Development of Acellular Matrix-Based Bioprinted Scaffold for Inferior Alveolar Nerve Regeneration.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Neuroscience

Background:

• Inferior alveolar nerve (IAN) injuries, often caused by trauma or surgery, result in significant sensory deficits and limited recovery due to the nerve's anatomical constraints.
• Current treatments for IAN injuries provide only partial functional recovery, necessitating the development of advanced therapeutic strategies.
• The mandibular canal restricts natural nerve regeneration, highlighting the need for innovative approaches to bridge nerve gaps and promote healing.

Purpose of the Study:

• To develop and evaluate a 3D-bioprinted scaffold for enhanced inferior alveolar nerve (IAN) regeneration.
• To assess the biocompatibility and regenerative potential of a novel scaffold composed of alginate, methylcellulose, and Schwann cell-derived acellular matrix (Alg/MC/ACM).
• To investigate the efficacy of the Alg/MC/ACM scaffold in promoting neural repair in an in vivo rat model of IAN injury.

Main Methods:

• Fabrication of a 3D-bioprinted scaffold using alginate, methylcellulose, and Schwann cell-derived acellular matrix (Alg/MC/ACM).
• Characterization of scaffold properties including mechanical stability, printability, rheology, and proteomic analysis of ACM.
• In vitro assessment of cytocompatibility using rat Schwann (RSC96) and neuronal (PC12) cells via MTT and Live/Dead assays.
• In vivo evaluation in a rat model of inferior alveolar nerve (IAN) crush injury, assessing behavioral recovery, cellular infiltration, axonal organization, and remyelination through histological staining.

Main Results:

• The Alg/MC/ACM hydrogel exhibited favorable mechanical stability, printability, and shear-thinning properties.
• In vitro studies demonstrated that Alg/MC/ACM2 significantly enhanced Schwann cell and neuronal cell proliferation and viability compared to controls.
• In vivo implantation of Alg/MC/ACM2 scaffolds in a rat IAN crush injury model led to improved behavioral responses and promoted axonal regeneration and remyelination.

Conclusions:

• The incorporation of Schwann cell-derived acellular matrix into alginate/methylcellulose scaffolds creates a bioactive microenvironment conducive to neural regeneration.
• The 3D-bioprinted Alg/MC/ACM scaffolds represent a promising therapeutic strategy for promoting inferior alveolar nerve (IAN) repair and functional recovery.
• This study provides the first evidence for the potential of these novel bioprinted scaffolds in addressing the challenges of IAN regeneration.