Clinically-sized biohybrid ossicular scaffolds: toward restoring native mechano-acoustic function of middle ear

This is the authors' abstract. We don't add key points for this paper.

Conductive hearing loss affects millions of individuals worldwide and frequently arises from degeneration or disruption of the ossicular chain (OC). Current reconstructive strategies rely on autologous grafts or alloplastic prostheses, yet complications such as graft resorption, prosthesis extrusion and limited long-term hearing restoration remain unresolved. Here, we propose a tissue-engineered approach to regenerate bone-like ossicular replacements by combining in vitro produced osseous extracellular matrix with mechanically and acoustically optimized polymer scaffolds. Using fused deposition modeling, we fabricated porous, anatomically relevant OC scaffolds (“nail-shaped”; stem: 2.2-mm diameter, 4-mm length; head: 3.5-mm diameter, 0.8-mm height) capable of supporting human mesenchymal stem cell attachment and osteogenic differentiation under clinically compliant conditions. The OC constructs exhibited consistent bone matrix deposition in vitro and achieved native mechano-acoustic transmission in human cadaveric ears, with no average loss below about 4 kHz and approximately 10 dB loss at 10 kHz. This work demonstrates the feasibility of acoustically-functional replacements and may establish a translational framework for next-generation biomimetic implants in middle ear reconstruction.