Glutaraldehyde Cross-linked Collagen Research Articles

A highly durable and biocompatible bionic collagen implant with exceptional anti-calcification and collagen regeneration capabilities for improved skin rejuvenation

Skin aging, a complex and inevitable biological process, considerably impacts an individual’s physical appearance and overall well-being. While collagen-based implants hold potential for skin rejuvenation, their clinical application is limited by the poor durability of non-crosslinked implants and the negative impacts of crosslinking agents, such as cytotoxicity and calcification. Herein, we report a highly durable and biocompatible bionic collagen implant for superior skin rejuvenation with advanced anti-calcification characteristics and enhanced collagen regeneration. Utilizing biomimetic self-assembly and covalent crosslinking approach, we successfully created long-lasting and biomimetic collagen implants with densely-packed collagen fibers. Crosslinking of collagen fibers with a low concentration of N-hydroxysuccinimide activated suberic acid (NHS-SA) was highly efficient, resulting in complete crosslinking and thicker collagen fiber formation with a uniform network structure. Compared with glutaraldehyde-crosslinked collagen fibers, NHS-SA-crosslinked assembled collagen fibers (NACF) demonstrated considerably improved thermal stability and durability. Furthermore, the NACF implant exhibited superior biocompatibility, establishing NHS-SA crosslinked collagen fibers as a safer and more bioactive choice for implant applications. In mouse subcutaneous implant models, the NACF implant outperformed other collagen implants, demonstrating exceptional biocompatibility, effective collagen regeneration, and excellent anti-calcification potential. The NACF implant shows immense promise in collagen regeneration, offering considerable potential to advance skin rejuvenation therapies.

Tissue Reactivity to, and Stability of, Glaucoma Drainage Device Materials Placed Under Rabbit Conjunctiva.

PurposeTo evaluate tissue reactivity to, and the stability of, glaucoma drainage device materials placed under rabbit conjunctiva in vivo.MethodsDisks (diameter, 3 mm; thickness, ∼0.3 mm) fabricated from poly(styrene-block-isobutylene-block-styrene) (SIBS), silicone, stainless-steel, or glutaraldehyde cross-linked collagen (GACLC) were inserted under rabbit conjunctiva. Conjunctival and scleral sections obtained at 4, 8, and 12 weeks after surgery were immunostained for α-smooth muscle actin (SMA). The ratio of the maximum thickness of the α-SMA–positive conjunctiva to the scleral thickness (α-SMA/S ratio) was calculated. The in vivo stability of the drainage devices at 12 weeks after insertion was evaluated.ResultsThe mean α-SMA/S ratios of the SIBS and silicone groups were lower than that of the stainless-steel group at 4 weeks after surgery (P < 0.05), and that of the SIBS group was lower than that of the GACLC group (P < 0.05). The ratios at 8 weeks after surgery were lower in the SIBS and silicone groups than in the GACLC group (P < 0.01). The ratios at 12 weeks after surgery were lower in the SIBS and silicone groups than in the GACLC group (P < 0.05). The surface areas of GACLC disks explanted from conjunctivae were significantly lower than that of intact disks (P < 0.01).ConclusionsSIBS and silicon were highly biostable and exhibited less tissue reactivity than GACLC in vivo.Translational RelevanceComparisons of materials using animal models can predict the clinical stability and safety of such materials in humans.

Adsorption and separation of flavonoid aglycones and flavonol aglycones by using Zr(IV) immobilized collagen fiber adsorbent as column packing material

Flavonoid aglycones and flavonol aglycones, are difficult to be separated due to their similar structures and limited hydroxyls. Herein, Zr(IV) immobilized collagen fiber (ZCF) was prepared by immobilizing Zr(IV) on glutaraldehyde cross-linked collagen fiber (GCF) to separate apigenin and kaempferol, the representative compounds of flavonoid aglycones and flavonol aglycones. TG, DSC, SEM and element mapping were applied to characterize ZCF. The static adsorption suggested that when the amount of immobilized Zr(IV) reached only 0.3 mmol/g, the adsorption difference between apigenin and kaempferol on ZCF was highly improved compared with GCF without Zr(IV). The adsorption rate of apigenin increased from 2.21% to 14.31%, while that of kaempferol significantly increased from 22.35% to 87.17%. In addition, the spectroscopy (UV–Vis, FT-IR) were applied to analyze the binding sites of flavonoids with Zr(IV), indicating that the strong adsorption of ZCF to kaempferol may be related to the 3-hydroxyl on the C-ring, while apigenin only can conduct a weak binding with ZCF through 5-hydroxyl on the A-ring. In ZCF column chromatography separation, apigenin and kaempferol could be separated effectively with purities of 94.02% and 89.23% by stepwise elution of 50% aqueous ethanol followed by 50% aqueous ethanol containing 0.005 mol/L citric acid. In separation on ZCF and GCF combined columns, the purities of apigenin and kaempferol reached 95.59% and 92.56%, respectively, and the trace amount of Zr(IV) shedding from ZCF was completely adsorbed by GCF avoiding contaminating the target components. In addition, the effective separation of apigenin and kaempferol in apium graveolens (celery) extract by ZCF column was also achieved. The above results indicated ZCF could selectively adsorb flavonol aglycones with 3-hydroxyl on the C-ring from the mixture with flavonoid aglycones. This investigation provides a novel column chromatography packing material for the fast separation of flavonoid aglycones and flavonol aglycones.

