Chitosan/MXene Composite Scaffolds for Bone Regeneration in Oral Cancer Treatment - A Review

Stem cell derived small extracellular vesicles (sEVs) have emerged as promising nanomaterials for the repair of bone defects. However, low retention of sEVs affects their therapeutic effects. Clinically used natural substitute inorganic bovine bone mineral (Bio-Oss) bone powder lacks high compactibility and efficient osteo-inductivity that limit its clinical application in repairing large bone defects. In this study, a poly ethylene glycol/hyaluronic acid (PEG/HA) hydrogel was used to stabilize Bio-Oss and incorporate rat bone marrow stem cell-derived sEVs (rBMSCs-sEVs) to engineer a PEG/HA-Bio-Oss (PEG/HA-Bio) composite scaffold. Encapsulation and sustained release of sEVs in hydrogel scaffold can enhance the retention of sEVs in targeted area, achieving long-lasting repair effect. Meanwhile, synergistic administration of sEVs and Bio-Oss in cranial defect can improve therapeutic effects. The PEG/HA-Bio composite scaffold showed good mechanical properties and biocompatibility, supporting the growth of rBMSCs. Furthermore, sEVs enhancedin vitrocell proliferation and osteogenic differentiation of rBMSCs. Implantation of sEVs/PEG/HA-Bio in rat cranial defect model promotedin vivobone regeneration, suggesting the great potential of sEVs/PEG/HA-Bio composite scaffold for bone repair and regeneration. Overall, this work provides a strategy of combining hydrogel composite scaffold systems and stem cell-derived sEVs for the application of tissue engineering repair.

PurposeThis evidence mapping aims to describe and assess the quality of available evidence in systematic reviews (SRs) on treatments for oral cancer.Materials and methodsWe followed the methodology of Global Evidence Mapping. Searches in MEDLINE, EMBASE, Epistemonikos and The Cochrane Library were conducted to identify SRs on treatments for oral cancer. The methodological quality of SRs was assessed using the Assessing the Methodological Quality of Systematic Reviews-2 tool. We organized the results according to identified Population–Intervention–Comparison–Outcome (PICO) questions and presented the evidence mapping in tables and a bubble plot.ResultsFifteen SRs met the eligibility criteria, including 118 individual reports, of which 55.1% were randomized controlled clinical trials. Ten SRs scored “Critically low” methodological quality. We extracted 30 PICOs focusing on interventions such as surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy; 18 PICOs were for resectable oral cancer, of which 8 were reported as beneficial. There were 12 PICOs for unresectable oral cancer, of which only 2 interventions were reported as beneficial.ConclusionThere is limited available evidence on treatments for oral cancer. The methodological quality of most included SRs scored “Critically low”. The main beneficial treatment reported by authors for patients with resectable oral cancer is surgery alone or in combination with radiotherapy or chemotherapy. Evidence about the benefits of the treatments for unresectable oral cancer is lacking. These findings highlight the need to address future research focused on new treatments and knowledge gaps in this field, and increased efforts are required to improve the methodology quality and reporting process of SRs on treatments for oral cancer.

