The role of inflammatory markers in Temporomandibular Myalgia: A systematic review.

Approximately 10 % of the general population is affected by temporomandibular disorder (TMD) pain. Diagnosis of myogenous TMD pain (i.e., TM myalgia) may be challenging, while an adequate assessment of this pain is crucial to establish an adequate management strategy. We aim to analyze if there is a relation between inflammation and TM myalgia, and if we can identify and measure inflammatory markers in patients suffering from this condition. An electronic literature search was conducted from inception up to July 14 2022 through the databases PubMed, Cochrane Library, Web of Science, and Embase in collaboration with a medical information specialist. Studies on patients with masticatory muscle inflammation and/or pain were included. After a screening procedure, only nine full-text articles met the criteria for inclusion. In the included studies 9-131 patients showed TM myalgia, and presence of inflammation was reported with analysis of interleukines IL-1, IL-6, IL-10, tumor necrosis factor alpha, and prostaglandins from blood, saliva, and extracellular fluid of masseter muscle using microdialysis. Our results contributed to the identification of the relation between inflammation and TM myalgia and established that measurement of inflammatory cytokines may be a valid diagnostic tool, which is an essential step towards finding a better treatment.

A Three-Dimensional Mechanical Loading Model of Human Osteocytes in Their Native Matrix.

Osteocytes are mechanosensory cells which are embedded in calcified collagenous matrix. The specific native matrix of osteocytes affects their regulatory activity, i.e., transmission of signaling molecules to osteoclasts and/or osteoblasts, in the mechanical adaptation of bone. Unfortunately, no existing in vitro model of cortical bone is currently available to study the mechanosensory function of human osteocytes in their native matrix. Therefore, we aimed to develop an in vitro three-dimensional mechanical loading model of human osteocytes in their native matrix. Human cortical bone explants containing osteocytes in their three-dimensional native matrix were cultured and mechanically loaded by three-point bending using a custom-made loading apparatus generating sinusoidal displacement. Osteocyte viability and sclerostin expression were measured 1-2 days before 5 min loading and 1 day after loading. Bone microdamage was visualized and quantified by micro-CT analysis and histology using BaSO4 staining. A linear relationship was found between loading magnitude (2302-13,811 µÉ›) and force (1.6-4.9 N) exerted on the bone explants. At 24 h post-loading, osteocyte viability was not affected by 1600 µÉ› loading. Sclerostin expression and bone microdamage were unaffected by loading up to 8000 µÉ›. In conclusion, we developed an in vitro 3D mechanical loading model to study mechanoresponsiveness of viable osteocytes residing in their native matrix. This model is suitable to study the effect of changed bone matrix composition in metabolic bone disease on osteocyte mechanoresponsiveness.

Blood Vessel Formation and Bone Regeneration Potential of the Stromal Vascular Fraction Seeded on a Calcium Phosphate Scaffold in the Human Maxillary Sinus Floor Elevation Model.

Bone substitutes are used as alternatives for autologous bone grafts in patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement. However, bone substitutes lack osteoinductive and angiogenic potential. Addition of adipose stem cells (ASCs) may stimulate osteogenesis and osteoinduction, as well as angiogenesis. We aimed to evaluate the vascularization in relation to bone formation potential of the ASC-containing stromal vascular fraction (SVF) of adipose tissue, seeded on two types of calcium phosphate carriers, within the human MSFE model, in a phase I study. Autologous SVF was obtained from ten patients and seeded on ß-tricalcium phosphate (n = 5) or biphasic calcium phosphate carriers (n = 5), and used for MSFE in a one-step surgical procedure. After six months, biopsies were obtained during dental implant placement, and the quantification of the number of blood vessels was performed using histomorphometric analysis and immunohistochemical stainings for blood vessel markers, i.e., CD34 and alpha-smooth muscle actin. Bone percentages seemed to correlate with blood vessel formation and were higher in study versus control biopsies in the cranial area, in particular in ß-tricalcium phosphate-treated patients. This study shows the safety, feasibility, and efficiency of the use of ASCs in the human MSFE, and indicates a pro-angiogenic effect of SVF.

Advances in Bioprinting Technologies for Craniofacial Reconstruction.

Recent developments in craniofacial reconstruction have shown important advances in both the materials and methods used. While autogenous tissue is still considered to be the gold standard for these reconstructions, the harvesting procedure remains tedious and in many cases causes significant donor site morbidity. These limitations have subsequently led to the development of less invasive techniques such as 3D bioprinting that could offer possibilities to manufacture patient-tailored bioactive tissue constructs for craniofacial reconstruction. Here, we discuss the current technological and (pre)clinical advances of 3D bioprinting for use in craniofacial reconstruction and highlight the challenges that need to be addressed in the coming years.

