Collagen Cross-linking Research Articles

Influence of Dextran Solution and Corneal Collagen Crosslinking on Corneal Biomechanical Parameters Evaluated by Corvis ST In Vitro

Purpose: To analyze the influence of dextran solution and corneal collagen crosslinking (CXL) on corneal biomechanical parameters in vitro, evaluated by Corneal Visualization Scheimpflug Technology (Corvis ST). Materials and Methods: Forty porcine eyes were included in this study. Twenty porcine eyes were instilled with dextran solution for 30 min (10 eyes in 2% dextran solution and 10 eyes in 20% dextran solution). CXL treatment was performed in 10 porcine eyes; the other 10 porcine eyes were regarded as the control group. Each eye was fixed on an experimental inflation platform to carry out Corvis measurements at different IOPs. Corneal biomechanical parameters were calculated based on Corvis measurement. Statistical analysis was used to analyze the influence of dextran solution and CXL on corneal biomechanical parameters based on Corvis parameters. Results: The corneal energy-absorbed area (Aabsorbed) decreased after being instilled with dextran solution under IOP of 15 mmHg (p < 0.001); the elastic modulus (E) of the cornea instilled with 20% dextran solution was significantly higher than that instilled with 2% dextran solution (p < 0.001), since it decreased after being instilled with 20% dextran solution (p = 0.030); the stiffness parameter at the first applanation (SP-A1) increased after CXL (p < 0.001). Conclusions: Both dextran solution and CXL can change corneal biomechanical properties; the concentration of dextran solution can influence the corneal biomechanical properties, which may, in turn, affect the effectiveness of CXL. SP-A1 may be used as an effective parameter for the evaluation of CXL.

Collagen crosslinking-induced corneal morphological changes: a three-dimensional light sheet Microscopy-based evaluation.

Stiffness-related eye diseases such as keratoconus require comprehensive visualization of the complex morphological matrix changes. The aim of this study was to use three-dimensional (3D) light sheet fluorescence microscopy (LSFM) to analyze unlabeled corneal tissue samples, qualitatively visualizing changes in corneal stiffness. Isolated porcine corneal tissue samples were treated with either NaCl or 0.1% glutaraldehyde (GTA) prior to clearing with benzyl alcohol/benzyl benzoate (BABB) and subsequently scanned with LSFM. After analysis of the LSFM data sets, the samples were embedded in paraffin to validate the results by conventional planar microscopy. In the unlabeled corneal tissue samples the 2D/3D morphology of the entire tissue volume was identified by specific autofluorescence signals. An enhancement of collagen crosslinking was induced by applying GTA to the corneal tissue. Subsequent LSFM scans showed specific morphological changes due to altered autofluorescence signals of the corneal stroma, which were confirmed by conventional histology. Therefore, LSFM analysis of corneal tissue samples allowed label-free 3D autofluorescence assessment of the corneal morphology in its anatomical context. It provides the technical basis for the examination of the pathologically altered cornea and facilitates ophthalmologic examinations of corneal diseases based on the altered tissue stiffness.

Epi-off riboflavin with vitamin E TPGS (Ribocross®) cross-linking: one-year outcome.

To assess the short and mid-term outcomes of epithelium-off (epi-off) corneal collagen cross-linking using Riboflavin with Vitamin E TPGS (Epi-off Ribocross® CXL) for progressive keratoconus (KC). Retrospective, single-center non-comparative interventional study. Patients with progressive keratoconus who underwent CXL using (Epi-off Ribocross® CXL) from May 2021 to May 2022 who completed at least 12months of follow-up in Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Corrected distance visual acuity with spectable (CDVA), tomographic parameters (Belin ABCD) and topographic parameters were evaluated at baseline and at last follow up. Twenty eyes of twenty patients fulfilled inclusion criteria. CDVA remained stable at last follow up (0.88 ± 0.19 from 0.83 ± 0.21, p = 0.45) with a significant reduction in cylinder (1.97 ± 1.69 from 2.78 ± 2.19, p = 0.03). Kmax significantly improved from 53.18D ± 6.32 to 50.96 ± 5.3D (p = 0.005). At the last follow up, no case of progression was noted. Epi-off Ribocross® CXL proved to be a safe treatment for progressive KC, with a stabilization of all cases at the one year follow up. Further studies are needed to confirm long-term stability.

