Immediate pain alleviation in oral mucositis and other oral ulcerative diseases through photobiomodulation therapy: the preemptive treatment concept.

OBJECTIVE: Photobiomodulation (PBM) therapy is recommended by multiple international societies for managing oral mucositis (OM). These recommendations are based on extensive evidence. However, the search for an optimal PBM protocol continues. This mapping review focuses on a novel aspect of PBM therapy which is the immediate effect on pain levels associated with oral ulcerative conditions. DATA SOURCES: This literature review systematically compiles and evaluates the evidence about OM, alongside other oral ulcerative conditions, as the protocols that achieved pain relief for these oral conditions may have potential applicability to OM management. The scientific database used was PubMed. CONCLUSION: Whereas most of the randomized controlled trials about PBM therapy for OM and other ulcerative oral diseases reported delayed pain relief, certain PBM therapy protocols reported immediate pain relief. The results of this review highlight the concept of preemptive PBM therapy, in which PBM therapy is delivered early in the development of OM throughout the oncotherapy and may achieve immediate pain relief consistently in most of the patients and close to a negligible pain level. PBM therapy, as a powerful non-pharmacologic tool for immediate pain relief, has a great beneficial value in patients suffering from OM and other painful oral ulcerative diseases such as recurrent aphthous stomatitis and chronic graft-versus-host disease.

[Photobiomodulation in the prevention and the management of side effects of cancer treatments: Bases, results and perspectives]. / Photobiomodulation dans la prévention et la prise en charge des effets secondaires des traitements anticancéreux : bases, bilan et perspectives.

BACKGROUND: Assess the current and potential indications of photobiomodulation (PBM) therapy and their level of evidence in the prevention or treatment of side effects related to oncology treatments (radiation therapy, and to a minimal extent favored and hematopoietic stem cell transplants). And report on the recommended modalities (parameters and doses) of PBM therapy. MATERIALS AND METHODS: The Embase, Medline/PubMed, Cochrane, EBSCO, Scopus, and LILACS databases were systematically reviewed to include and analyze publications of clinical studies that evaluated PBM in the prevention or management side effects related to cancer treatments. The keywords used were "photobiomodulation"; "low level laser therapy"; "acute oral mucositis"; "acute dysphagia"; "acute radiation dermatitis"; "lymphedema"; "xerostomia"; "dysgeusia"; "hyposalivation"; "lockjaw"; "bone necrosis"; "osteoradionecrosis"; "radiation induced fibrosis"; "voice and speech alterations"; "palmar-plantar erythrodysesthesia"; "graft versus host disease"; "peripheral neuropathy"; "chemotherapy induced alopecia". Prospective studies were included, while retrospective cohorts and non-original articles were excluded from the analysis. RESULTS: PBM in the red or infrared spectrum has been shown to be effective in randomized controlled trials in the prevention and management of certain complications related to radiotherapy, in particular acute mucositis, epitheliitis and upper limb lymphedema. The level of evidence associated with PBM was heterogeneous, but overall remained moderate. The main limitations were the diversity and the lack of precision of the treatment protocols which could compromise the efficiency and the reproducibility of the results of the PBM. For other effects related to chemo/radiation therapy (dysgeusia, osteonecrosis, peripheral neuropathy, alopecia, palmar-plantar erythrodysaesthesia) and haematopoietic stem cell transplantation (graft versus host disease), treatment with PBM suffers from a lack of studies or limited studies at the origin of a weakened level of proof. However, based on these results, it was possible to establish safe practice parameters and doses of PBM. CONCLUSION: Published data suggest that PBM could therefore be considered as supportive care in its own right for patients treated with radiation, chemotherapy, immunotherapy, hormone therapy or targeted therapies, whether in clinical practice or clinical trials. therapies. However, until solid data have been published on its long-term safety, the use of PBM should be considered with caution and within the recommended parameters and doses, particularly when practiced in areas of known or possible tumours. In this case, the patient should be informed of the theoretical benefits and risks of PBM in order to obtain informed consent before treatment.

Tideglusib-incorporated nanofibrous scaffolds potently induce odontogenic differentiation.

