The increasing incidence of resistance to chemotherapeutic agents has become a major issue in the treatment of oral cancer (OC). Epithelial-mesenchymal transition (EMT) has attracted a great deal of attention in recent years with regard to its relation to the mechanism of chemotherapy drug resistance. EMT-activating transcription factors (EMT-ATFs), such as Snail, TWIST, and ZEB, can activate several different molecular pathways, e.g., PI3K/AKT, NF-κB, and TGF-β. In contrast, the activated oncological signal pathways provide reciprocal feedback that affects the expression of EMT-ATFs, resulting in a peritumoral extracellular environment conducive to cancer cell survival and evasion of the immune system, leading to resistance to multiple chemotherapeutic agents. We present an overview of evidence-based chemotherapy for OC treatment based on the National Comprehensive Cancer Network (NCCN) Chemotherapy Order Templates. We focus on the molecular pathways involved in drug resistance related to the EMT and highlight the signal pathways and transcription factors that may be important for EMT-regulated drug resistance. Rapid progress in antitumor regimens, together with the application of powerful techniques such as high-throughput screening and microRNA technology, will facilitate the development of therapeutic strategies to augment chemotherapy.

The advent of bioresorbable materials to overcome limitations and replace traditional bone-reconstruction titanium-plate systems for bone fixation, thus achieving greater efficiency and safety in medical and dental applications, has ushered in a new era in biomaterial development. Because of its bioactive osteoconductive ability and biocompatibility, the forged composite of uncalcined/unsintered hydroxyapatite and poly L-lactic acid (u-HA/PLLA) has attracted considerable interest from researchers in bone tissue engineering, as well as from clinicians, particularly for applications in maxillofacial reconstructive surgery. Thus, various in vitro studies, in vivo studies, and clinical trials have been conducted to investigate the feasibility and weaknesses of this biomaterial in oral and maxillofacial surgery. Various technical improvements have been proposed to optimize its advantages and limit its disadvantages. This narrative review presents an up-to-date, comprehensive review of u-HA/PLLA, a bioactive osteoconductive and bioresorbable bone-reconstruction and -fixation material, in the context of oral and maxillofacial surgery, notably maxillofacial trauma, orthognathic surgery, and maxillofacial reconstruction. It simultaneously introduces new trends in the development of bioresorbable materials that could used in this field. Various studies have shown the superiority of u-HA/PLLA, a third-generation bioresorbable biomaterial with high mechanical strength, biocompatibility, and bioactive osteoconductivity, compared to other bioresorbable materials. Future developments may focus on controlling its bioactivity and biodegradation rate and enhancing its mechanical strength.

If the alveolar bone height of patients requiring dental implants in the maxillary molar region is inadequate, it is difficult to achieve satisfactory outcomes using existing bone graft materials. We previously reported the possible utility of bacterial cellulose (BC) as a new dental treatment material. BC has a high absorptive capacity, good mechanical strength, and good volume retention. BC loaded with bone morphogenetic protein-2 (BMP-2) might allow effective alveolar bone augmentation. We created critical frontal bone defect models in 12 male Japanese white rabbits and divided them into four groups: sham; BC (BC grafting only); BMP-2 (treated with BMP-2 solution only); and BC+BMP-2 (grafted with BC loaded with BMP-2). Newly formed bone volume was calculated via hematoxylin-eosin staining evaluation. The proliferating cell nuclear antigen and osteocalcin levels were determined by the immunohistochemical staining analysis. All measured indices of the BC+BMP-2 group were significantly superior to those of the other groups (all p < 0.05). BC maintained the graft space and released BMP-2 in a sustained manner, promoting optimal bone formation. The BC+BMP-2 combination enhanced bone regeneration and shows promise as a useful means of clinical pre-dental implant bone augmentation in the maxillary sinus.

Oral squamous cell carcinoma (OSCC) is a major type of cancer that accounts for over 90% of all oral cancer cases. Recently developed evidence-based therapeutic regimens for OSCC based on monoclonal antibodies (mAbs), such as cetuximab, pembrolizumab, and nivolumab, have attracted considerable attention worldwide due to their high specificity, low toxicity, and low rates of intolerance. However, the efficacy of those three mAbs remains poor because of the low rate of responders and acquired resistance within a short period of time. The epithelial–mesenchymal transition (EMT) process is fundamental for OSCC growth and metastasis and is also responsible for the poor response to mAbs. During EMT, cancer cells consume abundant energy substrates and create an immunosuppressive tumor microenvironment to support their growth and evade T cells. In this review, we provide an overview of the complex roles of major substrates and signaling pathways involved in the development of therapeutic resistance in OSCC. In addition, we summarize potential therapeutic strategies that may help overcome this resistance. This review aims to help oral oncologists and researchers aiming to manage OSCC and establish new treatment modalities.

A novel three-dimensional (3D) porous uncalcined and unsintered hydroxyapatite/poly-d/l-lactide (3D-HA/PDLLA) composite demonstrated superior biocompatibility, osteoconductivity, biodegradability, and plasticity, thereby enabling complex maxillofacial defect reconstruction. Mesenchymal stem cells (MSCs)—a type of adult stem cell—have a multipotent ability to differentiate into chondrocytes, adipocytes, and osteocytes. In a previous study, we found that CD90 (Thy-1, cluster of differentiation 90) and CD271 (low-affinity nerve growth factor receptor) double-positive cell populations from human bone marrow had high proliferative ability and differentiation capacity in vitro. In the present study, we investigated the utility of bone regeneration therapy using implantation of 3D-HA/PDLLA loaded with human MSCs (hMSCs) in mandibular critical defect rats. Microcomputed tomography (Micro-CT) indicated that implantation of a 3D-HA/PDLLA-hMSC composite scaffold improved the ability to achieve bone regeneration compared with 3D-HA/PDLLA alone. Compared to the sufficient blood supply in the mandibular defection superior side, a lack of blood supply in the inferior side caused delayed healing. The use of Villanueva Goldner staining (VG staining) revealed the gradual progression of the nucleated cells and new bone from the scaffold border into the central pores, indicating that 3D-HA/PDLLA loaded with hMSCs had good osteoconductivity and an adequate blood supply. These results further demonstrated that the 3D-HA/PDLLA-hMSC composite scaffold was an effective bone regenerative method for maxillofacial boney defect reconstruction.

Uncalcined and unsintered hydroxyapatite/poly l-lactide (u-HA/PLLA) material has osteoconductive characteristics and is available for use as a maxillofacial osteosynthetic reconstruction device. However, its bone regeneration ability in the maxillofacial region has not been fully investigated. This study is the first to assess the bone regenerative potential of osteoconductive u-HA/PLLA material when it is used for repairing maxillofacial bone defects. A total of 21 Sprague-Dawley male rats were divided into three groups—the u-HA/PLLA, PLLA, or sham control groups. A critical size defect of 4 mm was created in the mandible of each rat. Then, the defect was covered with either a u-HA/PLLA or PLLA sheet on the buccal side. The rats in each group were sacrificed at 2, 4, or 8 weeks. The rats’ mandibles were sampled for histological analysis with hematoxylin and eosin staining, histomorphometry, and immunohistochemistry with Runx2 and osteocalcin (OCN) antibody. The amount of newly formed bone in the u-HA/PLLA group was significantly higher than that of the PLLA group. The expression of Runx2 and OCN in the u-HA/PLLA group was also significantly higher. These results demonstrate that the u-HA/PLLA material has excellent bone regenerative ability and confirm its applicability as a reconstructive device in maxillofacial surgery.