The development of collagen based composite scaffolds for bone regeneration

Introduction: Cancer is an abnormality in body tissue cells that continues to grow and develop uncontrollably. One type of cancer that is dangerous and can cause death is oral cancer. The content of sea cucumbers is useful as an anti-virus, help the growth of new cells, and as an anti-cancer. Objective: The purpose of this literature is to look based on literature, the treatment of oral cavity cancer using sea cucumbers as herbs. Methods: Scientific evidence and clinical cases are taken from the literature to support this review and information about sea cucumber herbs as an alternative treatment for oral cancer. systematic review of the literature is carried out by searching for related articles. The article search begin on April 22nd, 2020, with keywords; cancer, sea cucumbers. The following searching database is: google. Results: It is using sea cucumbers or Holothuria atra as an ingredient to be assessed for its anti-cancer properties. This study used 20kg of sea cucumbers, which were then extracted by the maceration method with 96% alcohol for 24 hours, then filtered with Whatman paper and repeated up to 6 times at room temperature. Triterpene glycosides are a type of saponin in sea cucumbers whose structure contains a sugar group. Triterpene glycoside compounds are compounds that can inhibit the mechanism of division and trigger apoptosis of cancer cells. The effects of cytotoxic on three types of sea cucumbers such as H.scabra, H.parva, and H. leucospilota are then extracted using organic extracts namely, n-Hexane , ethyl acetate and methanol by using several organs in specimens such as body wall , gonads , intestine tract , respiratory tree , coelomic fluid and cuverien tubules. Conclusion: Bioactive compounds isolated from sea cucumbers for use as anti-cancer agents have attracted the attention of cancer researchers because of their natural origin and long history as nutritious foods. The detailed mechanism of anti-cancer activity of sea cucumber compounds is still unclear, and a comprehensive study identifying this mechanism is still needed. Sea cucumber extract has a promising future to be developed as a functional food. How to Cite this Article Pubmed Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani. Reviews on Use of Sea Cucumber as a Treatment for Oral Cancer. SRP. 2020; 11(5): 299-307. doi:10.31838/srp.2020.5.44 Web Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani. Reviews on Use of Sea Cucumber as a Treatment for Oral Cancer. http://www.sysrevpharm.org/?mno=108860 [Access: March 29, 2021]. doi:10.31838/srp.2020.5.44 AMA (American Medical Association) Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani. Reviews on Use of Sea Cucumber as a Treatment for Oral Cancer. SRP. 2020; 11(5): 299-307. doi:10.31838/srp.2020.5.44 Vancouver/ICMJE Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani. Reviews on Use of Sea Cucumber as a Treatment for Oral Cancer. SRP. (2020), [cited March 29, 2021]; 11(5): 299-307. doi:10.31838/srp.2020.5.44 Harvard Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani (2020) Reviews on Use of Sea Cucumber as a Treatment for Oral Cancer. SRP, 11 (5), 299-307. doi:10.31838/srp.2020.5.44 Turabian Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani. 2020. Reviews on Use of Sea Cucumber as a Treatment for Oral Reviews in Pharmacy, 11 (5), 299-307. doi:10.31838/srp.2020.5.44 Chicago Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani. A Reviews on Use of Sea Cucumber as a Treatment for Oral Cancer. Systematic Reviews in Pharmacy 11 (2020), 299-307. doi:10.31838/srp.2020.5.44 MLA (The Modern Language Association) Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani. A Reviews on Use of Sea Cucumber as a Treatment for Oral Cancer. Systematic Reviews in Pharmacy 11.5 (2020), 299-307. Print. doi:10.31838/srp.2020.5.44 APA (American Psychological Association) Style Amiruddin Eso, Herlina Uinarni, Thomas Tommy, Ryanto Karobuana Sitepu, Iwan Kurnia Effendi, Yustinus Charles Ariestiyanto, Hutasoit Charles Martamba, Evi Mustikawati Arifin, Ferra Olivia Mawu, Bayu Indra Sukmana, Huldani (2020) Reviews on Use of Sea Cucumber as a Treatment for Oral Reviews in Pharmacy, 11 (5), 299-307. doi:10.31838/srp.2020.5.44

In this work, we have discussed the preparation and characterization of composite scaffolds for bone regeneration. The scaffolds were made with different techniques: salt leaching / phase inversion,filament winding and stereolithography. The phase of preparation is followed by a characterization from a morphological, mechanical and biological point of view. Results were very promising especially regarding the biological response of the substrates that appear to be promising for future in vivo tests.

Throughout the world, oral cancer is a common and aggressive malignancy with a high risk of morbidity, mortality, and recurrence. The importance of early detection in cancer prevention and disease treatment cannot be overstated. Conventional therapeutic strategies have minor difficulties but considerable side effects and unfavourable consequences in clinical applications. Hence, there is a requirement for effective ways for early detection and treatment of oral cancer. At present, numerous forms of nanoparticles have piqued researchers’ interest as a potentially useful tool for diagnostic probes and medicinal devices. Because of their inherent physicochemical properties and customizable surface modification, they are able to circumvent some of restrictions and accomplish the intended diagnostic and therapeutic impact. Nanotechnology is a unique field that has revolutionised the industry and is paving the way for new treatments for oral cancer. It can help with a better diagnosis with less harmful substances and is setting current guidelines for treatment. The use of nanotechnology in cancer diagnosis, therapy, and care improves clinical practise dramatically. The different types of nanoparticles that have been developed for the diagnosis and therapy of oral cancers will be covered in this study. The difficulties and potential uses of nanoparticles in the treatment and diagnosis of oral cancer are then highlighted. In order to emphasise existing difficulties and potential remedies for oral cancer, a prospective view of the future is also provided.

