Objective: To evaluate if temporomandibular disorders (TMDs) are associated with genetic polymorphisms in ESR1 and ESR2, which are genes encoding oestrogen receptor alpha (ERα) and beta (ERβ). Also, we included an animal model to check if ERα and ERβ are expressed in the temporomandibular joint (TMJ) during adolescence. Materials and methods: A total of 139 teenagers and 93 adults were diagnosed according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMDs). The DNA was collected and the markers ESR1 and ERS2 were genotyped. Additionally, immunohistochemistry was performed in TMJ tissues from female Wistar rats during puberty. All data were submitted to statistical analysis with confidence interval of 95%. Results: Teenagers presented more disc displacement and arthralgia than adults (p < .05). The genetic polymorphism rs1256049 in ESR2 was associated with disc displacement (p = .040; OR = 10.50/95%CI 1.17–98.74) and arthralgia (p = .036; OR = 7.20/95%CI 1.10–46.88) in adults. The ERα and ERβ are expressed in rat TMJ tissues. Conclusions: We provide evidence that ESR2 is associated with TMD and could be a genetic marker for this condition in adult women. Furthermore, oestrogens receptors are presented in TMJ of adolescent female rats.

More than 500,000 bone grafting procedures are performed annually in the USA. Considering the significant limitations of available bone grafts, we previously invented a phase-separation technology to generate nanofibrous poly(l-lactic acid) (PLLA) scaffolds that mimic the bone matrix collagen in nanofiber geometry and enhance bone regeneration. Here we report the development of nanofibrous scaffolds with covalently attached synthetic peptides that mimic native collagen peptides to activate the two main collagen receptors in bone cells, discoidin domain receptor 2 (DDR2) and β1 integrins. We synthesized a PLLA-based graft-copolymer to enable covalent peptide conjugation via a click reaction. Using PLLA and the graft-copolymer, we developed 3D scaffolds with interconnected pores and peptides-containing nanofibers to activate DDR2 and β1 integrins of osteogenic cells. The degradation rate and mechanical properties of the scaffolds are tunable. The peptides-decorated nanofibrous scaffolds demonstrated 7.8 times more mineralized bone regeneration over the control scaffolds without the peptides in a critical-sized bone defect regeneration model after 8 weeks of implantation, showing a synergistic effect of the two peptides. This study demonstrates the power of scaffolds to mimic ECM at both nanometer and molecular levels, activating cell surface receptors to liberate the innate regenerative potential of host stem/progenitor cells.

The temporomandibular joint (TMJ), essential for jaw movements, is susceptible to osteoarthritis, impacting a significant portion of the population. This study introduces an innovative genetic mouse model to explore TMJ development, maintenance, and interactions with the mechanical environment. We exploited Evc2/Limbin conditional KO (Evc2 cKO) mice, specifically targeting neural crest cell-derived tissues (Wnt1Cre), to observe TMJ development. Disruption of Evc2 in neural crest cells contributed to morphological changes in the TMJ growth plate cartilage layers, predisposing the joint components to defects. Condyle defective regions presented a unique environment composed of cartilage, bone, stem cells, and an augmented polymorphic layer. Our findings further revealed that the Evc2 cKO mice presented TMJ components degeneration clinically like those observed in human TMJ-osteoarthritis (OA). Mandible condyle gene expression analysis showed augmented expression of general inflammatory and OA markers. Supplying the mice with regular chow worsens the phenotype, but soft chow fed partially rescued both condyle morphology and intra-articular space. The data suggest that changes in the loading environment critically affect the integrity and functionality of the TMJ, with direct implications for its preservation and disease management.

Bone, cartilage, and their composites in various joints are the most important components that form the skeletal structure and enable motion and movements of the body. Their disease and/or loss are most debilitating and afflict millions of Americans, reducing productivity and deteriorating quality of life. Due to limited treatments, scientists, engineers, and clinical doctors are investigating new tissue engineering solutions. In tissue engineering approaches, scaffolds are artificially designed temporary matrices that accommodate stem/progenitor cells and provide both physical and biological signals to guide cell differentiation and 3D tissue regeneration but eventually degrade and leave behind regenerated functional tissues or organs. Therefore, scaffolds often substantially benefit from mimicking certain features of the natural extracellular matrix (ECM) and designing certain engineered features to facilitate cell repopulation, mass transportation, and mechanical and biological cues for cells to regenerate tissue. This review article focuses on the design, synthesis, fabrication, and functionalization of nanofibrous materials to mimic the ECM, deliver biological signals, and integrate various engineering design features such as pore shape, size, connectivity, tissue architectures, and anatomic tissue/organ shapes to guide 3D tissue regeneration. In addition to biological and physical principles of scaffold design and fabrication, we also provide several examples of specific applications of these advanced nanofibrous scaffolds for bone, cartilage, and their associated composite tissue regeneration in osteochondral defects. We also discuss the interdisciplinary and multidisciplinary nature of these research directions, the importance of collaborations across disciplines, and the perspectives of future developments in the field.