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Severe corneal injuries can cause visual impairment even blindness. Surgically stitching or implanting biomaterials have been developed, but their implementation requires professional surgeons, failing to address the immediate need of medical treatment. The pressing challenge lies in developing multifunctional biomaterials that enable self-management of corneal injuries. This study introduces collagen-based hydrogels that can be used as contact lenses, incorporating macromolecular collagen into common polymer materials via a dual-step orthogonal cross-linking process. This method ensures superior optical and mechanical performance while preserving the bioactivity and structural stability of the incorporated materials. Specialized contact lens facilitates the controlled release of labile protein therapeutics such as acidic fibroblast growth factor (aFGF), eliminating the need for stabilizers like heparin. This capability allows the lens to deliver a wide range of labile proteins, thus expanding its therapeutic use across various ophthalmic and potentially other medical conditions. The lens's anti-inflammatory and anti-fibrotic properties effectively treat corneal alkali burn. Termed 'corneal first-aids lens', it can provide postoperative clinical care and serve as a viable and safe therapeutic alternative for patients with limited medical access., Competing Interests: Declaration of competing interest There are no conflicts of interest in this work., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Introduction: Collagen is essential to skin structure and integrity, and it is continually degraded with aging due to higher oxidative stress. Sleep deprivation accelerates skin aging and reduces collagen production. Good sleep may be a potential adjuvant to the efficacy of oral supplementation with collagenic peptides for the skin., Objectives: To summarize clinical benefits to the skin of collagen intake, and consider the role of sleep in its effectiveness., Methods: Studies in the PubMed database that reported the effects of oral administration of collagen peptides were searched; and studies presenting the association of collagen metabolism with sleep., Results: A total of 1117 articles were initially identified; 66 were reviewed in full. Most involved women at third or fourth decade of life. Daily collagen doses ranged from 1 to 10 g, with intervention periods lasting from 4 to 8 weeks. Consistent improvements in skin elasticity, hydration, and wrinkle reduction were observed, with increase in dermal density and structural proteins. Collagen combined with vitamins, minerals, and antioxidants provided additional benefits, including improved skin radiance and reduced pore size. Studies on sleep and skin indicated that poor sleep can impair skin hydration, increase transepidermic water loss, and reduce elasticity, highlighting the potential role of sleep in maximizing the benefits of collagen supplementation., Conclusions: Hydrolyzed collagen supplementation, particularly at 2.5 g/day, has shown benefits for skin after 4 weeks of use. Sleep quality may enhance these effects by supporting immune function and reducing oxidative stress. Further studies are needed on sleep's role in enhancing collagen supplementation benefits., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A recent study highlighted variability in complication rates among polylactic acid (PLA)-based collagen stimulator fillers, with notably high rate of complications linked to PLLA-Elleva. The study suggested that product-specific characteristics might have greater impact on outcomes than injection techniques., Methods/results: Through a critical analysis of pertinent literature, this commentary explores how PLLA-Elleva's unique physicochemical properties, particularly its bimodal degradation process, may contribute to the increased nodule formation observed., Conclusion: Although PLLA-Elleva's degradation pattern does not inherently compromise safety, it introduces variability that requires careful attention to dosage, injection technique, and patient selection., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Esthetic medicine has shifted significantly toward non-surgical procedures, with the collagen biostimulator poly-l-lactic acid (PLLA) becoming increasingly popular for facial rejuvenation. However, the safety and patient satisfaction associated with PLLA facial treatments remain largely unexplored., Objective: This study aimed to evaluate the safety profile of PLLA treatment and assess patient mid- and long-term satisfaction with the outcome., Methods: This prospective single-center study was conducted at Bravo Clinic in Rio de Janeiro from August 2023 to August 2024. The patients' mid and lower face was treated by injecting Rennova Elleva (a collagen biostimulator containing 210 mg of PLLA) into the zygomatic and pre-masseteric regions. All patients underwent monthly clinical evaluations for the first 150 days and kept diaries to self-record any adverse effects during the first 30 days. Patient satisfaction was measured using the Global Aesthetic Improvement Scale (GAIS) on days 90 and 150 post-injection., Results: The study included 52 female patients [mean age: 49.87 ± 10.7 years; mean body mass index (BMI): 23.99 ± 3.5 kg/m 2 ]. Patients reported mild to moderate injection site reactions, including redness, pain, hardening, swelling, lumps, bruises, and skin discoloration, with most symptoms resolving within a few days. Clinically, no major adverse events were noted, except for one small, painless nodulation that resolved without intervention. On post-injection Day 90, the average GAIS was rated at 2.32 ± 1.0. This rating remained stable at Day 150, with an average GAIS of 2.32 ± 0.8 (p = 0.862). Inverse correlations were identified between the duration of mild pain and GAIS (r s  = -0.546, p = 0.035), as well as between the duration of mild bruises and GAIS (r s  = -0.598, p = 0.019). The duration of moderate pain was significantly associated with age (r s  = -0.894, p = 0.041)., Conclusion: Rennova Elleva, a PLLA-based collagen biostimulator, is safe and well-tolerated with a low incidence of adverse effects. It provides long-lasting, satisfactory results for patients with mild to moderate facial sagging, rendering it an effective non-surgical option for enhancing facial esthetics., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objectives: The aim of this study was to assess the effect of Naturagen® 4 Joint product, containing type 1, 2, and 3 collagen, on pain associated with osteoarthritis (OA) and to evaluate its effects on quality of life and physical functioning., Patients and Methods: This double-blind, randomized, placebo-controlled clinical study included a total of 31 patients (8 males, 23 females; mean age: 53.5±9.1 years; range, 35 to 65 years) with Grade 2-3 OA according to the Kellgren-Lawrence (KL) classification system between June 2023 and November 2023. The patients were divided into two groups: a collagen group (n=16) and a placebo group (n=15). The Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS-PS), Oxford Knee Score (OKS), Tampa Scale for Kinesiophobia (TSK), Short Form Health Survey (SF-12), Foot Function Index (FFI), Timed Up and Go (TUG), 6-Min Walking Test (6MWT), Five Repetition Sit to Stand Test (5STS), Stair Climbing Test (SCT), and Berg Balance Scale (BBS) were used. All tests were performed before and after eight weeks of collagen supplementation., Results: Eight weeks of collagen supplementation yielded notable enhancements across all osteoarthritis-related pain and quality of life scales evaluated, including VAS, WOMAC, KOOS-PS, OKS, TSK, SF-12, and FFI scores (p<0.05). In functional evaluations, there were significant positive effects of collagen use in BBS and 6MWT results (p<0.05). In TUG, 5STS, and SCT tests, no significant difference was found between the groups (p>0.05)., Conclusion: Our study results suggest that the eight-week collagen-based supplement exerts a favorable effect on pain and quality of life levels, as well as some functional test results.