BackgroundProgrammed cell death (PCD) plays a crucial role in oral cancer pathogenesis and treatment. However, a comprehensive bibliometric analysis of the global research landscape in this field has not been conducted. This study aims to analyze the evolution and current trends of PCD research in oral cancer from 2000 to 2024.MethodsPublications were retrieved from the Web of Science Core Collection database using relevant keywords related to oral cancer and PCD. VOSviewer 1.6.20 and CiteSpace 6.1R6 software were employed to conduct bibliometric analysis, including publication trends, citation analysis, co-authorship networks, keyword co-occurrence, and research hotspots. The time span was set from January 2000 to December 2024.ResultsA total of 963 publications were identified and analyzed. The annual publication output showed a steady increase, with a significant growth rate after 2010, dividing the study period into three distinct phases. The most productive countries were China (58.42%), South Korea (12.27%), and Japan (10.04%), with China Medical University and Kaohsiung Medical University being the leading institutions. Research hotspots evolved from traditional apoptosis studies to emerging forms of PCD such as autophagy, ferroptosis, and pyroptosis. Keyword analysis revealed three major research clusters: basic molecular mechanisms (centered around ROS and oxidative stress), clinical aspects (including prognosis and cell proliferation), and cell death pathways. Citation burst analysis identified emerging trends in targeting multiple PCD pathways simultaneously for oral cancer therapy, with special focus on treatment resistance and survival.ConclusionThis bibliometric analysis provides a comprehensive overview of global research trends in PCD and oral cancer over the past two decades. The findings highlight the shift from basic mechanistic studies focusing on apoptosis to more diverse PCD pathways and translational research. Emerging research directions include the exploration of synergistic mechanisms among multiple PCD pathways, development of AI-based personalized treatment plans, investigation of microenvironment regulation of PCD, and application of novel drug delivery systems. These trends demonstrate the field's evolution toward more integrated, personalized approaches in oral cancer treatment. This study offers valuable insights for researchers and funding agencies to identify research gaps and potential collaboration opportunities in this rapidly developing field.

Tuning dual-drug release from composite scaffolds for bone regeneration

To meet the challenge of regenerating bone lost to disease or trauma, biodegradable scaffolds are being investigated as a way to regenerate bone without the need for an auto- or allograft. Here, we have developed a novel microsphere-based chitosan/nanocrystalline calcium phosphate (CaP) composite scaffold and investigated its potential compared to plain chitosan scaffolds to be used as a bone graft substitute. Composite and chitosan scaffolds were prepared by fusing microspheres of 500-900 microm in diameter, and porosity, degradation, compressive strength, and cell growth were examined. Both scaffolds had porosities of 33-35% and pore sizes between 100 and 800 . However, composite scaffolds were much rougher and, as a result, had 20 times more surface area/unit mass than chitosan scaffolds. The compressive modulus of hydrated composite scaffolds was significantly higher than chitosan scaffolds (9.29 +/- 0.8 MPa vs. 3.26 +/- 2.5 MPa), and composite scaffolds were tougher and more flexible than what has been reported for other chitosan-CaP composites or CaP scaffolds alone. Using X-ray diffraction, scaffolds were shown to contain partially crystalline hydroxyapatite with a crystallinity of 16.7% +/- 6.8% and crystallite size of 128 +/- 55 nm. Fibronection adsorption was increased on composite scaffolds, and cell attachment was higher on composite scaffolds after 30 min, although attachment rates were similar after 1 h. Osteoblast proliferation (based on dsDNA measurements) was significantly increased after 1 week of culture. These studies have demonstrated that composite scaffolds have mechanical properties and porosity sufficient to support ingrowth of new bone tissue, and cell attachment and proliferation data indicate composite scaffolds are promising for bone regeneration.

