Tackling Cell Transplantation Anoikis: An Injectable, Shape Memory Cryogel Microcarrier Platform Material for Stem Cell and Neuronal Cell Growth

Abstract

Highly macroporous semisynthetic cryogel microcarriers can be synthesized for culturing stem cells and neuronal type cells. Growth factors loaded to heparin-containing microcarriers show near zero-order release kinetics and cell-loaded microcarriers can be injected through a fine gauge cannula without negative effect on the cells. These carriers can be applied for cell transplantation applications.

Designing hydrogels for controlled drug delivery

“…First, because cells are micrometre-sized, they are typically entrapped inside a hydrogel, unless the hydrogel is macro-porous or degradable. Macro-porous hydrogels possess interconnected porous spaces in which cells can adhere and differentiate before and after implantation 63,197 . Microgels are particularly appealing for cell delivery, owing to a greater inward diffusion of oxygen and the nutrients required to maintain cell viability, rapid release of cell-excreted biomolecules and the capability for sorting 193 .…”

Glycosaminoglycan‐Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials

“…Therefore, the cryogelation technique was combined with an emulsion polymerization technique to create micrometer-scale cryogel particles that allowed cell growth in the interconnected pores while protecting the cells during injection through a narrow syringe needle for minimally invasive implantation, with the subsequent recovery of the initial size and shape. [67] Cryogel beads were prepared using a water-in-oil emulsion followed by rapid cooling of the mixture to −20°C to allow ice crystal formation and gelation. Subsequent lyophilization led to micropore formation.…”

“…[4a] Based on this property, we developed a biohybrid hydrogel utilizing HEP as a major building block together with star-shaped PEG to form cell-instructive hydrogel matrices. [16] The high HEP concentration of the hydrogel allows the efficient administration of HEP-affine growth factors, such as FGF-2, [16] VEGF, [133] BMP-2, [134] SDF-1α, [135] GDNF, [136] NGF, [67] and TGF-β, [137] as well as the less-affine EGF. [138] Due to the high HEP concentration (i.e., the high number of protein-binding sites) in HEP-based hydrogels, multiple factors can be independently administered, as was shown for the parallel release of FGF-2 and VEGF [139] as well as FGF-2 and GDNF.…”

“…[16] This concept was further developed using RGD-modified starPEG-HEP hydrogels that released a combination of FGF-2 and GDNF to trigger the differentiation and axodendritic outgrowth of dopaminergic neurons derived from primary murine midbrain cells. [136] Shape-memory microscale macroporous hydrogels that released GDNF and NGF, allowing minimally invasive injection through a narrow 27-gauge needle, were successfully utilized to cultivate human MSCs and neuronal PC12 cells, showing their potential as survival-boosting cell-transplantation carriers for Parkinson's disease [67] (see also section 3). Overall, this biohybrid material seems to be an adaptable platform suitable for applications in neurodegenerative disorders.…”

Targeting delivery in Parkinson's disease

“…To overcome these problems, highly macroporous microscale cryogel particles are currently being developed to which neurons can adhere, but, in a manner similar to a sponge, they can collapse to fit through a needle, and re-expand to the original shape if volume allows [58]. Most transplantation studies in the Parkinsonian animal brain use intrastriatal injection to make relevant reconnections because nigral grafts fail to project as far as the striatum.…”