Background: Neck wrinkles are a prominent characteristic of skin aging, with recent studies indicating that interventions such as platelet-rich plasma (PRP), microneedling (MN), and radiofrequency (RF) can effectively rejuvenate aging skin., Aims: This study aims to assess and compare the efficacy of three treatment modalities in addressing neck wrinkles., Methods: Fifteen female participants with a neck Lemperle Wrinkle Assessment Scale (WAS) score of 3-4 were enrolled in a randomized clinical trial. The subjects were randomly assigned to three treatment groups: PRP injection, MN + PRP topical PRP application, and RF + PRP injection. They received treatment once a month for three consecutive months, and a clinical outcome evaluation was performed at 1 and 6 months after the final treatment., Results: The WAS scores and global aesthetic improvement score (GAIS) demonstrated notable enhancements 1 month postfinal treatment across all three groups, with a notably greater number of participants experiencing improved outcomes in the RF + PRP group 6 months posttreatment. Specifically, at the 1-month follow-up, the RF + PRP group exhibited a statistically significant enhancement in skin elasticity and collagen, surpassing the improvements observed in the other two groups (p < 0.05). No significant disparities in skin elasticity and collagen were detected in all groups prior to and after 6 months of treatment. Adverse events were mild and transient, such as redness, swelling, bruising, and pain., Conclusion: This study revealed that all the treatments can effectively improve neck wrinkles 1 month after the last treatment. A better therapeutic effect could be observed in the RF + PRP group compared with the other two groups at 6 months after the last treatment., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Excess skin laxity over the upper face can contribute to aging over the mid and lower face. We describe an innovative nonsurgical technique of facial rejuvenation by injecting Lanluma V over the scalp's vertex and parietal regions. Lanluma V is a poly-l-lactic acid (PLLA)-based collagen stimulator which contains 210 mg of PLLA, distributed by Sinclair Pharmaceutical. Lanluma V works by stimulating collagen regeneration to provide support for the treated area., Method: A retrospective review of 12 consecutive patients treated with Lanluma V over the vertex and parietal regions of the scalp to achieve nonsurgical rejuvenation of the upper, middle, and lower thirds of the face was conducted. The patients were treated over two sessions, 1 month apart. The treated patients were reviewed by a plastic surgeon and rated under the Global Aesthetic Improvement Scale (GAIS) 6 months after treatment., Results: The patients achieved an overall average of 1.16 grade improvement in GAIS. The average follow-up period is 6 months following completion of treatment. There was no reported incidence of non-scarring alopecia, which has been reported in the use of other, more viscous fillers such as calcium hydroxyapatite or high G' hyaluronic acid., Conclusion: This innovative method of combined forehead and temporal lifting with Lanluma V allows for an average 1.16 grade improvement in GAIS. There is no reported incidence of non-scarring alopecia, which has been associated with other fillers., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Skin aging research often focuses on the dermis, overlooking the significance of the retinacular cutis (RC) in aging. This study aimed to investigate the efficacy, safety, and effect of an injectable solution containing hyaluronic acid, amino acids, and peptides, on facial sagging and laxity by targeting the RC., Methods: This single-center observational study recruited 28 female volunteers aged 25-65 years. The participants received four monthly injections of the studied solution. Objective measures included skin hydration, elasticity, color, thickness, collagen density evaluated via DermaLab Combo and high-resolution ultrasound imaging. Subjective measures included participant satisfaction evaluated using the Global Aesthetic Improvement Scale (GAIS). Adverse effects were monitored throughout the study period., Results: Significant improvements were observed in skin hydration, elasticity, and collagen density after treatment. Hydration increased by 25.9% at T1 (30 days after last session), sustaining a 15.9% increase at T2 (120 days after last session). Elasticity improved by 29.2% at T1 and 20.7% at T2. Collagen density increased by 20.27% at T1 and 16.71% at T2. Self-reported GAIS scores showed consistent increases. Adverse effects were minimal and included only transient ecchymosis and mild pain., Conclusion: Injections of the solution had a substantial hydrating effect, enhanced elasticity, and increased collagen density in the RC and dermis. Results persisted at the 120-day follow-up, indicating sustained benefits. Hence, this injectable solution may offer a safe and effective non-invasive treatment option for improving skin laxity and sagging, targeting the RC and other deep connective tissue such as retaining ligaments., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Injectable fillers for soft tissue augmentation stand out as one of the most favored procedures in the field of aesthetic medicine, especially in addressing the clinical signs of skin aging. Among soft tissue fillers, non-permanent fillers have been safely used in numerous medical applications for several decades., Aims: The aim of this post-market observational, open-label, uncontrolled, multicentered, prospective study (PMS) was to evaluate the effects of an injectable poly-L-lactic acid-based collagen stimulator (Lanluma®, the study product)., Participants/methods: This analysis is based on the clinical outcomes data (safety and effectiveness) collected from investigators and participants between the first injection (T0, September 2022) and 9 months thereafter (T3, June 2023) in the treatment of five body-contouring areas., Results: Overall, 70 participants had 99 treatment sessions of the neck (31%), upper arm (20%), hand (17%), thigh (16%) and décolleté (15%). Lumps (neck, upper arm, hand) and nodules (neck, hand, thigh) were the most frequent adverse events (AEs) reported by investigators. All were treatment related. None were serious, severe or fatal. No AEs were reported following treatment of the décolleté. Both investigators and participants reported high levels of satisfaction during the nine-month follow-up period with the treatments in five body areas., Conclusions: These positive clinical outcomes can be attributed to a proper implementation of best practices and recommendations, and the rheological properties of the study product. This 9-month follow-up analysis should be reconsidered in light of the study's objectives for the final analysis at the 25-month follow-up., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Rotator cuff tears are a prevalent cause of shoulder pain and dysfunction. For those who fail initial conservative treatment, operative intervention can be pursued. A significant and common complication after rotator cuff repair (RCR) is retearing or nonhealing. Numerous augmentations to traditional suture RCR have been studied. Of these, the Smith + Nephew Regeneten bioinductive collagen patch has had promising initial results; however, analytic data for its use are lacking, and there is no meta-analysis comparing the available data to historical RCR outcomes., Methods: A PRISMA-guided literature search was conducted using Ovid MEDLINE, PubMED, Cochrane, and ClinicalTrials.gov. Thirteen studies met inclusion and exclusion criteria. Only clinical trials on full and partial-thickness tears were included. American Shoulder and Elbow Surgeon score, Constant-Murley Score, the visual analog scale for pain, the minimal clinically important difference (MCID), tendon thickness, and complication rates were primary outcomes of interest. A meta-analysis was performed to determine the overall complication and retear rate from the included studies., Results: American Shoulder and Elbow Surgeon score, Constant-Murley Score, and visual analog scale for pain improved significantly in all studies that reported them, and most patients achieved MCID. Patient-reported outcome measure improvements were similar to historical improvements in standard RCR, and a similar proportion of patients achieved MCID after standard repair. Tendon thickness improved significantly and to a similar degree as standard RCR. Overall retear rate after full thickness RCR augmented with the bioinductive patch was 8.3%. For partial thickness RCR, total retear rate was of 1.1% across all patients. The overall complication rate with the bioinductive patch was 15.5% across all full-thickness RCR studies and 16.2% in partial thickness RCR. We found overall retear rate to be lower after augmentation with the bioinductive patch compared to traditional repair; however, the overall complication rate was similar for full-thickness tears and higher for partial-thickness tears. Lastly, adverse reactions to the bioinductive patch were noted at 0.2%., Conclusions: The bioinductive collagen patch appears to be a safe augmentation for rotator cuff repair. Patients are likely to experience significant subjective improvement in patient-reported outcome measures and significant increases in tendon thickness. Retear rate has been a concern after RCR for decades, and the bioinductive patch may help mitigate this risk. There is lack of case-control studies comparing the bioinductive patch to traditional suture RCR. Such data are needed to better determine the role of the bioinductive patch in the treatment of full and partial-thickness rotator cuff repairs., (Published by Elsevier Inc.)

Introduction: Over the past decade, collagen peptide (CP) supplements have received considerable attention in sports nutrition research. These supplements have shown promising results in improving personal health, enhancing athletic performance, and preventing injuries in some but not all studies., Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) has been conducted to investigate the effects of long-term daily collagen peptide (CP) supplementation on strength, musculotendinous adaptation, functional recovery, and body composition in healthy adults, both with and without concurrent exercise interventions over several weeks., Methods: The PRISMA with PERSiST guidelines were followed for this systematic literature review, which was conducted in December 2023 using PubMed, Scopus, CINAHL, and SPORTDiscus databases. Eligible studies included healthy, normal to overweight adults over 17 years of age who engaged in exercise and daily collagen peptide (CP) supplementation for a minimum of 8 weeks (except one 3-week trial only included for maximal strength). Studies examining recovery-related outcomes were also eligible if they included a 1-week supplementation period without exercise. Methodological study quality was assessed using the PEDro scale. A random-effects model with standardized mean differences (SMD) of change scores was chosen to calculate overall effect sizes., Results: Nineteen studies comprising 768 participants were included in both the systematic review and meta-analysis. Results indicate statistically significant effects in favor of long-term CP intake regarding fat-free mass (FFM) (SMD 0.48, p < 0.01), tendon morphology (SMD 0.67, p < 0.01), muscle architecture (SMD 0.39, p < 0.01), maximal strength (SMD 0.19, p < 0.01), and 48 h recovery in reactive strength following exercise-induced muscle damage (SMD 0.43, p = 0.045). The GRADE approach revealed a moderate certainty of evidence for body composition, a very low certainty for tendon morphology and mechanical properties, and a low certainty for the remaining., Conclusion: This systematic review and meta-analysis represents the first comprehensive investigation into the effects of long-term CP supplementation combined with regular physical training on various aspects of musculoskeletal health in adults. The findings indicate significant, though of low to moderate certainty, evidence of improvements in fat-free mass (FFM), tendon morphology, muscle mass, maximal strength, and recovery in reactive strength following exercise-induced muscle damage. However, further research is required to fully understand the mechanisms underlying these effects, particularly regarding tendon mechanical properties and short-term adaptations to collagen peptide (CP) intake without exercise, as observed in recovery outcomes. Overall, CP supplementation appears promising as a beneficial adjunct to physical training for enhancing musculoskeletal performance in adults. Open Science Framework (Registration DOI: https://doi.org/10.17605/OSF.IO/WCF4Y )., Competing Interests: Declarations Authors’ contributions D.K. and K.B. designed the review; A.M.M. and K.B. performed screening and study quality assessment; K.B. and SS analyzed the data; K.B. wrote the manuscript; A.M.M., D.K., K.B., and S.S. reviewed the manuscript. All authors read and approved the final version. Availability of data and material The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation upon request. Code availability No self-written code was used for the meta-analysis. The freeware Jamovi for Microsoft Windows 11 (https://www.jamovi.org/download.html) performed all meta-analyses and created all forest plots. Funding Open access funding provided by University of Vienna. No external funding was received for the preparation and writing of this manuscript. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

