Hyaluronic Acid Ester Research Articles

Evaluation of Topical Off-The-Shelf Therapies to Improve Prolonged Field Care of Burn-Injured Service Members.

Burns are common injuries on the battlefield. Given austere environments, surgical debridement of injured service members is often not feasible in these settings. Delays in surgical debridement create a risk of infection and deranged healing for burn patients. As such, this study attempts to identify the best commercially available off-the-shelf (OTS) therapies with field-deployable potential to improve prolonged field care (PFC) of burn-injured soldiers. Deep partial-thickness (DPT) burns (25 cm2) were created on the dorsum of 5 anesthetized pigs utilizing a thermocouple burn device at 100°C for 15 seconds. Nonsurgical debridement was done 1-hour after burn creation using sterile saline water and gauze to remove excess eschar tissue. Animals were then randomized into 5 experimental groups, and OTS therapies were applied to 6 of the 12 created DPT burns. The remaining 6 burns were treated with 1% silver sulfadiazine cream (Ascend Laboratories, LLC, Parsippany, NJ) as the PFC standard of care (SOC) controls. The 5 randomized OTS therapies were: irradiated sterile human skin allograft (IHS), biodegradable temporizing matrix (BTM), polylactic acid skin substitute, hyaluronic acid ester matrix (HAM), and decellularized fish skin graft (FSG). Wounds were serially assessed on post-burn days 3, 7, 14, 21, and 28. Assessments were conducted using a combination of photographs, histology, and quantitative bacteriology. Endpoints included burn wound progression, re-epithelialization, wound contraction, scar elevation index, and colony-forming units (CFU). The analysis demonstrated that by day 3, the FSG prevented burn wound progression the most efficiently. In terms of wound healing, the results showed re-epithelialization percentages close to 100% by day 28 for all treatment groups. No statically significant differences were observed. Quality of healing analyses demonstrated that the BTM-treated wounds had contracted less and the difference to the IHS-treated wounds was statistically significant (P < .05). As regards to antimicrobial properties, the CFU results showed no statistically significant differences between the OTS therapies and the SOC on days 3, 7, and 14. The impact of Food and Drug Administration-approved OTS therapies was compared to the current PFC SOC for the treatment of DPT burns in a porcine model. Several topical options exist for the management of burns prior to definitive treatment in the operating room and warrant further evaluation. These therapies are actively used on civilian burn counterparts and have far-forward, field-deployable potential for use at the point of injury so that injured service members may not need evacuation to higher roles of care and combat power may be preserved. Our results demonstrated that all the studied OTS therapies performed well when compared to the SOC in terms of burn wound progression, wound healing, quality of healing, and quantitative bacteriology.

Synergy of Hydeal-D® and Hyaluronic Acid for Protecting and Restoring Urothelium: In Vitro Characterization.

Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction due to an inflammatory condition, characterized by bladder pain and urinary frequency. Currently, no gold standard therapy is available since IC does not respond to conventional ones. Given these premises, the aim of this work was the in vitro characterization of biological properties (mucoadhesion and anti-inflammatory activity) of a commercial product (HydealCyst–HydC) based on hyaluronic acid (HA) and the benzyl ester of HA (Hydeal-D®) intended for bladder instillation to restore and/or protect the urothelial layer of glycosamino glycans (GAGs). The in vitro characterization demonstrated that an interaction product is formed between HA and Hydeal-D® that has a role in the rheological behavior and mucoadhesive properties. HA was identified as a key component to form the mucoadhesive joint, while the interaction of HA with Hydeal-D® improved polysaccharide stability and prolonged the activity ex vivo. Moreover, HydC is cytocompatible with urothelial cells (HTB-4) and possesses an anti-inflammatory effect towards these cells by decreasing the secretion of IL-6 and IL-8, which were both increased in patients with IC, and by increasing the secretion of sulfated GAGs. These two findings, along with the resilience properties of the formulation due to mucoadhesion, suggest the active role of HydC in protecting and restoring urothelium homeostasis.

