Next Generation of Biodegradeable Polymer Ceramic Biomaterial with Tuneable Physicomechanical Characteristics for Biomedical Applications

The acidic nature of the degradation products of biodegradable polymers leads to unpredictable clinical complications. Poly(propylene carbonate) (PPC) and starch composites are introduced as an alternative to biodegradable polymers. The degradation products of composites are mainly CO2 and water. The in vivo analyses of composite and polylactic acid (PLA) showed that PPC based composites were well-tolerated; whereas, PLA caused massive immune cell infusion and inflammation. Relatively low mechanical strength and hydrophobic surface were identified as shortfalls to further broaden the biomedical applications. Blends of PPC and starch was formed by the use of commercial plasticizers. The results showed that the addition of plasticizers increased the compression modulus of PPC-starch by two-fold. Bioglass were incorporated within the structure to enhance the potentials for bone-related applications. In vitro studies showed enhancement in osteoblast cells differentiation by more than 50 % after addition of bioglass. An in vivo degradation assay demonstrated that the bioactive composite loss nearly half of its volume within 6 months. A rat knee model showed outstanding osseointegration of the fabricated screws at bone after 3 and 12 weeks. This structure was also used for the controlled release of a model drug. A core-shell structure was designed based on the polymer ceramic shell and mesoporous nanoparticles. Gas foaming was used to create porous shell and enhance the release rate of active compound with a first order release profile. In summary, this study demonstrates the superior properties of PPC-starch blend for medical application. This material can be easily processed by techniques that involve heating such as extrusion and hot melt compression for the fabrication of various biomedical devices such as bone implants. The results of in vivo tests endorsed the biocompatibility of this material as it was degraded with no complication and also enhanced osseointegration

Biomedical Applications of Biodegradable Polyesters

The focus in the field of biomedical engineering has shifted in recent years to biodegradable polymers and, in particular, polyesters. Dozens of polyester-based medical devices are commercially available, and every year more are introduced to the market. The mechanical performance and wide range of biodegradation properties of this class of polymers allow for high degrees of selectivity for targeted clinical applications. Recent research endeavors to expand the application of polymers have been driven by a need to target the general hydrophobic nature of polyesters and their limited cell motif sites. This review provides a comprehensive investigation into advanced strategies to modify polyesters and their clinical potential for future biomedical applications

Influence of pre-polymerisation atmosphere on the properties of pre- and poly(glycerol sebacate)

