Silk-Derived 3D-Bioprinted Scaffolds for Neural Repair and Nerve Regeneration: A Comprehensive Review

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  • Adams, Alynah J.
    • Other Affiliation: Division of Plastic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
  • Challa, Sanjana
    • Other Affiliation: Division of Plastic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
  • Yan, Cynthia
    • Other Affiliation: Medical College of Wisconsin, School of Medicine, Milwaukee, WI
  • Beltz, Isabella
    • Other Affiliation: Medical College of Wisconsin, School of Medicine, Milwaukee, WI
  • Kambol, Alexa
    • Other Affiliation: Medical College of Wisconsin, School of Medicine, Milwaukee, WI
  • Shariati, Kaavian
    • Other Affiliation: Division of Plastic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
  • Hunt, Jocelyn
    • School of Medicine
  • Thomas, Charlotte
    • Other Affiliation: Division of Plastic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
  • Schonebaum, Dorien I.
    • Other Affiliation: Division of Plastic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
  • Foppiani, Jose A.
    • Other Affiliation: Division of Plastic and Reconstructive Surgery, University of Minnesota, Minneapolis, MN
  • Choudry, Umar
    • Other Affiliation: Division of Plastic and Reconstructive Surgery, University of Minnesota, Minneapolis, MN
  • Lin, Samuel J.
    • Other Affiliation: Division of Plastic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
Abstract
  • Traumatic injuries often result in nerve tissue damage and functional deficits due to limited regeneration. Silk fibroin, a biopolymer with inherent biocompatibility and tunable properties, is a promising material for 3D-bioprinted neural tissue scaffolds. This review highlights recent advancements in silk-derived composite scaffolds, often incorporating additional materials like collagen or conductive polymers to enhance their performance. This review examines how material composition, scaffold architecture, and fabrication strategy influence biological response and functional recovery. This comprehensive review follows PRISMA guidelines and uses comprehensive searches of PubMed, MEDLINE, Embase, Web of Science, Cochrane Central, and ClinicalTrials.gov for studies published through 2025. Studies were screened for eligibility based on substance type, mechanical properties, production methods, and outcomes. Findings were synthesized qualitatively. Twelve studies were included, comprising rat (50%), canine (8.3%), and in vitro (41.7%) models. Analysis reveals that silk fibroin acts as a highly adaptable mechanical backbone. It can consistently integrate with bioactive additives (collagen, dECM) or conductive polymers (Polypyrrole, MXene) to meet specific therapeutic demands. For spinal cord injuries, composites reached a compressive modulus capable of resisting physiological pressures and preventing scaffold collapse. In soft tissue applications, silk–hydrogel blends provided localized release of exosomes and small molecules during the acute injury phase, reducing neuroinflammatory markers. Additionally, adding conductive materials allowed the scaffolds to bridge electrical gaps and promote Schwann cell proliferation and neuronal differentiation. Furthermore, 3D bioprinting enabled the creation of defined microchannels that replicate native fascicular architecture. In vivo outcomes consistently showed superior axonal regeneration, myelination, and synaptic reconnection compared to controls, correlating with significant improvements in electrophysiological and motor function. This review highlights the clinical potential of silk fibroin-based 3D-printed biomaterials for nerve regeneration, including neural repair and neural tissue engineering. More recent studies place greater emphasis on integrating mechanical, architectural, and biological considerations into scaffold design, resulting in increasingly multifunctional scaffold systems. Despite promising efficacy, the heterogeneity of fabrication methods and the predominance of rodent models highlight the need for standardized protocols and evaluations in relevant models to facilitate clinical translation.
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  • In Copyright
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  • Attribution 4.0 International
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  • Life
Journal volume
  • 16
Journal issue
  • 6
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  • 892
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  • 2075-1729
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  • Multidisciplinary Digital Publishing Institute

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