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.

1st Faculty of Medicine Charles University Prague Katerinska 32 121 08 Prague 2 Czech Republic

Institute of Hematology and Blood Transfusion U nemocnice 2094 1 128 20 Prague 2 Czech Republic

Institute of Macromolecular Chemistry AS CR Heyrovsky Sq 2 162 06 Prague 6 Czech Republic

Zobrazit více v PubMed

Van Rappard J.H.A., Molenaar J., van Doom K., Sonneveld G.J., Borghouts J.M.H.M., Shively R.E. Surface-Area Increase in Tissue Expansion. Plast. Reconstr. Surg. 1988;82:833–837. doi: 10.1097/00006534-198811000-00016. PubMed DOI

Allen M.R., Hock J.M., Burr D.B. Periosteum: Biology, Regulation, and Response to Osteoporosis Therapies. Bone. 2004;35:1003–1012. doi: 10.1016/j.bone.2004.07.014. PubMed DOI

Von See C., Rücker M., Bormann K.-H., Gellrich N.-C. Using a Novel Self-Inflating Hydrogel Expander for Intraoral Gingival Tissue Expansion Prior to Bone Augmentation. Br. J. Oral Maxillofac. Surg. 2010;48:e5–e6. doi: 10.1016/j.bjoms.2009.10.025. PubMed DOI

Zeiter D.J., Ries W.L., Weir T.L., Mishkin D.J., Hendley T.H., Sanders J.J. The Use of a Soft Tissue Expander in an Alveolar Bone Ridge Augmentation for Implant Placement. Int. J. Periodontics Restor. Dent. 1998;18:403–409. PubMed

Cherry G.W., Austad E., Pasyk K., McClatchey K., Rohrich R.J., Cherry G.W. Increased Survival and Vascularity of Random-Pattern Skin Flaps Elevated in Controlled, Expanded Skin. Plast. Reconstr. Surg. 1983;72:680–685. doi: 10.1097/00006534-198311000-00018. PubMed DOI

Neumann C.G. The Expansion of an Area of Skin by Progressive Distention of a Subcutaneous Ballon. Plast. Reconstr. Surg. 1957;19:124–130. doi: 10.1097/00006534-195702000-00004. PubMed DOI

Uijlenbroek H.J.J., Liu Y., Wismeijer D. Soft Tissue Expansion: Principles and Inferred Intraoral Hydrogel Tissue Expanders. Dent. Oral Craniofac. Res. 2016;1:178–185. doi: 10.15761/DOCR.1000140. DOI

Swan M.C., Bucknall D.G., Czernuszka J.T., Pigott D.W., Goodacre T.E.E. Development of a Novel Anisotropic Self-Inflating Tissue Expander. Plast. Reconstr. Surg. 2012;129:79–88. doi: 10.1097/PRS.0b013e3182362100. PubMed DOI

Downes R., Lavin M., Collin R. Hydrophilic Expanders for the Congenital Anophthalmic Socket. Adv. Ophthalmic Plast. Reconstr. Surg. 1992;9:57–61. PubMed

Bergé S.J., Wiese K.G., von Lindern J.-J., Niederhagen B., Appel T., Reich R.H. Tissue Expansion Using Osmotically Active Hydrogel Systems for Direct Closure of the Donor Defect of the Radial Forearm Flap. Plast. Reconstr. Surg. 2001;108:1–5. doi: 10.1097/00006534-200107000-00001. PubMed DOI

Ronert M.A., Hofheinz H., Manassa E., Asgarouladi H., Olbrisch R.R. The Beginning of a New Era in Tissue Expansion: Self-Filling Osmotic Tissue Expander - Four-Year Clinical Experience. Plast. Reconstr. Surg. 2004 doi: 10.1097/01.PRS.0000135325.13474.D3. PubMed DOI

Obdeijn M.C., Nicolai J.-P.A., Werker P.M.N. The Osmotic Tissue Expander: A Three-Year Clinical Experience. J. Plast. Reconstr. Aesthetic Surg. 2009;62:1219–1222. doi: 10.1016/j.bjps.2007.12.088. PubMed DOI

Chummun S., Addison P., Stewart K.J. The Osmotic Tissue Expander: A 5-Year Experience. J. Plast. Reconstr. Aesthetic Surg. 2010;63:2128–2132. doi: 10.1016/j.bjps.2010.02.002. PubMed DOI

Al Madani J.O. Second Generation Self-Inflating Tissue Expanders: A Two-Year Experience. Plast. Surg. Int. 2014;2014:1–6. doi: 10.1155/2014/457205. PubMed DOI PMC

Kaner D., Friedmann A. Soft Tissue Expansion with Self-Filling Osmotic Tissue Expanders before Vertical Ridge Augmentation: A Proof of Principle Study. J. Clin. Periodontol. 2011;38:95–101. doi: 10.1111/j.1600-051X.2010.01630.x. PubMed DOI

