Chronic lower back pain is the leading cause of disability worldwide, generating a socioeconomic cost of over $100 billion annually in the United States. Among the prominent causes of low back pain (LBP) is degeneration of the intervertebral disk (IVD), a condition known as degenerative disk disease (DDD). Despite the prevalence of DDD and multiple studies demonstrating its relationship with LBP, the mechanisms by which it contributes to pain remain unknown.
View Article and Find Full Text PDFPeripheral nerve injuries represent the most common type of nervous system injuries, resulting in 5 million injuries per year. Current gold standard, autografts, still carry several limitations, including the inappropriate type, size, and function matches in grafted nerves, lack of autologous donor sites, neuroma formation, and secondary surgery incisions. Polymeric nerve conduits, also known as nerve guides, can help overcome the aforementioned issues that limit nerve recovery and regeneration by reducing tissue fibrosis, misdirection of regenerating axons, and the inability to maintain long- distance axonal growth.
View Article and Find Full Text PDFBackground: The Restoring Joint Health and Function to Reduce Pain (RE-JOIN) Consortium is part of the Helping to End Addiction Long-term® (HEAL) Initiative. HEAL is an ambitious, NIH-wide initiative to speed scientific solutions to stem the national opioid public health crisis. The RE-JOIN consortium's over-arching goal is to define how chronic joint pain-mediating neurons innervate different articular and -articular tissues, with a focus on the knee and temporomandibular joints (TMJ) across species employing the latest neuroscience approaches.
View Article and Find Full Text PDF. Engineered nerve conduits must simultaneously enhance axon regeneration and orient axon extension to effectively restore function of severely injured peripheral nerves. The dental pulp contains a population of stem/progenitor cells that endogenously express neurotrophic factors (NTFs), growth factors known to induce axon repair.
View Article and Find Full Text PDFThe objectives of this study were to compare the chondrogenic potential of cells derived from different layers of Mandibular condyle cartilage and to gain further understanding of the impact of chondrogenic cues when embedded into a novel hydrogel scaffold (PGH, a polymer blend of poly (ethylene glycol), gelatin, and heparin) compared to a gelatin hydrogel scaffold (GEL). Cartilage layer cells (CLCs) and fibroblastic superficial layer cells (SLCs) were harvested from the mandibular condyle of boer goats obtained from a local abattoir. After expansion, cells were seeded into PGH and GEL hydrogels and cultured in chondrogenic media for 3 weeks.
View Article and Find Full Text PDFTemporomandibular joint (TMJ) Meniscus removal is an option for the patient to regain full range of motion if the disc is irreversibly damaged or unable to be reduced. However, this procedure leaves the joint vulnerable to condylar remodeling and degeneration. We have shown that extracellular matrix (ECM) scaffolds remodel into a tissue with near native TMJ meniscus in previous studies.
View Article and Find Full Text PDFObjective: The aim of this study was to compare and characterize the structural and ultrastructural organization of the temporomandibular joint (TMJ) between two large animal models for use in the development of tissue engineering strategies.
Materials And Methods: Whole TMJs from sheep and pigs were evaluated with micro-computed tomography (μCT) for morphology and quantitative analyses of bone parameters. Histological examination was performed on the TMJ disc and its attachments to investigate regional distribution of collagen, elastin, and glycosaminoglycans (GAGs).
The temporomandibular joint (TMJ) disc is a fibrocartilaginous tissue located between the condyle of the mandible and glenoid fossa and articular eminence of the temporal bone. Damage or derangement of the TMJ disc can require surgical removal (discectomy) to restore function. Removal of the TMJ disc, however, leaves the joint space vulnerable to condylar remodeling and degradation, potentially leading to long-term complications.
View Article and Find Full Text PDFThis technical brief explores the validity and trueness of fit for using the transverse isotropic biphasic and Kelvin models (first and second order generalized) for characterization of the viscoelastic tensile properties of the temporomandibular joint (TMJ) discs from pigs and goats at a strain rate of 10 mm/min. We performed incremental stress-relaxation tests from 0 to 12% strain, in 4% strain steps on pig TMJ disc samples. In addition, to compare the outcomes of these models between species, we also performed a single-step stress-relaxation test of 10% strain.