Accelerated versus conventional corneal collagen cross-linking for keratoconus: A meta-analysis of randomized controlled trials.

To systematically compare the effectiveness of conventional corneal collagen cross-linking (CCXL) protocols and accelerated corneal collagen cross-linking (ACXL) protocols in cases with progressive keratoconus. The Cochrane library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for randomized controlled trials (RCTs). Outcomes were clinical results and changes in corneal properties. Standardized mean differences (SMD) and 95% confidence interval (CI) were used to estimate the clinical consequences. All outcomes were distributed by different follow-up durations (6 months, 12 months, and > 12 months). We also compared maximum keratometry (Kmax) and best spectacle-corrected visual acuity (BCVA) in subgroups, which were categorized by the discrepant impregnation time period of riboflavin. We included 14 RCTs that met the eligibility criteria in this meta-analysis. At the last follow-up, CCXL was superior in postoperative change in demarcation line (SMD: -1.573; 95% CI: -2.897 to -0.248) and in Kmax (SMD:0.302; 95% CI: 0.071 to 0.533), whereas ACXL provided a significantly lower reduction in central corneal thickness (SMD: 0.498; 95% CI: 0.125 to 0.871). No differences in the changes in uncorrected visual acuity, BCVA, manifest refraction spherical equivalent, corneal biomechanical properties, and the endothelial cell density were found among both groups. CCXL was superior to ACXL in greater corneal flattening and deeper demarcation line, while ACXL seemed to cause less reduction in CCT and allow for earlier UDVA stability. To clearly define the comparative safety and clinical consequences of the different regimens of CXL, more RCTs are required.

Abstract 4112931: The Nature of Collagen Cross-links Differs in Reversibly and Irreversibly Infarcted Myocardium

Background: Persistent scarring after myocardial infarction (MI) is a major driver of heart failure in mammals. However, unlike mammals, zebrafish exhibit a remarkable ability to resorb scar, which consists predominantly of collagen in both species. Aims: We aimed here to develop a toolbox of techniques to characterize the nature of collagen in infarcted mammalian and zebrafish hearts. Specifically, we aimed to characterize the early and late cross-links that form in collagen and determine whether differences in these cross-links exist in zebrafish and mammals. Methods: To characterize the initial oxidation and cross-linking of collagen we developed a novel fluorescent probe (TMR-O) that binds to lysine aldehydes on collagen and inform on the degree of collagen cross-linking. Additionally, we used high performance liquid chromatography (HPLC) to quantify degradation-resistant mature collagen cross-links, such as pyridinoline (Pyd), and its precursor, hydroxylysine. Results: TMR-O imaging revealed similar overall CCL levels in both zebrafish and mouse infarcts. However, the irreversible cross-link pyridinoline (Pyd) was abundant in mouse infarcts but completely absent in zebrafish (p<0.0001). High Pyd levels in mice were accompanied by a dynamic increase in lysine hydoxylation (>200%), which was not observed in zebrafish (<10%). Conclusions: While collagen in mammalian and zebrafish infarcts may appear histologically similar, marked biochemical differences exist. Mature degradation-resistant collagen cross-links, such as Pyd form, in murine but not zebrafish infarcts and likely explains why zebrafish can resorb myocardial scar. Targeting Pyd formation in mammals could pave the way for novel therapeutic strategies to promote scar resolution and improve cardiac function after MI.

Incidence and Outcomes of Infectious Keratitis After Corneal Collagen Cross-Linking Over 10 years From a Tertiary Care Center in South India.

