Urinary tract infections (UTIs) are among the most common infections worldwide, with many hospital-acquired cases linked to biofilm formation on urinary catheter surfaces. The growing problem of antimicrobial resistance limits the effectiveness of conventional antibiotics, and antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative. This approach is based on the combination of a photosensitizer (PS), dioxygen, and visible light to reduce bacterial concentration without promoting resistance. In this study, the potential of aPDT in controlling UTIs was evaluated using a well-studied PS, methylene blue (MB), alone or in the presence of potassium iodide (KI). Ex vivo assays in urine were conducted using the five most common UTI-causing bacteria: Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Proteus mirabilis, and Pseudomonas aeruginosa. MB alone effectively photoinactivated E. coli, P. mirabilis, and E. faecalis in planktonic form, with limited activity against K. pneumoniae and P. aeruginosa. The addition of KI significantly enhanced the photodynamic effect against all tested strains, resulting in a reduced treatment time, and was also effective against mixed bacterial populations in the planktonic state. The efficacy of the treatments was further evaluated against E. coli cells within biofilms formed on urinary catheter surfaces. The combined action of MB and KI successfully controlled E. coli biofilms, achieving reductions of 3.9 (> 99.987%) and 6.0 log10 CFU mL-1 after one and two aPDT treatment cycles, respectively. Overall, these findings highlight MB + KI-mediated aPDT as a promising strategy for the photoinactivation of planktonic uropathogens and E. coli biofilms formed on urinary catheter surfaces.
Acne vulgaris is a wordwide distressing skin condition which is often treated by topical antibiotics or retinoids, and in severe cases with oral medications. It is generated by a series of factors including excess sebum production clogging sebaceous glands and infection with Cutibacterium acnes producing inflammation. Photodynamic therapy (PDT) with topical aminolevulanic acid or its methyl ester plus red light has shown good results, especially for inflammatory lesions. The present study investigated the use of a new photosensitzer Rose Bengal acetate (RBAc) for acne PDT treatment. RBAc plus green light killed 6 logs of C. acnes bacteria in vitro at <1 μM. Three daily intradermal injections of C. acnes bacteria into the back of Balb/c mice produced acne-like lesions. A hyaluronic-acid gel containing RBAc (0-600 μM) was topically applied to the lesions followed after 1 h by 20 J/cm2 of 540 nm light. RBAc at a concentration of 200 μM gave the most pronounced reduction in lesion area at days 1-4 post-PDT. Histology, immunohistochemistry, TUNEL staining and Western blotting at 10 days showed that RBAc-PDT reduced the inflammatory response and promoted apoptosis in the lesion tissue. These findings support RBAc-PDT as a promising and well-tolerated topical candidate for further preclinical and clinical evaluation in acne management.
Extrinsic photobiomodulation (EPM) combined with microisland offers a universal approach to induce and direct mesenchymal stem cell differentiation. In this study, the dependencies of differentiation of human umbilical cord Wharton's Jelly mesenchymal stem cells driven by this method on various EPM parameters as well as initial cell stemness were investigated and an epigenetic landscape model was established to explain the results consistently. Furthermore, the signal cascade pathway was studied and it was found that photosensitizer binding to endoplasmic reticulum was the primary receptor and the increase of nuclear Ca2+ level was the second messenger. Moreover, the number, size, and concentration of bromodomain-containing protein 4 (BRD4)-containing nuclear condensates were reduced when the cells were on microislands and treated by EPM, indicating this change was involved in the alteration of epigenetic modification that led to the conversion of cell phenotype.
