transfer radical polymerisation of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, Mn = 475), 2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA) and poly(ethylene glycol) diacrylate PEGDA (Mn = 258). hADSCs embedded in the PEGMEMA–MEO2MA–PEGDA and HA hybrid hydrogel system (P-SH-HA) were monitored and analysed for their cell viability, cell proliferation and secretion of growth factors (vascular endothelial growth factor, transforming growth factor beta and placental-derived growth factor) and cytokines (IFNγ, IL-2 and IL-10) under three-dimensional culture conditions via the ATP activity assay, alamarBlue® assay, LIVE/DEAD® assay and multiplex ELISA, respectively.ResultshADSCs were successfully encapsulated in situ with high cell viability for up to 7 days in hydrogels. Although cellular proliferation was inhibited, cellular secretion of growth factors such as vascular endothelial growth factor and placental-derived growth factor production increased over 7 days, whereas IL-2 and IFNγ release were unaffected.ConclusionThis study indicates that hADSCs can be maintained in a P-SH-HA hydrogel, and secrete pro-angiogenic growth factors with low cytotoxicity. With the potential to add more functionality for further structural modifications, this stem cell hydrogel system can be an ideal living dressing system for wound healing applications.
Highlights
Cell therapy using adipose-derived stem cells has been reported to improve chronic wounds via differentiation and paracrine effects
A hyperbranched Polyethylene glycol (PEG)-based copolymer was recently synthesised using a one-pot and one-step synthesis method (Figure 1A). This synthesis creates a hydrogel with thermoresponsive properties and desired end functionality to provide an in situ crosslinking system that can crosslink with hyaluronic acid (HA)-SH via Michael-type addition (Figure 1B)
PEG-based thermoresponsive copolymer cross-linked with Thiol-modified hyaluronic acid (HA-SH) was studied for Human adipose-derived stem cell (hADSC) viability, proliferation and secretion of pro-angiogenic growth factors and inflammatory cytokines under 3D culture condition
Summary
Cell therapy using adipose-derived stem cells has been reported to improve chronic wounds via differentiation and paracrine effects. One such strategy is to deliver stem cells in hydrogels, which are studied increasingly as cell delivery vehicles for therapeutic healing and inducing tissue regeneration. At least 50% of chronic wounds remain resistant to advanced or standard treatments such as growth factor delivery or bioengineered skin substitutes [2]. Human adipose-derived stem cells (hADSCs) embedded in a collagen hydrogel secreted increased levels of growth factors to enhance wound healing [14]
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