Background: Regenerative endodontics' primary objective is to establish a favorable environment in the root canal by removing infection, providing a sturdy scaffold, and sealing the apical end of the tooth tightly. These actions should promote pulp regeneration and root development., Aim: This study evaluated histologically the regenerative potential of injectable hyaluronic acid (HA) hydrogel or collagen with blood clot as scaffolds during revascularization of immature necrotic dog's teeth., Methods: Sixteen permanent immature necrotic premolars with 32 roots were chosen from two 4-5-month-old mongrel dogs. Out of the 32 roots, 24 roots were sealed for 2 weeks after being cleaned with CaOH 2 . According to the treatment protocol, the 24 cleaned roots were randomly assigned to one of three treatment groups (each with 8 roots): blood clot + HA group, blood clot + collagen group, and blood clot group. The control group consisted of the eight infected roots that remained untreated. Three months after the surgery, the assessment of tissue ingrowth in the pulp cavity took into account the kind of cellular components, the intercellular matrix, angiogenesis, and the occurrence of any hard tissue formation. The pulp's capacity for regeneration was described descriptively, taking into account the type of regenerated tissue, the root's apical closure, and any potential periodontal and periapical histological alterations. Semi-quantitative analysis was used to assess the degree of pulp tissue regeneration. Tukey's post hoc test was used after a two-way ANOVA for statistical analysis of all the data., Results: When comparing the treated groups to the control group, a significant increase in tissue ingrowth and a significant decrease in the periapical inflammatory reaction were noted ( p < 0.05). It's interesting to note that blood clot + HA group's inflammatory cell count was significantly greater ( p < 0.05) than that of the other treatment groups. Furthermore, blood clot + collagen group and blood clot group did not differ significantly in inflammatory cell count from one another. Tissue ingrowth did not differ significantly ( p > 0.05) amongst treated groups., Conclusion: The tissue regeneration of the immature necrotic teeth is improved by revascularization, whether or not it is combined with HA or collagen scaffolds. After revascularization, using HA as a scaffold is less efficient in reducing the inflammation than collagen., Competing Interests: The authors declare no conflicts of interest to report.

Intra-articular injections aimed at correcting underlying pathophysiological processes and providing pain relief are essential for managing knee osteoarthritis (KOA). Collagen, the primary component of articular cartilage, has a long half-life, making it a promising candidate for intra-articular injections with a low risk of serious side effects. The first of the two cases in this report involved a woman in her early 70s with a 6-year history of persistent left knee pain. The second case involved a woman in her mid-50 s with a >7-year history of right knee pain. Both patients received hyaluronic acid injections every 6 months, totaling 10 injections over 5 years. They were diagnosed with Kellgren-Lawrence grade 2 KOA. The patients received two 3-mL intra-articular injections of 6% collagen, administered at baseline and 6 months later. Improvements in clinical outcomes, including visual analog scale scores and Western Ontario and McMaster Universities Osteoarthritis Index scores, were observed and maintained in both patients, with no side effects reported. In summary, when collagen injections were administered to these two patients with KOA, clinical improvements lasted approximately 6 months, and repeated treatments demonstrated efficacy and safety similar to the initial course., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A healthy skin provides protection against intrinsic and extrinsic factors. Skin aging is characterized by structural and morphological alterations affecting skin health, integrity, and functionality, resulting in visible aging signs., Aim: The primary objective of this study was to assess the effect of a collagen peptide dietary supplement on skin aging in the East Asian population., Methods: Eighty-five healthy women, aged from 43 to 65 years old, were randomly assigned to the collagen supplement (CP, 5 g) or placebo (maltodextrin, 5 g) group. To standardize daily skin care, the volunteers in both groups used a specific face cream for 28 days prior to and throughout the supplementation period, creating an equal baseline for the assessment of the efficacy of CP on several skin parameters. At baseline, day 28 and day 84, the following hallmarks of skin and nail aging were assessed: dermis density, skin moisture and elasticity, wrinkle visibility, beauty perception, and nail color., Results: After 84 days, a significant improvement of dermis density and skin moisture was observed in the collagen peptides group compared to the placebo group. Positive effects on skin elasticity, wrinkle visibility, nail color, and overall beauty perception were already observed within 28 days of supplementation in the CP group, while the same effects in the placebo group were only observed after 84 days., Conclusion: Taken together, these results show that, in addition to a standardized skin care, daily supplementation with 5 g of collagen peptides positively affects visible signs of skin and nail aging in the East Asian population., (© 2024 Rousselot BV. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Collagen, a key protein in the body maintains hair, skin and bone health and its production tends to decrease in synthesis as humans age. The demand for vegan collagen-builder has increased worldwide due to increased adaptability to vegan diet., Objective: This clinical study was designed aim to evaluate the safety and efficacy of vegan collagen builder (VEGCOL™️) at different dosages (2.5, 5, and 10 g) in adult participants., Methods: Total 66 subjects (22 subjects/dose) aged 30 to 50 years were enrolled, and 63 subjects completed the study. Duration of study was 60 days. Evaluations included change in skin elasticity, hydration, crow's feet area wrinkles, fine lines, skin, Glogau skin age, change in pain scale score, muscle strength and subject perception assessment about test treatment use., Results: After 60 days of treatment, there was significant improvement in hair growth rate by 45.01%, 38.54% and 50.37% with p < 0.01 for doses 2.5, 5, and 10 g respectively. Additionally, 19.64% (p < 0.0001) and 20.51% (p < 0.0001) increase in hair density and hair thickness respectively was observed with 10 g dose. 2.5 g dose resulted in 33.03% (p < 0.01) increase in skin smoothness and 49.94% (p < 0.0001) decrease in crow's feet area wrinkles, decreased retraction time by 21.71 milliseconds (p < 0.05). 52.54% reduction in pain score (p < 0.001). No any adverse events were reported., Conclusion: Vegan collagen-builder effectively improved multiple age-related concerns such as wrinkles, fine lines, joint pain, muscle strength and hair growth. All respondents perceived the product as beneficial in improving the aesthetics of the skin, hair, and nails. The findings support the use of vegan collagen-builder as safe and efficacious in promoting healthier skin, stronger muscles, and improved hair and nail conditions., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Purpose: Disproportional fat-free mass loss often occurs post-bariatric surgery, partly due to insufficient protein intake during the post-surgery recovery phase. We compared five protein-enhancing strategies (PES) on patient tolerability, satisfaction and protein intake., Materials and Methods: Ninety-four participants, scheduled for bariatric surgery, were enrolled and allocated to either of the following: (1) whey powder, (2) hydrolysed collagen powder, (3) plant-based powder, (4) protein-rich products, (5) protein gel, or control. PES groups were instructed to add 30 g of powder or 2 gels or protein products to their diet. Patient satisfaction and tolerability were evaluated with questionnaires. Dietary intake was assessed prior to and during PES use., Results: Seven patients dropped out (i.e. loss of contact, personal reasons or post-surgery complications) yielding an analytical cohort of 87 participants. The majority of patients (61%) did not experience dietary complaints from PES and could use PES ≥ 5 days of the week. PES non-usage was mainly related to taste dislike (58%). Hydrolysed collagen scored highest on tolerability and satisfaction: 86% of the participants could use HC ≥ 5 days and 71% were satisfied with the product. PES increased protein intake from 54.7 ± 21.5 g/day to 64.7 ± 23.4 g/day during the intervention (p = 0.002), which differed from the control group (+ 10.1 ± 24.5 g/day vs. - 6.3 ± 23.8 g/day for controls, p = 0.019). Whey showed the highest increase, namely + 18.3 ± 16.3 g/day (p = 0.009)., Conclusion: PES were tolerated by the majority of participants, and an improved protein intake with PES use was seen. However, the taste of the products could be improved to further enhance satisfaction and tolerability., (© 2024. The Author(s).)

