Simultaneously Physically and Chemically Gelling Polymer System Utilizing a Poly(NIPAAm-co-cysteamine)-Based Copolymer

Abstract

The objective of this work was to create an in situ physically and chemically cross-linking hydrogel for in vivo applications. N-Isopropylacrylamide (NIPAAm) was copolymerized with N-acryloxysuccinimide (NASI) via free radical polymerization. Poly(NIPAAm-co-NASI) was further modified to obtain poly(NIPAAm-co-cysteamine) through a nucleophilic attack on the carbonyl group of the NASI by the amine group of the cysteamine. Modification was verified by nuclear magnetic resonance. In addition to thermoresponsive physical gelling due to the presence of NIPAAm, this system also chemically gels via a Michael-type addition reaction when mixed with poly(ethylene glycol) diacrylate. The presence of both physical and chemical gelation resulted in material properties that are much improved compared to purely physical gels. The chemical gelation time of the copolymers was not significantly affected by the amount of thiol present due to the increased pKa of the copolymer containing more thiols. In addition, the swelling of the copolymers was highly dependent on the temperature and thiol content. Last, the rate of nucleophilic attack in the Michael-type addition reaction was shown to be highly dependent on pH and on the mole ratio of thiol to acrylate. Due to the improved mechanical properties, this material may be better suited for long-term functional replacement applications than other thermosensitive physical gels. With further development and biocompatibility testing, this material could potentially be applied as a temperature-responsive injectable biomaterial for functional embolization.

Injectable hydrogels

“…Alternatively, thiol-functionalized poly(NIPAAm) forms strong and elastic physical-chemical gels on mixing with PEGDA below the LCST, which, when heated, reach storage moduli near 1 MPa, an exceptionally high value for a hydrogel. 281 Alternatively, NIPAAm-based macromers can be polymerized in situ to obtain physical-chemical gels. 282 Yet some frequency response is still observed in physical-chemical gels when allowed to cross-link above the LCST, and the gel moduli plateaus at lower values when the gels are heated to 37 C more quickly, 280 which indicates that cross-linking may be incomplete when the polymers must cross-link at temperatures above the LCST.…”

Design of Polyphosphazene Hydrogels with Improved Structural Properties by Use of Star‐Shaped Multithiol Crosslinkers

“…Among the chemically crosslinkable gels, gels obtained through a Michael-type addition reaction between thiols and acrylates or vinylsulfones are well studied in the literature. [8][9][10] Recently, scientists have also been focusing on dual crosslinkable hydrogel systems, which include poly(N-isopropylacrylamide-co-cysteamine)s, [11] poly[N-isopropylacrylamide-co-(hydroxyethyl methacrylate)]s [12] and modified Pluronics, [13] to improve the properties of the hydrogel network. However, to serve as an ideal carrier material either for drug or cell delivery, hydrogel materials should possess controlled degradation in addition to the requisite mechanical properties.…”

Formulation and characterization of radio‐opaque conjugated in situ gelling materials

“…1 Calcium alginate exemplifies ionic gels, 2 and physical gels include precipitating solutions such as Onyx and those with temperature sensitivity such as N-isopropylacrylamide and poly(organophosphazenes), which form gels upon introduction to biologically analogous temperatures. [3][4][5] The form fitting, biocompatible gels allow use for drug delivery, tissue engineering, prevention of chronic bleeding, and treatment of fibroid tumors. [6][7][8][9][10] The behavior of these materials has driven research into their use as an effective method of vascular embolization.…”