Melanins are pigments that protect tissues against the damaging effects of solar radiation. Photodegradation of these pigments adversely alters their key physicochemical properties, diminishing redox buffering while increasing photochemical reactivity and driving supramolecular reorganization manifested as a decrease in the size of pigment-forming aggregates. In this study, UV-Vis, EPR, and FTIR were combined to directly correlate photodegradation-induced changes in optical and paramagnetic properties, with particular emphasis on alterations in the chemical groups present in the pigments. In addition, molecular electrostatic potential maps were computed for selected eumelanin and pheomelanin models spanning distinct redox states and levels of structural complexity. Upon aerobic photolysis, both pigments gradually bleached, their free radical content decreased and in pheomelanin, marked changes in radical character occurred. FTIR analysis revealed progressive loss of hydroxyl and amino groups, increased oxidation of carbonyl and aromatic functionalities, and alterations in aliphatic side chains and heterocycles, with distinct patterns for eumelanin and pheomelanin. The FTIR changes observed in photodegraded pheomelanin indicate a shift in ring character consistent with a benzothiazine-to-benzothiazole transformation, accompanied by a substantial reduction in bands associated with intermolecular interactions between structural motifs within the polymer network. In eumelanin, the spectral changes indicate a shift toward more conjugated structures. Analysis of molecular electrostatic potential maps indicated an increasing potential for hydrogen-bonded interactions upon eumelanin oxidation, as well as a greater propensity of eumelanin for stacking compared to pheomelanin, which has more H-bond donor and acceptor sites.
Brunfelsia acuminata (Pohl) Benth. exhibits a distinctive post-anthesis transition in flower color from purple to white, which is closely associated with anthocyanin degradation. However, the photobiological mechanisms regulating pigment stability during petal senescence remain poorly understood. In this study, we investigated how different light qualities affect anthocyanin degradation, flavonoid and phenolic metabolism, and the expression of key anthocyanin biosynthetic genes in detached petals and flowers on intact plants. Among nine continuous light-quality treatments, red light most effectively delayed petal discoloration, whereas blue light accelerated anthocyanin loss. Further analyses under fluorescent, white, red, and blue light confirmed that red light consistently maintained higher anthocyanin levels, whereas blue light led to the most rapid decline in pigment levels. HPLC analysis identified malvidin 3-O-glucoside, petunidin 3-O-glucoside, and delphinidin 3-O-glucoside as the major anthocyanins, with malvidin 3-O-glucoside as the predominant pigment retained under red light. Quantitative real-time PCR analysis of key structural genes in the anthocyanin biosynthetic pathway indicated that CHS (chalcone synthase), CHI (chalcone isomerase), F3'5'H (flavonoid 3'5'-hydroxylase), DFR (dihydroflavonol 4-reductase), ANS (anthocyanidin synthase), and UGT (anthocyanidin 3-O-glucoside 2″'-O-xylosyltransferase) declined during petal senescence, but red light significantly sustained the expression of DFR, ANS, and UGT relative to blue and fluorescent light. These results suggest that red light, likely through phytochrome-mediated signaling, delays petal fading by maintaining anthocyanin biosynthetic and glycosylation capacity, thereby enhancing pigment stability, whereas blue light, likely associated with cryptochrome-related signaling and greater photochemical stress, fails to sustain these pathways and is associated with accelerated pigment degradation. This study provides mechanistic insight into light-quality regulation of anthocyanin stability and identifies red-light treatment as a non-chemical approach for preserving postharvest ornamental quality.
Photobiomodulation therapy combined with static magnetic field (PBMT-sMF) has demonstrated beneficial effects on skeletal muscle cells under oxidative stress. However, its potential as a preconditioning strategy - applied prior to an oxidative challenge - remains poorly investigated at the cellular level. This study aimed to evaluate the cytoprotective effects of PBMT-sMF preconditioning in C2C12 myoblasts under oxidative stress induced by hydrogen peroxide (H₂O₂). Cells were irradiated at three energy doses (9, 30, and 60 J) and, after a 3-h interval, subjected to 700 μM H₂O₂ for 1 h. Cell viability, nitric oxide (NO) production, reactive oxygen species (ROS) generation, and extracellular double-stranded DNA (dsDNA) were assessed. Three composite indices - the Cytoprotective Index (CPI), ROS Production per Viable Cell (RPVC), and NO Production per Viable Cell (NOPVC) - were calculated to provide an integrated interpretation of the dose-dependent cytoprotective response. H₂O₂ significantly reduced cell viability and elevated both ROS and NO production. Preconditioning with 9 J fully restored cell viability, normalized ROS to control levels, and reduced NO production below basal values, with comprehensive protection confirmed across all three composite indices. The 30 J dose conferred partial protection, with significant reductions in ROS and NO production and partial restoration of cell viability, whereas 60 J not only failed to protect but, paradoxically, worsened the oxidative and nitrosative burden per surviving cell. No significant differences in dsDNA levels were observed across groups. These findings demonstrate that PBMT-sMF preconditioning exerts dose-dependent cytoprotective effects consistent with a hormetic dose-response pattern, with 9 J emerging as the most effective dose among the three tested (9, 30, and 60 J). The temporal interval between irradiation and oxidative challenge is identified as a biologically active parameter, contributing to a more rational design of prophylactic photobiomodulation protocols.