Lateral Ridge Augmentation Using Cross-Linked or Non-Cross-Linked Collagen Membrane: A Pilot Randomized Clinical Trial

Purpose: The aim of this investigation is to test, in a lateral ridge augmentation model without simultaneous implant placement, the effect of using a cross-linked collagen membrane and a non-cross-linked collagen membrane on guided bone regeneration. Material and Methods: Edentulous alveolar ridges of less than 5 mm width were treated with guided bone regeneration using a glutaraldehyde cross-linked collagen membrane (CL) or a non-cross-linked collagen membrane (NonCL). In all treated cases the bone graft used was a combination of autogenous bone scrapings and deproteinized bovine bone mixed in a 1:3 ratio. Ridge measurements were recorded clinically (during augmentation surgery and during implant placement surgery) and radiographically on the CBCT scans (pre-op, 1 week post-op and at implant placement). All ridge measurements were recorded at 1, 3 and 5 mm from the ridge crest. Soft tissue healing was assessed during the follow-up visits at 1, 2, 4, 8, 12, 16, 20 and 24 weeks post-op. A histological analysis was performed on core biopsies retrieved axially from implant or pontic sites. Results: Four patients were recruited and randomly allocated to treatment groups. Ridge width gain (RWgain) was significantly better for the CL group as assessed clinically. At 1, 3 and 5 mm from ridge crest, the clinically assessed gain was respectively 5.50 mm ± 2.121, 5.40 mm ± 2.074, 5.60 mm ± 1.140 for the CL group and -1.33 mm ± 0.577, 1.33 mm ± 2.517 and 2.00 mm ± 1.000 for the NonCL group. Graft volume resorption was significantly higher in the NonCL group (62%) in comparison to the CL group (10.9%). No soft tissue complications occurred during follow-ups in neither group. Histologically, both groups showed signs of bone remodeling and vital bone formation. New bone formation in the NonCL group was 23.64 % ± 0.64 and in the CL group was 15.75% ± 8.73. Conclusion: Despite the limitations of this pilot study, The CL membrane showed better performance than the NonCL membrane in terms of ridge width gain and in terms of graft volume consolidation as assessed clinically and radiographically. Although no statistical comparison was possible, the NonCL group presented a higher percentage of new bone formation than the CL group.

Metanalysis of alloplastic materials versus autologous fat for injection augmentation pharyngoplasty treatment of velopharyngeal insufficiency

BackgroundVelopharyngeal insufficiency (VPI) can cause resonance, speech and feeding problems. While reconstructive palatoplasty and surgical pharyngoplasty techniques are the mainstay of treatment for severe VPI, injection augmentation pharyngoplasty offers a minimally invasive approach in patients with mild-to-moderate VPI. MethodsWe conducted a systematic review of the literature available on PubMed and Embase from 1990 to 2019 including studies that addressed VPI, incompetence, or dysfunction managed with injection augmentation. Patient demographics, etiology of VPI, injection material, volume of injection, number of injections, complications and both subjective and objective outcomes were recorded. ResultsTwenty-nine studies met our inclusion criteria encompassing 587 patients, ages 3–75 years (mean = 16) who underwent injection pharyngoplasty. Injection materials included glutaraldehyde cross-linked (GAX) collagen (n = 5), calcium hydroxyapatite (n = 36), dextranomer and hyaluronic acid (n = 72) and autologous fat (n = 471). Follow-up averaged 15.4 months (range = 2–60 months). Functional improvements in nasality were recorded in a large proportion of patients (0.79, 95% CI 0.75 to 0.82). However, a greater proportion of patients in the synthetic materials group demonstrated either reduced or resolved hypernasality compared with those receiving autologous fat injections (χ2 = 7.035, n = 91/103 vs. 255/338, p = 0.008). Complete velopharyngeal gap closure post-injection was achieved at a higher frequency with injection of synthetic materials compared with autologous fat (χ2 = 11.270, n = 61/69 vs. 58/91 p = 0.001).r ConclusionInjection pharyngoplasty offers a minimally invasive alternative intervention for treatment of VPI secondary to small velopharyngeal gaps. Patients treated with synthetic materials experienced a greater improvement in velopharyngeal closure and a corresponding improvement in resonance balance.

