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This is in part due to poor drug efficacy to modulate neuroinflammation, angiogenesis and\/or promoting neuroprotection and is the combined result of challenges in getting drugs across the blood brain barrier, in a targeted approach. The negative impact of the injured extracellular matrix (ECM) has been identified as a factor in restricting post\u2010injury plasticity of residual neurons and is shown to reduce the functional integration of grafted cells. Therefore, new strategies are needed to manipulate the extracellular environment at the subacute phase to enhance brain regeneration. In this review, potential strategies are to be discussed for the treatment of TBI by using self\u2010assembling peptide (SAP) hydrogels, fabricated via the rational design of supramolecular peptide scaffolds, as an artificial ECM which under the appropriate conditions yields a supramolecular hydrogel. Sequence selection of the peptides allows the tuning of these hydrogels' physical and biochemical properties such as charge, hydrophobicity, cell adhesiveness, stiffness, factor presentation, degradation profile and responsiveness to (external) stimuli. This review aims to facilitate the development of more intelligent biomaterials in the future to satisfy the parameters, requirements, and opportunities for the effective treatment of TBI.<\/jats:p>","DOI":"10.1002\/advs.202303707","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T21:52:03Z","timestamp":1701294723000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Calming the Nerves via the Immune Instructive Physiochemical Properties of Self\u2010Assembling Peptide Hydrogels"],"prefix":"10.1002","volume":"11","author":[{"given":"Negar","family":"Mahmoudi","sequence":"first","affiliation":[{"name":"Laboratory of Advanced Biomaterials the John Curtin School of Medical Research Australian National University  Canberra ACT 2601 Australia"},{"name":"ANU College of Engineering &amp; Computer Science Australian National University  Canberra ACT 2601 Australia"},{"name":"The Graeme Clark Institute The University of Melbourne  Melbourne VIC 3010 Australia"},{"name":"Department of Biomedical Engineering Faculty of Engineering and Information Technology The University of Melbourne  Melbourne VIC 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmira","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Biomaterials the John Curtin School of Medical Research Australian National University  Canberra ACT 2601 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva Soltani","family":"Dehnavi","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Biomaterials the John Curtin School of Medical Research Australian National University  Canberra ACT 2601 Australia"},{"name":"ANU College of Engineering &amp; Computer Science Australian National University  Canberra ACT 2601 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilith M. 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