The hypoxic tumor microenvironment (TME) of hepatocellular carcinoma (HCC) featured overexpressed hypochlorite (ClO-), which represented both a biochemical hallmark and a potential therapeutic trigger. Herein, POR-CA, a near-infrared (NIR) activatable prodrug constructed by conjugating cinnamic acid to a 4-(4-aminophenyl) porphyrin fluorophore, was reported. Exposure to ClO- produced a concentration-dependent decrease in near-infrared fluorescence, enabling fluorescence-quenching sensing under the tested conditions. Spectroscopic characterization confirmed rapid and sensitive ClO- responsiveness with favorable pH stability. Notably, the porphyrin backbone acted as an intrinsic photosensitizer to generate reactive oxygen species (ROS) under 660 nm laser irradiation for photodynamic therapy (PDT). HRMS provided evidence consistent with ClO--induced cleavage and formation of a TAPP-related fragment. POR-CA exhibited differential dark cytotoxicity in HepG-2 and LO-2 cells and light-dependent phototoxicity under the tested conditions. These results supported POR-CA as an in vitro proof-of-concept platform integrating ClO--responsive fluorescence-quenching sensing with light-dependent phototoxicity, while the contribution of the released cinnamic-acid-derived component remained to be established. Nonetheless, this molecular design perspective served as a valuable reference for subsequent translational optimization.
This study investigated the effect of low-level laser therapy (LLLT) on the pulpal alterations caused by tooth movement in diabetic rats. Forty-eight Wistar rats were divided into control (CTR), diabetic (DBT), and LLLT-treated counterparts. Diabetes was induced with alloxan, and orthodontic movement was performed for 13 days. LLLT (780 nm, 35 J/cm2) was applied every 48 h for 7 days. Histological analyses assessed inflammation, stromal cell density (SCD), blood vessel count (BVC), odontoblastic layer thickness (OLT), and collagen deposition at 7 and 13 days. In 7 days, the DBT group showed significantly increased inflammation (p < 0.01), and decreased blood vessel count (p < 0.001) and cell rates (p < 0.01) compared to CTR. The DBT/LT group presented inflammatory, vascular, and cell rates comparable to CTR, meaning LLLT reversed these changes. However, DBT/LT still showed significantly increased collagenization at both 7 (p < 0.05) and 13 days (p < 0.001). LLLT attenuates diabetes-exacerbated histological pulpal damage during orthodontic movement, supporting its potential as an adjunctive therapy in hyperglycemic conditions.
Melatonin is traditionally classified as a melanogenesis inhibitor. However, in some tissues it has been recently found to stimulate melanogenesis, paradoxically, with a parallel decrease of tyrosinase activity. This study explores this paradox by examining melatonin's potential role in pigment formation. Pigments were synthesized from DL-DOPA and melatonin via autooxidation or enzymatic reaction with tyrosinase. The resulting biopolymers were characterized using dry-mass determination, Electron Paramagnetic Resonance (EPR) spectroscopy, potentiometric titration, Dynamic Light Scattering (DLS), and spectrophotometry. The biological effect of melatonin supplementation on the mitochondrial activity of primary melanocyte cell culture (HEMn-DP) after solar-simulated illumination was assessed using the MTT assay. The presence of melatonin during autooxidation increased the overall melanin free radical signal as determined using EPR, however did not impact the signal during enzymatic synthesis. More so, enzymatic oxidation of melatonin alone yielded a detectable pigment (Melat-Mel) with about 4.4% efficiency. EPR spectra of melatonin-derived polymers and copolymers in the presence of zinc (II) ions and after thermal treatment demonstrated behavior typical to melanin pigments. UV-Vis spectrometry showed a change in the absorption profile for copolymer (DOPA/Melat-Mel) with higher UV and lower VIS absorbance compared with homopolymer (DOPA-Mel). DLS measurements confirmed the formation of supramolecular aggregation for all the examined variants. Potentiometric titration showed that copolymer with melatonin exhibits the highest buffering capacity among examined pigments. Loading of HEMn-DP cells with melatonin yielded a dose-dependent reduction of mitochondrial activity following solar-simulated light treatment with no dark toxicity observed. The study provides a chemical model that may help explain part of the "melatonin paradox" in pigmentation, while emphasizing that direct confirmation of melatonin-containing pigment formation in cells remains to be established.
