Fibrin Glue Research Articles

Evaluating the Predictability and Regenerative Capacity of Novel Platelet Concentrate (PC)-Titanium Platelet Rich Fibrin (T-PRF) in the field of Dentistry- A Narrative Review

Periodontal disease treatment is always a challenging task. Various treatment modalities have been applied for treating this painless chronic condition. With advancement in the field of research in dentistry researchers shifted towards the autologous products hence came the usage of platelet concentrates in various branches of dentistry. Initially fibrin glue, platelet rich plasma (PRP) have been tried but because of their drawbacks platelet rich fibrin (PRF) came into play. Due to possible contamination of silica particles in silica tubes or silica coated plastic tubes and shorter resorption time, titanium attracted the researchers. This lead to introduction of titanium platelet rich fibrin (T-PRF) a second generation platelet concentrate. This had a thicker fibrin meshwork, better cellular entrapment, greater resorption rate and titanium tubes are inert, better haemocompatible and non-corrosive. It also eliminates the possible contamination of silica test tubes and silica coated plastic tubes. Present article is a review on T-PRF and its usage in the field of dentistry.

Modified alginate-based soft tissue adhesive: Synthesis, characterization, and application in the treatment of in vivo wound closure

The management of acute and chronic wounds is still a challenge around the world, despite the development of many wound dressing materials and techniques, such as cyanoacrylate-based glue, fibrin glue, suturing, and stapling. To get over this difficulty, a soft tissue adhesive (STA) has been developed by combining bioabsorbable chitosan (CS) and aldehyde sodium alginate (ASA) crosslinked by the Schiff base mechanism and are characterized via the FTIR spectroscopy analysis, Thermogravimetric Analysis (TGA) and Scanning Electron Microscopic (SEM) analysis. Sodium alginate (SA) was converted into aldehyde sodium alginate (ASA) by oxidation, which made it biodegradable (79.2% weight loss at the 9th day) and greatly affected the swelling behavior (only 60% in CS + ASA), and gelation time (7–10 s) of the soft tissue adhesive. The hydrogel's surface has an adhesive characteristic and is quite smooth, according to the SEM data. The antimicrobial test of the STA confirmed that the adhesive material had good antibacterial efficacy. The bonding ability and biocompatibility of the STA were evaluated by measuring the adhesive strength after sealing the skin incisions on the back of mice. These findings imply that the generated adhesive may be a strong and reliable tissue adhesive with great potential for use in soft tissue adhesion.

Could fibrin sealants be effective in the management of burn injuries?

Burn is a complex pathophysiologic phenomenon, which causes both direct tissue damage, such as extensive hemorrhage, and indirect consequences, such as infections due to external skin barrier destruction. Several therapeutic strategies have been implied so far, but none could provide a combined action against direct and indirect consequences of such a common and serious medical condition. Therefore, novel therapeutic approaches should be investigated. TISSEEL™ is a fibrin sealant which simulates the final steps of the coagulation cascade and could be utilized as an alternate treatment for the immediate burn management, especially in areas where specialized burn departments or surgeons are not available.The present study proposes an effective alternative therapeutic strategy for immediate burn injury. In that way, every surgeon even without huge expertise could successfully manage a burn injury and acute consequences could be prevented. However, future experimental studies should be designed in order to further assess the feasibility and safety of the proposed method and to compare it with the available therapeutic options.

Rigid but nonmetallic cranioplasty after pterional craniotomy: Technical note.

Given the popularity of pterional craniotomy, numerous modifications have been made to prevent postoperative deformities. With the advent of titanium plates, fixation has become both simple and excellent. However, titanium plates can cause skin problems, infection, or cause skull growth to fail. To develop a simple, cost-effective, and esthetically satisfactory fixation method, without the use of non-metallic materials, six young and older patients underwent pterional craniotomy. CranioFix Absorbable clamps were used to fix the bone flap in the frontal and temporal regions such that the frontal part was in close contact with the skull. After fixation, the bone chips and bone dust were placed in the bone gap and fixed with fibrin glue. We measured the computed tomography values of the reconstructed area and thickness of the temporal profiles postoperatively over time. Bone fusion was achieved in all patients by 1 year after surgery. Both the thickness of the temporalis muscle and the thickness of the temporal profile had changed within 2 mm as compared with the preoperative state. Our simple craniotomy technique, gentle tissue handling, and osteoplastic cranioplasty yielded satisfactory esthetic results and rigidness in pterional craniotomy.

