polymers Review State-of-Art of Standard and Innovative Materials Used in Cranioplasty Valentina Siracusa 1, * , Giuseppe Maimone 2 and Vincenzo Antonelli 2   Citation: Siracusa, V.; Maimone, G.; Antonelli, V. State-of-Art of Standard and Innovative Materials Used in Cranioplasty. Polymers 2021, 13, 1452. https://doi.org/10.3390/ polym13091452 Academic Editor: Jose-Ramon Sarasua Received: 30 March 2021 Accepted: 28 April 2021 Published: 30 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Chemical Science, University of Catania, Viale A. Doria 6, 95125 Catania, Italy 2 Department of Neurosurgery, Hospital M. Bufalini—AUSL della Romagna, Viale Ghirotti 286, 47521 Cesena, Italy; giuseppe.maimone@auslromagna.it (G.M.); vincenzo.antonelli@auslromagna.it (V.A.) * Correspondence: vsiracus@dmfci.unict.it; Tel.: +39-3387275526 Abstract: Cranioplasty is the surgical technology employed to repair a traumatic head injury, cere- brovascular disease, oncology resection and congenital anomalies. Actually, different bone substitutes are used, either derived from biological products such as hydroxyapatite and demineralized bone matrix or synthetic ones such as sulfate or phosphate ceramics and polymer-based substitutes. Considering that the choice of the best material for cranioplasty is controversial, linked to the best operation procedure, the intent of this review was to report the outcome of research conducted on materials used for such applications, comparing the most used materials. The most interesting challenge is to preserve the mechanical properties while improving the bioactivity, porosity, biocom- patibility, antibacterial properties, lowering thickness and costs. Among polymer materials, poly- methylmethacrylate and polyetheretherketone are the most motivating, due to their biocompatibility, rigidity and toughness. Other biomaterials, with ecofriendly attributes, such as polycaprolactone and polylactic acid have been investigated, due to their microstructure that mimic the trabecular bone, encouraging vascularization and cell–cell communications. Taking into consideration that each material must be selected for specific clinical use, the main limitation remains the defects and the lack of vascularization, consequently porous synthetic substitutes could be an interesting way to support a faster and wider vascularization, with the aim to improve patient prognosis. Keywords: cranioplasty; neurosurgery; synthetic cranioplasty; cranial defect; skull reconstruction; biomaterials; polymers; polymethylmethacrylate (PMMA); polyetheretherketone (PEEK); polyethereketoneketone (PEKK); polylactic acid (PLA); polycaprolactone (PCL); polyglycolide (PGA) 1. Introduction Cranioplasty is an old surgical procedure used to repair cranial defects, offering at the same time protective and cosmetic benefits for patients. The main causes that require cranioplasty are birth defects (absence of an intact cranial vault), infection of the cranial contents, tumor removal, decompressive craniectomies and traumatic injuries, for all age people [1–6]. This procedure can improve electroencephalographic abnormalities, cerebral blood flow abnormalities and other neurological abnormalities [1–6]. The contraindication for such procedure could be infections, hydrocephalus and brain swelling but delaying cranioplasty could cause preclusion in autograft devitalization or allograft infections. Further, in order to allow spontaneous ossification, studies reported that foreign materials should be implanted after 1 year [4]. As reported by several authors [1–6], materials used for cranioplasty have to be radiolucent, resistant to infections, non-conductive of heat or cold, malleable, mechanical resistant, ready and easy to use and of course allowed at low cost. Different materials were used over time, derived from biological sources or synthetic polymers, as reported in Figure 1: Polymers 2021, 13, 1452. https://doi.org/10.3390/polym13091452 https://www.mdpi.com/journal/polymers