Interventions for primary vesicoureteric reflux.

Interventions for primary vesicoureteric reflux.

Retrospective analysis after endoscopic urethral injections of glutaraldehyde-cross-linked-collagen or dextranomer/hyaluronic acid copolymer in bitches with urinary incontinence.

To evaluate the outcome of endoscopic injection of two different bulking agents, glutaraldehyde cross-linked collagen and dextranomer/hyaluronic acid copolymer into the urethral submucosa in female dogs with urinary incontinence caused by urethral sphincter mechanism incompetence. Retrospective review of records and follow-up communication with owners of dogs that received an endoscopically guided urethral bulking procedure. In each dog, either cross-linked collagen (2007 to 2011) or dextranomer/hyaluronic acid copolymer (2012 to 2015) was used. At least three injections were made in a circular arrangement in the midurethral region until the urethral lumen was closed. Complete questionnaires were available from 50 of 100 pet owners. The mean interval between the treatment and interview was 67 (range: 57 to 114) months in the cross-linked collagen group and 19 (range: 2 to 48) months in the dextranomer/hyaluronic acid copolymer group. The mean duration of continence was 45∙8 months (range: 12 to 84 months) in the cross-linked collagen group and 20∙5 months (range: 12 to 48 months) in the dextranomer/hyaluronic acid copolymer group. The success rate at 6 months or more after the procedure was 71% after the injection of cross-linked collagen and 58% after injection of dextranomer/hyaluronic acid copolymer. One minor complication (transient haematuria) occurred in one dog. There were no major complications. Urethral injection of dextranomer/hyaluronic acid copolymer in bitches with urethral sphincter mechanism incompetence is a useful alternative to cross-linked collagen injection, which is no longer available in the European market. Dextranomer/hyaluronic acid copolymer injection is a minimally invasive alternative to surgical procedures and has a low complication rate.

Rheological properties of glutaraldehyde-crosslinked collagen solutions analyzed quantitatively using mechanical models

Understanding the rheological behavior of collagen solutions crosslinked by various amounts of glutaraldehyde (GTA) [GTA/collagen (w/w)=0–0.1] is fundamental either to design optimized products or to ensure stable flow. Under steady shear, all the samples exhibited pseudoplasticity with shear-thinning behavior, and the flow curves were well described by Ostwald-de Waele model and Carreau model. With increased amounts of GTA, the viscosity increased from 6.15 to 168.54Pa·s at 0.1s−1, and the pseudoplasticity strengthened (the flow index decreased from 0.549 to 0.117). Additionally, hysteresis loops were evaluated to analyze the thixotropy of the native and crosslinked collagen solutions, and indicated that stronger thixotropic behavior was associated with higher amount of GTA. Furthermore, the values of apparent yield stress were negative, and a flow index <1 for all the systems obtained via Herschel–Bulkley model confirmed that the native and crosslinked collagen solutions belonged to pseudoplastic fluid without apparent yield stress. However, the increment of dynamic denaturation temperature determined by dynamic temperature sweep was not obvious. The viscoelastic properties were examined based on creep–recovery measurements and then simulated using Burger model and a semi-empirical model. The increase in the proportion of recoverable compliance (instantaneous and retardant compliance) reflected that the crosslinked collagen solutions were more resistant to the deformation and exhibited more elastic behavior than the native collagen solution, accompanied by the fact that the compliance value decreased from 39.317 to 0.152Pa−1 and the recovery percentage increased from 1.128% to 87.604%. These data indicated that adjusting the amount of GTA could be a suitable mean for manipulating mechanical properties of collagen-based biomaterials.

Role of Permacol Injection in the Treatment of Patients With Fecal Incontinence.