Surgical treatment in child’s congenital toe syndactyly: Risk factor of recurrence, complication and poor clinical outcomes

IntroductionSurgical treatment of toe syndactyly remains controversial. The strong demand from parents for a cosmetic release is increasing in our societies. But is it worth it? The objective was to assess medium-long term outcomes and to identify the risk factors of recurrence, complication and poor clinical outcomes. MethodsSixty-eight toe syndactylies (38 patients) undergoing surgery between 2008 and 2017 with a follow-up higher than two years were included consecutively and retrospectively. Four children (four syndactylies) were lost to follow-up and excluded. The mean age of the first surgery was 3.9 years old (0.8–16.7) and cohort mean follow-up was 6.9 years (2.8–11.2). In all patients, web release with a commissural dorsal flap was performed and associated a cutaneous resurfacing (spontaneous epithelialization, full-thickness skin graft taken from the popliteal crease, or a hyaluronic acid ester matrix). ResultsEighteen syndactylies (28.1%) in 14 patients recurred and one syndactyly required revision surgery. An age of surgery above two years was the only risk factor for recurrence found in univariate (OD = 0.27[0.08;0.85];p = 0.02) and multivariate studies (IC 95% = 0.05−0.68;p = 0.02). Seven complications (11.7%) in seven syndactylies (6 patients) were reported with six keloids (9.4%) and one scar retraction (1.6%). Each complication underwent an additional procedure. African ethnicity (N = 15) represents a risk factor (N = 4/15; OD = 0.12[0.009;0.97];p = 0.02) for keloids formation. Withey's average score is 4.9 (1–11), mean OxAFQ-C score was 52/60 (30–60), 67% would repeat the surgery and 69% felt satisfied at last follow-up. The simple syndactyly would appear less satisfied than complex or complicated (p = 0.02). ConclusionsSurgical treatment of child’s congenital syndactyly involves a risk of recurrence (28%) and potential complications (11,7%). Performed surgical procedure over two years old increase the risk of recurrence. African ethnicity is a risk factor in scarring complication. Only half of simple syndactylies are satisfied and prone to repeat the surgery.

Development of trigger sensitive hyaluronic acid/palm oil-based organogel for in vitro release of HIV/AIDS microbicides using artificial neural networks

BackgroundEfficient and effective chemotherapeutic methods designed to prevent the continuous spread of HIV/AIDS is essential to break the cycle of new infections. The use of condoms has been seen to be effective in prevention of HIV and STIs but its lack of use especially in vulnerable population is a deterrent to its overall success as a control method. Utilization of topical microbicide to curb the spread of HIV follows the current paradigm for HIV prevention in at risk individuals. The objective of this study was to develop and evaluate hyaluronic acid/palm oil-based organogel loaded with maraviroc (MRV) which would be released using hyaluronidase as the trigger for pre-exposure prophylaxis of HIV.ResultsThe organogels had average globules size 581.8 ± 3.9 nm, and were stable after three freeze thaw cycles; the thermosensitive and HA sensitivity was achieved via incorporation of hyaluronic acid and dicaprylate esters in the organogel with thermogelation occurring at 34.1 °C. Artificial neural network was used to model and optimize mucin absorption and flux. These responses were predicted using the multilayer full feed forward (MFFF) and the multilayer normal feed forward (MNFF) neural networks. Optimized organogel showed the mucin adsorption and flux was 70.84% and 4.962 μg/cm2/min1/2, hence MRV was adequately released via triggers of temperature and HA. The MRV organogel showed inhibition HIV − 1 via TZM-bl indicator cells. Compared to control HeLa cells without any treatment, MRV organogel was not cytotoxic for 14 days in vitro.ConclusionThese data highlight the potential use of hyaluronic acid/palm oil-based organogel for vaginal delivery of anti-HIV microbicides. This can serve as a template for more studies on such formulations in the area of HIV prevention.

