Hydrogel Tissue Expanders for Stomatology. Part II. Poly(styrene-maleic anhydride) Hydrogels.

Self-inflating soft tissue expanders represent a valuable modality in reconstructive surgery. For this purpose, particularly synthetic hydrogels that increase their volume by swelling in aqueous environment are used. The current challenge in the field is to deliver a material with a suitable protracted swelling response, ideally with an induction period (for sutured wound healing) followed by a linear increase in volume lasting several days for required tissue reconstruction. Here, we report on synthesis, swelling, thermal, mechanical and biological properties of novel hydrogel tissue expanders based on poly(styrene-alt-maleic anhydride) copolymers covalently crosslinked with p-divinylbenzene. The hydrogels exerted hydrolysis-driven swelling response with induction period over the first two days with minimal volume change and gradual volume growth within 30 days in buffered saline solution. Their final swollen volume reached more than 14 times the dry volume with little dependence on the crosslinker content. The mechanical coherence of samples during swelling and in their fully swollen state was excellent, the compression modulus of elasticity being between 750 and 850 kPa. In vitro cell culture experiments and in vivo evaluation in mice models showed excellent biocompatibility and suitable swelling responses meeting thus the application requirements as soft tissue expanders.

Reductively Degradable Poly(2-hydroxyethyl methacrylate) Hydrogels with Oriented Porosity for Tissue Engineering Applications.

Degradable poly(2-hydroxyethyl methacrylate) hydrogels were prepared from a linear copolymer (Mw = 49 kDa) of 2-hydroxyethyl methacrylate (HEMA), 2-(acethylthio)ethyl methacrylate (ATEMA), and zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC). The deprotection of ATEMA thiol groups by triethylamine followed by their gentle oxidation with 2,2'-dithiodipyridine resulted in the formation of reductively degradable polymers with disulfide bridges. Finally, a hydrogel 3D structure with an oriented porosity was obtained by gelation of the polymer in the presence of needle-like sodium acetate crystals. The pore diameter and porosity of resulting poly(2-hydroxyethyl methacrylate-co-2-(acethylthio)ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) [P(HEMA-ATEMA-MPC)] hydrogels varied between 59 and 65 µm and between 70 and 79.6 vol % according to Hg porosimetry, and complete degradation of these materials was reached in 86 days in 0.33 mmol solution of l-cysteine/L in phosphate buffer. The cross-linked P(HEMA-ATEMA-MPC) hydrogels were evaluated as a possible support for human mesenchymal stem cells (MSCs). No cytotoxicity was found for the un-cross-linked thiol-containing and protected P(HEMA-ATEMA-MPC) chains up to a concentration of 5 and 1 wt % in α-minimum essential medium, respectively.

Hydrogel tissue expanders for stomatology. Part I. Methacrylate-based polymers.

In order to create a soft tissue surplus, implantable volume expanders are often utilized in dental surgery. Implanted tissue expanders should gradually increase their volume, exerting a constant pressure on the surrounding tissue for weeks. Current tissue expanders are based predominantly on externally inflatable balloons or on osmotically active tissue expanders that use soft hydrogels wrapped in perforated plastic coatings, which limit fluid entry and swelling. We have designed and examined tissue expanders based on the controlled rate expansive hydrogels synthesized from copolymers of selected methacrylates and N-vinylpyrrolidone, cross-linked with a combination of non-degradable (glycol dimethacrylates) and hydrolytically degradable (N,O-dimethacryloylhydroxylamine) cross-linkers. These copolymers have close-to-linear volume expansion rates (up to 6-9 times their original volume) and exert an increasing swelling pressure in vitro. The anesthetic benzocaine has been incorporated into the hydrogels, and kinetic release experiments have shown that most of the drug (90%) was released within 48 h. Our proposed hydrogel expanders are homogeneous and have suitable mechanical properties, thus simplifying the surgical manipulations required. Further studies will be needed to completely evaluate their biocompatibility and tissue response to the implants.

Macroporous Biodegradable Cryogels of Synthetic Poly(α-amino acids).

We present an investigation of the preparation of highly porous hydrogels based on biodegradable synthetic poly(α-amino acid) as potential tissue engineering scaffolds. Covalently cross-linked gels with permanent pores were formed under cryogenic conditions by free-radical copolymerization of poly[N(5)-(2-hydroxyethyl)-L-glutamine-stat-N(5)-(2-methacryloyl-oxy-ethyl)-L-glutamine] (PHEG-MA) with 2-hydrohyethyl methacrylate (HEMA) and, optionally, N-propargyl acrylamide (PrAAm) as minor comonomers. The morphology of the cryogels showed interconnected polyhedral or laminar pores. The volume content of communicating water-filled pores was >90%. The storage moduli of the swollen cryogels were in the range of 1-6 kPa, even when the water content was >95%. The enzymatic degradation of a cryogel corresponded to the decrease in its storage modulus during incubation with papain, a model enzyme with specificity analogous to wound-healing enzymes. It was shown that cryogels with incorporated alkyne groups can easily be modified with short synthetic peptides using azide-alkyne cycloaddition "click" chemistry, thus providing porous hydrogel scaffolds with biomimetic features.