Selection of decalcification agents is an essential consideration when processing mineralized tissues because the integrity and immunohistochemical characteristics of the tissues may be affected. Here, we report results obtained from the decalcification of rat mandibles using 10% ethylenediaminetetraacetic acid (EDTA) at room temperature (RT), 10% EDTA at 37C, 5% nitric acid, and 10% formic acid at RT. Decalcification endpoints were determined by microcomputed tomography. Morphological preservation and antigenicity were evaluated by hematoxylin and eosin staining and immunohistochemistry. Decalcification of the anterior and posterior portions of the mandible took 220 and 191 hr in 10% EDTA RT, 102 and 73 hr in 10% EDTA 37C, 13.5 and 4.3 hr in 5% nitric acid, and 140 and 36 hr in 10% formic acid, respectively. Decalcification in 10% EDTA at 37C was accelerated, but 10% EDTA at RT provided optimal results for immunohistochemistry and cellular and structural details. Decalcification using 5% nitric acid was accomplished in the shortest time and exhibited good cellular and architectural morphology, whereas 10% formic acid was suboptimal with respect to tissue and cellular morphology. Despite being the slowest method, EDTA at RT is still the recommended method for decalcifying mineralized tissues; however, if rapid decalcification is needed, 5% nitric acid is the best option, yielding acceptable tissue integrity and speed.

The aim of this review was to provide an update on survival rates of osseointegrated implants into common composite free flaps used for maxillary and mandibular reconstructions and identify factors affecting outcomes. PubMed, Medline, Embase, and Cochrane databases were searched. Included studies reported implant survival by flap type. Results were pooled and survival was estimated with the Kaplan‐Meier method. Variables affecting survival were assessed using Cox regression. Thirty‐two of the 2631 articles retrieved were included, totaling 2626 implants placed into fibula, iliac crest, scapula, and radial forearm free flaps. Pooled survival showed 94% 5‐year survival of implants in fibula and iliac crest with no difference between groups (P = .3). Factors effecting survival included radiotherapy (HR 2.3, 95% CI 1.2‐4.6, P = .027) and malignant disease (HR 2.2, 95%CI 1.6‐3.1, P < .001). Implant survival appears adequate across common flap types; however, there are limited numbers reported in less common flaps.

We hypothesized that a composite of 3D porous melt-electrowritten poly-ɛ-caprolactone (PCL) coated throughout with a porous and slowly biodegradable fibrin/alginate (FA) matrix would accelerate bone repair due to its angiogenic potential. Scanning electron microscopy showed that the open pore structure of the FA matrix was maintained in the PCL/FA composites. Fourier transform infrared spectroscopy and differential scanning calorimetry showed complete coverage of the PCL fibres by FA, and the PCL/FA crystallinity was decreased compared with PCL. In vitro cell work with osteoprogenitor cells showed that they preferentially bound to the FA component and proliferated on all scaffolds over 28 days. A chorioallantoic membrane assay showed more blood vessel infiltration into FA and PCL/FA compared with PCL, and a significantly higher number of bifurcation points for PCL/FA compared with both FA and PCL. Implantation into a rat cranial defect model followed by microcomputed tomography, histology, and immunohistochemistry after 4- and 12-weeks post operation showed fast early bone formation at week 4, with significantly higher bone formation for FA and PCL/FA compared with PCL. However, this phenomenon was not extrapolated to week 12. Therefore, for long-term bone regeneration, tuning of FA degradation to ensure syncing with new bone formation is likely necessary.