Pulp-Dentin regeneration is a key aspect of maintain tooth vitality and enabling good oral-systemic health. This study aimed to investigate a nanofibrous scaffold loaded with a small molecule i.e. Tideglusib to promote odontogenic differentiation. Tideglusib (GSK-3ß inhibitor) interaction with GSK-3ß was determined using molecular docking and stabilization of ß-catenin was examined by confocal microscopy. 3D nanofibrous scaffolds were fabricated through electrospinning and their physicochemical characterizations were performed. Scaffolds were seeded with mesenchymal stem cells or pre-odontoblast cells to determine the cells proliferation and odontogenic differentiation. Our results showed that Tideglusib (TG) binds with GSK-3ß at Cys199 residue. Stabilization and nuclear translocation of ß-catenin was increased in the odontoblast cells treated with TG. SEM analysis revealed that nanofibers exhibited controlled architectural features that effectively mimicked the natural ECM. UV-Vis spectroscopy demonstrated that TG was incorporated successfully and released in a controlled manner. Both kinds of biomimetic nanofibrous matrices (PCLF-TG100, PCLF-TG1000) significantly stimulated cells proliferation. Furthermore, these scaffolds significantly induced dentinogenic markers (ALP, and DSPP) expression and biomineralization. In contrast to current pulp capping material driving dentin repair, the sophisticated, polymeric scaffold systems with soluble and insoluble spatiotemporal cues described here can direct stem cell differentiation and dentin regeneration. Hence, bioactive small molecule-incorporated nanofibrous scaffold suggests an innovative clinical tool for dentin tissue engineering.

Dual-Scan Photoacoustic Tomography for the Imaging of Vascular Structure on Foot.

Chronic leg ulcers are affecting approximately 6.5 million Americans, and they are associated with significant mortality, reduced quality of life, and high treatment costs. Since many chronic ulcers have underlying vascular insufficiency, accurate assessment of tissue perfusion is critical to treatment planning and monitoring. This study introduces a dual-scan photoacoustic (PA) tomography (PAT) system that can simultaneously image the dorsal and plantar sides of the foot to reduce imaging time. To account for the unique shape of the foot, the system employs height-adjustable and articulating baseball stages that can scan along the foot's contour. In vivo results from healthy volunteers demonstrate the system's ability to acquire clear images of foot vasculature, and results from patients indicate that the system can image patients with various ulcer conditions. We also investigated various PA features and examined their correlation with the foot condition. Our preliminary results indicate that vessel sharpness, occupancy, intensity, and density could all be used to assess tissue perfusion. This research demonstrated the potential of PAT for routine clinical tissue perfusion assessment.

Medication-Related Osteonecrosis of the Jaw: Successful Medical Management of Complex Maxillary Alveolus with Sinus Involvement.

Medication-related osteonecrosis of the jaw (MRONJ) in cancer patients presents a considerable challenge in management. Current management is primarily based on interventions in a limited number of cases assessing a single approach. Medical management typically is reported to include antimicrobial therapy with or without surgery. Advances in the understanding of pathogenesis have led to the investigation of additional medical interventions for early-stage necrosis. We present 3 patients with advanced-stage MRONJ of the maxilla using combined medical modalities including antimicrobial therapy, photobiomodulation therapy, pentoxifylline, vitamin E, and synthetic parathyroid hormone. All patients had a good outcome and avoided surgical intervention. We also report biological and functional imaging that may assist in more effective diagnosis and management of MRONJ. The 3 patients reported suggest that combined medical management should be considered in all cases of MRONJ (including stage III) prior to determining if surgical intervention is required. Functional imaging with a technetium bone scan or positron emission tomography scan correlated with diagnosis and confirmed resolution in patients. We present 3 challenging MRONJ patients that were effectively managed with a combined medical and nonsurgical therapy that demonstrated good clinical outcomes avoiding surgical interventions.

Dose-response relationship of photobiomodulation therapy and oxidative stress markers in healing dynamics of diabetic neuropathic ulcers in Wistar rats.