What is the Role of Hyaluronic Acid Ester in Myringoplasty? Systematic Review and Meta-Analysis.

To reveal odds of tympanic membrane closure and postoperative hearing outcomes for myringoplasty utilizing hyaluronic acid ester via systematic review and meta-analysis. 1) Search of English articles in PubMed/Medline, Embase, and Cochrane databases published between January 1, 1998 and March 31, 2018. Inclusion criteria: 1) English language; 2) clinical studies; 3) reported posttreatment perforation status, hearing outcomes, or complications. hyaluronic acid used for middle ear packing or topical application of hyaluronic acid solution. Number of patients, surgical technique, mean age, overall rate of tympanic membrane closure, success rate based on size of perforation, mean air-bone gap improvement, and postoperative speech scores and complications. Ten studies encompassing 531 patients met criteria. Reported success rates for closure of chronic perforation ranged from 70.0 to 92.7% (mean, 85.21%). Smaller perforation predicted success in complete closure. Mean air-bone gap closure was 10.6 dB (4-24 dB). There were five complications reported. Meta-analysis was performed on five studies. No difference was noted in the success rates between hyaluronic acid ester myringoplasty and conventional tympanoplasty using fascia or perichondrium, with an overall closure rates of 89.8 and 89.4%, respectively (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.59-1.82, p = 0.896). A higher closure rate was seen in hyaluronic acid ester myringoplasty (87.9%) when compared with fat graft myringoplasty (70.8%), (OR 3.01, 95% CI 1.42-6.35, p = 0.004). Hyaluronic acid (HA) ester myringoplasty appears to be safe and effective at attaining complete closure of tympanic membrane perforation, although there exists significant selection bias and inconsistent reporting among existing papers.

An in vitro model of renal inflammation after ischemic oxidative stress injury: nephroprotective effects of a hyaluronan ester with butyric acid on mesangial cells.

BackgroundAcute kidney injury, known as a major trigger for organ fibrosis and independent predictor of chronic kidney disease, is characterized by mesangial cell proliferation, inflammation and unbalance between biosynthesis and degradation of extracellular matrix. Therapeutic approaches targeting the inhibition of mesangial cell proliferation and matrix expansion may represent a promising opportunity for the treatment of kidney injury. An ester of hyaluronic acid and butyric acid (HB) has shown vasculogenic and regenerative properties in renal ischemic-damaged tissues, resulting in enhanced function recovery and minor degree of inflammation in vivo. This study evaluated the effect of HB treatment in mesangial cell cultures exposed to H2O2-induced oxidative stress.Materials and methodsLactate dehydrogenase release and caspase-3 activation were measured using mesangial cells prepared from rat kidneys to assess necrosis and apoptosis. Akt and p38 phosphorylation was analyzed to identify the possible mechanism underlying cell response to HB treatment. The relative expressions of matrix metallopeptidase 9 (MPP-9) and collagen type 1 alpha genes were also analyzed by quantitative real-time polymerase chain reaction. Cell proliferation rate and viability were measured using thiazolyl blue assay and flow cytometry analysis of cell cycle with propidium iodide.ResultsHB treatment promoted apoptosis of mesangial cells after H2O2-induced damage, decreased cellular proliferation and activated p38 pathway, increasing expression of its target gene MPP-9.ConclusionThis in vitro model shows that HB treatment seems to redirect mesangial cells toward apoptosis after oxidative damage and to reduce cell proliferation through p38 MAPK pathway activation and upregulation of MPP-9 gene expression involved in mesangial matrix remodeling.