Medication‐related osteonecrosis of the jaw (MRONJ) poses an ongoing challenge for clinicians and researchers. Currently, there is a lack of preventative measures available for at‐risk patients undergoing tooth extractions, especially those with prior bisphosphonate treatment due to osteoporosis or bone metastasis diagnoses. Here, these issues are addressed using a preventative tissue engineering strategy against MRONJ development. This study evaluates the efficacy of a poly(ethylene glycol)‐heparin hydrogel as a tool for the delivery of arginylglycylaspartic acid (RGD) and recombinant human bone morphogenic protein‐2 (rhBMP‐2). Three groups of skeletally mature rats each receive two doses of intravenous zoledronic acid prior to surgery and undergo extraction of the right first mandibular molar with gingival closure. Experimental groups either have the sockets left empty, filled with hydrogel minus rhBMP‐2, or filled with hydrogel plus rhBMP‐2. Eight weeks postoperatively specimens are analyzed using radiological, histological, and scanning electron microscopy (SEM) techniques. µCT analysis shows increased bone formation with hydrogel/rhBMP‐2 delivery compared to the empty socket. Hydrogel‐treated groups display increased presence of osteocytes and increased osteoclastic action compared to the empty sockets. These results represent the first step toward improved delivery of rhBMP‐2 and a potential MRONJ preventative for patients undergoing bisphosphonate treatment.

Restoration of critical sized defects of the mandible still poses a major problem in the field of Oral and Maxillofacial Surgery. The current gold standard of treatment relies on the use of autologous grafts and therefore, has associated disadvantages such as donor site morbidity and insufficient bone for prosthetic rehabilitation. Recent advances in the fields of bone tissue engineering and distraction osteogenesis provide an alternative treatment modality to restore the aforementioned critical sized defects. These alternative modalities offer patients and clinicians multiple advantages such as decreased morbidity and increased volume of bone for prosthetic restoration. The aim of this review was to evaluate the bone regeneration capacity of bone tissue engineering and distraction osteogenesis in preclinical in vivo animal models against the current gold standard.

Uncovering the inflammatory mechanisms underpinning initiation, progression, and promotion of oral squamous cell carcinoma (OSCC) development is fundamental to the rational pursuit of targeted therapeutics. Here we present a review of the current knowledge of the role of TNF-α in the aetiology, pathogenesis, and potential therapies with regards to OSCC. TNF-α is worthy of particular attention in OSCC, with its presence demonstrated to enhance cell proliferation and its downregulation demonstrated to inhibit proliferation and migration in other carcinomas in both in vitro and in vivo models and oral cancer patients. Increased TNF-α in the OSCC tumour microenvironment has been demonstrated to favour invasion through promotion of firstly the pro-inflammatory, pro-invasive phenotypes of OSCC cells and secondly its paracrine mechanism mediating recruitment and activation of inflammatory cells. Polymorphisms affecting the gene expression of TNF-α have been strongly associated with an increased risk for oral squamous cell carcinoma. A number of studies have considered TNF-α within biofluids, including saliva and serum, as a potential biomarker for the early detection of OSCC, as well as its staging, differentiation, and prognosis. The broad and multifaceted role that TNF-α plays in many inflammatory states presents an obvious confounder, particularly with demonstrated increased TNF-α levels in common oral disease states. Lastly, biologic agents targeting TNF-α are currently in clinical use for immune-mediated inflammatory rheumatological and gastrointestinal diseases. There is the potential that these biological agents might have an adjunctive role in OSCC prevention and treatment.

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A preclinical evaluation using a regenerative medicine methodology comprising an additively manufactured medical-grade ε-polycaprolactone β-tricalcium phosphate (mPCL-TCP) scaffold with a corticoperiosteal flap was undertaken in eight sheep with a tibial critical-size segmental bone defect (9.5 cm 3 , M size) using the regenerative matching axial vascularization (RMAV) approach. Biomechanical, radiological, histological, and immunohistochemical analysis confirmed functional bone regeneration comparable to a clinical gold standard control (autologous bone graft) and was superior to a scaffold control group (mPCL-TCP only). Affirmative bone regeneration results from a pilot study using an XL size defect volume (19 cm 3 ) subsequently supported clinical translation. A 27-year-old adult male underwent reconstruction of a 36-cm near-total intercalary tibial defect secondary to osteomyelitis using the RMAV approach. Robust bone regeneration led to complete independent weight bearing within 24 months. This article demonstrates the widely advocated and seldomly accomplished concept of “bench-to-bedside” research and has weighty implications for reconstructive surgery and regenerative medicine more generally.