1. Human Adipose Tissue Lysate-Based Hydrogel for Lasting Immunomodulation to Effectively Improve Spinal Cord Injury Repair.
- Author
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Wang Y, Chai YQ, Cai J, Huang SS, Wang YF, Yuan SS, Wang JL, Shi KQ, and Deng JJ
- Subjects
- Humans, Mice, Animals, Neurons metabolism, Macrophages metabolism, Anti-Inflammatory Agents therapeutic use, Hydrogels pharmacology, Spinal Cord Injuries drug therapy
- Abstract
The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 10
5 /100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration., (© 2023 Wiley‐VCH GmbH.)- Published
- 2024
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