Purpose: Diabetic foot ulcers are reported to be the most expensive complications of diabetes, with high morbidity and mortality rates. If the necessary care is not provided for the wound to heal, the individual may end up amputating the affected feet. Photobiomodulation therapy is a promising non-pharmacological treatment option for wound healing. The objective of the present study is to establish a dose-response relationship between photobiomodulation therapy and oxidative stress markers in the healing dynamics of diabetic neuropathic ulcers in Wistar rats. Methodology: Diabetic neuropathy was induced in 126 Albino Wistar rats. An excisional wound of an area of 2cm2 was made on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12, and 15 J/cm2 of wavelengths 655 and 808 nm was irradiated. The control group animals were kept un-irradiated. The outcome measures were assessed during wound healing's inflammatory, proliferative and remodelling phases. Results: In the experimental group, animals treated with photobiomodulation therapy at doses of 4, 6, and 8 J/cm2 showed better wound healing dynamics. Photobiomodulation therapy modulated the reactive oxygen species and antioxidant levels, thereby improving the oxidative status of the wound. Conclusion: Photobiomodulation therapy of dosages 4, 6, and 8 J/cm2 is effective and is a promising adjuvant modality in treating diabetic neuropathic ulcers. There was a strong dose-response relationship in the experimental groups treated with 4, 6 and 8 J/ cm2. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01157-2.

Quality assessment of PBM protocols for oral complications in head and neck cancer patients: part 2.

PURPOSE: To investigate the role of photobiomodulation (PBM) in patients undergoing head and neck cancer (HNC) treatment. We focused on the consequences of the main complications, such as quality of life (QoL), analgesia, functional impairment, and nutritional status, as well as on the impact on survival/ recurrences, radiotherapy (RT) interruption, adherence, cost-effectiveness, safety, feasibility, and tolerability. METHODS: An electronic search in PubMed and Scopus databases was performed. Full texts were carefully assessed, and data were assimilated into a tabular form for discussion and consensus among the expert panel. RESULTS: A total of 22 papers were included. Overall, a beneficial effect of PBM was evidenced in the amelioration of QoL, nutritional status, the reduction of pain, and functional impairment. Preventive PBM may reduce the incidence and duration of RT interruptions, potentially contributing to improved cancer treatment outcomes. PBM treatments are safe and recommended for routine use, with the caveat of avoiding direct tumor exposures where feasible. However, it does not appear to impact cancer survivorship/recurrences directly. Despite additional clinical efforts involving routine PBM use, the individual and public health benefits will positively impact oncology care. CONCLUSIONS: Quality of life, pain and functional impairment, nutritional status, and survival may be effectively improved with PBM. Given its established efficacy also in reducing RT interruptions and its safety, feasibility, and tolerability, PBM should be included in the field of supportive cancer care in HNC patients. Improved understanding of PBM mechanisms and precise dose parameters is enabling the generation of more robust, safe, and reproducible protocols; thus, it is imperative to support further clinical implementation as well as both applied and basic science research in this novel field.

Use of either transcranial or whole-body photobiomodulation treatments improves COVID-19 brain fog.

There is increasing recognition of post-COVID-19 sequelae involving chronic fatigue and brain fog, for which photobiomodulation (PBM) therapy has been utilized. This open-label, pilot, human clinical study examined the efficacy of two PBM devices, for example, a helmet (1070 nm) for transcranial (tPBM) and a light bed (660 and 850 nm) for whole body (wbPBM), over a 4-week period, with 12 treatments for two separate groups (n = 7 per group). Subjects were evaluated with a neuropsychological test battery, including the Montreal Cognitive Assessment (MoCA), the digit symbol substitution test (DSST), the trail-making tests A and B, the physical reaction time (PRT), and a quantitative electroencephalography system (WAVi), both pre- and post- the treatment series. Each device for PBM delivery was associated with significant improvements in cognitive tests (p < 0.05 and beyond). Changes in WAVi supported the findings. This study outlines the benefits of utilizing PBM therapy (transcranial or whole-body) to help treat long-COVID brain fog.

Photobiomodulation therapy mitigates cardiovascular aging and improves survival.