Soft Tissue Augmentation Techniques and Materials Used in the Oral Cavity: An Overview.

PURPOSE: Oral soft tissue augmentation or grafting procedures are often necessary to achieve proper wound closure after deficits resulting from tumor excision, clefts, trauma, dental implants, and tooth recessions. MATERIALS AND METHODS: Autologous soft tissue grafts still remain the gold standard to acquire a functionally adequate zone of keratinized attached gingiva. However, soft tissue substitutes are more commonly used because they minimize morbidity and shorten surgical time. RESULTS: This review aimed to assess soft tissue grafting techniques and materials used in the oral cavity from existing literature. There are a large variety of materials and techniques, including grafts, local flaps, allogenic derived matrices such as acellular dermal allograft, xenogenic tissue matrices from animal origin, and synthetic materials. CONCLUSIONS: Tissue engineering of oral mucosa represents an interesting alternative to obtain sufficient autologous tissue for reconstructing oral wounds using biodegradable scaffolds, and may improve vascularization and epithelialization, which are critical for successful outcomes.

Application of Additive Manufacturing in Oral and Maxillofacial Surgery.

Additive manufacturing is the process of joining materials to create objects from digital 3-dimensional (3D) model data, which is a promising technology in oral and maxillofacial surgery. The management of lost craniofacial tissues owing to congenital abnormalities, trauma, or cancer treatment poses a challenge to oral and maxillofacial surgeons. Many strategies have been proposed for the management of such defects, but autogenous bone grafts remain the gold standard for reconstructive bone surgery. Nevertheless, cell-based treatments using adipose stem cells combined with osteoconductive biomaterials or scaffolds have become a promising alternative to autogenous bone grafts. Such treatment protocols often require customized 3D scaffolds that fulfill functional and esthetic requirements, provide adequate blood supply, and meet the load-bearing requirements of the head. Currently, such customized 3D scaffolds are being manufactured using additive manufacturing technology. In this review, 2 of the current and emerging modalities for reconstruction of oral and maxillofacial bone defects are highlighted and discussed, namely human maxillary sinus floor elevation as a valid model to test bone tissue-engineering approaches enabling the application of 1-step surgical procedures and seeding of Good Manufacturing Practice-level adipose stem cells on computer-aided manufactured scaffolds to reconstruct large bone defects in a 2-step surgical procedure, in which cells are expanded ex vivo and seeded on resorbable scaffolds before implantation. Furthermore, imaging-guided tissue-engineering technologies to predetermine the surgical location and to facilitate the manufacturing of custom-made implants that meet the specific patient's demands are discussed. The potential of tissue-engineered constructs designed for the repair of large oral and maxillofacial bone defects in load-bearing situations in a 1-step surgical procedure combining these 2 innovative approaches is particularly emphasized.

A histomorphometric and micro-computed tomography study of bone regeneration in the maxillary sinus comparing biphasic calcium phosphate and deproteinized cancellous bovine bone in a human split-mouth model.

OBJECTIVE: The gain of mineralized bone was compared between deproteinized bovine bone allograft (DBA) and biphasic calcium phosphate (BCP) for dental implant placement. STUDY DESIGN: Five patients with atrophic maxillae underwent bilateral sinus elevation with DBA (Bio-Oss) and BCP (Straumann BoneCeramic). After 3 to 8 months, 32 Camlog implants were placed, and biopsies were retrieved. Bone and graft volume, degree of bone mineralization, and graft degradation gradient were determined using micro-computed tomography, and bone formation and resorption parameters were measured using histomorphometry. Implant functioning and peri-implant mucosa were evaluated up to 4 years. RESULTS: Patients were prosthetically successfully restored. All but one of the implants survived, and peri-implant mucosa showed healthy appearance and stability. Bone volume, graft volume, degree of bone mineralization, and osteoclast and osteocyte numbers were similar, but BCP-grafted biopsies had relatively more osteoid than DBA-grafted biopsies. CONCLUSIONS: The BCP and DBA materials showed similar osteoconductive patterns and mineralized bone, although signs of more active bone formation and remodeling were observed in BCP- than in DBA-grafted biopsies.

Short (15 minutes) bone morphogenetic protein-2 treatment stimulates osteogenic differentiation of human adipose stem cells seeded on calcium phosphate scaffolds in vitro.