See Article on Page 73-78 Fecal incontinence (FI) is defined as the uncontrolled passage of feces or gas over at least 1-month duration in an individual of at least 4 years of age who had previously achieved control [1,2,3,4]. Incontinence has a negative impact on self-esteem and quality of life (QoL) and may result in significant secondary morbidity, disability, and cost [1]. Prevalence rates vary widely depending on the method used for fecal incontinence examination and the target population examined, but, in general, they range between 1.4% and 18%. In institutionalized patients, however, incontinence may affect up to 50%, which is a frequent reason for transfer to nursing homes [2,3,4,5,6]. The Mature Woman's Health Study, which used Neilson data to survey women aged ≥45 years, indicated that nearly 20% of women have FI at least once per year and that 9.5% have at least 1 episode per month [7]. According to the recommended standard for the treatment of patients with FI specified by the American Society of Colon and Rectal Surgeons Clinical Practice Guideline, medical management is 1C, sphincter repair for external anal sphincter defects is 1B, biofeedback is 1B, and sacral neuromodulation is 1B as well. The recommended standard for injection of bulking agents is 2B, which is lower than other treatment methods [1]. Injection of bulking agents was first used on patients suffering from urinary incontinence, and the first report of such a method being used for anal incontinence was presented in 1993 when Shafik [8] injected polytetrafluoroethylene paste (Teflon, Dupont, Wilmington, DE, USA) into the anus to treat a patient with FI. An ideal bulking agent should be nonirritable, biocompatible, nonimmunogenic and durable. Other elements that must be considered when selecting a bulking agent are ease of implant, migration, inflammation reaction, and more [9]. Of the numerous bulking agents used, the main ones include bovine glutaraldehyde cross-linked collagen (Contigen, Bard Urological, Convington, GA, USA), autologous fat, and carbon-coated zirconium-oxide beads in water-based gel (Durasphere, Boston Scientific Corp., Boston, MA, USA) while dextranomer microspheres in nonanimal stabilized hyaluronic acid gel (Solesta, Oceana Therapeutics Inc., Edison. NJ, USA), porcine dermal collagen (Permacol, Covidien, Gosport, UK), polytetrafluoroethylene paste (Teflon, Dupont, Wilmington, DE, USA), polydimethylsiloxane elastomer in hydrogel carrier (PTQ, Uroplasty BU, Geleen, The Netherlands), synthetic calciumhydroxylapatite ceramic microspheres in an aqueous-based gel carrier (Coaptite, Bioform Medical Inc., San Mateo, CA, USA), and ethylene vinyl alcohol dissolved in dimethyl sulphoxide are also widely used. Newly created or enhanced bulking agents continue to be released into the market [9]. Permacol is cross-linked porcine dermal collagen. It has been designed to resist breakdown by collagenase in the body and maintain a long-standing increase in bulk. The product is biocompatible and once injected is incorporated into host tissue, with associated cellular and microvascular in growth. No evidence has been found for its being associated with irritancy or allergenicity [10,11]. Although the characteristics of Permacol are known, previous research about Permacol injection has shown that the number of patients with recurring symptoms of anal incontinence increases in as little as 6 weeks, which leads one to question the durability of Permacol [12]. In other words, the conditions just after an injection are not maintained, but rather the bulking agent is absorbed by surrounding tissues, often leading to the need for another injection. This research lacks objective data on, for example, anal pressure as it merely assessed patients' conditions centered on an evaluation of QoL. Also, the number of target patients is small while that of tracked and observed patients is even smaller. Six of the 9 research papers on anal manometry presented in this systematic journal review failed to show meaningful changes in the mean resting pressure [13]. Similarly, this research does not show a significant difference from previous research results [14]. Despite the relatively short period of tracking and observation, the QoL showed a meaningful change, which is a result similar to those of other studies done in the past. With the injection of bulking agents, the treatment method normally used in urology clinics has been applied to patients with anal incontinence. The action mechanisms are similar; however, a greater amount of inflating agent is used, and the procedure is less likely to be effective.

