Reprogramming metabolic microenvironment for nerve regeneration via waterborne polylactic acid-polyurethane copolymer scaffolds

Yuan Feng; Jinlin Chen; Xiao Wang; Chao Long; Wenbo Wang; Jingjing Lin; Yuanyuan He; Yanchao Wang; Feng Luo; Zhen Li; Jiehua Li; Hong Tan

doi:10.1016/j.biomaterials.2024.122942

Reprogramming metabolic microenvironment for nerve regeneration via waterborne polylactic acid-polyurethane copolymer scaffolds

Biomaterials. 2024 Nov 1:315:122942. doi: 10.1016/j.biomaterials.2024.122942. Online ahead of print.

Authors

Yuan Feng¹, Jinlin Chen¹, Xiao Wang¹, Chao Long¹, Wenbo Wang¹, Jingjing Lin¹, Yuanyuan He¹, Yanchao Wang², Feng Luo¹, Zhen Li¹, Jiehua Li³, Hong Tan⁴

Affiliations

¹ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X Center of Materials, Sichuan University, Chengdu, 610065, China.
² Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610000, China.
³ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X Center of Materials, Sichuan University, Chengdu, 610065, China. Electronic address: jiehua_li@scu.edu.cn.
⁴ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Med-X Center of Materials, Sichuan University, Chengdu, 610065, China. Electronic address: hongtan@scu.edu.cn.

PMID: 39515191
DOI: 10.1016/j.biomaterials.2024.122942

Abstract

Cell metabolism, as the key driver of inflammation, revascularization and even subsequent tissue regeneration, is controlled by and also conversely influenced by signal transduction. Incorporation of cell metabolism into tissue engineering research holds immense potential for in-situ treatment repair and further understanding of the host-biomaterial cues in body response. In this study, an anti-inflammatory waterborne polyurethane scaffold incorporated with poly-l-lactic acid (PLLA) block was served to repair nerve injuries (LAx-WPU). Lactate was released through the degradation of LAx-WPU scaffolds, and the content increased with the addition of PLLA block over the degradation times. Thenceforth, the production of adenosine triphosphate (ATP) in primary neurons and neuronal axon growth were achieved by taking up lactate through monocarboxylate transporters (MCT2) for energy metabolism under glucose-free environment treated with LAx-WPU degradation solution. After LAx-WPU was implanted to repair brain nerve defects in rats, filamentous neurons elongation, rapid vascularization, and nerve tissue regeneration were realized up to 28 days with the positive expression of microtubule-associated protein (MAP2), β-tubulin (Tuj1), and platelet endothelial cell adhesion molecule (CD31) in the scaffolds. Results highlighted that the LAx-WPU scaffolds up-regulated not only the ATP-ADP-AMP purine metabolism compounds to mainly bridge neuroactive ligand-receptor interaction genes, cAMP pathway genes, and calcium pathway genes for neurocytes but also the ATP-GMP purine metabolism to angiogenesis in Gene Ontology (GO) analysis. Further analysis in reverse showed axonal regeneration is restrained by the inhibition of MCT2, proving LAx-WPU promoted nerve repair depended on lactate for energy. Therefore, LAx-WPU scaffolds construct an expected way to modulate the metabolic microenvironment for inducing nerve regeneration by intrinsic biomaterial metabolism cues without any bioactive factors.

Keywords: Bioenergetic-active material; Metabolism reprogramming; Nerve regeneration; Polyurethane; Tissue engineering.