A one-step concept for bone regeneration has been postulated in which human adipose stem cells (hASCs) are harvested, triggered to differentiate, seeded on carriers, and implanted in the same operative procedure. Toward this goal it was investigated whether short (minutes) incubation with bone morphogenetic protein-2 (BMP-2) suffices to trigger osteogenic differentiation of hASCs seeded on calcium phosphate carriers. hASCs were treated with or without BMP-2 (10 ng/mL) for 15 min, and seeded on ß-tricalcium phosphate granules (ß-TCP; sized <0.7 mm or >0.7 mm) or biphasic calcium phosphate (BCP; 60%/40% or 20%/80% hydroxyapatite/ß-TCP). Attachment was determined after 10-30 min. Proliferation (DNA content) and osteogenic differentiation (alkaline phosphatase activity, gene expression) were analyzed up to 3 weeks of culture. hASC attachment to the different scaffolds was similar, and unaffected by BMP-2. It stimulated gene expression of the osteogenic markers core binding factor alpha 1, collagen-1, osteonectin, and osteocalcin in hASCs seeded on BCP and ß-TCP. Downregulation of osteopontin expression by BMP-2 was seen in BCP-seeded cells only. BMP-2 treatment inhibited expression of the adipogenic marker peroxisome proliferator-activated receptor gamma. In conclusion, 15 min BMP-2 preincubation of hASCs seeded on BCP/ß-TCP scaffolds had a long-lasting stimulating effect on osteogenic differentiation in vitro. These results strongly support a one-step clinical concept for bone regeneration.

Human maxillary sinus floor elevation as a model for bone regeneration enabling the application of one-step surgical procedures.

Bone loss in the oral and maxillofacial region caused by trauma, tumors, congenital disorders, or degenerative diseases is a health care problem worldwide. To restore (reconstruct) these bone defects, human or animal bone grafts or alloplastic (synthetic) materials have been used. However, several disadvantages are associated with bone graft transplantation, such as limited bone volume, donor-site morbidity, surgical and immune rejection risks, and lack of osseo-integration. Bone tissue engineering is emerging as a valid alternative to treat bone defects allowing the regeneration of lost bony tissue, thereby recovering its functionality. During the last decades, the increasing aged population worldwide has also raised the prevalence of maxillary atrophy. Maxillary sinus floor elevation (MSFE) has become a standard surgical procedure to overcome the reduced amount of bone, thus enabling the placement of dental implants. MSFE aims to increase the bone height in the posterior maxilla, by elevating the Schneiderian membrane and placing the graft material into the surgically created space in the maxillary sinus floor. Importantly, oral bone regeneration during MSFE offers a unique human clinical model in which new cell-based bone tissue engineering applications might be investigated, since biopsies can be taken after MSFE before a dental implant placement and analyzed at the cellular level. New approaches in oral bone regeneration are focusing on cells, growth factors, and biomaterials. Recently, adipose tissue has become interesting as an abundant source of mesenchymal stem cells, which might be applied immediately after isolation to the patient allowing a one-step surgical procedure, thereby avoiding expensive cell culture procedures and another surgical operation. In this new cell-based tissue engineering approach, stem cells are combined with an osteoconductive scaffold and growth factors, and applied immediately to the patient. In this review, MSFE is discussed as a valid model to test bone tissue engineering approaches, such as the one-step surgical procedure. This procedure might be applied in other regenerative medicine applications as well.

Buccal fat pad, an oral access source of human adipose stem cells with potential for osteochondral tissue engineering: an in vitro study.

Stem cells offer an interesting tool for tissue engineering, but the clinical applications are limited by donor-site morbidity and low cell number upon harvest. Recent studies have identified an abundant source of stem cells in subcutaneous adipose tissue. Adipose stem cells (ASCs) present in adipose tissue are able to differentiate to several lineages and express multiple growth factors, which makes them suitable for clinical application. Buccal fat pad (BFP), an adipose-encapsulated mass found in the oral cavity, could represent an easy access source for dentists and oral surgeons. The stromal vascular fraction obtained from fresh BFP-derived adipose tissue and passaged ASCs were analyzed to detect and quantify the percentage of ASCs in this tissue. Here we show that BFP contains a population of stem cells that share a similar phenotype with ASCs from abdominal subcutaneous fat tissue, and are also able to differentiate into the chondrogenic, adipogenic, and osteogenic lineage. These results define BFP as a new, rich, and accessible source of ASCs for tissue engineering purposes.