Collagen cross-linking increases scaffold stability while modulates pro-inflammatory macrophage response

Event Abstract Back to Event Collagen cross-linking increases scaffold stability while modulates pro-inflammatory macrophage response Luis Delgado1, 2, Kieran Fuller1, 2, Marc A. Fernandez-Yague2, Manus Biggs2, Abhay Pandit2 and Dimitrios Zeugolis1, 2 1 National University of Ireland Galway (NUI Galway), Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Ireland 2 National University of Ireland Galway (NUI Galway), Centre for Research in Medical Devices (CÚRAM), Ireland Introduction: Collagen materials have the ability to enhance wound healing and to facilitate functional repair. However, most of these collagen materials exhibit low resistance to degradation and mechanical stability. Therefore, exogenous cross-linking methods are widely used for collagen stabilisation. Unfortunately, chemical cross-linking is associated with impaired healing and foreign body reaction[1]. Specifically, macrophage interactions with cross-linked collagen materials have recently been demonstrated to play an important role in tissue remodelling outcomes; however, little is known about the underlying biological mechanism involved[2]. Within this context, our work explores modified material properties by cross-linking and to look for alternative cross-linking methods, based on plant extracts and polyethylene glycol (PEG). It is hypothesised that collagen films can be optimally cross-linked with PEG and plant extracts to induce adequate stability, while modulating macrophage response. Materials and Methods: Collagen type I films were cross-linked with 0.625% glutaraldehyde, 50 mM carbodiimide, 1 mM 4S-StarPEG, 0.625% genipin or 0.1% oleuropein. Stability was assessed by mechanical testing, DSC, swelling and collagenase assay. In vitro inflammatory response was assessed using human monocyte-derived THP-1 macrophages and subsequently by morphology, alamarBlue™, PicoGreen and multiplex assay for the main inflammatory cytokines. Statistical significance was set at p<0.05. Results: 4S-StarPEG and genipin were the only methods that preserved the fibrillar structure of collagen. Direct addition of carbodiimide and oleuropein into collagen solutions decreased free amine groups of collagen, whilst they did not increase enzymatic stability. Only 4S-StarPEG and genipin provided an enzymatic stability equivalent to glutaraldehyde cross-linked collagen films without increasing toxicity, while inducing a similar release profile of pro-inflammatory cytokines to non-cross-linked films. Moreover, cell culture assays using pre-conditioned media strongly suggest that sub-products potentially released from cross-linked collagen films are not responsible for the macrophage alteration. This is most likely associated with modifications in the collagen surface and structure by chemical cross-linking. Conclusions: Overall, this study advocates 4S-StarPEG and genipin as alternative cross-linkers for tissue engineering scaffolds. Moreover, we believe that macrophage alterations is most likely associated with surface and structure modifications because we did not observe effects from potential sub-products and the only two conditions that preserve fibrillar structure presented similar release profile of pro-inflammatory cytokines to non-cross-linked films. EU-7FP-263289-GNM

PTU-246 Augmentation of a sphincter repair

Introduction Faecal incontinence (FI) affects between 1–10% of adults in varying degrees. Current epidemiological studies have shown that up to 1% of adults have regular episodes of faecal incontinence that adversely impacts their quality of life. A variety of synthetic and biological agents have been used for both overlapping sphincter repair (OSR) and as an anal bulking agent. The aim of this review is to provide an overview of the use of biological materials in the augmentation of the sphincter repair. Method A systematic search of PubMed was conducted using the search terms ‘anal bulking agents’, ‘anal sphincter repair’ or ‘overlapping sphincter repair’. Studies that utilised biological material for either sphincter repair or as a bulking agent were included. Overall, 5 studies were indentified for analysis after inclusion and exclusion criteria were applied. Results There were 3 studies with 127 patients of which 122 underwent anal bulking with a biological agent. 105 patients received a cross-linked porcine dermal collagen in the form of PermacolTM and a further 17 received Glutaraldehyde cross-linked (GAX) collagen, a highly purified bovine dermal collagen. Anorectal physiology was carried out in 27 patients and demonstrated deterioration in maximum resting pressure, and no significant change in maximum squeeze increment. Quality of life scores such as St Mark’s incontinence score, SF-36 and the Cleveland Clinic Florida Incontinence Score (CCFIS) demonstrated an improvement in scores at 6 weeks and 6 months, but this had deteriorated at 12 month follow up. There were no complications reported. 10 patients received a cross-linked porcine dermal collagen (PermacolTM) for OSR and 13 patients received porcine intestinal submucosa (Surgisis©) to carry out an anal encirclement procedure. Improvements in Faecal Incontinence Severity Index (FISI), CCFIS and two subscales of Faecal Incontinence Quality of Life (FIQL) (coping/behaviour and embarrassment) were observed in the group of patients undergoing OSR. Furthermore, the FISI, Wexner score and all components of FIQL score (lifestyle, coping/behaviour, depression and embarrassment) showed an improvement following anal encirclement using biological material. Incontinence episodes decreased to an average of one per week from 8 to 10 preoperatively and no complications were reported. Conclusion Sphincter augmentation with biological material has demonstrated significantimprovement in continence and quality of life scores in the short term compared to traditional repair. Long-term studies are necessary to determine if this effect is sustained. Disclosure of interest None Declared.

