Daily Cosmetic Research Analysis
A multicenter phase III RCT shows red light photodynamic therapy with 10% 5-aminolevulinic acid gel achieves high histologic and clinical clearance in superficial basal cell carcinoma with favorable cosmetic outcomes. A mechanistic study reveals new methylene blue exerts light-independent mitochondrial toxicity, refining safety considerations for photodynamic applications. An in vitro, physiologically relevant dental study demonstrates quaternary ammonium methacrylate adhesives inhibit MMPs and
Summary
A multicenter phase III RCT shows red light photodynamic therapy with 10% 5-aminolevulinic acid gel achieves high histologic and clinical clearance in superficial basal cell carcinoma with favorable cosmetic outcomes. A mechanistic study reveals new methylene blue exerts light-independent mitochondrial toxicity, refining safety considerations for photodynamic applications. An in vitro, physiologically relevant dental study demonstrates quaternary ammonium methacrylate adhesives inhibit MMPs and biofilms, supporting restoration longevity.
Research Themes
- Noninvasive dermatologic oncology therapy (ALA-PDT) with cosmetic benefits
- Photosensitizer safety: light-independent mitochondrial toxicity
- Bioactive dental adhesives against biofilm-driven degradation
Selected Articles
1. Red light photodynamic therapy with 10% aminolevulinic acid gel showed efficacy for treatment of superficial basal cell carcinoma in a randomized, vehicle controlled, double-blind, multicenter phase III study.
In a pivotal multicenter RCT, red light PDT with 10% ALA gel achieved 75.9% histologic and 83.4% clinical clearance in superficial BCC versus 19.0% and 21.4% with vehicle. Safety was acceptable and 88.1% of patients rated cosmetic outcomes as good/very good; long-term durability is under follow-up.
Impact: Provides high-level evidence for a noninvasive alternative to surgery in superficial BCC with favorable cosmetic outcomes. Could broaden patient options in cosmetically sensitive areas pending long-term recurrence data.
Clinical Implications: ALA-PDT can be considered for superficial BCC when cosmetic preservation is prioritized or surgery is contraindicated; clinicians should counsel on potential need for retreatment and pending long-term recurrence data.
Key Findings
- Histologic clearance 75.9% with 10% ALA-PDT vs 19.0% with vehicle (P<.0001).
- Clinical clearance 83.4% with 10% ALA-PDT vs 21.4% with vehicle (P<.0001).
- 88.1% of patients rated cosmetic outcome as very good or good; no new safety signals.
- Few face/scalp lesions enrolled; 60-month follow-up ongoing.
Methodological Strengths
- Randomized, double-blind, vehicle-controlled, multicenter phase III design.
- Both histologic and clinical endpoints with prespecified timing.
Limitations
- Limited enrollment of face/scalp lesions limits generalizability to cosmetically critical sites.
- Long-term recurrence outcomes not yet available (ongoing 60-month follow-up).
Future Directions: Report 5-year clearance/recurrence, compare head-to-head with surgery and topical therapies (e.g., imiquimod), and evaluate outcomes specifically in facial/scalp lesions.
BACKGROUND: Surgical procedures remain the gold standard for treating basal cell carcinoma (BCC), although commonly associated with cosmetic defects. The demand for noninvasive alternatives remains high. OBJECTIVE: To determine efficacy and safety of red light photodynamic therapy (PDT) with 10% 5-aminolevulinic acid (ALA) gel vs vehicle for treatment of superficial BCC. METHODS: This randomized, double-blind, vehicle-controlled, pivotal phase III study was conducted at 21 centers in the US. Eligible participants had ≥1 naïve superficial BCC and received 1-2 PDT cycles (2 PDTs each cycle) followed by clinical and histological assessment 12 weeks after start of the last PDT cycle. RESULTS: Of 187 randomized participants, 145 received PDT with 10% ALA gel and 42 with vehicle. Histological clearance was 75.9% with 10% ALA gel vs 19.0% with vehicle (P < .0001). Clinical clearance was 83.4% with 10% ALA gel vs 21.4% with vehicle (P < .0001). A total of 88.1% of participants treated with 10% ALA gel rated the esthetic outcome as very good or good. No previously unknown adverse events occurred. LIMITATIONS: Few participants with lesions on face/scalp; to date, a 60-month follow-up is still ongoing. CONCLUSION: 10% ALA gel showed significantly higher clearance rates than vehicle with unproblematic safety and positive esthetic outcome.
