In vivo biocompatibility assessment of 3D printed bioresorbable polymers for brain tissue regeneration. A feasibility study

Abstract

Introduction: The limited capacity of brain tissue to regenerate after acute injury, hampered by cell death, edema and inflammation, has led to an interest in promising and innovative approaches such as implantable regenerative scaffolds designed to improve brain plasticity. Leveraging the capabilities of bioprinting, these scaffolds can be tailored to match the intricate architecture of the brain. Methods: In this methodological study, we performed in vivo biocompatibility assessments after a brain lesion on three distinct bioeliminable or bioresorbable materials: Poly(ethylene glycol) diacrylate (PEGDA), Polycaprolactone (PCL) and a PEGDA mixed with gelatin methacrylate (PEGDA-GelMA). Results: A scaffold with a complex shape was printed with patterns, spatial resolution and porosity adapted to cerebral cortex reconstruction. In vivo evaluations were complemented by behavioral monitoring, affirming the safety of these materials. High-resolution T2 MRI imaging effectively captured scaffold structures and demonstrated their non-invasive utility in monitoring degradability. ASL MRI imaging quantified cerebral blood flow and was positively and significantly correlated with lectin immunofluorescent labeling. It may be used to non-invasively monitor progressive revascularization of implants.PEGDA produced an intense foreign-body response, encapsulated by a fibro-inflammatory barrier. On the other hand, PCL provoked a controlled inflammatory reaction and facilitated cell migration into the scaffold, although it induced a fibrotic response around PCL fibers. Conversely, the PEGDA-GelMA composite emerged as a promising candidate for intracerebral implantation. It facilitated the creation of a permissive glial layer, while also inducing neovascularization and attracting neuronal progenitors. Conclusion: Behavior, MRI monitoring and histology allowed a thorough following of biomaterial biocompatibility. The collective findings position PEGDA-GelMA as a convincing biomaterial option as a basis for treating severe brain lesions, offering new avenues in the search for effective treatments.

Keywords

• 3D printing
• Scaffold
• Central nervous system
• Tissue bioengineering
• MRI
• Brain injury