{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:24:36Z","timestamp":1793298276165,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioTech"],"abstract":"<jats:p>Neurosurgery is undergoing a significant transformation driven by advances in biomaterials and tissue engineering. These interdisciplinary innovations address challenges in repairing and regenerating neural tissues, integrating cranial and spinal implants, and improving patient outcomes. The incidence of neurological injuries such as traumatic brain injury and spinal cord injury remains high, underscoring the need for improved therapeutic strategies. This review provides a comprehensive overview of current biomaterial and tissue engineering approaches in neurosurgery, highlighting developments in neural tissue repair, cranial and spinal implants, spinal cord injury treatment, and peripheral nerve regeneration. Key challenges\u2014such as ensuring biocompatibility, modulating the immune response, and bridging the gap between laboratory research and clinical application\u2014are discussed. Emerging technologies including 3D bioprinting, nanotechnology (removing microfluidics), and microfluidics are examined for their potential to revolutionize neurosurgical treatments. The need for interdisciplinary collaboration among neurosurgeons, material scientists, and biologists is emphasized as critical for overcoming translational barriers and accelerating the clinical translation of these promising technologies.<\/jats:p>","DOI":"10.3390\/biotech14030065","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T14:43:18Z","timestamp":1756219398000},"page":"65","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biomaterials and Tissue Engineering in Neurosurgery: Current Innovations and Future Directions"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5524-246X","authenticated-orcid":false,"given":"Jago\u0161","family":"Golubovi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia"},{"name":"Department of Neurosurgery, University Clinical Centre of Vojvodina, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0555-6089","authenticated-orcid":false,"given":"Damjan","family":"Vu\u010durovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Technology Novi Sad, University of Novi Sad, Bulevar Cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liao, W., Shi, Y., Li, Z., and Yin, X. (2025). Advances in 3D printing combined with tissue engineering for nerve regeneration and repair. J. Nanobiotechnol., 23.","DOI":"10.1186\/s12951-024-03052-9"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hammam, I.A., Winters, R., and Hong, Z. (2024). Advancements in the Application of Biomaterials in Neural Tissue Engineering: A Review. Biomed. Eng. Adv., 8.","DOI":"10.1016\/j.bea.2024.100132"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zeng, C.-W. (2023). Advancing Spinal Cord Injury Treatment through Stem Cell Therapy: A Comprehensive Review of Cell Types, Challenges, and Emerging Technologies in Regenerative Medicine. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814349"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Krishani, M., Shin, W.Y., Suhaimi, H., and Sambudi, N.S. (2023). Development of Scaffolds from Bio-Based Natural Materials for Tissue Regeneration Applications: A Review. Gels, 9.","DOI":"10.3390\/gels9020100"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.actbio.2020.05.042","article-title":"Interpenetrating polymer networks of collagen, hyaluronic acid, and chondroitin sulfate as scaffolds for brain tissue engineering","volume":"112","author":"Li","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mishchenko, T.A., Klimenko, M.O., Kuznetsova, A.I., Yarkov, R.S., Savelyev, A.G., Sochilina, A.V., Mariyanats, A.O., Popov, V.K., Khaydukov, E.V., and Zvyagin, A.V. (2022). 3D-printed hyaluronic acid hydrogel scaffolds impregnated with neurotrophic factors (BDNF, GDNF) for post-traumatic brain tissue reconstruction. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.895406"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hasanzadeh, E., Seifalian, A., Mellati, A., Saremi, J., Asadpour, S., Enderami, S.E., Nekounam, H., and Mahmoodi, N. (2023). Injectable hydrogels in central nervous system: Unique and novel platforms for promoting extracellular matrix remodeling and tissue engineering. Mater. Today Bio, 20.","DOI":"10.1016\/j.mtbio.2023.100614"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mohammadzadeh, V., Atapour-Mashhad, H., Shahvali, S., Salehi, B., Shaban, M., Shirzad, M., Salahvarzi, A., and Mohammadi, M. (2025). Hydrogels as advanced drug delivery platforms for cancer immunotherapy: Promising innovations and future outlook. J. Nanobiotechnol., 23.","DOI":"10.1186\/s12951-025-03613-6"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Modo, M. (2019). Bioscaffold-Induced Brain Tissue Regeneration. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01156"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, X., Zhang, Q., Luo, Z., Yan, S., and You, R. (2019). Biofunctionalized silk fibroin nanofibers for directional and long neurite outgrowth. Biointerphases, 14.","DOI":"10.1063\/1.5120738"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4103\/1673-5374.289436","article-title":"Laminin-coated multifilament entubulation, combined with Schwann cells and glial cell line-derived neurotrophic factor, promotes unidirectional axonal regeneration in a rat model of thoracic spinal cord hemisection","volume":"16","author":"Xu","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111858","DOI":"10.1016\/j.msec.2020.111858","article-title":"Biomimetic electrospun tubular PLLA\/gelatin nanofiber scaffold promoting regeneration of sciatic nerve transection in SD rat","volume":"121","author":"Niu","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M.R., Shariatzadeh, S., Bahrami, S., and Niknejad, H. (2023). Immunogenicity of decellularized extracellular matrix scaffolds: A bottleneck in tissue engineering and regenerative medicine. Biomater. Res., 27.","DOI":"10.1186\/s40824-023-00348-z"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Mungenast, L., Nieminen, R., Gaiser, C., Faia-Torres, A.B., R\u00fche, J., and Suter-Dick, L. (2023). Electrospun decellularized extracellular matrix scaffolds promote the regeneration of injured neurons. Biomater. Biosyst., 11.","DOI":"10.1016\/j.bbiosy.2023.100081"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Xiang, Z., Guan, X., Ma, Z., Shi, Q., Panteleev, M., and Ataullakhanov, F.I. (2023). Bioactive fibrous scaffolds with programmable release of polypeptides regulate inflammation and extracellular matrix remodeling. Regen. Biomater., 10.","DOI":"10.1093\/rb\/rbad010"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cong, Y., Wang, Y., Yuan, T., Zhang, Z., Ge, J., Meng, Q., Li, Z., and Sun, S. (2023). Macrophages in aseptic loosening: Characteristics, functions, and mechanisms. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1122057"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12967-020-02688-z","article-title":"Titanium-interlayer mediated hydroxyapatite coating on polyetheretherketone: A prospective study in patients with single-level cervical degenerative disc disease","volume":"19","author":"Zhu","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Frankenberger, T., Graw, C.L., Engel, N., Gerber, T., Frerich, B., and Dau, M. (2021). Sustainable Surface Modification of Polyetheretherketone (PEEK) Implants by Hydroxyapatite\/Silica Coating\u2014An In Vivo Animal Study. Materials, 14.","DOI":"10.3390\/ma14164589"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"444","DOI":"10.31616\/asj.2023.0407","article-title":"Innovative Developments in Lumbar Interbody Cage Materials and Design: A Comprehensive Narrative Review","volume":"18","author":"Chang","year":"2024","journal-title":"Asian Spine J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1097\/SCS.0000000000010064","article-title":"Polyetheretherketone Implant Cranioplasty for Large Cranial Defects: A Seven-Year Follow-Up","volume":"35","author":"Sanchez","year":"2024","journal-title":"J. Craniofacial Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1016\/j.stemcr.2023.03.016","article-title":"Human iPSC-derived neural progenitor cells secreting GDNF provide protection in rodent models of ALS and retinal degeneration","volume":"18","author":"Laperle","year":"2023","journal-title":"Stem Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yang, L., Liu, S.-C., Liu, Y.-Y., Zhu, F.-Q., Xiong, M.-J., Hu, D.-X., and Zhang, W.-J. (2024). Therapeutic role of neural stem cells in neurological diseases. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1329712"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Aranaz, I., Acosta, N., Revuelta, J., Bastida, A., G\u00f3mez-Casado, V., Civera, C., Garrido, L., Garc\u00eda-Junceda, E., Heras, \u00c1., and Alc\u00e1ntara, A.R. (2023). Fast and Sustained Axonal Growth by BDNF Released from Chitosan Microspheres. Mar. Drugs, 21.","DOI":"10.3390\/md21020091"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1097\/01.SCS.0000436700.65891.3b","article-title":"Combination of Chondroitinase ABC, Glial Cell Line\u2013Derived Neurotrophic Factor and Nogo A Antibody Delayed-Release Microspheres Promotes the Functional Recovery of Spinal Cord Injury","volume":"24","author":"Zhang","year":"2013","journal-title":"J. Craniofacial Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1021\/acsbiomaterials.0c00023","article-title":"Neurotrophin-3-Loaded Multichannel Nanofibrous Scaffolds Promoted Anti-Inflammation, Neuronal Differentiation, and Functional Recovery after Spinal Cord Injury","volume":"6","author":"Sun","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"322","DOI":"10.3390\/biomechanics3030028","article-title":"Stem Cell Scaffolds for the Treatment of Spinal Cord Injury\u2014A Review","volume":"3","author":"Hey","year":"2023","journal-title":"Biomechanics"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gao, Y., Wang, Y., Wu, Y., and Liu, S. (2024). Biomaterials targeting the microenvironment for spinal cord injury repair: Progression and perspectives. Front. Cell. Neurosci., 18.","DOI":"10.3389\/fncel.2024.1362494"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2603048","DOI":"10.34133\/2020\/2603048","article-title":"Construction of Dual-Biofunctionalized Chitosan\/Collagen Scaffolds for Simultaneous Neovascularization and Nerve Regeneration","volume":"2020","author":"Li","year":"2020","journal-title":"Research"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fornasari, B.E., Carta, G., Gambarotta, G., and Raimondo, S. (2020). Natural-Based Biomaterials for Peripheral Nerve Injury Repair. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.554257"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lazarevic, M., Petrovic, S., Pierfelice, T.V., Ignjatovic, N., Piattelli, A., Tovilovic, T.V., and Radunovic, M. (2023). Antimicrobial and Osteogenic Effects of Collagen Membrane Decorated with Chitosan\u2013Nano-Hydroxyapatite. Biomolecules, 13.","DOI":"10.3390\/biom13040579"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41536-021-00174-8","article-title":"Nerve-specific extracellular matrix hydrogel promotes functional regeneration following nerve gap injury","volume":"6","author":"Meder","year":"2021","journal-title":"NPJ Regen. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhang, M., An, H., Wan, T., Jiang, H.-R., Yang, M., Wen, Y.-Q., and Zhang, P.-X. (2023). Micron track chitosan conduit fabricated by 3D-printed model topography provides bionic microenvironment for peripheral nerve regeneration. Int. J. Bioprinting, 9.","DOI":"10.18063\/ijb.770"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.4103\/1673-5374.300458","article-title":"Collagen\/heparan sulfate porous scaffolds loaded with neural stem cells improve neurological function in a rat model of traumatic brain injury","volume":"16","author":"Zhang","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Xu, J., and Hsu, S.-h. (2023). Self-healing hydrogel as an injectable implant: Translation in brain diseases. J. Biomed. Sci., 30.","DOI":"10.1186\/s12929-023-00939-x"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Licciardello, M., Traldi, C., Bortolameazzi, M., Testore, D., Ciardelli, G., and Tonda-Turo, C. (2024). Aligned polycaprolactone\/polyaniline electrospun nanofibers for directing neural stem cell differentiation and neuron arrangement. Front. Biomater. Sci., 3.","DOI":"10.3389\/fbiom.2024.1362599"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2100107","DOI":"10.1002\/adhm.202100107","article-title":"Substance P\/Heparin-Conjugated PLCL Mitigate Acute Gliosis on Neural Implants and Improve Neuronal Regeneration via Recruitment of Neural Stem Cells","volume":"10","author":"Kim","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1039\/D4BM00848K","article-title":"Advances in implants and bone graft types for lumbar spinal fusion surgery","volume":"12","author":"Cheers","year":"2024","journal-title":"Biomater. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"da Silva, V.A., Bobotis, B.C., Correia, F.F., Lima-Vasconcellos, T.H., Chiarantin, G.M.D., De La Vega, L., Lombello, C.B., Willerth, S.M., Malmonge, S.M., and Paschon, V. (2023). The Impact of Biomaterial Surface Properties on Engineering Neural Tissue for Spinal Cord Regeneration. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713642"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"041001","DOI":"10.1088\/1741-2552\/ad628d","article-title":"Scaffold design considerations for peripheral nerve regeneration","volume":"21","author":"Yu","year":"2024","journal-title":"J. Neural Eng."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Liu, Z., Liu, Y., Yushan, M., and Yusufu, A. (2022). Enhanced Nerve Regeneration by Bionic Conductive Nerve Scaffold Under Electrical Stimulation. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.810676"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Toader, C., Eva, L., Tataru, C.-I., Covache-Busuioc, R.-A., Bratu, B.-G., Dumitrascu, D.-I., Costin, H.P., Glavan, L.-A., and Ciurea, A.V. (2023). Frontiers of Cranial Base Surgery: Integrating Technique, Technology, and Teamwork for the Future of Neurosurgery. Brain Sci., 13.","DOI":"10.3390\/brainsci13101495"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Villanueva-Flores, F., Garcia-Atutxa, I., Santos, A., and Armendariz-Borunda, J. (2023). Toward a New Generation of Bio-Scaffolds for Neural Tissue Engineering: Challenges and Perspectives. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061750"},{"key":"ref_43","first-page":"255","article-title":"Addressing the High Costs of Stem Cell Therapies","volume":"7","author":"Yael","year":"2024","journal-title":"Stem. Cell. Res. Reg. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Farjaminejad, S., Farjaminejad, R., Hasani, M., Garcia-Godoy, F., Abdouss, M., Marya, A., Harsoputranto, A., and Jamilian, A. (2024). Advances and Challenges in Polymer-Based Scaffolds for Bone Tissue Engineering: A Path Towards Personalized Regenerative Medicine. Polymers, 16.","DOI":"10.3390\/polym16233303"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wang, G., Liu, X.J., Zhang, X.-a., and Hu, M. (2025). Advances in hyaluronic acid hydrogel for meniscus repair. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1639034"},{"key":"ref_46","unstructured":"Patel, G., and Bouchard, L.-S. (2024). Applications of aligned nanofiber for tissue engineering. arXiv."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s10856-024-06816-9","article-title":"Assessment of cranial reconstruction utilizing various implant materials: Finite element study","volume":"35","author":"Shash","year":"2024","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Feng, C., Deng, L., Yong, Y.-Y., Wu, J.-M., Qin, D.-L., Yu, L., Zhou, X.-G., and Wu, A.-G. (2023). The Application of Biomaterials in Spinal Cord Injury. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010816"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zhang, A., Zhu, S., Sun, B., Nan, C., Cong, L., Zhao, Z., and Liu, L. (2025). 3D cell-laden scaffold printed with brain acellular matrix bioink. J. Nanobiotechnol., 23.","DOI":"10.1186\/s12951-025-03644-z"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100069","DOI":"10.1016\/j.ntm.2024.100069","article-title":"Nano Delivery Systems in Stem Cell Therapy: Transforming Regenerative Medicine and Overcoming Clinical Challenges","volume":"4","author":"Rajendran","year":"2025","journal-title":"Nano TransMed."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zeng, C.-W. (2023). Multipotent Mesenchymal Stem Cell-Based Therapies for Spinal Cord Injury: Current Progress and Future Prospects. Biology, 12.","DOI":"10.3390\/biology12050653"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tai, Z., Liu, J., Wang, B., Chen, S., Liu, C., and Chen, X. (2024). The Effect of Aligned and Random Electrospun Fibers Derived from Porcine Decellularized ECM on Mesenchymal Stem Cell-Based Treatments for Spinal Cord Injury. Bioengineering, 11.","DOI":"10.3390\/bioengineering11080772"}],"container-title":["BioTech"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-6284\/14\/3\/65\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:16Z","timestamp":1760034796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-6284\/14\/3\/65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["biotech14030065"],"URL":"https:\/\/doi.org\/10.3390\/biotech14030065","relation":{},"ISSN":["2673-6284"],"issn-type":[{"value":"2673-6284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]}}}