2. Beyond phototoxicity: The dark side of new methylene blue on mitochondrial and cellular bioenergetics.
Across isolated mitochondria, ex vivo liver, and hepatoma cells, new methylene blue uncoupled oxidative phosphorylation and impaired mitochondrial integrity even in the dark, with red light worsening these effects. Findings suggest intrinsic mitochondrial toxicity of NMB beyond classic phototoxicity considerations.
Impact: Refines risk assessments for NMB-based photodynamic or staining applications by revealing light-independent mitochondrial toxicity. Informs safer photosensitizer design and dosing.
Clinical Implications: Clinicians and developers should consider mitochondrial toxicity of NMB even without irradiation; preclinical screens should include dark toxicity on bioenergetics, and dosing/formulation may need adjustments or alternatives.
Key Findings
- NMB uncoupled oxidative phosphorylation in isolated rat liver mitochondria, reducing RC and ADP/O ratios without light.
- Increased inner mitochondrial membrane permeability (enhanced oxidation of exogenous NADH) and inhibited swelling.
- Red-light irradiation exacerbated mitochondrial dysfunction, including inhibition of respiratory chain complexes.
- Consistent effects observed across isolated mitochondria, ex vivo perfused liver, and HepG2 cells.
Methodological Strengths
- Triangulation across three complementary models (isolated mitochondria, ex vivo liver, and cells).
- Direct assessment of mitochondrial bioenergetics and membrane permeability under light and dark conditions.
Limitations
- Preclinical models; no in vivo whole-organism toxicity or human data.
- Dose–response thresholds and clinical exposure equivalence not fully defined.
Future Directions: In vivo toxicology and pharmacokinetic-pharmacodynamic mapping; compare NMB with alternative phenothiazines; rational design of photosensitizers minimizing dark mitochondrial toxicity.
New methylene blue (NMB) is a phenothiazine dye with recognized photodynamic properties. This study evaluated both light-dependent and intrinsic (light-independent) effects of NMB on mitochondrial function, hepatic metabolism, and cell viability using three models: isolated rat liver mitochondria, ex vivo perfused rat liver, and HepG2 cells. In isolated mitochondria, NMB uncoupled oxidative phosphorylation, decreasing the respiratory control (RC) and ADP/O ratios, even without irradiation. It increased inner membrane permeability, inferred from enhanced oxidation of exogenous NADH, and inhibited mitochondrial swelling. Red-light irradiation exacerbated these effects, leading to inhibition of respiratory chain complexes and F
3. Marginal integrity produced by quaternary ammonium methacrylate-based dental adhesive tested under physiologically relevant models.
A QAM (DMAHDM)-based adhesive enhanced dentin mechanical stability, reduced collagen solubilization, achieved higher degree of conversion, and strongly suppressed S. mutans biofilms, outperforming CHX in vitro under bioreactor conditions. Early marginal breakdown was driven by biofilm activity rather than mechanical stress.
Impact: Demonstrates a dual-function adhesive that inhibits MMP-mediated degradation and biofilms in clinically relevant models, supporting strategies to extend restoration longevity.
Clinical Implications: Incorporating QAM-based adhesives may reduce early marginal degradation and secondary caries risk by targeting biofilm activity and collagen breakdown; clinical trials are needed to confirm durability and safety.
Key Findings
- Increased dentin shear storage modulus after 72 h with 2% CHX or 10% QAM (p=0.005 and p=0.007).