[EN] Poly(glycerol sebacate) (PGS) is a versatile biodegradable biomaterial on account of its adjustable mechanical properties as an elastomeric polyester. Nevertheless, it has shown dissimilar results when synthesised by different research groups under equivalent synthesis conditions. This lack of reproducibility proves how crucial it is to understand the effect of the parameters involved on its manufacturing and characterize the polymer networks obtained. Several studies have been conducted in recent years to understand the role of temperature, time, and the molar ratio of its monomers, while the influence of the atmosphere applied during its pre-polymerisation remained unknown. The results obtained here allow for a better understanding about the effect of inert (Ar and N-2) and oxidative (oxygen, dry air, and humid air) atmospheres on the extent of the reaction. The molecular pattern of intermediate pre-polymers and the gelation time and morphology of their corresponding cured PGS networks were studied as well. Overall, inert atmospheres promote a rather linear growth of macromers, with scarce branches, resulting in loose elastomers with long chains mainly crosslinked. Conversely, oxygen in the latter atmospheres promotes branching through secondary hydroxyl groups, leading to less-crosslinked 'defective' networks. In this way, the pre-polymerisation atmosphere could be used advantageously to adjust the reactivity of secondary hydroxyls, in order to modulate branching in the elastomeric PGS networks obtained to suit the properties required in a particular application.Martín-Cabezuelo, R.; Vilariño, G.; Vallés Lluch, A. (2021). Influence of pre-polymerisation atmosphere on the properties of pre- and poly(glycerol sebacate). Materials Science and Engineering C. 119:1-10. https://doi.org/10.1016/j.msec.2020.111429S110119Wang, Y., Kim, Y. M., & Langer, R. (2003). In vivo degradation characteristics of poly(glycerol sebacate). Journal of Biomedical Materials Research, 66A(1), 192-197. doi:10.1002/jbm.a.10534Rai, R., Tallawi, M., Grigore, A., & Boccaccini, A. R. (2012). Synthesis, properties and biomedical applications of poly(glycerol sebacate) (PGS): A review. Progress in Polymer Science, 37(8), 1051-1078. doi:10.1016/j.progpolymsci.2012.02.001Kharazi, A., Shirazaki, P., & Varshosaz, J. (2017). Electrospun Gelatin/poly(Glycerol Sebacate) Membrane with Controlled Release of Antibiotics for Wound Dressing. Advanced Biomedical Research, 6(1), 105. doi:10.4103/abr.abr_197_16Wang, Y., Ameer, G. A., Sheppard, B. J., & Langer, R. (2002). A tough biodegradable elastomer. Nature Biotechnology, 20(6), 602-606. doi:10.1038/nbt0602-602Ulery, B. D., Nair, L. S., & Laurencin, C. T. (2011). Biomedical applications of biodegradable polymers. Journal of Polymer Science Part B: Polymer Physics, 49(12), 832-864. doi:10.1002/polb.22259Stafiej, P., Küng, F., Thieme, D., Czugala, M., Kruse, F. E., Schubert, D. W., & Fuchsluger, T. A. (2017). Adhesion and metabolic activity of human corneal cells on PCL based nanofiber matrices. Materials Science and Engineering: C, 71, 764-770. doi:10.1016/j.msec.2016.10.058Salehi, S., Fathi, M., Javanmard, S., Barneh, F., & Moshayedi, M. (2015). Fabrication and characterization of biodegradable polymeric films as a corneal stroma substitute. Advanced Biomedical Research, 4(1), 9. doi:10.4103/2277-9175.148291Frydrych, M., Román, S., MacNeil, S., & Chen, B. (2015). Biomimetic poly(glycerol sebacate)/poly(l-lactic acid) blend scaffolds for adipose tissue engineering. Acta Biomaterialia, 18, 40-49. doi:10.1016/j.actbio.2015.03.004Hu, J., Kai, D., Ye, H., Tian, L., Ding, X., Ramakrishna, S., & Loh, X. J. (2017). Electrospinning of poly(glycerol sebacate)-based nanofibers for nerve tissue engineering. Materials Science and Engineering: C, 70, 1089-1094. doi:10.1016/j.msec.2016.03.035Rai, R., Tallawi, M., Barbani, N., Frati, C., Madeddu, D., Cavalli, S., … Boccaccini, A. R. (2013). Biomimetic poly(glycerol sebacate) (PGS) membranes for cardiac patch application. Materials Science and Engineering: C, 33(7), 