BACKGROUND: Photobiomodulation (PBM) therapy, a form of low-dose light therapy, has been noted to be effective in several age-associated chronic diseases such as hypertension and atherosclerosis. Here, we examined the effects of PBM therapy on age-associated cardiovascular changes in a mouse model of accelerated cardiac aging. METHODS: Fourteen months old Adenylyl cyclase type VIII (AC8) overexpressing transgenic mice (n = 8) and their wild-type (WT) littermates (n = 8) were treated with daily exposure to Near-Infrared Light (850 nm) at 25 mW/cm2 for 2 min each weekday for a total dose of 1 Einstein (4.5 p.J/cm2 or fluence 3 J/cm2 ) and compared to untreated controls over an 8-month period. PBM therapy was administered for 3.5 months (Early Treatment period), paused, due to Covid-19 restrictions for the following 3 months, and restarted again for 1.5 months. Serial echocardiography and gait analyses were performed at monthly intervals, and serum TGF-ß1 levels were assessed following sacrifice. RESULTS: During the Early Treatment period PBM treatments: reduced the age-associated increases in left ventricular (LV) mass in both genotypes (p = 0.0003), reduced the LV end-diastolic volume (EDV) in AC8 (p = 0.04); and reduced the left atrial dimension in both genotypes (p = 0.02). PBM treatments substantially increased the LV ejection fraction (p = 0.03), reduced the aortic wall stiffness (p = 0.001), and improved gait symmetry, an index of neuro-muscular coordination (p = 0.005). The effects of PBM treatments, measured following the pause, persisted. Total TGF-ß1 levels were significantly increased in circulation (serum) in AC8 following PBM treatments (p = 0.01). We observed a striking increase in cumulative survival in PBM-treated AC8 mice (100%; p = 0.01) compared to untreated AC8 mice (43%). CONCLUSION: PBM treatment mitigated age-associated cardiovascular remodeling and reduced cardiac function, improved neuromuscular coordination, and increased longevity in an experimental animal model. These responses correlate with increased TGF-ß1 in circulation. Future mechanistic and dose optimization studies are necessary to assess these anti-aging effects of PBM, and validation in future controlled human studies is required for effective clinical translation.

Effect of photobiomodulation therapy on inflammatory cytokines in healing dynamics of diabetic wounds: a systematic review of preclinical studies.

CONTEXT: Delayed wound healing in diabetes mellitus (DM) is due to the overlapping phases of the healing process. The prolonged inflammation and altered levels of inflammatory cytokines lead to deformed cell proliferation. Photobiomodulation alleviates the expression of inflammatory cytokines and promotes tissue repair, thereby restoring the wound healing process. OBJECTIVE: To find out the effect of photobiomodulation therapy (PBMT) in the healing dynamics of diabetic wounds with particular emphasis on interleukin-6, interleukin-1ß, and tumour necrosis factor-α. METHODS: Scientific databases searched using keywords of the population: DM, intervention: PBMT, and outcomes: inflammatory cytokines. RESULTS: We have included five preclinical studies in the present systematic review for qualitative analysis. These studies evaluated the effect of PBMT at different wavelengths, dosage, and time on wound healing in DM. CONCLUSIONS: The systematic review concludes that PBMT regulates inflammatory cytokines levels, enhances cell proliferation, and migration, thereby improving the wound healing properties.

Dose-Response Relationship of Photobiomodulation Therapy on Matrix Metalloproteinase in Healing Dynamics of Diabetic Neuropathic Ulcers-An in vivo Study.

Individuals with diabetic foot ulcers have overlapped the inflammatory, proliferative and remodeling phase, making the tissue vulnerable to delayed healing responses. We aimed to establish the dose-response relationship of photobiomodulation therapy of different doses and matrix metalloproteinases in the healing dynamics of diabetic neuropathic ulcers. Diabetes was induced in 126 Albino Wistar rats, and neuropathy was induced to the hind paw by a sciatic nerve injury method. An excisional wound was created on the neuropathy-induced leg. Photobiomodulation therapy of dosages 4, 6, 8, 10, 12 and 15 J cm-2 and wavelength 655 nm and 808 nm was irradiated. Photobiomodulation therapy of dosages 4, 6 and 8 J cm-2 showed better wound healing properties with optimized levels of matrix metalloproteinases-1 and 8. We observed a strong dose response in the experimental group treated with 6 and 8 J cm-2 . The findings from the present study conclude that photobiomodulation therapy of dosages 4, 6 and 8 J cm-2 is suggestive of usefulness in diabetic neuropathic ulcer healing. Markers like matrix metalloproteinases may give a clear direction on response to the therapy. Based on the findings from the present study, we recommend to validate the findings for safety and efficacy in future through human prospective randomized controlled clinical trials.

Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.

Comparison of Pulsed and Continuous Wave Diode Laser at 940 nm on the Viability and Migration of Gingival Fibroblasts.

Gingival fibroblasts have critical roles in oral wound healing. Photobiomodulation (PBM) has been shown to promote mucosal healing and is now recommended for managing oncotherapy-associated oral mucositis. This study examined the effects of the emission mode of a 940 nm diode laser on the viability and migration of human gingival fibroblasts. Cells were cultured in a routine growth media and treated with PBM (average power 0.1 W cm-2 , average fluence 3 J cm-2 , every 12 h for six sessions) in one continuous wave and two pulsing settings with 20% and 50% duty cycles. Cell viability was assessed using MTT, and digital imaging quantified cell migration. After 48 and 72 h, all treatment groups had significantly higher viability (n = 6, P < 0.05) compared with the control. The highest viability was seen in the pulsed (20% duty cycle) group at the 72-h time point. PBM improved fibroblast migration in all PBM-treated groups, but differences were not statistically significant (n = 2, P > 0.05). PBM treatments can promote cell viability in both continuous and pulsed modes. Further studies are needed to elucidate the optimal setting for PBM-evoked responses for its rationalized use in promoting specific phases of oral wound healing.

Automation in Dentistry with Mechanical Drills and Lasers for Implant Osteotomy: A Narrative-Scoping Review.

The popularity of implants is increasing with the aging population requiring oral-dental rehabilitation. There are several critical steps in the implant workflow, including case selection, implant design, surgical procedure, biological tissue responses, and functional restoration. Among these steps, surgical osteotomy procedures are a crucial determinant of clinical success. This brief review was aimed at outlining the current state of the field in automation-assisted implant surgical osteotomy technologies. A broad search of the literature was performed to identify current literature. The results are outlined in three broad categories: semi-automated static (image-guided) or dynamic (navigation-assisted) systems, and fully-automated robotic systems. As well as the current mechanical rotary approaches, the literature supporting the use of lasers in further refinement of these approaches is reviewed. The advantages and limitations of adopting autonomous technologies in practical clinical dental practices are discussed. In summary, advances in clinical technologies enable improved precision and efficacious clinical outcomes with implant dentistry. Hard-tissue lasers offer further advancements in precision, improved biological responses, and favorable clinical outcomes that require further investigation.

Photobiomodulation therapy in management of cancer therapy-induced side effects: WALT position paper 2022.

Disclaimer: This article is based on recommendations from the 12th WALT Congress, Nice, October 3-6, 2018, and a follow-up review of the existing data and the clinical observations of an international multidisciplinary panel of clinicians and researchers with expertise in the area of supportive care in cancer and/or PBM clinical application and dosimetry. This article is informational in nature. As with all clinical materials, this paper should be used with a clear understanding that continued research and practice could result in new insights and recommendations. The review reflects the collective opinion and, as such, does not necessarily represent the opinion of any individual author. In no event shall the authors be liable for any decision made or action taken in reliance on the proposed protocols. Objective: This position paper reviews the potential prophylactic and therapeutic effects of photobiomodulation (PBM) on side effects of cancer therapy, including chemotherapy (CT), radiation therapy (RT), and hematopoietic stem cell transplantation (HSCT). Background: There is a considerable body of evidence supporting the efficacy of PBM for preventing oral mucositis (OM) in patients undergoing RT for head and neck cancer (HNC), CT, or HSCT. This could enhance patients' quality of life, adherence to the prescribed cancer therapy, and treatment outcomes while reducing the cost of cancer care. Methods: A literature review on PBM effectiveness and dosimetry considerations for managing certain complications of cancer therapy were conducted. A systematic review was conducted when numerous randomized controlled trials were available. Results were presented and discussed at an international consensus meeting at the World Association of photobiomoduLation Therapy (WALT) meeting in 2018 that included world expert oncologists, radiation oncologists, oral oncologists, and oral medicine professionals, physicists, engineers, and oncology researchers. The potential mechanism of action of PBM and evidence of PBM efficacy through reported outcomes for individual indications were assessed. Results: There is a large body of evidence demonstrating the efficacy of PBM for preventing OM in certain cancer patient populations, as recently outlined by the Multinational Association for Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Building on these, the WALT group outlines evidence and prescribed PBM treatment parameters for prophylactic and therapeutic use in supportive care for radiodermatitis, dysphagia, xerostomia, dysgeusia, trismus, mucosal and bone necrosis, lymphedema, hand-foot syndrome, alopecia, oral and dermatologic chronic graft-versus-host disease, voice/speech alterations, peripheral neuropathy, and late fibrosis amongst cancer survivors. Conclusions: There is robust evidence for using PBM to prevent and treat a broad range of complications in cancer care. Specific clinical practice guidelines or evidence-based expert consensus recommendations are provided. These recommendations are aimed at improving the clinical utilization of PBM therapy in supportive cancer care and promoting research in this field. It is anticipated these guidelines will be revised periodically.

