Project Summary
Approximately 10-25% of the population has degeneration of the temporomandibular joint (TMJ) condyle.
Cartilage does not heal itself, and there are no mid-stage interventions to prevent condylar degeneration which
can lead to life-threatening conditions such as changes to the airway. This proposal aims to improve translation
of tissue engineering strategies for TMJ condylar regeneration toward human use in the clinic via characterization
of the mandibular condyle of the Yucatan minipig, engineering neocartilage-bone implants with robust interfacial
properties, and in vivo studies using neocartilage-bone implants to regenerate osteochondral defects of the TMJ
condyle. Preliminary proteomics data show that spatial distributions of collagen types I and II can be achieved
using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), indicators of
fibrocartilage and hyaline articular cartilage, respectively. MALDI-IMS will serve as a powerful tool in a
characterization of the Yucatan minipig mandibular condyle, including the spatial distributions of collagen types
I, II, X, and XXVII. This characterization will provide gold standards for tissue-engineering approaches to treat
condylar defects. Preliminary ex vivo experiments indicate a high feasibility of creating osteochondral defects on
the TMJ condyle. Through these novel techniques, I will enhance tissue-engineering approaches for TMJ
condyle regeneration in three specific aims. In Specific Aim 1, many techniques, including MALDI-IMS, will be
used to characterize the TMJ condyle of the Yucatan minipig. This characterization will result in gold standard
values for engineered tissues. In Specific Aim 2, a novel tissue-engineering technique involving seeding of
mesenchymal stem cells into decellularized bone scaffolds, then combining with self-assembled neocartilage,
will be interrogated. This will result in the formation of neocartilage-bone implants with robust interfacial
properties for long term in vivo efficacy. Finally, in Specific Aim 3, neocartilage-bone implants will be used in a
large animal study, where they will regenerate defects of the Yucatan minipig TMJ condyle. Successful
completion of this proposal will enhance the translation of tissue engineering strategies for TMJ disorders toward
the FDA paradigm of clinical trials and human use in the clinic.