Effect of curcumin caged silver nanoparticle on collagen stabilization for biomedical applications

The current study aims at understanding the influence of curcumin caged silver nanoparticle (CCSNP) on stability of collagen. The results indicated that curcumin caged silver nanoparticles efficiently stabilize collagen, indicated by enhanced tensile strength, fibril formation and viscosity. The tensile strength of curcumin caged silver nanoparticle cross-linked collagen and elongation at break was also found to be higher than glutaraldehyde cross-linked collagen. The physicochemical characteristics of curcumin caged nanoparticle cross-linked collagen exhibited enhanced strength. The thermal properties were also good with both thermal degradation temperature and hydrothermal stability higher than native collagen. CD analysis showed no structural disparity in spite of superior physicochemical properties suggesting the significance of curcumin caged nanoparticle mediated cross-linking. The additional enhancement in the stabilization of collagen could be attributed to multiple sites for interaction with collagen molecule provided by curcumin caged silver nanoparticles. The results of cell proliferation and anti-microbial activity assays indicated that curcumin caged silver nanoparticles promoted cell proliferation and inhibited microbial growth making it an excellent biomaterial for wound dressing application. The study opens scope for nano-biotechnological strategies for the development of alternate non-toxic cross-linking agents facilitating multiple site interaction thereby improving therapeutic values to the collagen for biomedical application.

Two-dimensional infrared spectroscopic study on the thermally induced structural changes of glutaraldehyde-crosslinked collagen

The thermal stability of collagen solution (5mg/mL) crosslinked by glutaraldehyde (GTA) [GTA/collagen (w/w)=0.5] was measured by differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR), and the thermally induced structural changes were analyzed using two-dimensional (2D) correlation spectra. The denaturation temperature (Td) and enthalpy change (ΔH) of crosslinked collagen were respectively about 27°C and 88J/g higher than those of native collagen, illuminating the thermal stability increased. With the increase of temperature, the red-shift of absorption bands and the decreased AIII/A1455 value obtained from FTIR spectra indicated that hydrogen bonds were weakened and the unwinding of triple helix occurred for both native and crosslinked collagens; whereas the less changes in red-shifting and AIII/A1455 values for crosslinked collagen also confirmed the increase in thermal stability. Additionally, the 2D correlation analysis provided information about the thermally induced structural changes. In the 2D synchronous spectra, the intensities of auto-peaks at 1655 and 1555cm−1, respectively assigned to amide I band (CO stretching vibration) and amide II band (combination of NH bending and CN stretching vibrations) in helical conformation were weaker for crosslinked collagen than those for native collagen, indicating that the helical structure of crosslinked collagen was less sensitive to temperature. Moreover, the sequence of the band intensity variations showed that the band at 1555cm−1 moved backwards owing to the addition of GTA, demonstrating that the response of helical structure of crosslinked collagen to the increased temperature lagged. It was speculated that the stabilization of collagen by GTA was due to the reinforcement of triple helical structure.

Injectable biomaterials for the treatment of stress urinary incontinence: their potential and pitfalls as urethral bulking agents

Injectable urethral bulking agents composed of synthetic and biological biomaterials are minimally invasive treatment options for stress urinary incontinence (SUI). The development of an ideal urethral bulking agent remains challenging because of clinical concerns over biocompatibility and durability. Herein, the mechanical and biological features of injectable urethral biomaterials are investigated, with particular emphasis on their future potential as primary and secondary treatment options for SUI. A literature search for English language publications using the two online databases was performed. Keywords included "stress urinary incontinence", "urethral bulking agent" and "injectable biomaterial". A total of 98 articles were analysed, of which 45 were suitable for review based on clinical relevance and importance of content. Injectable biomaterials are associated with a lower cure rate and fewer postoperative complications than open surgery for SUI. They are frequently reserved as secondary treatment options for patients unwilling or medically unfit to undergo surgery. Glutaraldehyde cross-linked bovine collagen remains the most commonly injected biomaterial and has a cure rate of up to 53 %. Important clinical features of an injectable biomaterial are durability, biocompatibility and ease of administration, but achieving these requirements is challenging. In carefully selected patients, injectable biomaterials are feasible alternatives to open surgical procedures as primary and secondary treatment options for SUI. In future, higher cure rates may be feasible as researchers investigate alternative biomaterials and more targeted injection techniques for treating SUI.