The purpose of this study was to report the incidence and outcomes of infectious keratitis after corneal collagen cross-linking (CXL) over 10 years in South India. Patients who underwent CXL for progressive keratoconus between January 2011 and December 2020 and those with infectious keratitis were identified from an electronic database system. The clinical and microbiological profiles of those affected were extracted from the case files and included in the analysis, whereas viral keratitis was excluded. Eleven eyes with post-CXL infectious keratitis were identified, with 3842 CXL procedures (0.21%) occurring in-house, while 3 were referred from outside. The mean age of the patients was 21.8 ± 7.8 years, and 7 (64%) were male. Six eyes (54%) had conventional isotonic CXL, whereas 5 had hypotonic CXL when pachymetry was <400 μm. Six eyes (54%) presented with hypopyon at a median of 3 days after CXL. Culture of the corneal scrapings grew methicillin-sensitive Staphylococcus aureus in 4 patients, methicillin-sensitive Staphylococcus epidermidis in 2, Aspergillus fumigatus in 1, Aspergillus flavus in 1, Haemophilus parainfluenzae in 1, and no organisms in 2 patients. Almost all the isolates were resistant to ciprofloxacin and other fluoroquinolones. The majority of eyes responded well to intensive topical antibiotics guided by antibiograms and regained 6/18 vision (median). Therapeutic keratoplasty was needed in 2 eyes while cyanoacrylate glue was needed in another 2 eyes. Post-CXL infections are rare, most frequently caused by antibiotic-resistant commensals, and resemble the clinical spectrum and outcomes of non-CXL-related infectious keratitis in most cases.

Sociodemographic Predictors of Keratoconus (Severity, Treatment, and Progression) in a Tertiary Center in New York City.

To identify sociodemographic factors as predictors of keratoconus severity, progression, disease outcomes, and appropriate management in a tertiary care ophthalmology institute in the New York City metropolitan area. This is a retrospective chart review. Patients with keratoconus presenting at a tertiary eye institute in an urban setting seen between 2015 and 2022 were included. Sociodemographic data including age, sex, race, ethnicity, income derived from zip code, insurance coverage, and preferred language were recorded. These sociodemographic factors were analyzed as possible predictors of keratoconus severity at presentation (Amsler-Krumeich grades III and IV): patients presenting with acute hydrops, patients receiving corneal cross-linking or corneal transplant, patients showing 1 or more diopters of increase of Kmax during their follow-up, and patients having longer time between the provider's recommendation of corneal cross-linking and the time of the procedure. The retrospective review included 634 patients with a clinical diagnosis of keratoconus. Factors associated with severe keratoconus at presentation in the multivariate analysis were non-White (P < 0.001), lowest income (Q1) (P = 0.018), Q2 income (P = 0.012), and having Medicaid/Medicare coverage (P = 0.021). Medicaid/Medicare coverage was the only factor associated with acute hydrops (P < 0.001), and younger age was the only factor associated with disease progression (P < 0.001). Younger patients and patients with commercial insurance coverage were more likely to receive corneal collagen cross-linking (P < 0.001 and P < 0.001, respectively), whereas patients with Medicaid/Medicare coverage, lowest income, and non-White race were more likely to receive corneal transplantation (P = 0.012, P = 0.062, and P = 0.028, respectively). Medicaid/Medicare was the only factor associated with delay in receiving corneal collagen cross-linking (P = 0.013). Our study demonstrates that there are sociodemographic predictors of keratoconus disease severity, progression, and the type and the time of treatment the patients received. This confirms eye health disparities among patients with keratoconus.

Sequential Irradiation Does Not Improve Fatigue Crack Propagation Resistance of Human Cortical Bone at 15 kGy