Purpose: To review and compare the available literature on bone regeneration using titanium mesh and map the current evidence on bone gain outcomes and complications while comparing this scaffold with collagen membranes., Materials and Methods: A comprehensive electronic and manual search was performed to identify randomised and non-randomised prospective controlled clinical trials that involved the use of titanium mesh in at least one arm, with outcomes including complications and vertical and/or horizontal bone gain. The focused questions were defined as follows: What are the outcomes of using titanium mesh in ridge augmentation compared to other types of barrier membrane, and what is the complication rate (membrane exposure and infection) when titanium mesh is used in these procedures?, Results: A total of 22 articles were included in the qualitative analysis. Overall, the studies that measured bone gain resulted in 3.36 mm vertical (196 subjects; 95% confidence interval 2.44 to 4.64 mm, range 1.4 to 5.7 mm) and 3.26 mm horizontal augmentation (81 subjects; 95% confidence interval 2.93 to 3.63 mm, range 2.6 to 3.7 mm), with variability among studies. The most commonly noted complication was mesh exposure, regardless of the type of mesh used, and the second most common was graft failure. The overall pooled complications rate reported in clinical trials was 10.8%. The meta-analysis comparing titanium mesh and collagen membranes, controlling for the type of bone regeneration (staged or simultaneous with implant placement), failed to show a significant difference in horizontal bone gain between the two techniques., Conclusions: Within the limitations of the present study and acknowledging the heterogeneity among the articles included, titanium mesh can serve as a feasible protective scaffold for bone regeneration with a relatively acceptable complication rate and in defects requiring around 4 mm 3D reconstruction. Data on patient-reported outcomes were scarce., Conflict-Of-Interest Statement: None of the authors have any financial interests, either directly or indirectly, in the products or information mentioned in the present article.

Background: Complications of temporary and permanent fillers have been extensively studied. However, there is a lack of comparative data regarding poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), and polycaprolactone (PCL) known as collagen biostimulators., Aims: This study addressed the complications of collagen biostimulators concerning their diagnosis, type of product, treatment, and monitoring., Patients/methods: An electronic questionnaire was sent to Brazilian dermatologic ultrasound experts to identify complications related to biostimulators. The type of biostimulator, location of application, number of vials injected, application plan, time between injection treatment and complication, injector profile, treatment, and prognosis were assessed., Results: Fifty-five cases were identified, of which 49.1% were caused by PLLA-Elleva®, 23.6% by CaHA (alone or combined with hyaluronic acid), 20.0% by PLLA-Sculptra®, and 7.3% by PCL. The most affected area was the face (72.7%), with nodules being the most common clinical form (89.1%), generally occurring late (60.0%) (>1 month). Only one case was injected at an incorrect depth (musculoaponeurotic system-SMAS). Despite several treatments, including saline (45.5%), hyaluronidase (25.5%), diluted corticosteroids (23.6%), and energy-based devices (10.9%), only five cases showed complete resolution. Hyaluronidase was beneficial in complications related to fillers when there was an association of calcium hydroxyapatite with hyaluronic acid (p < 0.01)., Conclusions: Complications from collagen biostimulators were more common on the face, typically manifesting about 1 month after treatment. These issues seemed to be related more to the properties of the products rather than inadequate technique. Furthermore, hyaluronidase demonstrated efficacy only in cases where there was an association with HA., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Skin aging can be observed at various levels in the epidermis, dermis, and dermo-epidermal junction. Reducing the cosmetic effects of skin aging in the facial region is a widespread demand due to common aesthetic concerns. Consequently, many injectable products on the market promise antiaging effects and cosmetic improvements. We aimed to evaluate the cosmetic efficacy of a high molecular weight sodium hyaluronate and amino acids mixture for the facial region using morphometric analysis., Methods: This study evaluates the morphometric effectiveness of an injectable mixture (high molecular weight sodium hyaluronate, glycine, L-Proline, L-leucine, L-lysine HCL, L-valine, and L-alanine collagen active ingredient) on the mid-face and jawline in women aged 30-55. We used morphological measurements and digital image data to assess changes and determine effectiveness. Various computational methods were applied simultaneously with statistical tests for validation., Results: The hydration assessment showed a significant increase on both sides of the face. A noticeable decrease was observed in gonion angle, bitragion breadth, bigonion breadth, and marionette wrinkle scale. These results suggest combining mechanical and chemical stimulation from the injection and its components (hyaluronic and amino acids) effectively enhances skin quality., Conclusions: The study indicates that the mechanical stimulation of the injection improves skin quality. Combining hyaluronic and amino acids (collagen, elastin, and pro-synthetic) is a safe and effective alternative for antiaging treatments., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Collagen-based aerogels have great potential for topical biomedical applications. Collagen's natural affinity with skin, biodegradability, and gelling behavior are compelling properties to combine with the structural integrity of highly porous matrices in the dry form (aerogels). This work aimed to produce a novel collagen-based aerogel and to perform the material's solid-state and physicochemical characterization. Aerogels were obtained by performing different solvent exchange approaches of a collagen-gelled extract and drying the obtained alcogels with supercritical CO 2 . The resulting aerogels showed a sponge-like structure with a relatively dense mesoporous network with a specific surface area of 201-203 m 2 /g, a specific pore volume of 1.08-1.15 cm 3 /g, and a mean pore radius of ca. 14.7 nm. Physicochemical characterization confirmed that the obtained aerogels are composed of pure collagen, and the aerogel production process does not impact protein tertiary structure. Finally, the material swelling behavior was assessed at various pH values (4, 7, and 10). Collagen aerogels presented a high water uptake capacity up to ~2700 wt. %, pH-dependent stability, and swelling behavior in aqueous media. The results suggest that this collagen aerogel could be a promising scaffold candidate for topical biomedical applications., (© 2024 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

Using a flap in a large wound with a very small area of exposed vital structures may be an excessive intrusion and cause unnecessary donor site morbidity. Dermal matrix (DuraGen) was applied onto critical areas where bone or tendons were exposed and a split skin graft was placed thereon. All patients had satisfactory wound closure without the need for a flap. DuraGen appears to be a safe, single-stage alternative, to a flap for the healing of complex wounds., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Collagen dietary supplements are becoming increasingly popular as a means to reduce signs of skin ageing. The objective of this three-way, randomised, placebo-controlled, double-blind study was to examine and contrast the effects of dietary supplementation with a daily dose of 5 g hydrolysed collagen with 80 mg of vitamin C (CP product) and their combination with 30 mg of hyaluronic acid (CPHA product) over 16 weeks. Validated methods were utilised for the objective evaluation of skin parameters. In total, 87 subjects (women, 40-65 years) completed the entire trial, distributed across the groups as follows: placebo group ( n = 29), CPHA group ( n = 28), and CP group ( n = 30). The results showed beneficial effects of both test products, with notable enhancements in dermis density, skin texture, and a reduction in the severity of wrinkles. In contrast, the administration of either of the products did not yield any significant impacts on skin elasticity or hydration. Observation of the investigated skin parameters did not show superior effects of the addition of hyaluronic acid (HA) to collagen. Therefore, the ability of supplementation with HA to improve the effects on investigated skin parameters beyond the supplementation of collagen alone cannot be confirmed.