View Article and Find Full Text PDFHydrogel-based biomaterials have advanced bone tissue engineering approaches in the last decade, through their ability to serve as a carrier for potent growth factor, bone morphogenic protein-2 (BMP-2). However, biophysical properties of hydrogels such as multiscale structural hierarchy and bone extracellular matrix (ECM)-mimetic microarchitecture are underutilized while designing current bone grafts. Incorporation of these properties offers great potential to create a favorable biomimetic microenvironment to harness their regenerative potential.
View Article and Find Full Text PDFTemporomandibular joint (TMJ) disorders (TMDs) are not well understood and the mechanical differences between the regions of the mandibular condylar cartilage (MCC) and the TMJ disc have not been thoroughly compared. As of now, there are no commercially available regenerative therapies for the TMJ. Elucidating the mechanical properties of these two structures of the articulating joint will help future efforts in developing tissue engineering treatments of the TMJ.
View Article and Find Full Text PDFThe ideal combination of hydrogel components for regeneration of cartilage and cartilaginous interfaces is a significant challenge because control over differentiation into multiple lineages is necessary. Stabilization of the phenotype of stem cell derived chondrocytes is needed to avoid undesired progression to terminal hypertrophy and tissue mineralization. A novel ternary blend hydrogel composed of methacrylated poly(ethylene glycol) (PEG), gelatin, and heparin (PGH) was designed to guide chondrogenesis by bone marrow derived mesenchymal stem cells (BMSCs) and maintenance of their cartilaginous phenotype.
View Article and Find Full Text PDFControlling oxidative stress through the activation of antioxidant pathways is crucial in bone homeostasis, and impairments of the cellular defense systems involved contribute to the pathogenesis of common skeletal diseases. In this work we focused on the dipeptidyl peptidase 3 (DPP3), a poorly investigated ubiquitous zinc-dependent exopeptidase activating the Keap1-Nrf2 antioxidant pathway. We showed Dpp3 expression in bone and, to understand its role in this compartment, we generated a Dpp3 knockout (KO) mouse model and specifically investigated the skeletal phenotype.
View Article and Find Full Text PDFThe sixth temporomandibular joint (TMJ) Bioengineering Conference (TMJBC) was held on June 14-15 2018, in Redondo Beach, California, 12 years after the first TMJBC. Speakers gave 30 presentations and came from the United States, Europe, Asia, and Australia. The goal of the conference has remained to foster a continuing forum for bioengineers, scientists, and surgeons and veterinarians to advance technology related to TMJ disorders.
View Article and Find Full Text PDFThe purpose of this cohort study was to identify associations between combined oral and bone disease phenotypes and genes present in cell regulatory pathways. The studied pathways play important roles in cellular growth, proliferation, differentiation, and homeostasis. DNA samples extracted from whole saliva of 3,912 individuals were genotyped and these data analyzed according to dental caries experience, periapical lesions, periodontitis, osteoporosis, or temporomandibular joint discomfort.
View Article and Find Full Text PDFSpecies of the Ostreidae family are key ecosystem engineers and many of them - including and - are commercially important aquaculture species. Despite similarities in their morphology and ecology, these two species differ in their ability to defend against pathogens, potentially reflecting species-specific differential specialization of hemocytes on immune defense versus biomineralization. To test this hypothesis, we investigated the expression levels of immune- and biomineralization-related genes as well as mineralogical and mechanical properties of the shells and the calcium sequestration ability of the hemocytes of and The expression of biomineralization-related genes was higher in than in in multiple tissues including the mantle edge and hemocytes, while the expression of immune genes was higher in the hemocytes of Hemocytes of contained more calcium (stored intracellularly as calcium carbonate mineral) compared with those of Analysis of the adult shells showed that the crystallinity of calcite was higher and the laths of the foliated layer of the shell were thicker in than in Mechanically, the shells of were stiffer, harder and stronger than those of Taken together, our results show that the species-specific differences in physiology (such as disease resistance and exoskeleton properties) are reflected at the cellular and molecular levels in the differential specialization of hemocytes on potentially competing functions (immunity and biomineralization) as well as different expression profiles of other tissues involved in biomineralization (such as the mantle edge).
