- Thermosensitive chitosan hydrogel loaded with cell-derived nanovesicles for cutaneous wound healing
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Abstract:
- Advanced wound care management remains a significant clinical challenge nowadays. Developments of effective therapies to treat hard-to-heal wound have presented stem cells as promising agents for their renewal and regenerative potencies. With latest progresses in understanding their curative mechanism, top-down methods to fabricate cell-derived nanovesicles (CDNs) can mimic the critical paracrine functions of stem cells and enable reproducibility and scalability.
The aim of this 8-month project is to develop a thermosensitive hydrogel dressing capable of in-situ gelation on human cutaneous wound sites, which can house stem cell derived nanovesicles in the hydrogel matrix for sustained release. By combining the conventional passive dressing with bioactive CDNs, the project proposes an integrated solution to address the wound healing challenge.
Hydrogel was successfully synthesized with a physical-crosslinking mechanism using chitosan, β-Glycerophosphate(βGP)/αβ-Glycerophosphate(αβGP) and NaHCO3. The resultant hydrogels exhibited desired thermosensitive behaviours: the gelation kinetics at room temperature were slow enough for hours of necessary manipulation in its liquid state; yet upon temperature elevation to 37°C, gelation occurs within minutes. Such characteristics of the developed hydrogels demonstrate great potentials for translation into applications at human physiological temperature.
With the high water content percentage in the hydrogel wound dressing, a moist environment is ensured to promote healing. The interconnected pores in the inherent structure of hydrogel matrix have supported its suitability for loading and release of particles.
Hydrogel CH1.36:βGP0.267:SHC0.025 with homogenously dispersed CDNs has provenly acted as a monolithic drug delivery system, functioning through diffusional outlet of encapsulated CDNs. Diffusivity of the released CDNs were calculated to be 0.53 μm2s-1 in the hydrogel matrix, about ¼ of that in the suspension conditions, providing evidences on the retention of CDNs in hydrogel and the control over CDN release rate.
Future works shall continue to confirm the cytotoxicity and therapeutic efficacies with appropriate in vitro and in vivo models. As the state-of-art knowledge has not addressed how CDNs mediated their curative capabilities, further studies can be performed to explore how CDNs preserve properties from their cell sources.
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