Thermosensitive Injectable Chitosan/Collagen/β-Glycerophosphate Composite Hydrogels for Enhancing Wound Healing by Encapsulating Mesenchymal Stem Cell Spheroids

Abstract

Chronic wounds caused by diabetic or venous diseases remain a social and healthcare burden. In this work, a new strategy is proposed in which injectable thermosensitive chitosan/collagen/β-glycerophosphate (β-GP) hydrogels were combined with three-dimensional mesenchymal stem cell (3D MSC) spheroids to accelerate chronic wound healing by enhanced vascularization and paracrine effects. Chitosan/collagen/β-GP solution mixed with 3D MSC spheroids was rapidly transformed to a gel at body temperature by physical cross-linking, then overlapped the wounds fully and fitted to any shape of the wound. The results showed that the combination therapy exhibited a markedly therapeutic effect than the hydrogel-loaded two-dimensional (2D) MSCs or 2D MSCs alone. The hydrogel could provide an environment conductive to the attachment and proliferation of encapsulated MSCs, especially accelerating the proliferation and paracrine factor secretion of 3D MSC spheroids. These results supplied a novel alternative approach to treat chronic wounds caused by diabetic or venous diseases.

3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing

“…It has been reported that chitosan-poly(vinyl alcohol) hydrogels loaded with SNAP can promote angiogenesis [ 14 ]. In addition, mesenchymal stem cells cultured in 3D hydrogels accelerated wound healing through enhanced vascularization and paracrine effects in wounds [ 24 ]. The higher wound healing efficiency of the 3D cell matrix may be caused by the higher survival rate of stem cells and the hypoxic environment in the 3D constructs [ 43 ].…”

“…Moreover, culturing cells in a 3D construct is more suitable for simulating the microenvironment and subsequently influencing behaviour and gene expression [ 23 ]. Recent studies have intended to improve stem cell retention at wound sites by using spheroids, hydrogel systems, and biological scaffolds [ 24–26 ]. At present, few studies have focussed on the combination of stem cells and nitric oxide (NO) in 3D bioscaffolds.…”

Injectable Hydrogels for Chronic Skin Wound Management: A Concise Review

“…This biomatrix showed to exert an excellent therapeutic effect compared to other control groups. This technique was then examined by the elevation of cells attachment and proliferation for further investigation for the future use of chronic and venous wound management [ 64 ].…”

3D Printing of Thermoresponsive Hydrogel Laden with an Antimicrobial Agent towards Wound Healing Applications

“…In response to this, nowadays, personalizable bioengineered wound dressings and bio-fabrication techniques are being extensively developed. New research in chronic wound healing presents an innovative therapeutic strategy by using three-dimensional (3-D) hydrogel-based materials with superior therapeutic potential [3,4]. Hydrogel-based chronic wound dressings exhibit multifunctional properties, such as biodegradability, biocompatibility, sustained diffusion of bioactive molecules, high cell/drug embedding rate, pore structure, and appropriate mechanical strength [5].…”