Combeau Maylis, Colitti Nina, Clauzel Julien, Desmoulin Franck, Brilhault Adrien, Fitremann Juliette, Chabbert Mickaël, Becker Matthew L, Blanquer Sébastien, Robert Lorenne, Parny Melissa, Raymond-Letron Isabelle, Cirillo Carla, Loubinoux Isabelle
Univ Toulouse, Inserm, ToNIC, Toulouse, France.
SOFTMAT Chemistry of Colloids, Polymers & Complex Assemblies, CNRS, Toulouse, France.
Regen Ther. 2025 Aug 19;30:641-655. doi: 10.1016/j.reth.2025.08.008. eCollection 2025 Dec.
Brain regeneration after injury is a challenge being tackled by numerous therapeutic strategies in pre-clinical development. There is growing interest in scaffolds implanted in brain lesions. Developments in 3D printing offer the possibility of designing complex structures of varying compositions adapted to tissue anatomy.
This feasibility study assessed the cerebral biocompatibility of four bioeliminable Digital Light Processing (DLP) printed materials in the rat model: gelatin methacrylate (GelMA), poly(ethylene glycol)diacrylate (PEGDA) mixed with GelMA (PEGDA-GelMA), poly(trimethylene carbonate) trimethacrylate (PTMC-tMA) and an ABA triblock copolymer of polypropylene fumarate-b-poly γ-methyl ε-caprolactone-b-polypropylene fumarate (P(PF-MCL-PF)). Their tolerance was compared to that of polydioxanone Ethicon (PDSII), a neurosurgery suture component commonly used in clinical practice. A one-month MRI and behavioral follow-up aided in safety assessment.
High-resolution T2 MRI imaging effectively captured the scaffold structures and demonstrated its non-invasive utility in monitoring degradability. PDSII served as a control of the acceptable inflammatory response to implantable foreign bodies. GelMA, PEGDA-GelMA and PTMC-tMA did not affect the permissive glial barrier, promoted cell migration, and neovascularization without additional perilesional microglial inflammation (median mean of 6.5 %, compared to 8.2 % for the PDSII control). However, the GelMA scaffold core was not colonized and allowed a limited neuronal progenitors recruitment. The rigidity of PTMC-tMA facilitated insertion, but posed histological issues. The brain hardly reacted to the P(PF-MCL-PF).
All these materials can serve as a basis for brain regeneration. PEGDA-GelMA emerged as a promising candidate for intracerebral implantation, combining biophysical and bioprinting advantages while maintaining an acceptable level of inflammation compared with clinically used suture, paving the way for innovative therapies.
损伤后脑再生是临床前开发中众多治疗策略所面临的一项挑战。人们对植入脑损伤部位的支架越来越感兴趣。3D打印技术的发展使得设计适应组织解剖结构、具有不同成分的复杂结构成为可能。
本可行性研究在大鼠模型中评估了四种生物可消除的数字光处理（DLP）打印材料的脑生物相容性：甲基丙烯酸明胶（GelMA）、与GelMA混合的聚乙二醇二丙烯酸酯（PEGDA-GelMA）、聚碳酸三亚甲基酯三甲基丙烯酸酯（PTMC-tMA）以及富马酸聚丙烯酯-b-聚γ-甲基ε-己内酯-b-富马酸聚丙烯酯的ABA三嵌段共聚物（P(PF-MCL-PF)）。将它们的耐受性与聚二氧六环乙二酮（PDSII）（一种临床实践中常用的神经外科缝合组件）进行比较。为期一个月的磁共振成像（MRI）和行为随访有助于安全性评估。
高分辨率T2 MRI成像有效地捕捉到了支架结构，并证明了其在监测降解性方面的非侵入性用途。PDSII作为对可植入异物可接受炎症反应的对照。GelMA、PEGDA-GelMA和PTMC-tMA不影响许可性胶质屏障，促进细胞迁移和新血管形成，且病变周围无额外的小胶质细胞炎症（中位平均值为6.5%，而PDSII对照为8.2%）。然而，GelMA支架核心未被定植，且允许有限的神经元祖细胞募集。PTMC-tMA的刚性便于插入，但存在组织学问题。大脑对P(PF-MCL-PF)几乎没有反应。
所有这些材料都可作为脑再生的基础。PEGDA-GelMA作为脑内植入的一个有前景的候选材料脱颖而出，它结合了生物物理和生物打印优势，同时与临床使用的缝线相比保持了可接受的炎症水平，为创新疗法铺平了道路。
