Convergent Design Principles for Functional Sensory Innervation in Bioprinted and Engineered Skin Constructs

Area of Science:

• Biomaterials Science
• Neurobiology
• Tissue Engineering

Background:

• Engineered skin often lacks functional sensory innervation, hindering neurocutaneous interactions.
• Current skin substitutes fail to replicate complex sensation, neuroimmune communication, and tissue homeostasis.
• Restoring sensory perception is a critical unmet need in skin biofabrication.

Purpose of the Study:

• To comprehensively review strategies for engineering innervated skin constructs.
• To analyze biological determinants and emerging platforms for sensory integration.
• To propose a Minimum Functional Validation Framework (MFVF) for assessing sensory competence.

Main Methods:

• Analysis of biomaterial integration, sensory neurobiology, and biofabrication technologies.
• Evaluation of multicellular co-culture systems and functional validation methodologies.
• Review of humanized platforms like induced pluripotent stem cell-derived neurons and organ-on-chip systems.

Main Results:

• Identified key biological determinants for sensory integration, including neuronal specification and neurotrophic signaling.
• Highlighted the gap between structural innervation and functional sensory performance in current approaches.
• Proposed a determinant-based framework and the MFVF for standardized validation.

Conclusions:

• Moving beyond simple neurite incorporation is essential for developing integrated neurocutaneous platforms.
• Standardized validation criteria are crucial for advancing sensory-capable skin constructs.
• The proposed framework guides experimental design for regenerative medicine and neuroprosthetic applications.