Viscosity of Materials for Laryngeal Injection: A Review of Current Knowledge and Clinical Implications

Over the past several decades, researchers have sought the ideal substances for use in injection laryngoplasty. This search has inspired several basic science studies centering on the viscoelastic properties of popularly used injectables as well as of experimental substances. Unfortunately, these studies have used various techniques and different units for measuring viscosity. For clinical purposes, there has been a need for a concise compilation of these data, converted into consistent units, to permit easy comparison of the reported viscosities of various substances. The literature has been reviewed to address this need. Scholarly review. Comparable data are available for various substances, including vocal fold mucosa, subcutaneous fat, bovine dermal collagen, glutaraldehyde cross-linked collagen, polytetrafluoroethylene, and hyaluronic acid products. The values for difference substances vary widely. There appears to be a growing body of useful knowledge about viscosity of substances used for medial (vibratory margin) injection. However, decisions regarding viscosity of substances for lateral injection medialization appear to have been made without the benefit of evidence-based research. It is possible that the trend toward relatively low viscosity materials for lateral injection is based on ease of surgical use through a small needle, but that the low viscosity may adversely affect the control over the position of the injected substance. Research is needed comparing viscosity with predictability of surgical deposition of injected substances.

Adsorption chromatography separation of the flavonols kaempferol, quercetin and myricetin using cross‐linked collagen fibre as the stationary phase

Kaempferol, quercetin and myricetin are typical flavonols that are most concentrated in many medicinal herbs. However, the separation of these flavonols is very challenging due to their similar molecular structures. In the present investigation, the chromatographic separation of the flavonols kaempferol, quercetin and myricetin was performed using glutaraldehyde cross-linked collagen fibre (GCF) as the stationary phase. Kaempferol, quercetin and myricetin could be completely separated from each other by the GCF column by using gradient elution with different solutions of aqueous ethanol (100% to 70%) and 50% acetone. When the chromatographic separation was carried out at a flow rate of 0.75 bed volume h(-1) with a sample loading of 30 mg 7 g(-1) GCF, the purity of kaempferol, quercetin and myricetin was 98.17%, 93.81% and 81.76%, respectively. The separation resolution was influenced by column length, flow rate and sample loading amount. The separation efficiency of GCF was not obviously reduced after applications had been repeated five times. In the fifth repeated application, the purity of the recovered kaempferol, quercetin and myricetin was still higher than 97%, 94% and 78%, respectively. GCF is a promising adsorbent for use as a stationary phase in the chromatographic separation of flavonols from their mixtures.

Anal bulking agents for faecal incontinence

The aim of this review was to assess and evaluate reports of studies on the efficacy of anal bulking agents used in the treatment of faecal incontinence. A systematic review of the literature was carried out to identify studies that have reported on the use of anal bulking agents. A variety of biomaterials have been employed for anal bulking. These include autologous fat, bovine glutaraldehyde cross-linked collagen, carbon-coated zirconium oxide beads, dextranomer microspheres in a gel, hydrogel cross-linked with polyacrylamide, polydimethylsiloxane elastomer in a gel, porcine dermal collagen and synthetic calcium hydroxylapatitie ceramic microspheres. Although the ideal site of injection (submucosal or intramuscular) and the mechanism of action remain the subject of debate, most published studies report a significant improvement in continence in at least 50% of subjects with mild to moderate symptoms with little or no associated morbidity.We concluded that anal bulking agents may be used to alleviate symptoms of faecal seepage and soilage.

Preliminary Report of Vocal Fold Augmentation with Cross‐Linked Porcine Collagen

To evaluate the short-term outcomes of using cross-linked porcine collagen for vocal fold augmentation. Case series with planned data collection. Tertiary referral hospital. Twenty consecutive patients of unilateral vocal fold paralysis (UVFP) were recruited, including 10 males and 10 females. All the subjects received videolaryngostroboscopic (VLS) evaluation for the glottic closure pattern, perceptual grading using the GRB scale (grade, roughness, breathiness), acoustic analysis, maximal phonation time (MPT), and Voice Handicap Index (VHI) questionnaire. Purified telopeptide-free, glutaraldehyde cross-linked porcine collagen was injected under local anesthesia with fiberscopic guidance. Treatment outcomes were evaluated 3 months after the injection. Fifteen (75%) of 20 patients reported complete resolution of symptoms, whereas the other 5 (25%) patients had substantial improvements. The median score of perceptual analysis of voice quality showed significant improvements from G2/R2/B2 to G1/R1/B0 (P < .001). Glottic closure pattern under stroboscopy had improved from "predominantly open" before the procedure to a "half-open and half-close" pattern after the procedure (P < .001). Acoustic analysis demonstrated significant improvements of jitter and normalized noise energy (P < .05). Maximal phonation time revealed a significant improvement from 7.5 ± 3.2 seconds to 13.1 ± 3.9 seconds (P < .01). The VHI had also decreased from 53 ± 25 points to 27 ± 20 points (P < .01). No patients had serious adverse events during the follow-up period. This case series demonstrated that porcine collagen may be a suitable material for temporary vocal fold augmentation.