Sweet’s Syndrome as a Possible Consequence of Azacitidine Subcutaneous Administration in IPSS Intermediate-2 Myelodysplastic Syndrome

Sweet’s Syndrome (SS) is also called “acute febrile neutrophilic dermatoses”. The salient features are pyrexia, elevated neutrophil count, painful red skin lesions and a dense and diffuse dermal infiltrate consisting predominantly of mature neutrophils. We describe the clinical course of an 69-year-old women with myelodsysplastic syndrome who developed rapidly ulcerative skin lesion on whole right arm. Skin biopsy confirmed the diagnosis of Sweet syndrome. It is a peculiar case because the patient received azacitidine and developed Sweet’s Syndrome. The optimal treatment has not been defined. Systemic corticosteroids are the gold therapy for SS. Other firstline systemic treatments for SS are potassium iodide and colchicines. The lesion presented advanced dressings and was targed as having an hith degree of difficulty to cure. The use of Hyaff, an ester of hyaluronic acid, has proven to be a valid and advanced topical tool for the treatment of such cases. Following unsuccessful treatment with standard therapeutic strategies, we needed to move through more advanced treatments. We report that Sweet’s Syndrome is a possible complication of azacitidine administration and suggest paying maximum attention to cases in which skin lesions are probably related to the drug.

ROS-triggered and regenerating anticancer nanosystem: An effective strategy to subdue tumor's multidrug resistance

Drug delivery strategies utilizing tumor microenvironment are recognized as a critical doorway to overcome multidrug resistance (MDR). However, the variability of tumor microenvironment at different disease stages would definitely minimize stimuli generation and eventually the therapeutic effects of these stimuli sensitive systems. Herein, we report a unique reactive oxygen species (ROS) triggered nanosystem that can replenish the ROS upon disassembly to maintain its high level. This was accomplished by a new amphiphilic polymer (TBH) composed of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), hyaluronic acid (HA) and arylboronic ester. As a linker of TPGS to HA, arylboronic ester could efficiently degrade in response to ROS resulting in dismantling of nanosystem followed by rapid release of TPGS. Owing to ROS inducing activity of TPGS with mitochondrial respiratory complex II, ROS regeneration was observed for TBH nanosystem both in MCF-7/ADR cells and tumor tissues xenografted with MCF-7/ADR cells. Furthermore, doxorubicin-loaded TBH nanosystem (DOX-TBH) revealed higher drug cytotoxicity due to enhanced retention effect on account of ROS triggered DOX release and P-gp inhibitory mechanism of TPGS. Moreover, HA significantly improved tumor targeting capability of DOX-TBH, while ROS based triggering and regenerating mechanism lead to marked inhibition of the tumor growth in the xenograft MCF-7/ADR tumor-bearing nude mice.

Surgical treatment of the neglected achilles tendon rupture with Hyalonect.

The purpose of this study was to report the management and outcomes of ten patients with chronic Achilles tendon rupture treated with a turndown gastrocnemius-soleus fascial flap wrapped with a surgical mesh (Hyalonect). Ten men with neglected Achilles tendon rupture were treated with a centrally based turndown gastrocnemius fascial flap wrapped with Hyalonect. Hyalonect is a knitted mesh composed of HYAFF, a benzyl ester of hyaluronic acid. The Achilles tendon ruptures were diagnosed more than 1 month after injury. The mean patient age was 41 years. All of the patients had weakness of active plantarflexion. The mean preoperative American Orthopaedic Foot and Ankle Society score was 64.8. The functional outcome was excellent. The mean American Orthopaedic Foot and Ankle Society score was 97.8 at the latest follow-up. There were significant differences between the preoperative and postoperative scores. Ankle range of motion was similar in both ankles. Neither rerupture nor major complication, particularly of wound healing, was observed. For patients with chronic Achilles tendon rupture with a rupture gap of at least 5 cm, surgical repair using a single turndown fascial flap covered with Hyalonect achieved excellent outcomes.