View Article and Find Full Text PDFA subset of temporomandibular joint (TMJ) disorders is attributed to joint degeneration. The pig has been considered the preferred in vivo model for the evaluation of potential therapies for TMJ disorders, and practical considerations such as cost and husbandry issues have favored the use of young, skeletally immature animals. However, the effect of growth on the biochemical and biomechanical properties of the TMJ disk and articulating cartilage has not been examined.
View Article and Find Full Text PDFJ Oral Maxillofac Surg
September 2018
Purpose: Biodegradable polymeric scaffolds have been used for tissue engineering approaches and can be used to regenerate temporomandibular joint (TMJ) tissues. Synthetic acellular polymeric poly(glycerol sebacate) (PGS) scaffolds and natural scaffolds made from gelatin are polymeric scaffold sponges that could provide a substrate for cell infiltration and remodeling. The authors studied the regenerative potential of these 2 scaffolds in addition to a bioactive signal, magnesium (Mg), in a novel fibrocartilage defect model in the goat mandibular condylar cartilage (MCC).
View Article and Find Full Text PDFThere is a paucity of in vivo studies that investigate the safety and efficacy of temporomandibular joint (TMJ) tissue regeneration approaches, in part due to the lack of established animal models. Review of disease models for study of TMJ is presented herein with an attempt to identify relevant preclinical animal models for TMJ tissue engineering, with emphasis on the disc and condyle. Although degenerative joint disease models have been mainly performed on mice, rats, and rabbits, preclinical regeneration approaches must employ larger animal species.
View Article and Find Full Text PDFThe inability of fibrocartilage, specifically the temporomandibular joint (TMJ) disc, to regenerate and remodel following injury presents a unique problem for clinicians. Tissue engineering then offers a potential regenerative therapy. In vitro testing provides a valuable screening tool for potential tissue engineered solutions.
View Article and Find Full Text PDFBackground: The limitations of autologous and alloplastic reconstruction for craniofacial bone defects have created a clinical need for viable tissue-engineering strategies. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has shown promise in this setting. The aim of this study was to determine the long-term biomechanical properties of rhBMP-2-mediated calvarial reconstruction.
View Article and Find Full Text PDFPurpose: Musculoskeletal tissue engineering has advanced to the stage where it has the capability to engineer temporomandibular joint (TMJ) anatomic components. Unfortunately, there is a paucity of literature identifying specific indications for the use of TMJ tissue engineering solutions. The objective of this study was to establish an initial set of indications and contraindications for the use of engineered tissues for replacement of TMJ anatomic components.
View Article and Find Full Text PDFJ Oral Facial Pain Headache
July 2015
Aims: To determine whether behavioral, anatomical, and physiologic endpoints widely used to infer the presence of pain in rodent models of temporomandibular disorders (TMD) were applicable to the rabbit model of TMD associated with altered joint loading.
Methods: Unilateral molar dental splints were used to alter temporomandibular joint (TMJ) loading. Changes in nociceptive threshold were assessed with a mechanical probing of the TMJ region on nine splinted and three control rabbits.
J Oral Maxillofac Surg
September 2015
Purpose: Analysis of mandibular biomechanics could help with understanding the mechanisms of temporomandibular joint (TMJ) disorders (TMJDs), such as osteoarthritis (TMJ-OA), by investigating the effects of injury or disease on TMJ movement. The objective of the present study was to determine the functional kinematic implications of mild TMJ-OA degeneration caused by altered occlusion from unilateral splints in the rabbit.
Materials And Methods: Altered occlusion of the TMJ was mechanically induced in rabbits by way of a unilateral molar dental splint (n = 3).