Novel biological/biohybrid prostheses for the ossicular chain: fabrication feasibility and preliminary functional characterization

Abstract

Alternatives for ossicular replacements were fabricated in order to overcome persisting rejections in middle ear prosthetization. Unlike the synthetic prostheses in fashion, we propose biological and biohybrid replacements containing extra cellular matrix (ECM) molecules to improve biointegration. In this study, ECM-containing devices shaped as Partial Ossicular Replacement Prostheses (PORPs) were fabricated reproducing the current synthetic models. Biological PORPs were obtained from human decellularized cortical bone allografts by computer numerically controlled ultraprecision micromilling. Moreover, porous PORP-like scaffolds were produced and cultured with osteoinduced human mesenchymal stromal cells to generate in vitro bone ECM within the scaffold porosity (biohybrid PORPs). The acoustic responses of such devices were investigated and compared to those of commercial prostheses. Results showed that biological PORPs transmit mechanical signals with appropriate frequencies, amplitudes, and with early extinction time. Although signal transmission in biohybrid PORPs showed insufficient amplitude, we believe that tissue engineered constructs represent the new challenge in ossiculoplasty.

Histologic Characterization of Human Ear Ossicles for the Development of Tissue-Engineered Replacements

“…As an alternative to prosthetics or autografting, we have recently proposed a tissue engineering approach, which theoretically combines the most favorable aspects of both synthetic and biological materials (8,11). Indeed, because biohybrid replacements (i.e., the MSC/scaffold constructs) contain autologous living cells and ECM molecules, they might enhance device biointegration with the ME.…”

“…Owing to these considerations, our in vitro model was based on the osteogenic commitment of human MSCs on PORP-shaped porous scaffolds containing a mesenchymal ECM, pregenerated by the MSCs by a preliminary culture step. This biomimetic strategy ensures cellularity and expression of ECM molecules, extracellular collagen type I and mineralization higher than those obtained with traditional culture methods (8,11); however, how far is this from targeting ossicular bone regeneration? FIG.…”

“…In recent years, our group has faced these problems by means of different strategies that combine the best favorable aspects of synthetic and biologic substitutes (8). One of these is the fabrication of ''out-of-the shelf'' preformed OC prostheses from the banked femoral bone (9).…”

“…In the last decade, expectations about the pivotal role of TE in ME have been hypothesized (10); in this respect, TE devices could combine the best favorable aspects of both autologous (e.g., total biocompatibility, self-remodeling) and synthetic replacements (e.g., shape-reproducibility, controlled bioresorption). In preliminary studies, we have developed the first biohybrid OC substitutes, showing that the in vitro regeneration of TE PORPs is approachable, owing to the small size of these replacements (8,11). Recently, the use of biomimetic in vitro strategies has been promoted by the TE community to regenerate mature tissues from immature cells, such as the mesenchymal stem cells (MSCs) (12).…”

Good Manufacturing Practices—Grade Preformed Ossicular Prostheses from Banked Bone via Computer Numerically Controlled Micromilling

“…14 The aim of this study was the fabrication of ossicular replacement prostheses (ORPs) from decellularized banked cortical bone via computer numerically controlled (CNC) ultraprecision micromilling, such as preformed clinical-grade products, with shape, size, and details perfectly comparable to those of hydroxyapatite devices. 14 The aim of this study was the fabrication of ossicular replacement prostheses (ORPs) from decellularized banked cortical bone via computer numerically controlled (CNC) ultraprecision micromilling, such as preformed clinical-grade products, with shape, size, and details perfectly comparable to those of hydroxyapatite devices.…”