Background: Tear trough filling is a popular facial rejuvenation procedure, and hyaluronic acid is typically used as the filler of choice. However, Tyndall's phenomenon, a common complication following hyaluronic acid injection, can occur, leading to skin discoloration of the lower eyelid., Aims: This single-center, prospective, comparative clinical study aimed to evaluate the efficacy of collagen and hyaluronic acid injections in treating tear trough deformity., Methods: Sixty patients were enrolled between June 2022 and January 2023. Patients were randomly allocated into three groups: Group A received hyaluronic acid, Group B received hyaluronic acid combined with collagen, and Group C received collagen alone. Baseline characteristics, including age, sex, and tear trough deformity grade were considered before therapy. Changes in tear trough deformity scores, Global Aesthetic Improvement Scores, and the presence of the Tyndall effect were analyzed at 1 and 3 months postinjection to determine differences among the three groups., Results: Baseline profiles of the three groups were similar. In the first month postinjection, there was no difference in the Global Aesthetic Improvement Scores and tear trough deformity between the three groups. However, in the third-month postinjection, there was a significant difference in scores between patients in Group C and those in Groups A or B. The Tyndall effect manifested in three patients in Group A, which was significantly different from that in Groups B and C., Conclusion: The combined use of hyaluronic acid with collagen in injectable fillers corrected tear trough deformities and reduced the occurrence of the Tyndall phenomenon, which can be problematic with hyaluronic acid alone. Additionally, this combination may help overcome the disadvantage of a shorter retention period when using collagen alone., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Microneedling (MN) and microcoring (MCT) are both methods used for percutaneous collagen induction. This minimally invasive technique involves creating controlled damage in cutaneous tissue to induce neocollagenesis and neoelastogenesis. MN utilizes solid microneedles and is commonly combined with radiofrequency (RF) to add thermal energy, while MCT involves hollow microneedles capable of removing excess tissue without inducing scar formation., Aims: The purpose of this review was to summarize recent literature for MN and MCT, with the goal of assisting clinical decision making regarding the use of these technologies., Methods: PubMed search was conducted for relevant articles published within the last 10 years. Scoping literature review was then performed with pertinent findings reported., Results: Existing literature investigating MCT is sparse. Limited data on in vivo, human effects of this technology exist. Two out of 14 studies in this review pertained to MCT., Conclusion: Additional high-powered clinical studies are needed to guide future cosmetic treatments with MN and MCT., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The mood status of fatigue can impact daily activities. Dietary collagen peptides have been reported to be beneficial for health conditions. A randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of collagen peptides on mood status including fatigue, physical condition, and immunological status. The participants who were healthy but easily fatigued consumed active food containing collagen peptides (10 g/day) ( n  = 33) or placebo food ( n  = 33) for eight weeks. POMS® 2 was used to assess the perceived fatigue and other mood status. The primary outcome was the T-scores of Fatigue-Inertias at eight weeks. In addition, their physical condition and immunological parameters were evaluated. The data set was a per protocol set of 31 participants each in both groups. As for POMS® 2, the T-score of Fatigue-Inertias at eight weeks was significantly lower in the active group than in the placebo group (47.0 ± 7.4 versus 51.5 ± 9.0, p = 0.045). The T-score of Vigor-Activity was significantly higher in the active group than in the placebo group after eight weeks (53.9 ± 10.7 versus 47.3 ± 9.6, p  = 0.002). Regarding the questionnaire on the physical condition, the Likert scale score on fatigue after a night's sleep at eight weeks was significantly lower in the active group than in the placebo group (median; 3.0 versus 4.0, p  = 0.038). There were no significant differences in the measured values of immunological parameters. No safety-related issues were reported in this trial. The intake of collagen peptides (10 g/day) for eight weeks ameliorated the mood status of fatigue and vigor and increased the feeling of sleep restfulness. Dietary collagen peptides were efficient and safe nutritional ingredients for healthy but easily fatigued individuals. Clinical trial registry number and website: UMIN-CTR, UMIN000042291 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000048280.

Background: Topical skin care products often do not reach the deeper layers of the skin, and oral hydrolyzed collagen is one of the newest and most popular systemic supplementations for skin rejuvenation. However, there are limited information in case of Middle Eastern consumers OBJECTIVE: The purpose of this study was to evaluate the tolerability and efficacy of an oral collagen supplement for improvement of skin elasticity, hydration, and roughness in Middle Eastern consumers., Methods and Materials: It was a 12-week, before-after clinical study, conducted on 20 participants (18 women and 2 men) aged 44.15 ± 5.36 years with skin type III-IV. Skin elasticity parameters (R0, R2, R5, and R7), skin hydration and friction, as well as the thickness and echo density of the dermis, were measured after six and 12 weeks daily intake of the study product, as well as 4 weeks after stopping its use (week 16). Participants' satisfaction was assessed on the basis of their answers to the standard questionnaire, and tolerability of the product was assessed by monitoring the adverse effects., Results: A significant improvement was detected in R2, R5, and skin friction at week 12 (p-values 0.041, 0.012 and <0.01, respectively). At week 16, the values remained at an increased level, which indicates the persistence of the results. The increase of dermis density in week 16 was also significant (p-value = 0.03). Moderate overall satisfaction was reported with the treatment, and a few gastrointestinal complications were reported., Conclusion: The study demonstrated that oral collagen peptides could significantly improve the skin elasticity, roughness, and dermis echo density, and they also proved to be safe and well-tolerated., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Collagen-derived dipeptides and tripeptides have various physiological activities. In this study, we compared the plasma kinetics of free Hyp, peptide-derived Hyp, Pro-Hyp, cyclo(Pro-Hyp), Hyp-Gly, Gly-Pro-Hyp, and Gly-Pro-Ala after ingestion of four different collagen samples: AP collagen peptide (APCP), general collagen peptide, collagen, and APCP and γ -aminobutyric acid (GABA) combination. Each peptide was measured by high-performance liquid chromatography and triple quadrupole mass spectrometer. We found that, among all the peptides that were analyzed, only Gly-Pro-Hyp was significantly increased after ingestion of APCP compared with that of general collagen peptides and collagen. In addition, ingestion of the APCP and GABA combination improved the absorption efficiency of Gly-Pro-Ala. Finally, we reveal that Gly-Pro-Hyp was effective for preventing H 2 O 2 -induced reduction in extracellular matrix (ECM)-related genes, COL1A , elastin , and fibronectin , in dermal fibroblasts. Taken together, APCP significantly enhances the absorption of Gly-Pro-Hyp, which might act as an ECM-associated signaling factor in dermal fibroblasts, and the APCP and GABA combination promotes Gly-Pro-Ala absorption. Clinical Trial Registration number: UMIN000047972.

Skin photoaging is one of the most serious public health problems in the 21st century that may lead to thin, saggy, and structurally weakened skin. Adipokine therapy toward skin photoaging is always associated with poor permeability, biologic stability and the short in vivo release duration. Our laboratory previously extracted an extracellular matrix component of adipose tissue by purely physical methods, namely "adipose collagen fragment (ACF)", which holds promise for preventing skin photoaging. However, the injection treatment of ACF requires repeated preparation processes and injection procedures, which may be time-consuming and painful. Therefore, we describe the fabrication and assessment of a detachable ACF-microneedle (ACF-MN) patch that creates minimally invasive dermal microtrauma upon application. And we evaluated the morphology characterization, mechanical properties and puncture performance in vitro. The delivery efficiency of ACF from the patches was estimated in vitro and vivo. Then, the therapeutic efficacy was identified through applying ACF-MN patches into the dermis of UVA-induced photoaging mice and the related detection of skin photoaging was estimated. Our results demonstrated that ACF-MN exhibited well skin puncture performance and could release ACF component slowly. Meanwhile, this microneedle device loaded with ACF exhibited the treatment efficiency on skin photoaging in a mouse model. Therefore, implantation of the microtrauma-mediated, long-acting ACF-MN system can be utilized as a potential candidate for preventing skin photoaging in the clinic., (Copyright © 2022. Published by Elsevier B.V.)

The sympathetic nervous system (SNS) contributes to immune balance by promoting anti-inflammatory B cells. However, whether B cells possess a self-regulating mechanism by which they modulate regulatory B cell (Breg) function is not well understood. In this study, we investigated the ability of B cells to synthesize their own catecholamines upon stimulation with different B cell activators and found that expression of the enzyme tyrosine hydroxylase (TH), required to generate catecholamines, is up-regulated by Toll-like receptor (TLR)9. This TLR9-dependent expression of TH correlated with up-regulation of adrenergic receptors (ADRs), enhanced interleukin (IL)-10 production, and overexpression of the co-inhibitory ligands programmed death ligand 1 (PD-L1) and Fas ligand (FasL). Moreover, concomitant stimulation of ß1-3-ADRs together with a B cell receptor (BCR)/TLR9 stimulus clearly enhances the anti-inflammatory potential of Bregs to suppress CD4 T cells, a crucial population in the pathogenesis of autoimmune diseases, like rheumatoid arthritis (RA). Furthermore, TH up-regulation was also demonstrated in B cells during the course of collagen-induced arthritis (CIA), a mouse model for the investigation of RA. In conclusion, our data show that B cells possess an autonomous mechanism to modulate their regulatory function in an autocrine and/or paracrine manner. These findings help to better understand the function of B cells in the regulation of autoimmune diseases and the interplay of SNS., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Low back pain (LBP) is a frequent symptom. Among the causes that can determine it, lumbar osteoarthritis plays an important role. Therapeutic exercise, according to McKenzie method, has been shown to be effective in the treatment of LBP. Oral supplementation with collagen peptides represents a new therapeutic possibility in osteoarthritis. The aim of this study is to evaluate the combined efficacy of therapeutic exercise and oral administered viscosupplements in the treatment of osteoarthritis-related chronic LBP., Methods: Sixty patients were recruited and randomly divided into two groups (Group A and B). Group A performed only kinesitherapy, Group B carried out the same kinesitherapy combined with the daily administration of food supplements such as Fortigel®, Vitamin C, sodium hyaluronate, manganese and copper, during the whole treatment period. Patients were evaluated at the time of recruitment (T0), at the end of the treatment (T1 - 3 weeks after T0) and 6 weeks after T1 (T2). The outcome measures used were: Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Short Form-12 (SF-12)., Results: All the outcomes improved significantly at T1 in both groups, but more markedly in group B. Furthermore, in group A at T2, there was a statistically significant worsening in the scores of VAS, ODI and physical component of the SF-12, while in group B, this variation has not been detected., Conclusion: The combination of rehabilitation based on McKenzie back exercises and oral viscosupplementation with Fortigel®, Vitamin C, sodium hyaluronate, manganese and copper represents a valid option in patients with chronic LBP, as it ensures pain relief and improvement in the quality of life and in lumbar spine functionality. These therapeutic benefits are more evident and long-lasting compared to those obtained with rehabilitation alone., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The stratum corneum (SC) is the outermost layer of the epidermis and plays an important role in maintaining skin moisture and protecting the skin from the external environment. Ceramide and natural moisturizing factor (NMF) are the major SC components that maintain skin moisture. In this study, we investigated whether the oral intake of enzymatically decomposed AP collagen peptides (APCPs) can improve skin moisture and barrier function by assessing changes in the ceramide and NMF contents in the SC after APCP ingestion with the aim to develop a skin functional food. Fifty participants orally ingested APCP (1000 mg) or placebo for 12 weeks, and then, skin hydration and skin texture were evaluated. SC samples were collected to analyze skin scaling, ceramide, and NMF contents. Participants in the APCP group exhibited improved skin moisture content by 7.33% ( p = 0.031) and roughness by -4.09% ( p = 0.036) when compared with those in the placebo group. NMF content; the amounts of amino acids (AA), including glycine and proline; and AA derivatives were significantly increased in the APCP group (31.98 μg/mg protein) compared to those in the placebo group (-16.01 μg/mg protein) ( p = 0.006). The amounts of total ceramides and ceramide subclasses were significantly higher in the APCP group than in the placebo group ( p = 0.014). In conclusion, our results demonstrate that APCP intake improves skin moisture and increase the ceramide and NMF contents in the SC, thereby enhancing the skin barrier function.