Sequential irradiation has been advocated for mitigating the reduction in fatigue properties of tendon compared to a single dose. However, to our knowledge, its capability of mitigating fatigue losses in bone is unknown. Recently, we reported that sequential irradiation did not mitigate losses in high-cycle S-N fatigue life of cortical bone at 15 kGy; however, it is unclear if sequential irradiation provides a benefit to fatigue crack propagation resistance. Our previous study also showed that radiation-induced collagen chain fragmentation and crosslinking increased from 0 to 15 kGy, suggesting that both likely contribute to the reduction in high-cycle S-N fatigue life within this dose range. Our objectives were: 1) to evaluate the fatigue crack propagation resistance of cortical bone and the effect of radiation on fracture plane damage zone thickness (DZT) at the crack tip in the dose range of 0 to 15 kGy, and 2) to evaluate whether sequential irradiation at 15 kGy mitigates the loss of fatigue crack propagation resistance of cortical bone compared to a single irradiation dose. Compact tension specimens from four male donor femoral pairs (ages 21-61 years old) were divided into 5 treatment groups (0 kGy, 5 kGy, 10 kGy, 15 kGy, and a 15 kGy sequential irradiation dose of 5 kGy sequentially irradiated with 10 kGy) and subjected to fatigue crack propagation testing (n=3-4 specimens per group) where fatigue crack growth rate da/dN and cyclic stress intensity factor ΔK were determined. Following testing, specimens were bulk stained in basic fuchsin, embedded in poly(methylmethacrylate), sectioned, and mounted on acrylic slides to evaluate fracture plane DZT at known crack lengths. Sections were then imaged with a fluorescence microscope, and fracture plane DZT was measured using ImageJ (n=3-4 specimens per group) and analyzed as a function of ΔK. We observed a decrease in fatigue crack propagation resistance at 15 kGy compared to doses of 10 kGy or lower (p≤0.013). Fracture plane DZT decreased overall with increasing radiation dose from 0 to 15 kGy. Sequential irradiation offered no improvement in fatigue crack propagation resistance (p=0.98). Radiation-induced collagen chain fragmentation and crosslinking in this dose range likely contribute to a decrease in energy dissipation capability with increasing radiation dose. Other alternative radiation sterilization methods besides sequential irradiation may be warranted to mitigate radiation-induced tissue damage and extend the functional lifetime of structural cortical bone allografts.

Family-based whole-exome sequencing implicates a variant in lysyl oxidase like 4 in atypical femur fractures.

Atypical femur fractures (AFFs) are rare adverse events associated with bisphosphonate use, having unclear pathophysiology. AFFs also cluster in families and have occurred in patients with monogenetic bone diseases sometimes without bisphosphonate use, suggesting an underlying genetic susceptibility. Our aim was to identify a genetic cause for AFF in a Caucasian family with seven members affected by osteoporosis, including three siblings with bisphosphonate-associated AFFs. Using whole-exome sequencing, we identified a rare pathogenic variant c.G1063A (p.Gly355Ser) in lysyl oxidase like 4 (LOXL4) among 64 heterozygous rare, protein-altering variants shared by the three siblings with AFFs. The same variant was also found in a fourth sibling with a low-trauma femur fracture above the knee, not fulfilling all the ASBMR criteria of AFF and in one of 73 unrelated European AFF patients. LOXL4 is involved in collagen cross-linking and may be relevant for microcrack formation and bone repair mechanisms. Preliminary functional analysis showed that skin fibroblast-derived osteoblasts from the unrelated patient with the LOXL4 variant expressed less collagen type I and elastin, while osteogenic differentiation and mineralization were enhanced compared with two controls. In conclusion, this LOXL4 variant may underlie AFF susceptibility possibly due to abnormal collagen metabolism leading to increased formation of microdamage or compromised healing of microcracks in the femur.

Age-related changes in the biochemical composition of the human aorta and their correlation with the delamination strength

Various studies have correlated the mechanical properties of the aortic wall with its biochemical parameters and inner structure. Very few studies have addressed correlations with the cohesive properties, which are crucial for understanding fracture phenomena such as aortic dissection, i.e. a life-threatening process. Aimed at filling this gap, we conducted a comprehensive biochemical and histological analysis of human aortas (the ascending and descending thoracic and infrarenal abdominal aorta) from 34 cadavers obtained post-mortem during regular autopsies. The pentosidine, hydroxyproline and calcium contents, calcium/phosphorus molar ratio, degree of atherosclerosis, area fraction of elastin, collagen type I and III, alpha smooth muscle actin, vasa vasorum, vasa vasorum density, aortic wall thickness, thicknesses of the adventitia, media and intima were determined and correlated with the delamination forces in the longitudinal and circumferential directions of the vessel as determined from identical cadavers. The majority of the parameters determined did not indicate significant correlation with age, except for the calcium content and collagen maturation (enzymatic crosslinking). The main results concern differences between enzymatic and non-enzymatic crosslinking and those caused by the presence of atherosclerosis. The enzymatic crosslinking of collagen increased with age and was accompanied by a decrease in the delamination strength, while non-enzymatic crosslinking tended to decrease with age and was accompanied by an increase in the delamination strength. As the rate of calcification increased, the presence of atherosclerosis led to the formation of calcium phosphate plaques with higher solubility than the tissue without or with only mild signs of atherosclerosis. Statement of significance: This study presents a detailed biochemical and histological analysis of human aortic samples (ascending thoracic aorta, descending thoracic aorta and infrarenal abdominal aorta) taken from 34 cadavers. The contribution of this scientific study lies in the detailed biochemical comparison of the enzymatic and non-enzymatic glycosylation-derived cross-links of vascular tissues and their influence on the delamination strength of the human aorta since, to the best of our knowledge, no such comprehensive studies exist in the literature. A further benefit concerns the notification of the limitations of the various analytical methods applied; an important factor that must be taken into account in such studies.

