Hydrogel-Based Cell Therapies for Kidney Regeneration: Current Trends in Biofabrication and In Vivo Repair

Abstract

Facing the problems of limited renal regeneration capacity and the persistent shortage of donor kidneys, dialysis remains the only treatment option for many end-stage renal disease patients. Unfortunately, dialysis is only a medium-term solution because large and protein-bound uremic solutes are not efficiently cleared from the body and lead to disease progression over time. Current strategies for improved renal replacement therapies (RRTs) range from whole organ engineering to biofabrication of renal assist devices and biological injectables for in vivo regeneration. Notably, all approaches coincide with the incorporation of cellular components and biomimetic micro-environments. Concerning the latter, hydrogels form promising materials as scaffolds and cell carrier systems due to the demonstrated biocompatibility of most natural hydrogels, tunable biochemical and mechanical properties, and various application possibilities. In this review, the potential of hydrogel-based cell therapies for kidney regeneration is discussed. First, we provide an overview of current trends in the development of RRTs and in vivo regeneration options, before examining the possible roles of hydrogels within these fields. We discuss major application-specific hydrogel design criteria and, subsequently, assess the potential of emergent biofabrication technologies, such as micromolding, microfluidics and electrodeposition for the development of new RRTs and injectable stem cell therapies.

Combining Stem Cells and Biomaterial Scaffolds for Constructing Tissues and Cell Delivery

“…They also have been used successfully to deliver stem cells in vivo and they can often be formulated to be injectable, which is highly desirable for clinical applications [10]. Recent reviews have summarized the wide body of work detailing how hydrogels have been used to successfully deliver stem cells in vivo for a variety of applications, including vascularization, tendon repair, healing kidney damage, and for neural regeneration [11][12][13][14] Ensuring long-term stability can be challenging as well as matching the desired release rate for molecules embedded in the hydrogel matches the desired degradation rate. However, both natural and synthetic hydrogels remain popular tools for engineering tissues from stem cells.…”

Topographic Guidance in Melt-Electrowritten Tubular Scaffolds Enhances Engineered Kidney Tubule Performance

“…To allow for rapid exchange of solutes between blood and urine, the epithelial and endothelial BM should be virtually the only barriers between both cell types. To date, tubular tissue engineering mostly relies on non-porous, large diameter tubular scaffolds (Ø > 2 mm) for sufficient self-support, or smaller tubular lumens (Ø <1 mm) surrounded by hydrogels to account for physiological functions, including vectorial transport (Homan et al, 2016 ; Jansen et al, 2017 ; Rayner et al, 2018 ; Lin et al, 2019 ; Singh et al, 2020 ). The latter has been addressed recently in valuable in vitro tools for drug screening and disease modeling, with proven apical-basal cell polarity, and active reabsorption and transepithelial secretion function.…”

Fabrication of Kidney Proximal Tubule Grafts Using Biofunctionalized Electrospun Polymer Scaffolds

“…For the creation of kidney proximal tubules, recent approaches have mainly been focusing on the use of hydrogels. [ 12 – 18 ] Although promising results have been obtained, these tubules are either intended for in vitro testing only, too fragile for transplantation, or embedded in bulk gels, which would hamper nutrient supply and clearance capacity if not adequately vascularized. Thus, other technologies are required for the fabrication of implantable kidney tubule constructs that display both high diffusibility and mechanical stability.…”