Maxillofacial bone defect repair and regeneration remains a tremendous challenge in the field of stomatology. However, the limited osteoinductivity of artificial materials and the high cost of bioactive agents restrain their clinical translation. This study aimed to construct an economical and efficient concentrated growth factor/mesoporous bioactive glass (CGF/MBG) composite scaffold for bone regeneration. The biochemical composition and biological effects of different forms of CGFs were systematically compared, and the results showed that CGF-conditioned medium effectively promoted proliferation, migration and osteogenesis of allogenic BMSCs. Gel phase CGF (gpCGF) exhibited superior bioactivity and osteoinductivity to liquid phase CGF (lpCGF) and liquid/gel mixed phase CGF (lgpCGF), and was further applied to construct CGF/MBG scaffolds. In vitro studies demonstrated that co-culture with gpCGF-conditioned medium further enhanced the biocompatibility of MBG, increasing cell adhesion and proliferation on the scaffold. On this basis, two compositing approaches to construct the scaffold by fibrin gel formation (CGF/FG/MBG) and freeze-drying (fdCGF/MBG) were applied, and the biological efficacy of CGFs was compared in vivo. In a rabbit mandibular defect model, higher osteogenic efficiency in in situ bone regeneration of CGF/FG/MBG composite scaffolds was proved, compared with fdCGF/MBG. Taken together, the CGF/FG/MBG composite scaffold is expected to be an efficient bone repairing therapy for clinical translation, and the CGF-composited scaffold using gpCGF and the fibrin gel formation method is a promising way to enhance the bioactivity and osteoinductivity of current clinical bone repairing materials, providing new thoughts on the development of future orthopedic biomaterials.

Tissue-engineered bone material is one of the effective methods to repair bone defects, but the application is restricted in clinical because of the lack of excellent scaffolds that can induce bone regeneration as well as the difficulty in making scaffolds with personalized structures. 3D printing is an emerging technology that can fabricate bespoke 3D scaffolds with precise structure. However, it is challenging to develop the scaffold materials with excellent printability, osteogenesis ability, and mechanical strength. In this study, graphene oxide (GO), attapulgite (ATP), type I collagen (Col I) and polyvinyl alcohol were used as raw materials to prepare composite scaffolds via 3D bioprinting. The composite materials showed excellent printability. The microcosmic architecture and properties was characterized by scanning electron microscopy, Fourier transform infrared and thermal gravimetric analyzer, respectively. To verify the biocompatibility of the scaffolds, the viability, proliferation and osteogenic differentiation of Bone Marrow Stromal Cells (BMSCs) on the scaffolds were assessed by CCK-8, Live/Dead staining and Real-time PCR in vitro. The composited scaffolds were then implanted into the skull defects on rat for bone regeneration. Hematoxylin-eosin staining, Masson staining and immunohistochemistry staining were carried out in vivo to evaluate the regeneration of bone tissue.The results showed that GO/ATP/COL scaffolds have been demonstrated to possess controlled porosity, water absorption, biodegradability and good apatite-mineralization ability. The scaffold consisting of 0.5% GO/ATP/COL have excellent biocompatibility and was able to promote the growth, proliferation and osteogenic differentiation of mouse BMSCs in vitro. Furthermore, the 0.5% GO/ATP/COL scaffolds were also able to promote bone regeneration of in rat skull defects. Our results illustrated that the 3D printed GO/ATP/COL composite scaffolds have good mechanical properties, excellent cytocompatibility for enhanced mouse BMSCs adhesion, proliferation, and osteogenic differentiation. All these advantages made it potential as a promising biomaterial for osteogenic reconstruction.

Surgery is the current first choice for oral cancer treatment. Intensity-modulated radiation therapy, molecular targeted drugs, and immune checkpoint inhibitors are still used as adjuvant therapy for advanced cancer. In addition, postoperative rehabilitation and multidisciplinary treatment have also been developed in recent years. Multidisciplinary team approaches and supportive care in oral cancer treatment reportedly shorten the time to treatment and improve outcomes. Although there is enough evidence confirming the role of oral and maxillofacial surgeons, dentists, and dental hygienists in supportive care in oral cancer treatment, there are very few systematic studies. In particular, oral health management is a concept that encompasses oral function management, oral hygiene management, and oral care during oral cancer treatment. We provide a narrative review focusing on oral health management from a multidisciplinary and supportive care perspective, applicable in oral cancer treatment.