Surgical approach to management of oroantral communications. Case report

Abstract One of the most frequent post-extraction complications of posterior maxillary teeth is oroantral communication, which consists of direct communication between the maxillary sinus and the oral cavity. The recommendation is to make an immediate closure within the first 48 hours to avoid possible complications that may include an oroantral fistula or chronic sinus disease. Currently, different techniques have been described for closing communication, including various types of materials. Some of the techniques are exclusively oriented toward closure, while others seek to achieve bone regeneration by using bone substitutes for the subsequent placement of dental implants. The aim of this study is to describe a simple surgical technique for managing oroantral communication using a collagen sponge with hydroxyapatite and ribose and covering it with overlapping double layers of ribose cross-linked collagen membrane without fixation.

Biofilm-Induced Bone Degradation in Osteomyelitis

Objectives: Osteomyelitis, marked by bone inflammation due to microbial infection, presents significant healthcare challenges. While the protective role of biofilm in bacterial immunity and persistence is well-documented, its direct impact on bone degradation in osteomyelitis remains inadequately characterized. This study aims to comprehensively examine the direct effects of biofilm-forming pathogens on human bone, providing new insights into the mechanisms of bone destruction in osteomyelitis. Methods: Bone sections were collected from patients undergoing total knee replacement surgery between January 2021 and December 2022 for this study at Sultan Qaboos University Hospital. Then samples were inoculated with Staphylococcus aureus to simulate in-vitro bone infection. We then used Raman spectroscopy and Scanning Electron Microscopy (SEM) for detailed analysis of the bacterial interaction with bone tissue. Results: SEM images depicted trabecular destruction caused by biofilm. Biofilm-forming pathogens contribute directly to bone exhibited by SEM images with marked trabecular destruction. Raman analysis showed a significant increase in the carbonate-phosphate ratio in inoculated samples (619%) compared to controls (47%). Mineral content decreased in inoculated samples, and the carbonate-to-amide I ratio reduced by 47% in inoculated and 80% in controls. The inoculated samples exhibited an 82% shift in collagen crosslinking compared to 72% in controls. Conclusion: This research enhances our comprehension of the mechanisms behind bone destruction in osteomyelitis and underscores the intricate role of biofilm in the disease's development. These findings highlight the importance of biofilm in bone degradation and its potential implications for managing infections.

Chemical Tools for Monitoring and Targeting Collagen Cross-linking.

The formation of collagen, the most abundant protein in mammals, is vital for the integrity of skin, tendons, and tissue in essentially any organ. Excessive collagen formation is, however, characteristic of fibrotic and malignant diseases, which include major global health issues. The diagnosis of abnormal collagen production and deposition is, therefore, critical for disease prognosis and helps guide treatment decisions. Here, we summarize our research on the development of tailored tools for monitoring and targeting excessive collagen crosslinking. We anticipate these tools will provide a deep understanding at the molecular level of collagen formation in normal and disease conditions with applications in imaging and disease treatment.

Effects and safety of combined corneal collagen crosslinking and intrastromal corneal ring segment treatment in patients with keratoconus: a retrospective study

