Viable Vitreous Grafts of Whole Porcine Menisci for Transplant in the Knee and Temporomandibular Joints.

The shortage of suitable donor meniscus grafts from the knee and temporomandibular joint (TMJ) impedes treatments for millions of patients. Vitrification offers a promising solution by transitioning these tissues into a vitreous state at cryogenic temperatures, protecting them from ice crystal damage using high concentrations of cryoprotectant agents (CPAs). However, vitrification's success is hindered for larger tissues (>3 ml) due to challenges in CPA penetration. Dense avascular meniscus tissues require extended CPA exposure for adequate penetration; however, prolonged exposure becomes cytotoxic. Balancing penetration and reducing cell toxicity is required. To overcome this hurdle, a simulation-based optimization approach was developed by combining computational modeling with microcomputed tomography (μCT) imaging to predict three-dimensional CPA distributions within tissues over time accurately. This approach minimized CPA exposure time, resulting in 85% viability in 4-ml meniscal specimens, 70% in 10-ml whole knee menisci, and 85% in 15-ml whole TMJ menisci (i.e., TMJ disc) post-vitrification, outperforming slow-freezing methods (20%-40%). The extracellular matrix (ECM) structure and biomechanical strength of vitreous tissues remained largely intact. Vitreous meniscus grafts demonstrated clinical-level viability (≥70%), closely resembling the material properties of native tissues, with long-term availability for transplantation. The enhanced vitrification technology opens new possibilities for other avascular grafts. This article is protected by copyright. All rights reserved.