Long‐term Outcomes of Treating Middle Ear Cholesteatoma with Intact‐Canal Wall and Scute Repairing Techniques

Objectives: Assess the long-term outcomes of treating middle ear cholesteatoma with multiple techniques including intact-canal wall and scute repairing techniques. Methods: One hundred thirteen patients had been treated between 2001 and 2006. Multiple techniques including harvesting bone chips with air drill, sculpting of autologous bone grafts, chorda tympani nerve tightening prosthesis, preventing adhesion with hyaluronic acid ester membrane, lesion cleaning, reconstruction of ear canal wall, re-gasification of attic and/or mastoid cavity, and early catheterization of the Eustachian tube were performed. Results: One hundred twelve ears only received the operation once, and the preoperative air bone conduction gap (ABG) was 33.61 ± 12.35 dB, which was significantly higher than postoperative ABG (13.58 ± 9.27 Db, t = 18.35, P &lt; .01 [G1]). Success rate of the treatment was 85.48% (106/124), and the effective rate was 47.58% (59/124). Significant improvement in the bone conduction threshold was also found (17.3 ± 13 vs 15.15 ± 11.79 dB, t = 4.77, P &lt; .01). Twenty-one ears (16.93%) had increased bone conduction, 61 ears (49.19%) had decreased bone conduction, and the other 42 ears (33.87) had no change in the bone conduction. The long-term success rate was 83.87% (104/124), and the effective rate was 38.7% (48/124). No significant difference was found in the GAP, GAP change, and AC between the values measured at the last follow-up of the long- and short-term follow-up study ( P &gt; .05). Conclusions: Treating middle ear cholesteatoma with intact-canal wall and scute repairing techniques is safe. These surgical procedures involve low relapse rate, and treating patients with relapsed cholesteatoma with these procedures could also result in good outcomes.

Allogeneic epidermal substitutes in the treatment of chronic diabetic leg and foot ulcers

Aim: Diabetic foot ulcers are the most common cause of nontraumatic lower extremity amputations in the industrialized world. Tissue-engineering products offer a lower extremity salvage strategy when healing does not proceed according to the standard of care. New allogeneic sheets are available for the management of diabetic leg and foot ulcers. Methods: The endpoints of this case series study regard preliminary outcomes of the application of allogeneic keratinocytes composed of benzyl ester of hyaluronic acid to 16 diabetic foot and leg ulcers in 11 patients with type 2 diabetes mellitus. Results: Between 21 and 70 days after cellular therapy, 6 out of 16 lesions were completely healed, reducing the wound dimension by 70% and improving the wound bed score by 52%. Conclusion: The clinical results of the new allogeneic sheets indicate that allogeneic keratinocytes may represent an effective and safe therapy for diabetic foot and leg ulcers in the multidisciplinary approach to this diabetes-related complication.

Hyalonect in the treatment of pseudarthrosis

The aim of this study was to evaluate union rates and complications of Hyalonect, a knitted mesh composed of HYAFF, a benzyl ester of hyaluronic acid, and a naturally occurring constituent of the extracellular matrix, for the treatment of pseudarthrosis. The study included 11 patients (8 male, 3 female; mean age: 44.6 years; range: 23 to 57 years) operated for pseudarthrosis using Hyalonect. Average time between initial treatment and surgical procedure was 12.9 (range: 8 to 48) months. Pseudarthrosis of the tibia, femur and humerus was present in 4, 2 and 5 patients, respectively. All patients had undergone prior surgery (1 to 6 times). Each patient underwent open reduction and internal fixation. Allograft was applied to the pseudarthrosis area and covered with Hyalonect. Mean follow up period was 31 (range: 12 to 48) months. Union was achieved in all patients after an average of 6 (range: 4 to 8) months. One patient had a discharge for two weeks. Another developed an infection which responded well to appropriate antibiotic treatment. No malunion or implant failure was observed. One patient with pre-existing radial nerve palsy maintained the condition. Use of Hyalonect appears to be a safe method with a positive impact on union in the surgical treatment of pseudarthrosis, particularly in the absence of any infection.