PurposeTo evaluate the safety and efficacy of different time-point combinations of intrastromal corneal ring segment (ICRS) implantation using femtosecond technology) and corneal collagen crosslinking (CXL) for the treatment of moderate-to-severe keratoconus (KCC).MethodsThis study included 69 eyes of 69 patients with keratoconus who underwent ICRS and CXL treatment at an Eye Hospital between March 2020 and March 2023. The patients were divided into two groups: Group 1 (n = 33 eyes of 33 patients), which received ICRS and CXL treatment in one session, and Group 2 (n = 36 eyes of 36 patients), which included treatment with ICRS for at least 6 months following CXL application. Preoperative and postoperative evaluations included visual acuity, autorefractometer refraction, corneal tomographic measurements using the Sirius (CSO) Scheimpflug camera and the TONOREF™ III device, and documentation of observed complications. Uncorrected visual acuity (UCVA) and best-corrected spectacle visual acuity (BCVA) were measured in each eye individually, and visual acuity was assessed using the logarithm of the minimum angle of resolution (logMAR).ResultsIn Group 1, mean UCVA improved from 0.81 ± 0.34 to 0.45 ± 0.25 (p < 0.01), and mean BCVA improved from 0.76 ± 0.35 to 0.38 ± 0.20 (p < 0.01). In Group 2, mean UCVA improved from 0.71 ± 0.32 to 0.43 ± 0.30 (p < 0.01), and mean BCVA improved from 0.65 ± 0.25 to 0.31 ± 0.23 (p < 0.01). Both groups showed significant reductions in manifest spherical and cylindrical refraction (p < 0.01). Group 1 exhibited greater reductions in maximum keratometry (Kmax), flat keratometry (K1), steep keratometry (K2) (p < 0.05), and astigmatic aberration compared with group 2 (p < 0.01). The use of simultaneous or separate CXL and ICRS does not significantly increase the incidence of complications.ConclusionsBoth combined and separate CXL and ICRS treatments resulted in significant improvement in UCVA and BCVA and reduced manifest refraction. Although improvements were observed in groups 1 and 2 in terms of K1, K2, and Kmax at 6 months, the improvements were more pronounced in Group 1. These results highlight the potential benefits of simultaneous ICRS + CXL treatment and underscore the importance of optimising the timing of CXL treatment to achieve the best visual outcomes.

Type I and III collagen contents and μ-calpain autolysis as a function of dry ageing time for eight different muscles from Hanwoo cattle.

Type I and III collagen content exert contrasting influences on meat tenderness. μ-calpain autolysis has shown a correlation with beef tenderness. Thus, the study was designed to determine the changes in these proteins. Three hundred twenty-four Hanwoo cattle, including cows and steers, and eight muscles were evaluated for proteolysis during dry ageing period. The ratios of type I and III collagen were determined by densitometric scans of bands resolved by SDS-PAGE, and μ-calpain activity was determined using casein zymography. Proteins involved in proteolysis were analysed by LC-MS/MS. The ratio of type I and III collagen in every muscle showed a significant difference with increasing ageing times (p < 0.05). In steers, the ratio decreased with increased ageing time, and in cows, except for BF and DP muscles, a similar decreasing trend was observed. Significant differences in the ratio of type I and III collagen were found between different muscles of cows at the same ageing time (p < 0.05), but no significant differences were found in steer muscles at the same ageing time (p > 0.05). Casein zymogram results showed an inverse relationship between pH values and μ-calpain autolysis in every muscle. A significant reduction in μ-calpain activity was observed in all muscles with extended ageing times, while the rate of autolysis differed greatly (p < 0.05) between muscles at the same ageing time. Interestingly, electropherogram analysis showed that cow muscles had a higher μ-calpain activity than steer muscles. Ageing time significantly influenced proteolysis, with 24 proteins showing marked changes and being identified. The ageing times significantly affect the ratio of type I and III collagen, which coincided with the rate of μ-calpain autolysis in steers. The ratio of type I and III collagen had a significant changes during the ageing period from cows, which may be related to the amount of collagen cross-linking.

Keratoconus.

Keratoconus is a progressive eye disorder primarily affecting individuals in adolescence and early adulthood. The ectatic changes in the cornea cause thinning and cone-like steepening leading to irregular astigmatism and reduced vision. Keratoconus is a complex disorder with a multifaceted aetiology and pathogenesis, including genetic, environmental, biomechanical and cellular factors. Environmental factors, such as eye rubbing, UV light exposure and contact lens wearing, are associated with disease progression. On the cellular level, a complex interplay of hormonal changes, alterations in enzymatic activity that modify extracellular membrane stiffness, and changes in biochemical and biomechanical signalling pathways disrupt collagen cross-linking within the stroma, contributing to structural integrity loss and distortion of normal corneal anatomy. Clinically, keratoconus is diagnosed through clinical examination and corneal imaging. Advanced imaging platforms have improved the detection of keratoconus, facilitating early diagnosis and monitoring of disease progression. Treatment strategies for keratoconus are tailored to disease severity and progression. In early stages, vision correction with glasses or soft contact lenses may suffice. As the condition advances, rigid gas-permeable contact lenses or scleral lenses are prescribed. Corneal cross-linking has emerged as a pivotal treatment aimed at halting the progression of corneal ectasia. In patients with keratoconus with scarring or contact lens intolerance, surgical interventions are performed.

