Polysaccharide-Based Hydrogels for Microencapsulation of Stem Cells in Regenerative Medicine

Abstract

Stem cell-based therapy appears as a promising strategy to induce regeneration of damaged and diseased tissues. However, low survival, poor engraftment and a lack of site-specificity are major drawbacks. Polysaccharide hydrogels can address these issues and offer several advantages as cell delivery vehicles. They have become very popular due to their unique properties such as high-water content, biocompatibility, biodegradability and flexibility. Polysaccharide polymers can be physically or chemically crosslinked to construct biomimetic hydrogels. Their resemblance to living tissues mimics the native three-dimensional extracellular matrix and supports stem cell survival, proliferation and differentiation. Given the intricate nature of communication between hydrogels and stem cells, understanding their interaction is crucial. Cells are incorporated with polysaccharide hydrogels using various microencapsulation techniques, allowing generation of more relevant models and further enhancement of stem cell therapies. This paper provides a comprehensive review of human stem cells and polysaccharide hydrogels most used in regenerative medicine. The recent and advanced stem cell microencapsulation techniques, which include extrusion, emulsion, lithography, microfluidics, superhydrophobic surfaces and bioprinting, are described. This review also discusses current progress in clinical translation of stem-cell encapsulated polysaccharide hydrogels for cell delivery and disease modeling (drug testing and discovery) with focuses on musculoskeletal, nervous, cardiac and cancerous tissues.

Engineering a material-genetic interface as safety switch for embedded therapeutic cells

“…Although the gap to regulatory approval of encapsulated cell therapy has not been closed yet 9,16 , several clinical trials are underway, for example with encapsulated genetically modified cells which release neurotrophic factors for neurodegenerative diseases 17,18 . Additionally, other application areas are opening up in encapsulated cell therapy, such as the use of encapsulated cells for ocular drug delivery 19 or encapsulation of stem cells for regenerative medicine [20][21][22] .…”

Engineering Bio-Adhesives Based on Protein–Polysaccharide Phase Separation

“…Interestingly, it has been found in biological systems that proteins and polysaccharides can form electrostatic complexes and coacervates, thus exhibiting phase separation behaviors [ 34 , 35 , 36 ]. These complexes, or coacervates, have many applications in the food and biomedical fields, including fat substitution [ 37 ], protein purification [ 38 ], and drug delivery [ 39 , 40 ]. However, the exploration of bio-adhesives based on protein–polysaccharide phase separation has rarely been reported.…”

Natural Biopolymers as Additional Tools for Cell Microencapsulation Applied to Cellular Therapy

“…Cell immobilization displays an important advantage compared to protein encapsulation, allowing for the sustained and controlled delivery of 'de novo'-produced therapeutic products at constant rates, leading to physiological concentrations [15]. The versatility of this approach has stimulated its use in the treatment of numerous medical diseases including diabetes [17,18], cancer [19], central nervous system diseases [20], heart diseases [21] and endocrinological disorders, among others [22]. In addition, immunosuppressive drugs may also be incorporated in hydrogels as an additional mechanism to avoid immune-mediated rejection, leading, in principle, only to local transplanted encapsulated cell effects.…”