Turrin Giulia, Crugeiras Jose, Bisquoli Chiara, Barboni Davide, Catani Martina, Rodríguez-Meana Bruno, Boaretto Rita, Albicini Michele, Caramori Stefano, Trapella Claudio, Stieglitz Thomas, Baslan Yara, Karlsson-Fernberg Hanna, Narvaez-Chicaiza Fernanda L, Marchini Edoardo, Cavazzini Alberto, López-Vales Ruben, Asplund Maria, Navarro Xavier, Carli Stefano
Department of Environmental and Prevention Sciences, University of Ferrara, Via Luigi Borsari, 46, Ferrara, 44121, Italy.
Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Av. Can Domènech, ed M, Bellaterra, 08193, Spain.
Adv Healthc Mater. 2025 Aug;14(21):e2405004. doi: 10.1002/adhm.202405004. Epub 2025 Jun 17.
Neural implants are widely used in prosthetic applications to interact with the peripheral nervous system, but their long-term functionality is compromised by foreign body reactions (FBR). Thanks to its high biocompatibility, polyimide poly (biphenyl dianhydride)-p-phenylenediamine (BPDA-PDA) represents a suitable material to fabricate ultrathin and ultra-flexible neural implants. This study explores the surface functionalization of BPDA-PDA, the electrically inert component of the neural implant. The novelty of this approach relies on the fact that dexamethasone (DEX covalently bound to BPDA-PDA, enabling its sustained release over a period of at least 9 weeks. In vitro assays demonstrate that this strategy reduce the production of pro-inflammatory markers in macrophages. In addition, the biocompatibility of the functionalized material has been ensured by evaluating the viability of dorsal root ganglia (DRG) neurons. Furthermore, in vivo implantation of DEX functionalized BPDA-PDA substrates shows a significant reduction in inflammatory cell infiltration and fibrotic capsule thickness formed around the devices. These findings suggest that local release of DEX from the electrically inactive scaffold of neural implants may enhance their long-term stability and performance by mitigating the FBR.
神经植入物广泛应用于假肢应用中,以与周围神经系统相互作用,但其长期功能会受到异物反应(FBR)的影响。由于具有高生物相容性,聚酰亚胺聚(联苯二酐)-对苯二胺(BPDA-PDA)是制造超薄和超柔性神经植入物的合适材料。本研究探讨了神经植入物的电惰性成分BPDA-PDA的表面功能化。这种方法的新颖之处在于,地塞米松(DEX)与BPDA-PDA共价结合,使其能够持续释放至少9周。体外试验表明,该策略可减少巨噬细胞中促炎标志物的产生。此外,通过评估背根神经节(DRG)神经元的活力,确保了功能化材料的生物相容性。此外,DEX功能化BPDA-PDA底物的体内植入显示,装置周围形成的炎性细胞浸润和纤维化囊厚度显著降低。这些发现表明,从神经植入物的电惰性支架中局部释放DEX可能通过减轻FBR来提高其长期稳定性和性能。