A prospective controlled trial comparing spontaneous closure and Epifilm® patching in traumatic tympanic membrane perforations

The objective was to compare the outcomes of spontaneous closure and hyaluronic acid (HA) ester patching (Epifilm®) in subjects with traumatic tympanic membrane (TM) perforation. This was a prospective, controlled study performed at a tertiary teaching and research hospital. During 6-month period, subjects were divided into spontaneous closure (group A) and HA ester patch-Epifilm® (group B) group. Demographic data, presenting symptoms, closure rate, closure time and audiometric data were evaluated and compared between groups. In total, 155 subjects were evaluated. Group A consisted of 62.6 % (n = 97) of the subjects, whereas group B consisted of 37.4 % (n = 58) of the subjects. Group B had significantly shorter closure times when compared with group A (6.61 ± 4.59 vs. 10.60 ± 5.23 weeks, p = 0.001). When the closure time was evaluated according to perforation size both grade 1 and 2 perforations have significantly shorter closure times when compared with group A (6.33 ± 4.54 vs. 10.80 ± 5.69 weeks, for grade 1 and 6.650 ± 2.07 vs. 10.30 ± 4.32 weeks for grade 2 perforations). Closure rates were not significant between groups (85.6 % for group A and 94.8 % for group B). When the closure rate was evaluated according to perforation size no significant difference exists for grade 1, 2 and 3 perforations between groups. Both air conduction and air-bone gap were significantly improved in both groups. HA ester patch (Epifilm®) is a non-toxic material that can be used in traumatic tympanic membrane perforations. In this study, use of HA ester patching was resulted with earlier closure time but not resulted with higher closure rates.

Interaction between a Regenerative Matrix and Wound Bed in Nonhealing Ulcers: Results with 16 Cases

A chronic wound is a wound that is delayed in one of the wound-healing stages and cannot progress any further. A chronic wound leaves the patient at risk of infection and hospitalization. In these case series, 16 patients affected by venous ulcers underwent Hyalomatrix PA grafting for reconstructive surgery. Hyalomatrix PA is a bilayered, sterile, flexible, and conformable three-dimensional matrix made of fibers of HYAFF, a benzyl ester of hyaluronic acid, and a semipermeable silicone membrane. Hyalomatrix PA acts as a substitutive and regenerative permanent matrix able to replace the dermis providing a three-dimensional matrix for cellular invasion and capillary growth. The silicon layer controls water vapor loss avoiding an excessive loss of fluids and acts as a semipermeable barrier to the external agents. In the presented cases, the average area grafted per procedure was 153 cm2. The length of followup ranged from 0.5 to 1 year. The final results were considered to be good in 12 cases, fair in 3 cases, and poor in one case. This study suggests that the combination of wound bed preparation with application of the hyaluronic regenerative matrix can be a valid approach for treatment of partial thickness ulcers.

Design of Functional Polymer and Composite Scaffolds for the Regeneration of Bone, Menisci, Osteochondral and Peripheral Nervous Tissues

In order to mimic the behaviors of natural tissue, the optimal approach for designing novel biomaterials has to be inspired to nature guidelines. One of the major challenge consists in the development of well-organized structures or scaffolds with controlled porosity in terms of pore size, pore shape and interconnection degree able to guide new tissue formation during the in vivo degradation following the scaffold implantation. Scaffolds endowed with molecular cues together to a controlled degradation profile should contribute to cell proliferation and differentiation, controlled vascularization, promoting the remodeling of neo tissue through a gradual transmission of bio-chemicals and biophysical signals as performed by the extracellular matrix (ECM). Here, different polymers and composites have been investigated to design scaffolds with peculiar micro and/or nanometric morphological features in order to satisfy all these requirements: a) bioactive scaffolds, with tailored porosity and high pores interconnectivity were developed by integrating PLA fibres, Calcium Phosphates particles or Hyaff11 phases into a Poly(ε-caprolactone) (PCL) matrix by the combination of filament winding technology and phase inversion/salt leaching technique as mineralised ECM analogue for bone regeneration; b) custom made PCL/hydroxyapatite scaffolds were designed by imaging and rapid prototyping technologies for the osteochondral defect. c) Ester of Hyaluronic Acid reinforced with degradable fibres were processed by composite technology, phase inversion and salt leaching technique, to obtain scaffolds for meniscus regeneration. d) PCL and gelatin nanofibres were obtained by highly customized fibre deposition via electrospinning to guide the nerve outgrowth in nerve regeneration. All the proposed approaches offer the chance of realizing tailor-made platforms with micro/nanoscale architecture and chemical composition suitable for the regeneration of the extracellular matrix of a large variety of natural tissues (i.e, bone, menisci, osteochondral and peripheral nervous tissues).