The goal of this study was to develop strategies to localize human collagen-based hydrogels within an infarcted mouse heart, as well as analyze its impact on endogenous extracellular matrix (ECM) remodeling. Collagen is a natural polymer that is abundantly used in bioengineered hydrogels because of its biocompatibility, cell permeability, and biodegradability. However, without the use of tagging techniques, collagen peptides derived from hydrogels can be difficult to differentiate from the endogenous ECM within tissues. Imaging mass spectrometry is a robust tool capable of visualizing synthetic and natural polymeric molecular structures yet is largely underutilized in the field of biomaterials outside of surface characterization. In this study, our group leveraged a recently developed matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technique to enzymatically target collagen and other ECM peptides within the tissue microenvironment that are both endogenous and hydrogel-derived. Using a multimodal approach of fluorescence microscopy and ECM-IMS techniques, we were able to visualize and relatively quantify significantly abundant collagen peptides in an infarcted mouse heart that were localized to regions of therapeutic hydrogel injection sites. On-tissue MALDI MS/MS was used to putatively identify sites of collagen peptide hydroxyproline site occupancy, a post-translational modification that is critical in collagen triple helical stability. Additionally, the technique could putatively identify over 35 endogenously expressed ECM peptides that were expressed in hydrogel-injected mouse hearts. Our findings show evidence for the use of MALDI-IMS in assessing the therapeutic application of collagen-based biomaterials.

Objective: Collagen disruption is one of the underlying causes of knee pain in patients with osteoarthritis and/or diverse cartilage defects. Atelocollagen is a type of collagen that lacks telopeptides and thus has reduced antigenicity. The intra-articular injection of type I atelocollagen supplements collagen levels in the disrupted articular cartilage. This randomized controlled trial evaluated the effects of the intra-articular injection of atelocollagen for the management of knee pain., Design: Two hundred patients with osteoarthritis, chondromalacia, or other cartilage defects were randomly assigned to receive a 3-mL intra-articular injection of atelocollagen (BioCollagen group) or saline (Placebo group). Clinical improvement was evaluated over a 24-week period using the 100-mm visual analogue scale (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the 36-item Short-Form Health Survey (SF-36)., Results: VAS scores were significantly better in the BioCollagen group as compared with the Placebo group at 24 weeks. More patients in the BioCollagen group reported exceeding 20% and 40% VAS improvements. The WOMAC and SF-36 scores were also significantly improved from baseline after the intra-articular injection of atelocollagen; although, the differences between the BioCollagen and Placebo groups were not significant. There were no unexpected or severe adverse events reported for either group., Conclusions: The results show that an intra-articular injection of atelocollagen effectively alleviates knee pain, as intended. Therefore, the intra-articular injection of atelocollagen can be considered an alternative solution to controlling knee pain due to osteoarthritis and diverse cartilage defects.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation, synovial hyperplasia, cartilage degeneration, bone erosion, and pannus. Immunoglobulin D (IgD) plays an important role in autoimmune diseases although the content of it in vivo is low. Increased concentrations of anti-IgD autoantibodies have been detected in many RA patients. IgD-Fc-Ig fusion protein is constructed by connecting human IgD Fc domain and IgG1 Fc domain, which specifically block the IgD/ IgDR pathway and regulate the function of cells expressing IgDR to treat RA. The expression levels of Wnt5A and Frizzled 5 are higher in RA synovial tissue specimens. The complex of Wnt5A-Fzd5-LRP5/6-CTHRC1 promotes the expression of hypoxia inducible factor-1α by activating nuclear factor kappa-B (NF-κB), leading to high expression of VEGF and participating in angiogenesis. VEGF is the strongest angiogenic factor found so far. Here, we aimed to explore whether IgD participates in synovitis by binding to IgDR and regulating the activation of Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in fibroblast synovial cells (FLSs), whether IgD-Fc-Ig fusion protein inhibits VEGF production in FLS of CIA and explore mechanism. We found that IgDR is expressed on MH7A and FLS. IgD promotes VEGF expression by activating Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in MH7A and FLS. After activation of Fzd5 with Wnt5A, IgD-Fc-Ig reduced VEGF-A level in the culture supernatant of MH7A stimulation by IgD. The expressions of CTHRC1, Fzd5, p-P65 and VEGF in MH7A and FLSs were down-regulated after IgD-Fc-Ig treatment. IgD-Fc-Ig suppressed the combination of CTHRC1 and Fzd5 as well. By using the animal model, we demonstrated that IgD-Fc-Ig suppress ankle CTHRC1 and Fzd5 production resulted in inhibition of index of joint inflammation of CIA rats, which were consistent with vitro results. Conclusively, IgD-Fc-Ig inhibits IgD and Wnt5A-induced angiogenesis and joint inflammation by suppressing the combination of CTHRC1 and Fzd5. Our results show that IgD-Fc-Ig exerts its suppressive effect on IgD and Wnt5A by Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Proper regulation of B-cell function is essential for effective humoral immunity and maintenance of immune tolerance. Here, we found that FBW7 (F-box/WD40 repeat-containing protein 7) is highly expressed in germinal centre B and B1 cells, and confirmed that it has an intrinsic role in maintaining homeostasis of mature B cells and B-1 cells. FBW7 deletion led to an impairment of antibody response, and although germinal centre formation was not affected, antibody class-switch recombination and affinity maturation processes were defective. Likewise, memory immune response was severely impaired. Moreover, FBW7 ablation ameliorated the pathogenesis of an autoimmune disease model, collagen-induced arthritis, by reducing the production of anti-collagen II autoantibodies. Taken together, these data suggest that FBW7 may be an attractive target for developing new therapeutics for the treatment of autoimmune diseases., (© 2021 John Wiley & Sons Ltd.)

Novel multifunctional biomimetic injectable hybrid systems were synthesized. The physicochemical as well as biological in vitro and in vivo tests demonstrated that they are promising candidates for bone tissue regeneration. The hybrids are composed of a biopolymeric collagen/chitosan/hyaluronic acid matrix and amine group-functionalized silica particles decorated with apatite to which the alendronate molecules were coordinated. The components of these systems were integrated and stabilized by cross-linking with genipin, a compound of natural origin. They can be precisely injected into the diseased tissue in the form of a viscous sol or a partially cross-linked hydrogel, where they can serve as scaffolds for locally controlled bone tissue regeneration/remodeling by supporting the osteoblast formation/proliferation and maintaining the optimal osteoclast level. These materials lack systemic toxicity. They can be particularly useful for the repair of small osteoporotic bone defects.

