Formation of the first injectable poly(vinyl alcohol) hydrogel by mixing of functional PVA precursors

Abstract

In this study we describe the development of an injectable, in situ chemical hydrogel forming system. The gelation occurs under neutral pH and at room temperature immediately upon mixing of the two aqueous poly (vinyl alcohol) components specifically derivatized through carbamate linkages with aldehyde (PVA-AL) and hydrazide (PVA-HY) functional groups, respectively. Aldehyde and hydrazide pendant groups were incorporated with a low degree of substitution (DS) into the PVA backbone to keep PVA structural homogeneity minimally altered. As a result, the hydrazone crosslinks are formed rapidly between aldehyde and hydrazide pendant groups when the correspondingly modified PVA components are brought in contact as water solutions. To assess in situ hydrazone crosslinks formation for in vitro cytocompatibility, murine neuroblastoma N2a cells were suspended in cell culture medium with the dissolved PVA-HY prior to addition to the PVA-AL aqueous solution. Thus, the cells were chemically encapsulated in a polymer network that was formed by mixing of the corresponding aqueous solutions of PVA functional precursors. Biochemical analysis revealed that cells survived chemical crosslinking and remained viable in the hydrogel for 4 days of culture.

Calcium phosphates compounds in conjunction with hydrogel as carrier for BMP-2: A study on ectopic bone formation in rats

“…12 mg of recombinant human BMP-2 were dissolved . Hydrazide-modified polyvinyl alcohol (PVAH) was prepared as previously described [12], through dissolution at a concentration of 3.3 mg ml À1 in BMP-2 formulation buffer (0.833% glycine, 0.167% sucrose, 0.033% polysorbate 80, 0.01% sodium chloride, and 0.025% L-glutamic acid) and filter sterilized. BMP-2 was added to the hydrazide component at a concentration of 0.3 mg ml À1 .…”

“…Cross-linking produces stable hydrazones in aqueous solution at physiological pH, making it ideal for injection [11][12][13][14]. Similar hyaluronan-based injectable systems have been developed by others, including Prestwich and Langer [15][16][17][18].…”

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

“…10 PVA (400 mg, 9.1 mmol of repeating units) was dissolved in 8 mL of DMSO that had been dried with 4 Å molecular sieves. The solution was heated at 85 C with mixing for 2 h to dissolve the polymer.…”

“…10 PVAHY (1 mg) was dissolved in 2 mL of borate buffer solution (0.1 M, pH 9.3). The sample (0.1 mL) was diluted with 2.8 mL of borate buffer solution and 75 mL of 0.025 M TNBS solution (prepared from 5% solution by diluting with borate buffer solution) was added.…”

Hydrogels in Regenerative Medicine

“…Biodegradable synthetic hydrogels include various vinylic monomers such as 2-hydroxyethyl methacrylate (HEMA), N-isopropylacrylamide (NIPAM), 2-hydroxypropyl methacrylate (HPMA), acrylamide (AAm), acrylic acid (AAc) or macromers [53][54][55] N,N′-methylenebis and methoxyl poly(ethylene glycol) (PEG), monoacrylate (mPEGMA or PEGMA), and diacrylate (PEGDA) with cross-linkers such as ethylene glycol diacrylate (EGDA), and these nonbiodegradable polymers such as self-assembly of Pluronic® polymers that have poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO structure [53][54][55] are modified with poly(vinyl alcohol) (PVA) via chemical cross-linking.…”