Rheological Characterization of Hyaluronic Acid Derivatives as Injectable Materials Toward Nucleus Pulposus Regeneration

Nucleus pulposus (NP) is the soft center of the intervertebral disc (IVD), able to resist compressive loads, while the annulus fibrosus withstands tension and gives mechanical strength. NP function may be altered as consequence of several pathologies or injury and when a damaged IVD does not properly play its role. In the past years, a great effort has been devoted to the design of injectable systems as NP substitutes. The different synthetic- and natural hydrogel-based materials proposed, present many drawbacks and, in particular, they do not seem to mimic the required behavior. In the search for natural-based systems a dodecylamide of hyaluronic acid (HA), HYADD3®, has been proved as bioactive and suitable vehicle to carry cells for NP tissue engineering, while a crosslinked HA ester, HYAFF120® showed interesting results if used as injectable acellular material. Even though these derivatives showed appropriate biological behavior up to now, data on mechanical behavior of these derivatives are still missing. In this frame, the aim of this study was to provide a rheological characterization of these HA derivatives to asses their biomechanical compatibility with the NP tissue. To this, the rheological properties of these derivatives were studied through dynamic shear tests before and after injection through needles used in the current surgical procedure. Both HA derivatives showed a 'gel-like' rheological behavior similar to the native NP tissue and this behavior was not altered by injection.

Morphology and degradation properties of PCL/HYAFF11® composite scaffolds with multi-scale degradation rate

The analysis of scaffold degradation is a promising strategy for understanding the dynamic changes in texture and pore morphology which accompany polymer resorption, and for collecting same fundamental indicators regarding the potential fate of the scaffold in the biological environment. In this study, we investigate the morphology and degradation properties of three composite scaffolds based on poly(ε-caprolactone) (PCL) embedded with benzyl ester of hyaluronic acid (HYAFF11®) phases, and, in turn, different reinforcement systems – i.e., calcium phosphate particles or continuous poly(lactic acid) (PLA) fibres. Scanning electron microscopy (SEM) and μ-tomography supported by digital image analysis enabled a not invasive investigation of the scaffold morphology, providing a quantitative assessment of porosity (which ranged from 63.1 to 82.8), pore sizes (which varied from 170.5 to 230.4μm) and pore interconnectivity. Thermal analyses (DSC and TGA) and Raman spectroscopy demonstrated the multi-scale degradation of the composite with highly tailoring degradation kinetics depending on the component material phases and scaffold architecture changes, due to their conditioning in simulated in vivo environment (i.e., SBF solution). These results demonstrate that the judicious mixing of materials with faster (i.e., HYAFF11) and slower (i.e., PLA and PCL) degradation kinetics, different size and shape (i.e., domains, particles or long fibres), certainly concurs to design a smart composite scaffold with time-controlled degradation which can support the regeneration of a large variety of tissues, from the cartilage to the bone.