(1) Aim: To immunohistochemically evaluate the effect of a volume-stable collagen scaffold (VCMX) on periodontal regeneration. (2) Methods: In eight beagle dogs, acute two-wall intrabony defects were treated with open flap debridement either with VCMX (test) or without (control). After 12 weeks, eight defects out of four animals were processed for paraffin histology and immunohistochemistry. (3) Results: All defects (four test + four control) revealed periodontal regeneration with cementum and bone formation. VCMX remnants were integrated in bone, periodontal ligament (PDL), and cementum. No differences in immunohistochemical labeling patterns were observed between test and control sites. New bone and cementum were labeled for bone sialoprotein, while the regenerated PDL was labeled for periostin and collagen type 1. Cytokeratin-positive epithelial cell rests of Malassez were detected in 50% of the defects. The regenerated PDL demonstrated a larger blood vessel area at the test (14.48% ± 3.52%) than at control sites (8.04% ± 1.85%, p = 0.0007). The number of blood vessels was higher in the regenerated PDL (test + control) compared to the pristine one ( p = 0.012). The cell proliferative index was not statistically significantly different in pristine and regenerated PDL. (4) Conclusions: The data suggest a positive effect of VCMX on angiogenesis and an equally high cell turnover in the regenerated and pristine PDL. This VCMX supported periodontal regeneration in intrabony defects.

Spinal cord injury (SCI) causes histological alterations which in turn affects functional activity. Studies have demonstrated that dental pulp-derived stem cells conditioned medium has beneficial effects on the nervous system. Besides, collagen hydrogel acts as a drug releasing system in SCI investigations. This research aimed to evaluate effects of dental pulp-derived stem cells conditioned medium loaded in collagen hydrogel in SCI. After culturing of Stem cells from human exfoliated deciduous teeth (SHEDs), SHED-conditioned medium (SHED-CM) was harvested and concentrated. Collagen hydrogel containing SHED-CM was prepared. The rats were divided into five groups receiving laminectomy, compressive SCI with or without intraspinal injection of biomaterials (SHED-CM and collagen hydrogel with or without SHED-CM). After 6 weeks, histological parameters were estimated using stereological methods. The total volume of preserved white matter and gray matter (p < 0.05) as well as the total number of neurons and oligodendrocytes in the rats received SHED-CM loaded in collagen hydrogel were significantly higher, and also lesion volume and lesion length were significantly lower (p < 0.05) compared to those of the other injured groups. In conclusion, intraspinal administration of SHED-CM loaded in collagen hydrogel leads to neuroprotection, proposing a cell-free therapeutic approach in SCI., (Copyright © 2021. Published by Elsevier B.V.)

Dry and eczema-prone skin conditions such as atopic dermatitis and xerotic eczema primarily indicate an impaired skin barrier function, which leads to chronic pruritus. Here, we investigated the effects of a novel emollient containing H.ECM TM liposome, which contains a soluble proteoglycan in combination with hydrolyzed collagen and hyaluronic acid. A prospective, single-arm study was conducted on 25 participants with mild atopic dermatitis or dry skin to assess the hydration and anti-inflammatory effect of the novel emollient applied daily over four weeks. All efficacy parameters, including itching severity, transepidermal water loss, and skin hydration, improved significantly after four weeks. The in vitro and ex vivo studies confirmed the restoration of the skin's barrier function. The study revealed the clinical and laboratory efficacy of H.ECM TM liposome in reducing itching and improving the skin's barrier integrity. Thus, the use of H.ECM TM liposome can be considered a therapeutic option for dry and eczema-prone skin.

Objectives/hypothesis: Test a new jellyfish collagen biomaterial aimed to increase duration of injection medialization laryngoplasty (IL) against two products in clinical practice., Study Design: Animal model., Methods: Left recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits (N = 6/group). Group 1 received micronized cross-linked jellyfish collagen (MX-JC) and adipose derived stem cells (ADSCs), Group 2, MX-JC alone, Group 3, cross-linked hyaluronic acid (X-HA), and Group 4, micronized acellular dermis (MACD). Animals were sacrificed at 4 and 12 weeks. Major outcomes were MRI tissue volumes and histopathology., Results: After 100 μL IL MRI volumes (means ± STD) at 4 and 12 weeks were: Group 1: 27.2 ± 15.6 and 13.1 ± 5.2 μL, Group 2: 60.8 ± 18 and 27.8 ± 2.47 μL, Group 3: 27.4 ± 12 and 10.6 ± 8 μL, and Group 4: 37.5 ± 11 and 9.85 ± 1 μL. Group 2 volumes were largest and Group 3 were smallest in all comparisons (P < .05). Histologically, low grade inflammatory responses were observed in Group 1, mild histiocytic infiltration in Group 2, widespread muscle fiber loss in Group 3, and plasmocytic infiltration in Group 4., Conclusions: MX-JC showed the least resorption at 4 and 12 weeks among all groups. T cell inflammatory responses were observed with MX-JC but were reduced by 12 weeks while B cell immune responses, indicative of antibody priming, were predominantly noted with MACD. MX-JC + ADSC showed low grade immunity while the XHA showed greater myocyte loss compared to the other groups., Level of Evidence: NA Laryngoscope, 131:E2452-E2460, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

The clinical application of most materials used to fill severe bone defects is limited owing to the insufficient ability of such materials to induce bone regeneration over a long repair period. The purpose of this study was to establish a model for the alveolar process cleft in rabbits to evaluate the effect of active bone material in bone defect repair. The active bone material used in this study is a new bone repair material composed of a heterogeneous collagen membrane implanted with modified recombinant human bone morphogenetic protein 2. This proposed active bone material can specifically bind to collagen. Twenty-four young Japanese white rabbits (JWRs) were selected and randomly divided into four groups (normal, control, material, and bone morphogenetic protein groups). The alveolar process cleft model was established by removing an equal volume bone at the left maxillary position. Blood samples were collected from the JWRs 3 and 6 months after the surgery to evaluate the biocompatibility of the active bone materials. Subsequently, the skull model was established, and the appearance was observed. Imaging methods (including X-ray examination and micro-computerized tomography scanning), tissue staining, and immunohistochemistry were employed for the evaluation. The bone collagen material and active bone material exhibited high biocompatibility. In addition, the ability of the active bone material to induce bone repair and regeneration was higher than that of the bone collagen material. The active bone material exhibited satisfactory bone regeneration performance in rabbits, indicating its potential as an active material for repairing congenital alveolar process clefts in humans., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Active collagen oligopeptides (ACOP) are bioactive collagen-derived peptides detected by a recently-established ELISA. To facilitate studies of the function and metabolism of these products, this study aims to determine which of these peptides is recognized by a novel anti-ACOP antibody used in this ELISA. We then investigate the effect of collagen peptide (CP) ingestion and exercise on urinary ACOP concentrations in a cohort of university student athletes using colorimetric, LC-MS/MS, and ELISA. We observed that the antibody showed strong cross-reactivity to Pro-Hyp and Gly-Pro-Hyp and weak cross-reactivity to commercial CP. CP ingestion increased the urinary level of ACOP over time, which correlated highly with urinary levels of peptide forms of Hyp and Pro-Hyp. Physical activity significantly decreased the urinary ACOP level. This study demonstrates changes in urinary ACOP following oral CP intake and physical activity using ELISA with the novel anti-ACOP antibody. Thus, ACOP may be useful as a new biomarker for collagen metabolism.

We demonstrated the safety and efficacy of autologous chondrocyte precursor (CP) cell therapy in repairing Grade 4 cartilage defects of medial femoral condyles. The autologous bone marrow mesenchymal stem cells of each participant were isolated, amplified, and then differentiated into CPs in atelocollagen. Neotissues made of CPs were implanted into cartilage defects with an average cell density of 4.9 ± 2.1 × 10 6 cells/cm 2 through arthrotomy. The knee function was evaluated with the International Knee Documentation Committee (IKDC) subjective knee form. Patients' knee functions significantly improved by the 28th week (IKDC score = 68.3 ± 12.1), relative to the initial functionality before the CP therapy (IKDC score = 46.1 ± 16.4, p -value = 0.0014). Nine of these twelve patients maintained good knee functions for 9 years post-implantation (IKDC score = 69.8 ± 12.3) at levels higher than the pre-implantation values ( p -value = 0.0018). Patients were evaluated with MRI and arthroscopy, and the defective sites exhibited a smooth surface without a gap between the implant and host tissue. This study demonstrates that autologous CPs successfully engraft into the host tissue and result in the re-formation of hyaline-like cartilage, thereby improving the impaired knee functions. Most importantly, no adverse event was reported during this long-term follow-up period.

