MSCs-laden injectable self-healing hydrogel for systemic sclerosis treatment

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Immunology

Background:

• Mesenchymal stem cells (MSCs) show therapeutic potential for systemic sclerosis (SSc) due to their anti-inflammatory and immunomodulatory properties.
• Clinical application of MSCs is hindered by poor survival, short persistence, and limited engraftment after administration.
• Developing advanced delivery systems is crucial to overcome these limitations and enhance MSC efficacy in SSc treatment.

Purpose of the Study:

• To develop a novel injectable, self-healing hydrogel for enhanced delivery and therapeutic efficacy of MSCs in SSc treatment.
• To investigate the impact of the hydrogel on MSC proliferation, survival, immunomodulatory functions, and angiogenic potential.
• To evaluate the anti-fibrotic effects and therapeutic outcomes of the MSC-laden hydrogel in a bleomycin-induced SSc mouse model.

Main Methods:

• Fabrication of a self-healing hydrogel using N, O-carboxymethyl chitosan (CS-CM) and 4-armed benzaldehyde-terminated polyethylene glycol (PEG-BA) via reversible Schiff-base crosslinking.
• Encapsulation of MSCs within the hydrogel matrix to create an MSC-laden injectable system.
• In vitro assessment of MSC proliferation, survival, immunomodulatory capacity, and angiogenic potential (tube formation assay).
• In vivo evaluation of the MSC-laden hydrogel in a mouse model of SSc induced by subcutaneous bleomycin injection, assessing fibrosis and disease progression.

Main Results:

• The developed hydrogel exhibited self-healing properties and effectively supported MSC proliferation and prolonged survival in vivo.
• MSCs within the hydrogel demonstrated enhanced immunomodulatory functions and significantly promoted angiogenesis.
• The MSC-laden hydrogel effectively inhibited collagen synthesis, ameliorated fibrosis, and improved disease progression in SSc model mice.
• The injectable hydrogel facilitated sustained release and improved therapeutic outcomes compared to MSCs alone.

Conclusions:

• The novel MSCs-laden self-healing hydrogel represents a promising advanced delivery platform for SSc treatment.
• This system enhances MSC survival, function, and therapeutic efficacy, offering a potential strategy to overcome current clinical limitations.
• The findings highlight the potential clinical applicability of this biomaterial for treating chronic fibrotic diseases like SSc.