Bioresorbable Surface-Adhered Enzymatic Microreactors Based on Physical Hydrogels of Poly(vinyl alcohol)

Abstract

Hydrogel biomaterials based on poly(vinyl alcohol), PVA, have an extensive history of biomedical applications, yet in their current form suffer from significant shortcomings, such as a lack of mechanism of biodegradation and poor opportunities in controlled drug release. We investigate physical hydrogels of PVA as surface-adhered materials and present biodegradable matrices equipped with innovative tools in substrate-mediated drug release. Toward the final goal, PVA chains with narrow polydispersities (1.1-1.2) and molecular weights of 5, 10, and 28 kDa are synthesized via controlled radical polymerization (RAFT). These molecular weights are shown to be suitably high to afford robust hydrogel matrices and at the same time suitably low to allow gradual erosion of the hydrogels with kinetics of degradation controlled via polymer macromolecular characteristics. For opportunities in controlled drug release, hydrogels are equipped with enzymatic cargo to achieve an in situ conversion of externally added prodrug into a final product, thus giving rise to surface-adhered enzymatic microreactors. Hydrogel-mediated enzymatic activity was investigated as a function of polymer molecular weight and concentration of solution taken for assembly of hydrogels. Taken together, we present, to the best of our knowledge, the first example of bioresorbable physical hydrogel based on PVA with engineered opportunities in substrate-mediated enzymatic activity and envisioned utility in surface-mediated drug delivery and tissue engineering.

RAFT Polymerization of Vinyl Esters: Synthesis and Applications

“…Hydrogels of PVA are three-dimensional polymer networks with interesting properties for biotechnology and biomedicine. Zelikin et al [166] have investigated physical hydrogels of PVA as biodegradable surface-adhered materials for substrate-mediated drug release devices. PVA chains with narrow polydispersities (1.1-1.2) and molecular weights of 5, 10, and 28 kDa have been synthesized via RAFT.…”

Poly(vinyl alcohol) Physical Hydrogel Nanoparticles, Not Polymer Solutions, Exert Inhibition of Nitric Oxide Synthesis in Cultured Macrophages

“…26 Further to this, quantitative data on polymer incorporation into PVA hydrogels revealed that with increased molecular weight, a progressively higher fraction of polymer chains is retained within the hydrogel. 28 Thus, it is highly likely that HNP as used in this study are significantly differed in the polymer content and plausibly softness. The latter parameter is known to significantly affect behaviour of mammalian cells at a biomaterials interface 11 and for HNP, matrix elasticity was shown to define the mechanism of internalization by macrophages.…”

“…26,27 Furthermore, in our recent report we have used molecular weight of PVA as a tool of effective control over spontaneous degradation of physical hydrogels in physiological conditions. 28 Finally, retention and elimination of PVA from the human body is to large extent controlled by the polymer molecular weight. 29 Thus, it is imperative to identify a technique for production of PVA HNP which affords uniform nanoparticles with control over particles size and accommodating polymer samples over a wide range of molecular weights.…”

Biotechnical Micro-Flow Processing at the EDGE – Lessons to be learnt for a Young Discipline

“…16). 74 Polyvinyl alcohol (PVA) chains with narrow polydispersities (1.1−1.2) and molecular weights of 5, 10, and 28 kDa were synthesized via controlled radical polymerization (RAFT). The substrate-me-diated in-situ conversion of an externally added prodrug into a final product was monitored as a function of the polymer molecular weight and concentration of solution taken for assembly of the hydrogels.…”