Hypochlorous acid (HOCl), an essential endogenous reactive oxygen species, is integral to various physiological and pathological processes. It is a crucial biomarker linked to inflammation and hepatic damage. The application of near-infrared fluorescence probes for in vivo biological imaging has increased recently, due to their little tissue damage and superior tissue penetration. This paper presents the synthesis of a novel near-infrared fluorescence probe, NS-Id, for the sensitive detection of HOCl. The NS-Id probe exhibits remarkable selectivity, elevated sensitivity (51 nM), and ultrafast response (20 s) to HOCl at an emission wavelength of 591 nm. Furthermore, it has been effectively utilized for visualizing HOCl in both cells and zebrafish. We also proved its capacity to monitor viscosity changes during cell deaths (apoptosis or ferroptosis) at an emission wavelength of 562 nm. These findings underscore the extensive applicability of NS-Id, establishing it as a potential chemical tool for real-time, selective monitoring of HOCl and viscosity.
PURPOSE:To systematically evaluate the dose-dependent ocular safety profile and biological mechanisms of 650 nm repeated red-light (RL) therapy using the chick model. METHODS:Chicks received monocular 650 nm red-light exposure. Dosimetry was strictly defined as corneal irradiance (power density measured at the corneal surface) under two regimens: a dose-escalation regimen (1, 5, 10, 15 mW/cm2 for 7 days) and a mid-term (5 mW/cm2 for 30 days) regimens (n = 7 per group). Safety assessments included axial length measurements, in vivo macroscopic imaging via swept-source optical coherence tomography and angiography (SS-OCTA), in vivo full-field electroretinography (ffERG), high-resolution ex vivo cellular imaging via full-field OCT (ffOCT), histology/TUNEL assay and untargeted metabolomic profiling coupled with computational toxicology screening. RESULTS:Physiological axial growth was maintained across all irradiances. Retinal architecture, photoreceptor integrity and retinal ganglion cell survival remained intact, with no apoptotic signaling detected. SS-OCTA revealed a significant dose-dependent increase in the choroidal vessel volume per unit area (CVV/a) without accompanying changes in choroidal thickness or vascular index, indicating physiological vascular modulation rather than structural changes. Dual mode of ffOCT demonstrated preserved photoreceptor and retinal ganglion cell layer densities with stable intracellular metabolic motility, ruling out subcellular damage or metabolic stress. ffERG parameters remained stable across all treatment groups. Metabolomic profiling indicated adaptive shifts toward anabolic and bioenergetic pathways, while computational screening detected no enrichment of photochemical or redox-active risk signatures with dose escalation. CONCLUSIONS:The chick retina demonstrates a wide biological safety margin for 650 nm repeated red-light exposure, tolerating both supraphysiological irradiance and extended treatment duration without structural, functional or molecular evidence of photochemical injury. These preclinical findings provide evidence evaluating the biological safety margin of repeated 650 nm red light therapy in the retina.
Currently, developing effective treatments for epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) resistant non-small cell lung cancer (NSCLC) is one of the main research focuses in the field. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the receptor tyrosine kinase family, whose knockdown could effectively inhibit the growth of EGFR-TKIs resistant NSCLC. Targeted inhibitor therapy and photodynamic therapy (PDT) combination is a promising strategy for reducing drug resistance and side effects. 12d, a novel small molecule ROR1 inhibitor we synthesized previously, exhibited promising antitumor activity both in vitro and in vivo. However, its poor water solubility significantly compromised therapeutic efficacy and bioavailability. Here, to improve the solubility of 12d and to take advantage of the PDT benefits of the photosensitizer Ce6, we constructed a light-activatable liposomal co-delivery system (12d/Ce6-LP) for the treatment of EGFR-TKIs resistant NSCLC. In vitro assays demonstrated that 12d/Ce6-LP significantly enhanced cellular uptake, provoked G2/M cell cycle arrest, promoted apoptosis, and impeded the ROR1, protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) signaling pathways through a synergistic treatment with targeted inhibitor therapy and PDT. Furthermore, 12d/Ce6-LP revealed potent tumor growth inhibition in EGFR-TKIs resistant NSCLC xenograft models, prolonged systemic circulation, and excellent biodistribution. In summary, 12d/Ce6-LP represented a novel nanotherapeutic strategy of the EGFR-TKIs resistant NSCLC through a synergistic mechanism of "targeted inhibitor therapy and photodynamic" offering a promising paradigm for the treatment of drug-resistant malignancies.