Quantitative Assessment of New Frontiers in Dermatochalasis and Periorbital Hyperpigmentation Treatment: The Role of Cross-Linked Porcine Collagen.

Collagen dermal fillers have shown efficacy in addressing age-related changes in facial appearance. However, their potential in rejuvenating the periorbital region remains unexplored. The aim of this study was to evaluate the effectiveness, clinical safety, and patient satisfaction associated with the utilization of collagen dermal fillers in individuals with dermatochalasis and periorbital hyperpigmentation. This study was reviewed and approved by the institutional review board of China Medical University Hospital (IRB No. CMUH107-REC2-157). Adults diagnosed with dermatochalasis or periorbital hyperpigmentation received periorbital injections of a sterile cross-linked highly-purified specific antigen free porcine dermal collagen (FACIALGAIN® Collagen Implant with Lidocaine, Sunmax Biotechnology Co. Ltd., Taipei, Taiwan) and were assessed for hydration, elasticity, pigmentation index, redness index, lightness value, and density with the DermaLab® Combo Multiparameter Skin Analysis System (Cortex Technology, Hadsund, Denmark) and Cutometer® Dual MPA 580 (Courage+Khazaka electronic GmbH, Köln, Germany). Data was collected prior to injection and at 1 week, 4 weeks, and 12 weeks after injection. Patient satisfaction on volume augmentation, decrease in hyperpigmentation, persistence, and overall satisfaction were also recorded. A total of 12 samples each were recruited for dermatochalasis and periorbital hyperpigmentation. For dermatochalasis subjects, hydration of the periorbital tissue significantly increased at week 1 and 4 (p = 0.011 and p = 0.015). Elasticity decreased by week 4 and persisted until week 12 (p = 0.001 and 0.014). For periorbital hyperpigmentation patients, lightness value increased significantly starting week 1 (p = 0.016), tapering off at week 12. Elasticity decreased by week 4 and persisted until week 12 (p = 0.002 and p = 0.002). Median overall patient satisfaction was 4 out of 5 for the dermatochalasis group and 4.5 out of 5 for the periorbital hyperpigmentation group, with a mild but insignificant decrease by week 12. DermaLab® Combo and Cutometer® Dual MPA 580 are considered effective methods for evaluating patients undergoing dermal filler injections. The utilization of cross-linked porcine collagen dermal filler injections can serve as a minimally invasive approach to enhance skin laxity in dermatochalasis and address discoloration in periorbital hyperpigmentation. However, it is important to note that regular treatments may be necessary to sustain the desired outcomes. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/0026 .

Zr4+ and Al3+ coordinated cross-linked conductive collagen fibers/solvent-free polyurethane foam with ultra-low reflective electromagnetic shielding properties

In recent years, electromagnetic shielding materials with low reflectance have developed rapidly. However, high material cost, poor bonding fastness, weak mechanical properties and other problems seriously limit its effect in practical use. In this work, flexible conductive collagen fibers (CLF-Zr4+/Al3+-CNTs) were prepared using chromium tanned waste leather as ingredient, carbon nanotubes (CNTs) as conductive filler and transition metal ions as coordination crosslinking agents, and their molecular dynamics were investigated by quantum chemical simulation software. On this basis, a flexible conductive foam with the double layer and double core-clad structure containing carbon nanotubes was constructed using the solvent-free polyurethane (SFPU) chemical foaming technology, and their electromagnetic shielding properties and reflectance were studied. The experiment results showed that when the ratio of CLF-Zr4+/Al3+-CNTs to SFPU polyol is 1:9 and the impregnation times of CNTs are 2, the loading capacity of CNTs in conductive foam is 0.14 mg/cm3, the electrical conductivity is 57.8 S/m, and the thermal conductivity is 0.061 W/(m·K). Meanwhile, when the thickness is 3 cm, the electromagnetic shielding performance is 42.09 dB, and the reflection efficiency is 0.66 %, the lowest reflection efficiency reaches 0.16 % in the experiment. The mechanism of electromagnetic shielding in conductive foams with the double layer and double core-clad structure has been further explored. The experiment results proved that the flexible conductive foam has excellent mechanical properties, stability, heat insulation and flame retardant properties, and has excellent electromagnetic shielding and low reflection characteristics due to its abundant holes, functional group, interface and hierarchical structure.