- QAM more effectively reduced collagen solubilization than CHX (hydroxyproline assay, p=0.02).
- QAM adhesive achieved higher degree of conversion vs control and CHX (p<.001).
- QAM markedly inhibited planktonic growth, biofilm biomass, and viability (all p<.001), outperforming CHX.
- Biofilm challenge increased perimeter gap length and occlusal gap width over time in all groups, whereas mechanical loading alone did not.
Methodological Strengths
- Physiologically relevant bioreactor models simulating mechanical and bacterial challenges.
- Multi-assay approach (MMP inhibition, rheology, hydroxyproline, conversion, biofilm metrics) with comparator (CHX).
Limitations
- Preclinical in vitro design without clinical outcomes or long-term intraoral validation.
- Gap metrics increased under biofilm challenge across all groups, indicating room for optimization.
Future Directions: Conduct randomized clinical trials to assess restoration longevity and secondary caries; optimize QAM concentration and evaluate cytocompatibility and pulp safety.
OBJECTIVES: Endogenous metalloproteinases (MMPs) lead to dentin collagen degradation when exposed to demineralizing events, such as during the cariogenic process. Quaternary ammonium compounds are known to be antibacterial, and there is also evidence for their action as a MMP inhibitor. The aim of this study was to evaluate a quaternary ammonium-based methacrylate (dimethylaminohexadecyl methacrylate - DMAHDM, QAM) as an experimental adhesive, tested for bond stability and gap formation under physiologically-relevant conditions using a bioreactor system. MATERIALS AND METHODS: The inhibition of MMP activity was assessed using a fluorescence-based assay, in the presence of serial concentrations of chlorhexidine (CHX) or QAM (n = 3). Shear storage modulus (G') was measured on demineralized dentin slices before and after incubation into the inhibitor's solutions, using a rheometer (n = 5). Collagen solubilization was quantified through hydroxyproline assay, using powdered dentin obtained from extracted human third molars (n = 6). Adhesives were formulated with BisGMA/HEMA, added of either 2 % CHX or 10 % QAM, and the degree of conversion was evaluated by near-IR (n = 6). Microtensile bond strength (μTBS) was assessed on restored dentin beams after storage in dH RESULTS: Dentin disks treated with either 2 % CHX or 10 % QAM exhibited a significant increase in shear storage modulus after 72 h (p = 0.005 and p = 0.007, respectively), indicating enhanced mechanical stability. The hydroxyproline assay demonstrated that both CHX and QAM effectively reduced collagen degradation, with QAM showing superior inhibition (p = 0.02). In terms of the degree of conversion, the QAM adhesive achieved significantly higher values compared to the control and CHX groups (p = <.001). Biological assays showed that QAM markedly inhibited planktonic bacterial growth (p = <.001), biofilm biomass (p = <.001), and biofilm viability (p = <.001), outperforming CHX. In the S. mutans biofilm challenge model, both 2 % CHX and 10 % QAM groups showed a significant increase in perimeter gap length, PGL (p = <.001 and p = 0.039, respectively) and occlusal gap width, OGW (p = <.001 for both) from initial to final measurements, although no differences were observed across groups at each time point. In contrast, when exposed to mechanical loading in the bioreactor (in water), none of the groups, including QAM, exhibited significant changes in either PGL or OGW (p = 0.989, and p = 0.118). These findings indicate that biofilm activity, rather than mechanical stress, is the primary driver of marginal breakdown in the early stages. CONCLUSIONS: In summary, this study demonstrates that QAM-based adhesives outperform CHX by providing stronger protection against MMP activity, improving dentin's mechanical properties, and offering robust antimicrobial effects. The fact that these results were obtained in a clinically-relevant model increase the confidence that this approach can be employed as a tool to extend the lifespan of restorations. CLINICAL RELEVANCE: Results obtained in a simulated cavity preparation subjected to mechanical and bacterial challenges demonstrated the potential for QAM-based materials to serve as both antimicrobial and collagen-preserving.