It is reported that there are approximately 2.2 million bone graft procedures every year due to injuries, bone tumors, marginal bone defects, and aging of the population. However, the scarcity of natural donors and graft rejection make it difficult to adequately fulfill clinical demands for bone repair. While β-tricalcium phosphate (β-TCP) is a key material in bone tissue engineering, it remains insufficient for treating large bone defects. Therefore, researchers have started investigating the combination of β-TCP with other biomaterials to achieve improved clinical outcomes. Such composite scaffolds possess excellent biocompatibility and effectively provide structural support to promote cell adhesion, proliferation, and differentiation-thereby accelerating new bone tissue formation. This review examines β-tcp-based composite scaffolds for bone regeneration, analyzing design innovations and biological mechanisms, and bone repair principles-with a focus on cellular dynamics and microenvironmental regulation. The discussion valuates β-TCP's osteoconductive properties while addressing its clinical limitations in mechanical strength and degradation control. Additionally, it systematically elucidates the specific application of β-TCP-based composite scaffolds in bone repair. These include osteoinductive, osteogenic, osteoconductive and inflammatory regulation. Moreover, clinical translation progress is discussed, highlighting applications in craniomaxillofacial reconstruction and osteonecrosis management. Finally, we summarize that β-TCP composite scaffolds face challenges including poor mechanical strength, asynchronous degradation-regeneration, and manufacturing limitations. Future directions should focus on developing synchronously degradable materials and intelligent scaffolds via 4D printing and AI-optimized designs, and clinical translation systems to achieve precise bone regeneration.

Introduction:Cancer of oral cavity is the uncontrolled expansion of damaged cell within the mouth cavity. 5-fluorouracil (5-FU) chemotherapy was focused to kill the cancer cell, but it would affect the surrounding normal cells during oral cancer treatment. This study included the evaluation of chemoprotective effects of curcumin (CU), as an herbal remedy, on 5-FU-induced-cytotoxicity toward oral cancer treatment, loaded within a nanocarrier system. CU was combined with 5-FU chemotherapy as a combinational drug-delivery system to evaluate synergistic effects.Materials and Methods:Nanoformulation of CU (nano-CU) and nanoformulation of 5-FU (nano-FU) were prepared by employing homogenization with high-energy sonication. The characterizations of prepared nanoformulations were evaluated on the basis of particle size, zeta potential, and polydispersity index (PDI) values. The chemopreventive effect of nano-CU on 5-FU induced-toxicity and synergistic efficacy were optimized through different in-vitro assays.Results:The average particle size of nano-CU and nano-FU were up to 200 nm, negatively-charged, and shown up to 4th-day control release of the drug within the acceptable concentration. IC50 value for growth inhibition was calculated as 47.89 and 26.19 μg/ml, respectively, for nano-CU and nano-FU. OCC was pretreated with nano-CU and shown the protective effect by reducing 5-FU induced-cytotoxicity by preventing normal cells through reduced viability. The DPPH-indicated fluorescence-tagged cells had quantified for antioxidant effect as it reduces intracellular reactive oxygen species level in OCC. Along with alteration in cell protein expression, Blc2, and Bax, shows enhanced apoptosis rate in OCC.Conclusion:Nano-CU provides chemoprotective nature towards 5-FU induced-toxicity, along with synergistic effects in oral cancer treatment.

Mucoadhesive nanoparticles loaded with curcumin were developed as a new approach to deliver curcumin for the local treatment of oral cancer. PCL nanoparticles coated with chitosan displaying different molar masses were prepared by using the nanoprecipitation technique. The mucoadhesive properties of nanoparticle suspensions were demonstrated by their strong ability to interact with the glycoprotein mucin through electrostatic interactions. Similar permeation profiles of curcumin loaded in uncoated and chitosan-coated nanoparticles across porcine esophageal mucosa were verified. Curcumin concentrations retained in the mucosa suggest the possibility of a local effect of the drug. In vitro studies demonstrated that free curcumin.and curcumin loaded into nanoparticles coated with chitosan caused significant reduction of SCC-9 human oral cancer cell viability in a concentration and time-dependent manner. However, no significant cell death was observed after 24 h of treatment with unloaded nanoparticles coated with chitosan. In addition, curcumin-loaded nanoparticles showed reduced cytotoxicity, when compared with the free drug. Therefore, chitosan-coated PCL nanoparticles may be considered a promising strategy to deliver curcumin directly into the oral cavity for the treatment of oral cancer.