Biomaterial scaffold stiffness influences the foreign body reaction, tissue stiffness, angiogenesis and neuroregeneration in spinal cord injury

Zheng, Yifeng and Nuetzl, Maximilian and Schackel, Thomas and Chen, Jing and Weidner, Norbert and Mueller, Rainer and Puttagunta, Radhika (2025) Biomaterial scaffold stiffness influences the foreign body reaction, tissue stiffness, angiogenesis and neuroregeneration in spinal cord injury. BIOACTIVE MATERIALS, 46. pp. 134-149. ISSN 2452-199X

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Abstract

Biomaterial scaffold engineering presents great potential in promoting axonal regrowth after spinal cord injury (SCI), yet persistent challenges remain, including the surrounding host foreign body reaction and improper hostimplant integration. Recent advances in mechanobiology spark interest in optimizing the mechanical properties of biomaterial scaffolds to alleviate the foreign body reaction and facilitate seamless integration. The impact of scaffold stiffness on injured spinal cords has not been thoroughly investigated. Herein, we introduce stiffnessvaried alginate anisotropic capillary hydrogel scaffolds implanted into adult rat C5 spinal cords post-lateral hemisection. Four weeks post-implantation, scaffolds with a stiffness approaching that of the spinal cord effectively minimize the host foreign body reaction via yes-associated protein (YAP) nuclear translocation. Concurrently, the softest scaffolds maximize cell infiltration and angiogenesis, fostering significant axonal regrowth but limiting the rostral-caudal linear growth. Furthermore, as measured by atomic force microscopy (AFM), the surrounding spinal cord softens when in contact with the stiffest scaffold while maintaining a physiological level in contact with the softest one. In conclusion, our findings underscore the pivotal role of stiffness in scaffold engineering for SCI in vivo, paving the way for the optimal development of efficacious biomaterial scaffolds for tissue engineering in the central nervous system.

Item Type: Article
Uncontrolled Keywords: SUBSTRATE STIFFNESS; AXONAL REGENERATION; SCHWANN-CELLS; ORIENTATION; MECHANICS; OUTGROWTH; NETWORKS; PROMOTES; RECOVERY; GROWTH; Spinal cord injury; Alginate anisotropic capillary hydrogel; Stiffness; Foreign body reaction; Angiogenesis; Axonal regrowth; Atomic force microscopy
Subjects: 500 Science > 540 Chemistry & allied sciences
Divisions: Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie > Chair of Chemistry VI - Physical Chemistry (Solution Chemistry) > Prof. Dr. Werner Kunz
Depositing User: Dr. Gernot Deinzer
Date Deposited: 22 Apr 2026 04:33
Last Modified: 22 Apr 2026 04:33
URI: https://pred.uni-regensburg.de/id/eprint/67255

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