Degradation of Partially Oxidized Alginate and Its Potential Application for Tissue Engineering

Abstract

Alginate has been widely used in a variety of biomedical applications including drug delivery and cell transplantation. However, alginate itself has a very slow degradation rate, and its gels degrade in an uncontrollable manner, releasing high molecular weight strands that may have difficulty being cleared from the body. We hypothesized that the periodate oxidation of alginate, which cleaves the carbon-carbon bond of the cis-diol group in the uronate residue and alters the chain conformation, would result in promoting the hydrolysis of alginate in aqueous solutions. Alginate, oxidized to a low extent (approximately 5%), degraded with a rate depending on the pH and temperature of the solution. This polymer was still capable of being ionically cross-linked with calcium ions to form gels, which degraded within 9 days in PBS solution. Finally, the use of these degradable alginate-derived hydrogels greatly improved cartilage-like tissue formation in vivo, as compared to alginate hydrogels.

Cell colonization in degradable 3D porous matrices

“…28 One way to overcome the heterogeneity in natural matrices uses polymers to fabricate degradable 3D porous matrices. Scaffolds generated from natural polymers such as alginates, [29][30][31] chitosan, [32][33][34][35][36][37][38] collagen, 39 GAGs and elastin, [40][41][42][43] gelatin [44][45][46] and fibrin [47][48][49] have also been used as scaffolding materials. [50][51][52] A commonly used system is collagen/GAGs; 53,54 collagen/GAG based skin equivalents are already in clinical use 41,42 and under investigation for other applications such as heart valves, vascular grafts [55][56][57][58][59][60] and vascular networks.…”

Refilling drug delivery depots through the blood

“…S5). To carry i.v.-administered drug payloads, alginate was partially oxidized to introduce aldehyde functional groups, allowing coupling of hydrazine-doxorubicin through a hydrolyzable hydrazone linker (15,36). Oxidized alginate demonstrated sustained release of doxorubicin ( Fig.…”

“…Alginate is biocompatible and nonimmunogenic and can be gelled under gentle conditions, allowing encapsulation of drugs or biological factors with minimal trauma. Additionally, alginate is readily chemically modified for cell adhesion or as a drug carrier (12)(13)(14) and has tunable degradation rates (15), and chemically modified forms of alginate are currently used clinically as a drug delivery vehicle for proteins that promote regeneration of mineralized tissue (16) and have been used as a carrier for transplanted cells (14,(17)(18)(19). Drug-eluting injectable alginate hydrogels were chosen due to their ability to be introduced into the body in a minimally invasive manner (14).…”

 

“…This is beneficial for chondrocytes because chondrocytes can be de-differentiated into fibroblast phenotype in monolayer cultures, which is unfavorable for cartilage regeneration. [23] Nevertheless, unmodified alginate hydrogels are non-biodegradable [24] and can cause foreign body cell reactions and immunological responses. [25,26] Furthermore, there is no special interaction between alginates and cells.…”