Endo180 and MT1-MMP are involved in the phagocytosis of collagen scaffolds by macrophages and is regulated by interferon-gamma

Subcutaneously implanted disks of hexamethylenediisocyanate or glutaraldehyde cross-linked sheep collagen (referred to as HDSC and GDSC, respectively) in mice show large differences in degradation rate. Although comparable numbers of macrophages are seen in HDSC and GDSC, phagocytosis of collagen by macrophages occurred only in GDSC. The molecular mechanisms involved in the phagocytosis of collagen by macrophages are essentially unknown. Immunofluorescence and RT-PCR showed that Endo180 was expressed in GDSC only. TissueFaxs showed that Endo180 co-localized with MT1-MMP on F4÷80 positive cells, which is likely responsible for the phagocytosis in GDSC. RT-PCR further showed that Endo180 expression correlated with high levels of IFN-γ mRNA. In vitro, IFN-γ induced the expression Endo180 and MT1-MMP in murine macrophages cultured on collagen type I (although too high levels of IFN-γ dampened the expression of Endo180 and MT1-MMP). Moreover, the expression of Endo180 and MT1-MMP induced by IFN-γ can be inhibited through IL-10. The differences in microenvironment between GDSC and HDSC (high IFN-γ and low IL-10 levels in GDSC, low IFN-γ and high IL-10 levels in HDSC) provide an explanation why phagocytosis of collagen by macrophages is only seen in GDSC. In summary, we show for the first time that the IFN-γ dependent co-expression of Endo180 and MT1-MMP on macrophages coincides with collagen phagocytosis, thus providing evidence that the mechanism of collagen phagocytosis operating in the foreign body reaction by macrophages is comparable with the mechanism of intracellular collagen degradation by fibroblasts seen under physiological conditions.

Cystoscopic Injections of Dextranomer Hyaluronic Acid Into Proximal Urethra for Urethral Incompetence: Efficacy and Adverse Outcomes

To determine whether dextranomer/hyaluronic acid would be more efficacious or would produce fewer complications when using the material in a standard proximal-urethra cystoscopically-directed injection technique. Injectable periurethral bulking agents are an alternative to stress incontinence surgery. Dextranomer, a highly hydrophilic dextran polymer, solubilized in a base of nonanimal stabilized hyaluronic acid, has been approved as an injectable agent for the treatment of childhood vesicoureteric reflux (Deflux, Q-Med AB, Uppsala, Sweden), and in Europe for women with stress urinary incontinence (SUI) (Zuidex, Q-Med AB, Uppsala, Sweden). A previous multicenter trial demonstrated nonequivalence compared with bovine glutaraldehyde cross-linked collagen with a high complication rate. We sought to determine whether the failure of the treatment lay in the material itself or the use of a blind, midurethral injection technique. A retrospective case series of 56 patients undergoing cystoscopically guided bladder neck injections of dextranomer/hyaluronic acid with follow-up in 42, included 35 women with intrinsic sphincter deficiency (ISD), 4 men with postprostatectomy incontinence, 2 men with sphincteric denervation secondary to spinal cord injury, and 1 woman with sphincteric failure after a neobladder. Outcome assessment used gender-appropriate International Consultation on Incontinence Questionnaire, clinical records, and/or urodynamic assessment. Of 35 women with ISD, 4 developed pseudoabscess formation with outlet obstruction requiring multiple operative interventions. Patient-defined treatment failure occurred in all 4 carefully selected postprostatectomy incontinent men, and in 23 of 35 females with ISD. Complications with cystoscopically injected dextranomer hyaluronic acid at the bladder neck occurred at a high rate, and using a validated questionnaire, the efficacy of dextranomer hyaluronic acid applied in this manner for ISD was poor.