3677-3687. doi:10.1016/j.msec.2013.04.058Masoumi, N., Johnson, K. L., Howell, M. C., & Engelmayr, G. C. (2013). Valvular interstitial cell seeded poly(glycerol sebacate) scaffolds: Toward a biomimetic in vitro model for heart valve tissue engineering. Acta Biomaterialia, 9(4), 5974-5988. doi:10.1016/j.actbio.2013.01.001Lin, D., Yang, K., Tang, W., Liu, Y., Yuan, Y., & Liu, C. (2015). A poly(glycerol sebacate)-coated mesoporous bioactive glass scaffold with adjustable mechanical strength, degradation rate, controlled-release and cell behavior for bone tissue engineering. Colloids and Surfaces B: Biointerfaces, 131, 1-11. doi:10.1016/j.colsurfb.2015.04.031Tevlek, A., Hosseinian, P., Ogutcu, C., Turk, M., & Aydin, H. M. (2017). Bi-layered constructs of poly(glycerol-sebacate)-β-tricalcium phosphate for bone-soft tissue interface applications. Materials Science and Engineering: C, 72, 316-324. doi:10.1016/j.msec.2016.11.082Masoudi Rad, M., Nouri Khorasani, S., Ghasemi-Mobarakeh, L., Prabhakaran, M. P., Foroughi, M. R., Kharaziha, M., … Ramakrishna, S. (2017). Fabrication and characterization of two-layered nanofibrous membrane for guided bone and tissue regeneration application. Materials Science and Engineering: C, 80, 75-87. doi:10.1016/j.msec.2017.05.125Hu, T., Wu, Y., Zhao, X., Wang, L., Bi, L., Ma, P. X., & Guo, B. (2019). Micropatterned, electroactive, and biodegradable poly(glycerol sebacate)-aniline trimer elastomer for cardiac tissue engineering. Chemical Engineering Journal, 366, 208-222. doi:10.1016/j.cej.2019.02.072Wu, Y., Wang, L., Hu, T., Ma, P. X., & Guo, B. (2018). Conductive micropatterned polyurethane films as tissue engineering scaffolds for Schwann cells and PC12 cells. Journal of Colloid and Interface Science, 518, 252-262. doi:10.1016/j.jcis.2018.02.036Wu, Y., Wang, L., Guo, B., & X Ma, P. (2014). Injectable biodegradable hydrogels and microgels based on methacrylated poly(ethylene glycol)-co-poly(glycerol sebacate) multi-block copolymers: synthesis, characterization, and cell encapsulation. Journal of Materials Chemistry B, 2(23), 3674. doi:10.1039/c3tb21716gGultekinoglu, M., Öztürk, Ş., Chen, B., Edirisinghe, M., & Ulubayram, K. (2019). Preparation of poly(glycerol sebacate) fibers for tissue engineering applications. European Polymer Journal, 121, 109297. doi:10.1016/j.eurpolymj.2019.109297Wu, Y., Wang, L., Zhao, X., Hou, S., Guo, B., & Ma, P. X. (2016). Self-healing supramolecular bioelastomers with shape memory property as a multifunctional platform for biomedical applications via modular assembly. Biomaterials, 104, 18-31. doi:10.1016/j.biomaterials.2016.07.011Zhao, X., Wu, Y., Du, Y., Chen, X., Lei, B., Xue, Y., & Ma, P. X. (2015). A highly bioactive and biodegradable poly(glycerol sebacate)–silica glass hybrid elastomer with tailored mechanical properties for bone tissue regeneration. Journal of Materials Chemistry B, 3(16), 3222-3233. doi:10.1039/c4tb01693aNagata, M., Machida, T., Sakai, W., & Tsutsumi, N. (1999). Synthesis, characterization, and enzymatic degradation of network aliphatic copolyesters. Journal of Polymer Science Part A: Polymer Chemistry, 37(13), 2005-2011. doi:10.1002/(sici)1099-0518(19990701)37:133.0.co;2-hKemppainen, J. M., & Hollister, S. J. (2010). Tailoring the mechanical properties of 3D-designed poly(glycerol sebacate) scaffolds for cartilage applications. Journal of Biomedical Materials Research Part A, 94A(1), 9-18. doi:10.1002/jbm.a.32653Conejero-García, Á., Gimeno, H. R., Sáez, Y. M., Vilariño-Feltrer, G., Ortuño-Lizarán, I., & Vallés-Lluch, A. (2017). Correlating synthesis parameters with physicochemical properties of poly(glycerol