Swan M.C., Bucknall D.G., Goodacre T.E.E., Czernuszka J.T. Synthesis and Properties of a Novel Anisotropic Self-Inflating Hydrogel Tissue Expander. Acta Biomater. 2011;7:1126–1132. doi: 10.1016/j.actbio.2010.10.017. PubMed DOI

Hrib J., Sirc J., Lesny P., Hobzova R., Duskova-Smrckova M., Michalek J., Smucler R. Hydrogel Tissue Expanders for Stomatology. Part I. Methacrylate-Based Polymers. J. Mater. Sci. Mater. Med. 2017;28:12. doi: 10.1007/s10856-016-5818-y. PubMed DOI

Huang J., Turner S.R. Recent Advances in Alternating Copolymers: The Synthesis, Modification, and Applications of Precision Polymers. Polymer. 2017;116:572–586. doi: 10.1016/j.polymer.2017.01.020. DOI

Dörr J.M., Scheidelaar S., Koorengevel M.C., Dominguez J.J., Schäfer M., van Walree C.A., Killian J.A. The Styrene–Maleic Acid Copolymer: A Versatile Tool in Membrane Research. Eur. Biophys. J. 2016;45:3–21. doi: 10.1007/s00249-015-1093-y. PubMed DOI PMC

Popescu I., Suflet D.M., Pelin I.M., Chiţanu G.C. Biomedical Applications of Maleic Anhydride Copolymers. Rev. Roum. Chim. 2011;56:173–188.

Subramanian B., Rameshbabu A.P., Ghosh K., Jha P.K., Jha R., Murugesan S., Chattopadhyay S., Dhara S., Mondal K.C., Basak P., et al. Impact of Styrene Maleic Anhydride (SMA) Based Hydrogel on Rat Fallopian Tube as Contraceptive Implant with Selective Antimicrobial Property. Mater. Sci. Eng. C. 2019;94:94–107. doi: 10.1016/j.msec.2018.09.023. PubMed DOI

Banerjee S., Pal T.K., Guha S.K. Probing Molecular Interactions of Poly(Styrene-Co-Maleic Acid) with Lipid Matrix Models to Interpret the Therapeutic Potential of the Co-Polymer. Biochim. Biophys. Acta Biomembr. 2012;1818:537–550. doi: 10.1016/j.bbamem.2011.12.010. PubMed DOI

Maeda H. SMANCS and Polymer-Conjugated Macromolecular Drugs: Advantages in Cancer Chemotherapy. Adv. Drug Deliv. Rev. 2001;46:169–185. doi: 10.1016/S0169-409X(00)00134-4. PubMed DOI

Dušek K., Dušková-Smrčková M. Polymer Networks. In: Matyjaszewski K., Gnanou Y., Leibler L., editors. Macromolecular Engineering: Precise Synthesis, Materials Properties, Applications. Wiley-VCH Verlag GmbH & Co. KGaA; Weinheim, Germany: 2011. pp. 1687–1730.

Mayo F.R., Lewis F.M., Walling C. Copolymerization. VIII. The Relation Between Structure and Reactivity of Monomers in Copolymerization 1. J. Am. Chem. Soc. 1948;70:1529–1533. doi: 10.1021/ja01184a070. DOI

Klumperman B. Mechanistic Considerations on Styrene–Maleic Anhydride Copolymerization Reactions. Polym. Chem. 2010;1:558. doi: 10.1039/b9py00341j. DOI

Garnier G., Duskova-Smrckova M., Vyhnalkova R., Van De Ven T.G.M., Revol J.F. Association in Solution and Adsorption at an Air-Water Interface of Alternating Copolymers of Maleic Anhydride and Styrene. Langmuir. 2000;16:3757–3763. doi: 10.1021/la991440a. DOI

Kopf A.H., Koorengevel M.C., van Walree C.A., Dafforn T.R., Killian J.A. A Simple and Convenient Method for the Hydrolysis of Styrene-Maleic Anhydride Copolymers to Styrene-Maleic Acid Copolymers. Chem. Phys. Lipids. 2019;218:85–90. doi: 10.1016/j.chemphyslip.2018.11.011. PubMed DOI

Brandrup J., Immergut E.H. Polymer Handbook. 3rd ed. Wiley-Interscience; Chichester, UK: 1989.

Heng Z., Zeng Z., Zhang B., Luo Y., Luo J., Chen Y., Zou H., Liang M. Enhancing Mechanical Performance of Epoxy Thermosets: Via Designing a Block Copolymer to Self-Organize into “Core-Shell” Nanostructure. RSC Adv. 2016;6:77030–77036. doi: 10.1039/C6RA15283J. DOI