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  • Review Article
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Biology-driven material design for ischaemic stroke repair

Nature Reviews Bioengineering volume 2, pages 44–63 (2024)Cite this article

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Abstract

Ischaemic stroke remains a leading cause of disability, with current clinical treatment options mainly focusing on mitigating immediate damage. The limited self-renewing capacity of the brain hinders tissue regeneration and prevents full recovery for many patients. However, the injury environment also creates an opportunity for biomaterials to promote inherently reparative phenomena, such as angiogenesis, axonal sprouting and synaptogenesis, and ultimately achieve functional recovery. In this Review, we summarize the dynamic temporal stages of repair following ischaemic stroke that facilitate neural plasticity and outline key physiological phenomena that participate to functional recovery. We then discuss the design of biomaterials, such as injectable hydrogels and granular materials, that can engage and modulate these pro-repair mechanisms in the brain. Such biomaterials can also be engineered to deliver therapeutics, such as proteins, peptides and extracellular vesicles, and provide electrical stimulation. Finally, we outline key challenges that remain to be addressed to translate the preclinical success of biomaterial-based treatment strategies to the clinic.

Key points

  • Ischaemic stroke occurs if a blood vessel in the brain is obstructed, preventing blood flow to the brain, which creates a localized area of tissue necrosis known as the infarct.

  • Stroke is a leading cause of long-term disability, affecting more than half of survivors who are 65 years and older.

  • To improve repair after ischaemic stroke and promote functional improvement, therapies must alter endogenous inhibitory structures while promoting endogenous remodelling phenomena in and surrounding the infarct tissue.

  • The subacute time window (~3 months post incidence in humans) provides a period of high endogenous neural plasticity, offering an opportunity for therapeutic interventions.

  • Biomaterial therapies can rehabilitate the infarct environment towards reparative phenomena by delivering therapeutic molecules and by acting as mechanotransducive cues.

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Fig. 1: Temporal healing of ischaemic stroke and preclinical stroke models.
Fig. 2: Subacute phase of ischaemic stroke.
Fig. 3: Biomaterials for ischaemic stroke repair.
Fig. 4: New directions for biomaterial-based ischaemic stroke treatments.

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Acknowledgements

The authors thank K. Erning and K. Wilson for helpful discussions during the preparation of this article. This work was funded in part by the National Institutes of Health (RO1NS079691-08 & R01 NS112940-03). E.M.R. acknowledges funding from the University of California, Los Angeles Council Diversity Fellowship and Brain Research Institute Neuroscience Scholarships as well as the Achievement Rewards for College Scientists Scholarship.

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  1. These authors contributed equally: Nhi V. Phan, Elle M. Rathbun.

Authors and Affiliations

  1. Department of Biomedical Engineering, Duke University, Durham, NC, USA

    Nhi V. Phan, Yunxin Ouyang & Tatiana Segura

  2. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Elle M. Rathbun & S. Thomas Carmichael

  3. Department of Neurology, Duke University, Durham, NC, USA

    Tatiana Segura

  4. Department of Dermatology, Duke University, Durham, NC, USA

    Tatiana Segura

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Contributions

N.V.P. and E.M.R. contributed equally. N.V.P., E.M.R., Y.O., T.S. and S.T.C. wrote, edited and reviewed the article prior to submission. All authors contributed to the discussion.

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Phan, N.V., Rathbun, E.M., Ouyang, Y. et al. Biology-driven material design for ischaemic stroke repair. Nat Rev Bioeng 2, 44–63 (2024). https://doi.org/10.1038/s44222-023-00117-6

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