sebacate). European Polymer Journal, 87, 406-419. doi:10.1016/j.eurpolymj.2017.01.001Ravichandran, R., Venugopal, J. R., Mukherjee, S., Sundarrajan, S., & Ramakrishna, S. (2015). Elastomeric Core/Shell Nanofibrous Cardiac Patch as a Biomimetic Support for Infarcted Porcine Myocardium. Tissue Engineering Part A, 21(7-8), 1288-1298. doi:10.1089/ten.tea.2014.0265Gao, J., Crapo, P. M., & Wang, Y. (2006). Macroporous Elastomeric Scaffolds with Extensive Micropores for Soft Tissue Engineering. Tissue Engineering, 12(4), 917-925. doi:10.1089/ten.2006.12.917Mitsak, A. G., Dunn, A. M., & Hollister, S. J. (2012). Mechanical characterization and non-linear elastic modeling of poly(glycerol sebacate) for soft tissue engineering. Journal of the Mechanical Behavior of Biomedical Materials, 11, 3-15. doi:10.1016/j.jmbbm.2011.11.003Hsu, C.-N., Lee, P.-Y., Tuan-Mu, H.-Y., Li, C.-Y., & Hu, J.-J. (2017). Fabrication of a mechanically anisotropic poly(glycerol sebacate) membrane for tissue engineering. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 106(2), 760-770. doi:10.1002/jbm.b.33876Li, X., Hong, A. T.-L., Naskar, N., & Chung, H.-J. (2015). Criteria for Quick and Consistent Synthesis of Poly(glycerol sebacate) for Tailored Mechanical Properties. Biomacromolecules, 16(5), 1525-1533. doi:10.1021/acs.biomac.5b00018Aydin, H. M., Salimi, K., Rzayev, Z. M. O., & Pişkin, E. (2013). Microwave-assisted rapid synthesis of poly(glycerol-sebacate) elastomers. Biomaterials Science, 1(5), 503. doi:10.1039/c3bm00157aLau, C. C., Bayazit, M. K., Knowles, J. C., & Tang, J. (2017). Tailoring degree of esterification and branching of poly(glycerol sebacate) by energy efficient microwave irradiation. Polymer Chemistry, 8(26), 3937-3947. doi:10.1039/c7py00862gBhanu, V. A., & Kishore, K. (1991). Role of oxygen in polymerization reactions. Chemical Reviews, 91(2), 99-117. doi:10.1021/cr00002a001Conley, R. T. (1967). Studies of the Stability of Condensation Polymers in Oxygen-Containing Atmospheres. Journal of Macromolecular Science: Part A - Chemistry, 1(1), 81-106. doi:10.1080/10601326708053918SZWARC, M. (1956). ‘Living’ Polymers. Nature, 178(4543), 1168-1169. doi:10.1038/1781168a0Chen, Q.-Z., Bismarck, A., Hansen, U., Junaid, S., Tran, M. Q., Harding, S. E., … Boccaccini, A. R. (2008). Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue. Biomaterials, 29(1), 47-57. doi:10.1016/j.biomaterials.2007.09.010Vallés-Lluch, A., Gallego Ferrer, G., & Monleón Pradas, M. (2010). Effect of the silica content on the physico-chemical and relaxation properties of hybrid polymer/silica nanocomposites of P(EMA-co-HEA). European Polymer Journal, 46(5), 910-917. doi:10.1016/j.eurpolymj.2010.02.004Gaharwar, A. K., Patel, A., Dolatshahi-Pirouz, A., Zhang, H., Rangarajan, K., Iviglia, G., … Khademhosseini, A. (2015). Elastomeric nanocomposite scaffolds made from poly(glycerol sebacate) chemically crosslinked with carbon nanotubes. Biomaterials Science, 3(1), 46-58. doi:10.1039/c4bm00222aChen, Q., Liang, S., & Thouas, G. A. (2013). Elastomeric biomaterials for tissue engineering. Progress in Polymer Science, 38(3-4), 584-671. doi:10.1016/j.progpolymsci.2012.05.003Ma, Y., Feng, X., Rogers, J. A., Huang, Y., & Zhang, Y. (2017). Design and application of ‘J-shaped’ stress–strain behavior in stretchable electronics: a review. Lab on a Chip, 17(10), 1689-1704. doi:10.1039/c7lc00289kIfkovits, J. L., Padera, R. F., & Burdick, J. A. (2008). Biodegradable and radically polymerized elastomers with enhanced processing capabilities. Biomedical Materials, 3(3), 034104. doi:10.1088/1748-6041/3/3/03410