Photodynamic therapy (PDT) is a promising treatment strategy for resistant or non-surgical tumors. To develop photosensitizers tailored to specific cancer types, new chemical scaffolds are needed. Macrofungi have recently been identified as a potent source of such compounds, particularly dimeric anthraquinones. However, the sources previously described (i.e., dermocyboid Cortinarii) cannot be cultivated in a biotechnologically applicable way. Thus, in this proof-of-concept study, we explored Talaromyces species (Ascomycota) for their potential to produce similar light-activated metabolites. Six species (T. islandicus, T. pinophilus, T. rotundus, T. ruber, T. stipitatus, and T. thailandensis) were selected and cultivated following a strict strain management protocol. Photobiological studies of their extracts lead to the identification of two new fungal photosensitizers that are structurally related to the fungal photosensitizer 7,7'-biphyscion. Subsequent cultivation experiments with changing conditions confirmed the potential to enhance production, turning T. islandicus into a promising microbial cell factory for the sustainable generation of novel photosensitizers.
Diabetic foot ulcers have a substantial negative impact on patients' quality of life. This double blind, randomized clinical trial evaluated the association of antimicrobial photodynamic therapy (aPDT) used as an adjunct to standard wound care with wound quality and tissue repair using the Bates-Jensen Wound Assessment Tool (BWAT). Patients were randomly allocated into an aPDT group or a control group, both receiving standard wound care. The intervention consisted of treatment with a cluster of red lasers (660 nm) combined with a 1% methylene blue photosensitizer. Clinical evaluations were performed over ten treatment sessions, with an additional follow-up conducted 30 days after the final application. The aPDT group demonstrated a significant reduction in BWAT clinical scores from the third treatment session onward, with improvements maintained at the 30-day follow-up, indicating significant short-term improvement in tissue repair. Additional clinical assessment scales also showed significant improvements exclusively in the aPDT group, particularly regarding ischemic condition, epithelialization, and overall skin integrity. No worsening of clinical outcomes was observed, and no treatment-related adverse events were reported during the study period. In conclusion, adjunctive antimicrobial photodynamic therapy was associated with significant short-term improvements in wound quality and tissue repair when combined with standard wound care, and was well tolerated during the study period.
Despite abundant solar radiation year-round, vitamin D deficiency remains paradoxically widespread in Saudi Arabia - a persistent "sunshine paradox." This study presents the first integrated, decade-long assessment of potential cutaneous vitamin D production in Riyadh, combining high-resolution ground-based solar radiation measurements (2015-2025), rigorous clear-sky atmospheric correction, and culturally tailored scenario-based modelling that reflects real Saudi behavioural and physiological conditions. Vitamin D-effective irradiance (UVD) showed a strong seasonal cycle, with summer values ∼130% higher than winter. Cloud cover further modulated this baseline, reducing UVD by 34% under partly cloudy and 71% under overcast skies. Scenario modelling demonstrated that exposure duration and exposed body surface area (linked to clothing practices) are the most powerful modifiable determinants, producing up to seven- to eight-fold differences in daily IU production. Skin pigmentation and age imposed significant physiological constraints, while realistic population/lifestyle profiles revealed more than a ten-fold variation in vitamin D synthesis potential under identical seasonal UV availability. This work breaks new ground by moving beyond static prevalence studies to provide quantitative, context-specific evidence on how environmental UV availability interacts with modifiable human behaviours in a sun-rich environment. The findings offer a robust scientific foundation for developing season-specific, culturally appropriate sun-exposure guidelines and targeted supplementation strategies. Implementing these insights has substantial potential to reduce the public health burden of vitamin D deficiency across Saudi Arabia and similar MENA settings.