Biomaterials derived from natural resources have increasingly been used for versatile applications in the central nervous system (CNS). Thanks to their biocompatibility and biodegradability, natural biomaterials offer vast possibilities for future clinical repair strategies for the CNS. These materials can be used for diverse applications such as hydrogels to fill the tissue cavities, microparticles to deliver drugs across the blood-brain barrier, and scaffolds to transplant stem cells. In this review, various uses of prominent protein and polysaccharide biomaterials, with a special focus on collagen, in repair and regenerative applications for the brain are summarized together with their individual advantages and disadvantages., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Even though mesenchymal stem cells (MSCs) are known for cartilage regeneration, their therapeutic efficacy needs to be enhanced. In the present study, we produced genome-edited silent information regulator 2 type 1 ( Sirt1 )-overexpressing MSCs, and evaluated their therapeutic potential in a damaged cartilage mouse liver fibrosis model. The Sirt1 gene was successfully inserted into a 'safe harbor' genomic locus in amniotic mesenchymal stem cells (AMMs), and the chondrogenic properties of the Sirt1 gene overexpressing AMMs (AMM/S) were characterized using quantitative PCR and histology. Therapeutic potentials were investigated in a collagen-induced arthritis (CIA) mouse model. Chondrocyte-differentiated AMM/S expressed cartilage-specific genes and were positive for Safranin O staining. Transplantation of AMM/S attenuated CIA progression and suppressed T helper (Th)-17 cell activation while increasing the Treg cell population in CIA mice. Pro-inflammatory factors, such as interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α were significantly decreased in AMM/S-injected joint tissues. In conclusion, genome-edited AMM/S may represent a safe and alternative therapeutic option for the treatment and repair of damaged cartilage, or in inflammatory joint arthritis.

Degenerated intervertebral discs (IVDs) were treated with autologous adipose-derived stem cells (ASC) loaded into an injectable collagen scaffold in a sheep model to investigate the implant's therapeutic potential regarding the progression of degeneration of previously damaged discs. In this study, 18 merino sheep were subjected to a 3-step minimally invasive injury and treatment model, which consisted of surgically induced disc degeneration, treatment of IVDs with an ASC-loaded collagen hydrogel 6 weeks post-operatively, and assessment of the implant's influence on degenerative tissue changes after 6 and 12 months of grazing. Autologous ASCs were extracted from subcutaneous adipose tissue and cultivated in vitro. At the end of the experiment, disc heights were determined by µ-CT measurements and morphological tissue changes were histologically examined.Histological investigations show that, after treatment with the ASC-loaded collagen hydrogel implant, degeneration-specific features were observed less frequently. Quantitative studies of the degree of degeneration did not demonstrate a significant influence on potential tissue regeneration with treatment. Regarding disc height analysis, at both 6 and 12 months after treatment with the ASC-loaded collagen hydrogel implant a stabilization of the disc height can be seen. A complete restoration of the intervertebral disc heights however could not be achieved.The reported injection procedure describes in a preclinical model a translational therapeutic approach for degenerative disc diseases based on adipose-derived stem cells in a collagen hydrogel scaffold. Further investigations are planned with the use of a different injectable scaffold material using the same test model.

Background: The purpose of the study was to evaluate the association between microfibrillar collagen hemostat and anastomotic leakage after anterior resection., Method: Between March 2015 and December 2019, a total of 203 consecutive rectal cancer patients who underwent elective anterior resection were included. Patient parameters were analyzed. The relevant risk factors were identified by univariate and multivariate analysis. Propensity score matching was performed to reduce the selection bias., Results: In total, 26 (12.8%) of the 203 study patients developed clinical anastomotic leakage. The length of hospital stay was significantly prolonged by anastomotic leakage. In univariate analysis and multivariate analysis, male sex, low tumor location, and intraoperative application of microfibrillar collagen hemostat significantly increased the risk of anastomotic leakage. Furthermore, analysis after propensity score matching confirmed the independent role of microfibrillar collagen hemostat in anastomotic leakage. In addition, the median time of anastomotic leakage occurrence from the initial operation in patients with microfibrillar collagen hemostat was 9.00 days, which was significantly later than that in patients without microfibrillar collagen hemostat., Conclusion: In addition to male sex and low tumor location, intraoperative application of microfibrillar collagen hemostat was demonstrated to be a significant risk factor for anastomotic leakage. This finding suggested that surgeons should be fully aware of this potential risk in anterior resection. Because of the limitation of retrospective study, however, randomized controlled trials are needed to confirm this association in the future., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Spinal cord injury (SCI) causes intractable disease and leads to inevitable physical, financial, and psychological burdens on patients and their families. SCI is commonly divided into primary and secondary injury. Primary injury occurs upon direct impact to the spinal cord, which leads to cell necrosis, axon disruption, and vascular loss. This triggers pathophysiological secondary injury, which has several phases: acute, subacute, intermediate, and chronic. These phases are dependent on post-injury time and pathophysiology and have various causes, such as the infiltration of inflammatory cells and release of cytokines that can act as a barrier to neural regeneration. Another unique feature of SCI is the glial scar produced from the reactive proliferation of astrocytes, which acts as a barrier to axonal regeneration. Interdisciplinary research is investigating the use of biomaterials and tissue-engineered fabrication to overcome SCI. In this review, we discuss representative biomaterials, including natural and synthetic polymers and nanomaterials. In addition, we describe several strategies to repair spinal cord injuries, such as fabrication and the delivery of therapeutic biocomponents. These biomaterials and strategies may offer beneficial information to enhance the repair of spinal cord lesions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The role of the innate immune system has been established in the initiation and perpetuation of inflammatory disease, but less attention has been paid to its role in the resolution of inflammation and return to homeostasis. Toll-like receptor (TLR) expression profiles were analysed in tissues with differing disease status in rheumatoid arthritis (RA), ankylosing spondylitis (AS), and in experimental arthritis. TLR gene expression was measured in whole blood and monocytes, before and after TNF blockade. In RA and osteoarthritis synovia, the expression of TLRs was quantified by standard curve qPCR. In addition, four distinct stages of disease were defined and validated in collagen-induced arthritis (CIA), the gold standard animal model for RA - pre-onset, early disease, late disease and immunised mice that were resistant to the development of disease. TLR expression was measured in spleens, lymph nodes, blood cells, liver and the paws (inflamed and unaffected). In RA whole blood, the expression of TLR1, 4 and 6 was significantly reduced by TNF blockade but the differences in TLR expression profiles between responders and non-responders were less pronounced than the differences between RA and AS patients. In RA non-responders, monocytes had greater TLR2 expression prior to therapy compared to responders. The expression of TLR1, 2, 4 and 8 was higher in RA synovium compared to control OA synovium. Circulating cytokine levels in CIA resistant mice were similar to naïve mice, but anti-collagen antibodies were similar to arthritic mice. Distinct profiles of inflammatory gene expression were mapped in paws and organs with differing disease status. TLR expression in arthritic paws tended to be similar in early and late disease, with TLR1 and 2 moderately higher in late disease. TLR expression in unaffected paws varied according to gene and disease status but was generally lower in resistant paws. Disease status-specific profiles of TLR expression were observed in spleens, lymph nodes, blood cells and the liver. Notably, TLR2 expression rose then fell in the transition from naïve to pre-onset to early arthritis. TLR gene expression profiles are strongly associated with disease status. In particular, increased expression in the blood precedes clinical manifestation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Stem cell therapy is an attractive approach for recovery from myocardial infarction (MI) but faces the challenges of rapid diffusion and poor survival after transplantation. Here we developed an injectable collagen scaffold to promote the long-term retention of transplanted cells in chronic MI. Forty-five minipigs underwent left anterior descending artery (LAD) ligation and were equally divided into three groups 2 months later (collagen scaffold loading with human umbilical mesenchymal stem cell (hUMSC) group, hUMSC group, and placebo group (only phosphate-buffered saline (PBS) injection)). Immunofluorescence staining indicated that the retention of transplanted cells was promoted by the collagen scaffold. Echocardiography and cardiac magnetic resonance imaging (CMR) showed much higher left ventricular ejection fraction (LVEF) and lower infarct size percentage in the collagen/hUMSC group than in the hUMSC and placebo groups at 12 months after treatment. There were also higher densities of vWf-, α-sma-, and cTnT-positive cells in the infarct border zone in the collagen/cell group, as revealed by immunohistochemical analysis, suggesting better angiogenesis and more cardiomyocyte survival after MI. Thus, the injectable collagen scaffold was safe and effective on a large animal myocardial model, which is beneficial for constructing a favorable microenvironment for applying stem cells in clinical MI.