Glycosaminoglycan-based biomaterials for growth factor and cytokine delivery: Making the right choices

Abstract

Controlled, localized drug delivery is a long-standing goal of medical research, realization of which could reduce the harmful side-effects of drugs and allow more effective treatment of wounds, cancers, organ damage and other diseases. This is particularly the case for protein “drugs” and other therapeutic biological cargoes, which can be challenging to deliver effectively by conventional systemic administration. However, developing biocompatible materials that can sequester large quantities of protein and release them in a sustained and controlled manner has proven challenging. Glycosaminoglycans (GAGs) represent a promising class of bio-derived materials that possess these key properties and can additionally potentially enhance the biological effects of the delivered protein. They are a diverse group of linear polysaccharides with varied functionalities and suitabilities for different cargoes. However, most investigations so far have focused on a relatively small subset of GAGs – particularly heparin, a readily available, promiscuously-binding GAG. There is emerging evidence that for many applications other GAGs are in fact more suitable for regulated and sustained delivery. In this review, we aim to illuminate the beneficial properties of various GAGs with reference to specific protein cargoes, and to provide guidelines for informed choice of GAGs for therapeutic applications.

Polymer Hydrogels to Guide Organotypic and Organoid Cultures

“…Cardiac grafts based on fetal rat ventricular muscle, [214] angiogenesis, [215a] colonoids, [223] cardiac fibrosis [339] Biopolymer-based hydrogels: Hyaluronic acid From rooster combs, shark skin, bovine eyeballs, or human umbilical cords [335] Animal-free produc- BMP, [343] NGF, SDF-1α) [342] Allows for hyaluronidases-mediated remodeling [267] or for degradation by reactive oxygen species [346] Engineered MMP degradation sites allow further degradation Undifferentiated hESC growth, [344] bone and cartilage engineering, [345] neural differentiation, [266] tumor modeling [229][230][231] [347] Microbial fermented HA synthesis provides pure, well-defined batches [348] Biopolymer-based hydrogels: Alginate…”

“…Allows for material processing for controlled cross-scale cell alignment and organization [135][136][137] Mediates cell adhesion via [342] Hyaluronidasesmediated remodeling [359] Human neural stem/progenitor cells [266] murine inner medullary collecting duct, [269b] human intestinal organoids [270] PEG requires careful consideration as, for instance, a fibroblastderived matrix was found to be unsuitable to sufficiently mimic the lung microenvironment in composition, structure and complexity. [101] Various types of matrices deposited by different cells (including fibroblasts, mesenchymal stroma/stem cells (MSCs), HEK293 cells, chondrocytes) have been investigated for their capability to sustain cell growth, maintain stemness, or guide differentiation.…”

Biomaterials Loaded with Growth Factors/Cytokines and Stem Cells for Cardiac Tissue Regeneration

“…For example, the half-life of VEGF is approximately thirty-four minutes in plasma [ 51 ]. Therefore, biomaterials can serve as promising tools for the protection, delivery, and sustained release of growth factors and cytokines [ 52 ]. Table 1 summarizes the use of biomaterials loaded with growth factors and cytokines for cardiac tissue regeneration.…”

Engineered biomaterial strategies for controlling growth factors in tissue engineering

“…Basic fibroblast growth factor (bFGF) was incorporated into the microcarriers and showed a sustained release pattern, which promoted cell adhesion and proliferation on . Nanoparticles (Saito & Takaoka, 2003), Scaffolds, Microspheres (Dinoro et al, 2019), Hydrogels (Hachim et al, 2019) based on biodegradable materials for delivering growth factors.…”