Photobiomodulation (PBM) involves the application of low-intensity visible or near-infrared light (600-1100 nm) to tissues. PBM demonstrates considerable potential in chronic wound healing, neurodegenerative disease intervention, and adjunctive cancer therapy. The core mechanism of PBM relies on photon absorption at specific wavelengths by mitochondrial cytochrome c oxidase. By activating the mitochondrial electron transport chain, enhancing ATP synthesis, and regulating reactive oxygen species signaling, PBM mediates multiple downstream signaling pathways, including PI3K/Akt, MAPK, and NF-κB, thereby exhibiting significant wavelength- and dose-dependent bidirectional regulatory characteristics. Currently, domestic and international research primarily focuses on single signaling pathways or therapeutic effects for specific diseases, while lacking a systematic review of their multidimensional regulatory mechanisms and multisystem biological effects. This hinders the standardization of treatment parameters and optimization of clinical protocols. Accordingly, this review systematically summarizes the molecular mechanisms and research progress of PBM across five major areas: tissue repair and regeneration, anti-inflammatory and immunomodulatory effects, regulation of glucose and lipid metabolism, tumor intervention, and neuroprotection and analgesia. We identify current research bottlenecks and recognize the uncertainty in therapeutic efficacy caused by parameter variations, along with outlining pathways for its precise and personalized clinical translation. PBM offers unique advantages, including safety, minimal tissue damage, and low cost. These features make it a promising, novel adjunctive therapeutic modality and provide a systematic theoretical basis for developing non-invasive adjunctive phototherapy regimens for various refractory diseases.
This study used ultraviolet (UV)-C light-emitting diodes (LEDs) and titanium dioxide (TiO2) photocatalyst to design a high-efficiency bioaerosol disinfection reactor. It conducted experiments and simulations to investigate the effects of baffle angle (-10°, 0°, and 10°) on the airflow field, irradiance distribution, and photocatalytic efficiency of the designed reactor. When baffle surfaces were not coated with photocatalyst, a baffle angle of 0° effectively prolonged the microbial residence time, causing bacteria to receive the maximum UV fluence of 22.07 mJ/cm2, which led to the highest log inactivation value of 1.91. However, when the baffle surfaces were coated with TiO2 photocatalyst, a baffle angle of -10° resulted in the highest photocatalytic disinfection efficiency and log inactivation value. After the baffles were coated, the log inactivation value under a baffle angle of -10° increased from 1.67 to 2.40, representing an increase of approximately 44%. This improvement was attributable to the baffle angle of -10° substantially increasing the photocatalytic efficiency at the channel turns and the probability of bioaerosols coming into contact with the photocatalyst. Overall, the current findings can provide a reference for the design of bioaerosol disinfection reactors comprising UV-C LEDs and TiO2 photocatalyst.
Bone tissue possesses intrinsic regenerative capacity after bone defect repairs; however, delayed or compromised healing may require adjuvant therapeutic interventions. This controlled experimental study investigated the effects of low-level laser therapy (LLLT) and silver nanoparticles (AgNPs) synthesized via a green pathway using stingless bee honey on the repair of femoral bone defects in Wistar rats. Forty male rats were randomly allocated to control and treatment groups and subjected to standardized femoral bone defects, followed by the application of LLLT, AgNPs, or a combination of both. Histological and histomorphometric assessments were performed on days 7 and 14 post-bone defect repair to evaluate the inflammatory infiltrate and the relative areas of fibrous tissue, cartilage, and newly formed bone. The control group exhibited a pronounced inflammatory response and a predominance of immature bone callus formation, particularly on day 7. The combined AgNPs + LLLT treatment significantly attenuated the inflammatory response compared with the control group (p < 0.05), whereas the laser-only and honey-derived AgNP treatments showed intermediate inflammatory scores. Although LLLT and AgNPs applied individually produced comparable results, the combined therapy also resulted in the greatest extent of bone matrix formation on day 14. Taken together, these findings indicate that the association of LLLT with honey-derived AgNPs may enhance early bone defect repair by modulating inflammation and promoting bone matrix deposition. These findings suggest that the combined therapy may enhance early bone repair in a preclinical experimental model.