Hyaluronic acid ester in myringoplasty

To investigate the use of a new technique to close persistent tympanic membrane perforations under general anaesthesia, in patients in whom this has previously been considered impractical. Twenty patients aged 50 years and over were recruited. All had a persistent, symptomatic tympanic membrane perforation in at least one ear. Pre-operatively, an audiogram was performed and the tympanic membrane was assessed in order to establish the site and size of the perforation. Under general anaesthesia, the edges of the perforation were freshened and a sheet of Epifilm, trimmed to a size roughly 2 mm larger in diameter than the perforation, was tucked through the perforation. The ear was dressed appropriately. Patients were seen two weeks post-operatively in the out-patients department and reassessed. The study was based at Poole General Hospital, a District General Hospital. Twenty patients were recruited from the out-patients clinics of Poole Hospital ENT department. (1) closure of the perforation, as a percentage of the original size; (2) improvement of hearing, as an average across all frequencies, expressed in dB hearing level; and (3) presence or absence of discharge. Five patients were operated upon and assessed six weeks post-operatively. The Epifilm had dissolved but the perforations remained the same size in all five patients. There were no other adverse effects. Pure tone audiometry at this stage was redundant. The study was subsequently aborted. The authors conclude that repair of tympanic membrane perforations with hyaluronic acid ester films is not to be recommended.

Hyalomatrix ® – A novel dermal pre-treatment

Aims: It is well accepted that Hyaluronic Acid is crucial to wound healing. The aim of this study was to test in-vivo an esterified Hyaluronic Acid scaffold - Hyalomatrix®, to act as a dermal pre-treatment and substitute prior to the application of epidermal replacement in full thickness wounds. Hyalomatrix® is a partial benzyl ester (80% esterified) of Hyaluronic acid coupled with a thin silicone layer providing fluid loss control and a microbial barrier to function as a temporarily epidermis. Investigation of the optimal pre-treatment time was also part of the study.

Autologous fibroblasts transplant after infliximab administration: a new approach in Crohn’s perianal fistulas?

The transmural nature of the inflammatory process in Crohn’s Disease (CD) is the most important predisposing factor to the development of anal and perianal fistulae, which occur in 3–80% of patients affected with CD, a variation related to different defining criteria. Although several local and general treatments have been proposed, the management of perianal CD is still considered difficult and unsatisfactory, and the rate of recurrences remains really high. Azathioprine or 6-mercaptopurine, and in many cases, infliximab, have been proposed as alternative therapy to surgery for CD. Infliximab, a monoclonal antibody directed against tumor necrosis factor, has been found effective in the treatment of fistulizing CD. However reopening of apparently healed fistulas (treated only with infliximab infusion, without surgery) is frequent, and it has been related to the persistence of deep fistulas tracts, which could otherwise be detectable using anal endosonography. Novel approaches in healing of chronic wounds include the use of tissueengineered skin substitutes as human autologous fibroblasts; these cells have yet been successfully used for healing of diabetic or venous ulcers. In this preliminary report, the first procedure to manage CD perianal fistulas by combining fistulectomy with a transplantation of autologous fibroblasts seeded onto biocompatible HYAFF scaffolds (three-dimensional biodegradable scaffolds entirely composed of a benzylic ester of hyaluronic acid) is described. The patient was 61 years old, male, who was found affected with CD since 1996 and had undergone several medical approaches (steroid drugs, azathioprine, 6-mercaptopurine administration) with low clinical benefits; in 2001, he underwent surgical bowel resection for ileal multiple stenosis. In January 2004, a relapse of the disease with diarrhoea, perianal pain and fever occurred. Right kidney lithiasis, hepatic angioma and a diffuse thickening of the residual ileum were reported by ultrasonography and computed tomography (CT) exams. The inspection of the perianal region and an anal examination showed a trans-sphinteric fistula with a large abscess in the ischio-rectal fossa. The patient underwent drainage of the abscess and the loose-seton technique was applied; then the patient underwent a series of three infliximab administrations (5 mg/kg/die in a slow drip) at 1, 2, 6 weeks after surgery, followed by azathioprine administration (150 mg/ die) for 2 months. In October 2004, the patient was admitted to the autologous fibroblasts transplantation protocol. The patient was informed about the treatment and agreed to the implant of autologous S. Ascanelli . D. de Tullio . C. Gregorio . G. Azzena . S. Occhionorelli Department of Surgical, Anesthesiological, Radiological Sciences, Surgical Clinic Institute of the University of Ferrara, Ferrara, Italy