Quality Assessment of PBM Protocols for Oral Complications in Head and Neck Cancer Patients: Part 1.

Background: Radiotherapy and chemotherapy are frequently employed in head and neck cancer (HNC) patients causing significant side effects that impair life quality and prognosis. Photobiomodulation (PBM) has become a growing approach to managing such oral complications. Despite its proven efficacy and absence of contraindications, there is still a lack of universally accepted disease-specific PBM protocols. Objective: A narrative review was conducted to identify the current proposals relating to the use of PBM to treat complications of oncological treatments in HNC patients. Methods: An electronic search in PubMed and Scopus databases was performed with the following keywords: ("photobiomodulation" OR "PBM" OR "laser therapy" OR "LLLT" OR "laser") AND ("head and neck cancer" OR "oral cancer") AND ("mucositis" OR "oral mucositis" OR "dysgeusia" OR "oedema" OR "xerostomia" OR "dermatitis" OR "trismus") until October 2021. Results: A total of 35 papers were included in the narrative review. Oral mucositis was the most studied complication, and advisable protocols are conceivable. Although there is a growing interest in PBM to manage of xerostomia, radiodermatitis, pain, and trismus, literature is still scarce to propose a universally feasible protocol. Conclusions: PBM therapy could significantly prevent or reduce the severity of many side effects related to cancer therapies. More research is needed to obtain recommendations over the preferable parameters.

Redox signaling induces laminin receptor ribosomal protein-SA expression to improve cell adhesion following radiofrequency glow discharge treatments.

Current biomaterials effectively replace biological structures but are limited by infections and long-term material failures. This study examined the molecular mechanisms of radio frequency glow discharge treatments (RFGDT) in mediating the disinfection of biomaterial surfaces and concurrently promoting cell attachment and proliferation. Dental biomaterials were subjected to RFGDT, and viability of oral microbial species, namely Streptococcus mutants (SM), Streptococcus gordonii (SG), Moraxella catarrhalis (MC), and Porphyromonas gingivalis (PG), were assessed. Cell attachment and survival of a pre-odontoblast cell line, MDPC-23, was examined. Finally, mechanistic investigations into redox generation and biological signaling were investigated. Based on their compositions, dental biomaterials induced reactive oxygen species (ROS) following dose-dependent RFGDT. Reduced microbial viability was evident following RFGDT in the catalase-negative (SM and SG) species more prominently than catalase-positive (MC and PG) species. Cell adhesion assays noted improved MDPC-23 attachment and survival. Pretreatments with N-acetylcysteine (NAC) and catalase abrogated these responses. Immunoassays noted redox-induced downstream expression of a laminin receptor, Ribosomal Protein SA, following RFGDT. Thus, RFGDT-induced redox mediates antimicrobial and improves cell responses such as adhesion and proliferation. These observations together provide a mechanistic rationale for the clinical utility of RFGDT with dental biomaterials for regenerative clinical applications.

Photobiomodulation treatments drive osteogenic versus adipocytic fate of bone marrow mesenchymal stem cells reversing the effects of hyperglycemia in diabetes.

