Trends in hydrogel-based encapsulation technologies for advanced cell therapies applied to limb ischemia

Author(s)

Rodrigues Costa, Ana Leticia ; Willerth, Stephanie M. ; de la Torre, Lucimara Gaziola ; Han, Sang Won

• Document type: Journal article
• Source: MATERIALS TODAY BIO; v. 13, p. 19-pg., 2022-01-01.

Abstract

Ischemia occurs when blood flow is reduced or restricted, leading to a lack of oxygen and nutrient supply and removal of metabolites in a body part. Critical limb ischemia (CLI) is a severe clinical manifestation of peripheral arterial disease. Atherosclerosis serves as the main cause of CLI, which arises from the deposition of lipids in the artery wall, forming atheroma and causing inflammation. Although several therapies exist for the treatment of CLI, pharmacotherapy still has low efficacy, and vascular surgery often cannot be performed due to the pathophysiological heterogeneity of each patient. Gene and cell therapies have emerged as alternative treatments for the treatment of CLI by promoting angiogenesis. However, the delivery of autologous, heterologous or genetically modified cells into the ischemic tissue remains challenging, as these cells can die at the injection site and/or leak into other tissues. The encapsulation of these cells within hydrogels for local delivery is probably one of the promising options today. Hydrogels, three-dimensional (3D) cross-linked polymer networks, enable manipulation of physical and chemical properties to mimic the extracellular matrix. Thus, specific biostructures can be developed by adjusting prepolymer properties and encapsulation process variables, such as viscosity and flow rate of fluids, depending on the final biomedical application. Electrostatic droplet extrusion, micromolding, micro fluidics, and 3D printing have been the most commonly used technologies for cell encapsulation due to their versatility in producing different hydrogel-based systems (e.g., microgels, fibers, vascularized architectures and perfusable single vessels) with great potential to treat ischemic diseases. This review discusses the cell encapsulation technologies associated with hydrogels which are currently used for advanced therapies applied to limb ischemia, describing their principles, advantages, disadvantages, potentials, and innovative therapeutic ideas. (AU)

• FAPESP's process: 18/06635-1 - Development of effective biomaterial-based systems for the efficient and safe delivery of iPSC-derived macrophages into the skeletal muscle to treat limb ischemia
• Grantee: Sang Won Han
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/19537-8 - MICROFLUIDICS AS A TECHNOLOGICAL PLATFORM FOR NANO & BIOTECHNOLOGY
• Grantee: Lucimara Gaziola de la Torre
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/02313-0 - Microfluidic and 3D bioprinting routes for the development of macrophage encapsulation systems based on hybrid gellan and fibrin hydrogels
• Grantee: Ana Leticia Rodrigues Costa Lelis
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia
• Grantee: Sang Won Han
• Support Opportunities: Research Projects - Thematic Grants