Poly(vinyl alcohol) Cross-Linkers for in Vivo Injectable Hydrogels

Abstract

New poly(vinyl alcohol) (PVA) derivatives containing different pendant chemoselective functionalities have been prepared for the in situ formation of hydrogels at physiological conditions. Particularly, incorporations of thiol, cysteine 1,2-aminothiol, and aminooxy side chains to PVA were performed for the first time by direct coupling of the protected nucleophilic functionalities to PVA's hydroxyl groups via carbamate linkages followed by acidic deprotection. In the second approach, PVA was first derivatized to a low degree (3%) with amino groups which were used to quantitatively react with different N-hydroxysuccinimide esters of carboxylic acids containing maleimide, R-iodoacetyl, or acrylate thiophilic functionalities. The utility of the aminoderivatized PVA was also demonstrated for further functionalization with semicarbazide terminated side chains. The ability of the new PVA derivatives to act as multifunctional cross-linking agents was examined in the course of in situ cross-linking reactions with hyaluronic acid carrying aldehyde groups. Use of multifunctional PVA cross-linkers was shown to give short gelation times, i.e., within half a minute, which is critical for clinical applications. The hyaluronan hydrogels were enzymatically degradable as evidenced by the results of in vitro degradation by hyaluronidase. Moreover, these hydrogels were found to be nontoxic to human dermal fibroblasts. Hence, PVA-based multifunctional cross-linkers can extend the scope of in situ preparation and properties of hydrogel-based synthetic mimics of extracellular matrix as compared with well established bifunctional poly(ethylene glycol) analogs.

Control of swelling properties of polyvinyl alcohol/hyaluronic acid hydrogels for the encapsulation of chondrocyte cells

“…The cross-linking through Schiff base reaction between primary amine and aldehyde functional groups producing C@N double bond (Scheme S1, supplementary data) was confirmed with 13 C CP/MAS NMR spectroscopy. The solid-state NMR spectra of PVAHY, HAALD, and PVA/HA hydrogel are presented in Figure 1.…”

“…Several studies have been reported on the formation of biocompatible hydrogels from chemoselective multifunctional polymers. 12,13 This approach offers fast gelation times with a well-defined network and a possibility for injectable hydrogels. A Schiff base reaction 12 between aldehyde and amino groups of polymer derivatives is a good example, because the formation of C@N double bond is fast and does not produce any toxic by-products.…”

Hydrogels for the Application of Articular Cartilage Tissue Engineering: A Review of Hydrogels

“…In the use of functional hydrogel for treating articular cartilage damage, suitable manufacture approaches and superb bio-materials act as important parts in developing perfect injectable polymeric hydrogels which could be considered as bio-scaffolds for bone and articular cartilage tissue engineering uses. A choice of biomedical materials, either synthetic or natural, has been elucidated to fabricate injectable polymeric hydrogels; those materials comprise poly(vinyl alcohol) [69], poly(ethylene glycol) (PEG) [70] or collagen, hyaluronic acid [71] (Figure 2, [72]), alginate [73], Advances in Materials Science and Engineeringchondroitin sulfate [74], heparin [75], gelatin [76,77] ( Figure 3, [78]), and chitosan [79]. Injectable polymeric hydrogel enables to be prepared via both chemical and physical ways.…”

Preparation of Fully Hydrolyzed Ultra-High-Molecular-Weight Polyvinyl Alcohol Nanofibers by Viscosity Control and Improvement of Fiber Hot Water Resistance by Annealing

“…Nano-scale PVA fibers have several interesting characteristics, such as high surface area to mass ratio, significant possibilities for surface functionalization, and high mechanical performance due to an improvement in the molecular organization of the spun fiber. These properties make electrospun PVA fibers excellent candidates for many applications, such as filtration, reinforcing materials, wound dressings and drug releasing carriers [6][7][8][9][10][11].…”