Diabetes mellitus (DM) is a chronic metabolic disease that affects bone metabolism, which can be related to a reduced osteogenic potential of bone marrow mesenchymal stem cells (BM-MSCs). MSCs from diabetic rats (dBM-MSC) have shown a tendency to differentiate towards adipocytes (AD) instead of osteoblasts (OB). Since photobiomodulation (PBM) therapy is a non-invasive treatment capable of recovering the osteogenic potential of dBM-MSCs, we aimed to evaluate whether PBM can modulate MSC's differentiation under hyperglycemic conditions. BM-MSCs of healthy and diabetic rats were isolated and differentiated into osteoblasts (OB and dOB) and adipocytes (AD and dAD). dOB and dAD were treated with PBM every 3 days (660 nm; 5 J/cm2; 0.14 J; 20 mW; 0.714 W/cm2) for 17 days. Cell morphology and viability were evaluated, and cell differentiation was confirmed by gene expression (RT-PCR) of bone (Runx2, Alp, and Opn) and adipocyte markers (Pparγ, C/Ebpα, and C/Ebpß), production of extracellular mineralized matrix (Alizarin Red), and lipid accumulation (Oil Red). Despite no differences on cell morphology, the effect of DM on cells was confirmed by a decreased gene expression of bone markers and matrix production of dOB, and an increased expression of adipocyte and lipid accumulation of dAD, compared to heatlhy cells. On the other hand, PBM reversed the effects of dOB and dAD. The negative effect of DM on cells was confirmed, and PBM improved OB differentiation while decreasing AD differentiation, driving the fate of dBM-MSCs. These results may contribute to optimizing bone regeneration in diabetic patients.

Precision-engineered niche for directed differentiation of MSCs to lineage-restricted mineralized tissues.

The major difference between tissue healing and regeneration is the extent of instructional cues available to precisely direct the biological response. A classic example is reparative or osteodentin that is seen in response to physicochemical injury to the pulp-dentin complex. Dentin regeneration can direct the differentiation of dental stem cells using concerted actions of both soluble (biomolecules, agonists, and antagonists) and insoluble (matrix topology) cues. The major purpose of this study was to examine the synergistic combination of two discrete biomaterial approaches by utilizing nanofiber scaffolds in discrete configurations (aligned or random) with incorporated polymeric microspheres capable of controlled release of growth factors. Further, to ensure appropriate disinfection for clinical use, Radio-Frequency Glow Discharge (RFGD) treatments were utilized, followed by seeding with a mesenchymal stem cell (MSC) line. SEM analysis revealed electrospinning generated controlled architectural features that significantly improved MSC adhesion and proliferation on the aligned nanofiber scaffolds compared to randomly oriented scaffolds. These responses were further enhanced by RFGD pre-treatments. These enhanced cell adhesion and proliferative responses could be attributed to matrix-induced Wnt signaling that was abrogated by pre-treatments with anti-Wnt3a neutralizing antibodies. Next, we incorporated controlled-release microspheres within these electrospun scaffolds with either TGF-ß1 or BMP4. We observed that these scaffolds could selectively induce dentinogenic or osteogenic markers (DSPP, Runx2, and BSP) and mineralization. This work demonstrates the utility of a novel, modular combinatorial scaffold system capable of lineage-restricted differentiation into bone or dentin. Future validation of this scaffold system in vivo as a pulp capping agent represents an innovative dentin regenerative approach capable of preserving tooth pulp vitality.

Thermodynamic basis for comparative photobiomodulation dosing with multiple wavelengths to direct odontoblast differentiation.

Multiple wavelength devices are now available for photobiomodulation (PBM) treatments, but their dosimetry for individual or combinatorial use remains unclear. The present work investigated the effects of 447, 532, 658, 810, 980 and 1064 nm wavelengths on odontoblast differentiation at 10 mW/cm2 using either equal treatment time for conventional fluence (300 seconds for 3 J/cm2 ) or varying times to adjust for individual wavelength photon fluence (4.6 p.J/cm2 ). Both 447 and 810 nm significantly increased alkaline phosphatase (ALP) activity, while 1064 nm showed reduced ALP activity at 3 J/cm2 . However, ALP induction was significantly improved when equivalent photon fluence dosing was used. Other wavelengths did not show significant changes compared to untreated controls. The data suggest that accounting for wavelength-specific photon energy transfer during PBM dosing could improve clinical safety and efficacy.