Ancient and modern bone diagnosis: Towards a better understanding of chemical and structural feature alterations

Chemical and structural alterations hold great importance in the field of diagenesis. Attenuated Total Reflectance − Fourier Transform Infrared Spectroscopy (ATR-FTIR) is a valuable method for examining bio-apatite composition changes. Infrared spectroscopy (IR) and X-ray diffraction (XRD) were employed to analyze both modern and archaeological bone specimens. Organic and mineral component changes in modern and ancient samples were investigated. Ancient bone samples were collected from two archaeological sites in Jordan, dating back to the Iron and Byzantine ages. IR results indicated that collagen cross-links and mineral maturity are higher in modern bones compared to ancient bones. Additionally, the crystallinity index is higher in modern bones than in archaeological bones, while the carbonate to phosphate ratio (C/P) is lower in modern bones than in ancient ones. Curve fitting was applied to reveal the carbonate substitution inside the hydroxyapatite lattice within the IR region from 850 to 890 cm−1. A2-type carbonates (identified as υ2 of CO32−) denote hydroxyl site substitution, and B-type carbonates represent a substitution to the phosphate site. The full width at half maximum (FWHM) of the peak at 604 cm−1 from IR spectra reveals that crystallinity is higher in modern bones, as confirmed by the FWHM of the (002)-apatite pattern in XRD. Statistical analysis was conducted to validate these findings, ensuring the robustness of the results. Finally, the results obtained in this investigation align with previous literature reports regarding ATR-FTIR ratios. This suggests that modern bones have better crystallinity compared to ancient bones. Furthermore, the ATR-FTIR ratios indicate that the hydroxyl and phosphate sites of modern bones undergo more substitution than older bones. The findings of this study not only enhance our understanding of the diagnostic processes in archaeological bone specimens but also have broader implications for fields such as archaeology, anthropology, and forensics, where the analysis of bone composition and structural changes can provide valuable insights into the history and characteristics of ancient remains.

Progression of corneal thinning and melting after collagen cross-linking for keratoconus.

To study the aetiology, diverse clinical manifestations, therapeutic interventions, and prognoses in patients with corneal thinning after collagen cross-linking (CXL) treatment. a retrospective observational study of all patients presenting with corneal thinning after collagen cross-linking, in a tertiary eye care hospital in south India from 2011 to 2017. Preoperative details were noted. Patients who presented with corneal thinning were subjected to investigative measures to assess thinning, received appropriate management, and underwent follow-up evaluations. Among the 12 patients, 8 were female and 4 were male, all of whom had undergone standard classical CXL. The duration between CXL and corneal melting/thinning onset varied from 5 to 12 years. Notably, among female patients, 2 were pregnant, 2 were lactating mothers, 1 was undergoing in vitro fertilization (IVF) treatment, and 1 had comorbid diabetes mellitus and hyperthyroidism. Clinical examination revealed corneal thinning accompanied by hypopyon in 1 patient, corneal perforation with shallow anterior chamber in 1 patient, and epithelial defect with crystalline deposit in another patient, the remaining patients exhibited corneal thinning. Corneal thinnest corneal thickness measurements ranged from 212 to 351 µm. Treatment approaches included penetrating keratoplasty (PKP) in 2 patients, deep anterior lamellar keratoplasty (DALK) in 1 patient, cyanoacrylate glue application in 1 patient, and awaiting DALK/PKP in three patients, 4 patients showing no signs of increased thinning. The incidence of corneal thinning after collagen cross-linking is less but fulminant, requiring timely and appropriate management to prevent visual complications.