Endoscopic Salvage of Gastrointestinal Anastomosis Leaks—Past, Present, and Future—A Narrated Review

Background: Anastomotic leakage, which is defined as a defect in the integrity of a surgical join between two hollow viscera leading to communication between the intraluminal and extraluminal compartments, continues to be of high incidence and one of the most feared complications following gastrointestinal surgery, with a significant potential for a fatal outcome. Surgical options for management are limited and carry a high risk of morbidity and mortality; thus, surgeons are urged to look for alternative options which are minimally invasive, repeatable, non-operative, and do not require general anesthesia. Methods: A narrative review of the international literature took place, including PubMed, Scopus, and Google Scholar, utilizing specific search terms such as “Digestive Surgery AND Anastomotic Leakage OR leak OR dehiscence”. Results: In the present review, we try to describe and analyze the pros and cons of the various endoscopic techniques: from the very first (and still available), fibrin gluing, to endoclip and over-the-scope clip positioning, stent insertion, and the latest suturing and endoluminal vacuum devices. Finally, alongside efforts to improve the existing techniques, we consider stem cell application as well as non-endoscopic, and even endoscopic, attempts at intraluminal microbiome modification, which should ultimately intervene pre-emptively, rather than therapeutically, to prevent leaks. Conclusions: In the last three decades, this search for an ideal device for closure, which must be safe, easy to deploy, inexpensive, robust, effect rapid and stable closure of even large defects, and have a low complication rate, has led to the proposal and application of a number of different endoscopic devices and techniques. However, to date, there is no consensus as to the best. The literature contains reports of only small studies and no randomized trials, failing to take into account both the heterogeneity of leaks and their different anatomical sites.

Role of EhretialaevisRoxb.. (Ajan Vruksha/Khandu Chakka) Medicated Thread in Fistula- In- Ano: - Randomised Clinical Trial

Ehretialaevisroxb. is a traditional herbal plant used for various purposes, mainly wound healing and pain relief. This plant isalso known as AjanVruksha and commercially known as Khandu Chakk. Wound healing & pain relief activities of Ehretialaevisroxb.(AjanVruksha/Khandu Chakka) are used for making a novel herbal medicated thread in fistula- in- ano to avoid the untoward effects oftraditional Ksharsutra, commonly used in Ayurved practice for Fistula-in ano management. Fistula in ano is the abnormal tract having oneopening inside the anal canal and one opening at the perianal skin. Many modalities are available for the treatment of fistula in ano, likeKsharsutra, fistulotomy, fibrin glue injection, and fistula plug. Sometimes there are many tracts. Novel herbal thread comprisesehretialaevisroxb., Achyranthesaspera Linn., Ficusracemosa. A novel herbal thread was applied in group A of 75 patients and in group B of 75patients, a conventional thread was applied. The study is based on a superior clinical trial. To determine the efficacy of the compositionof the present invention, the clinical parameters of pain, bleeding, discharge, itching, tenderness, hyper granulation, and unit cutting timewere evaluated after every week. The novel thread was found more efficient in pain relief, discharge, etching, cutting rate, bleeding, andhyper granulation, than a conventional thread in this study. We aim to provide a medicated thread for fistula-in- ano, which canovercome deficiencies associated with the known arts and provide effective and safe treatment for affected patients. And to achieve thisaim, our objectives are to assess the efficacy of Novel Medicated thread and Conventional Ksharsutra in promoting healing in fistula- inano,along with comparing the efficacy of both threads.

Importance of Multimodal Spinal Cord Monitoring and Hemodynamic Augmentation during High Thoracic Ventral Dural Tear Repair Using the Posterior Approach

AbstractCerebrospinal fluid (CSF) leakage due to large ventral dural tears (VDT) often requires surgical intervention. Surgical closure of a high thoracic VDT is challenging and associated with high morbidity, especially if it is performed after multiple epidural blood patch (EBP)/fibrin glue injections. A 44-year-old woman was diagnosed with spontaneous intracranial hypotension due to VDT at T1-T2, causing CSF leakage. Multiple EBP and fibrin glue injections failed to treat her symptoms; hence, the patient underwent surgical closure using the posterior approach. The patient was anesthetized using standard anesthetic drugs and was maintained under total intravenous anesthesia to facilitate continuous motor-evoked potential (MEP) monitoring. The surgical course was complicated by bleeding, hypotension, and MEP loss. Continuous MEP monitoring, effective team communication, quick restoration of blood pressure(BP) and BP augmentation with fluid, blood, and vasopressor helped to restore the MEP back to baseline. Hence, the patient recovered without neurological morbidity. This case report highlights the importance of adequate vascular access, multimodal spinal cord monitoring, and BP augmentation during a high thoracic VDT repair.

A CASE STUDY ON A COMPLEX FISTULA-IN-ANO BY AYURVEDIC MANAGEMENT

Fistula-in-ano can be a complicated disease to manage. An anal fistula is divided into simple and complex fistula. Managing complex fistula is even more challenging, which typically affects younger people and causes persistent morbidity. It is pertinent to define complex anal fistula. From a practical point of view, a fistula that is difficult to manage has a higher risk of recurrence, poses a greater threat to continence and is classified as a complex fistula. Due to its difficulty in treating medically and surgically, Bhagandara (fistula-in-ano) is one of the eight major disorders classified under Astamahagada in Ayurveda. Ayurvedic surgeons frequently use the effective fistula treatment known as Ksharasutra; however, cutting the passage takes a very long time. As a result, this procedure is now sometimes referred to as partial fistulectomy with Ksharasutra ligation, fibrin glue, fistula plug (FP), Fistula-tract Laser Closure (FiLaC), Seton techniques, video-assisted anal fistula treatment (VAAFT), LIFT (ligation of intersphincteric fistulous tract), and IFTAK (interception of fistulous tract with application of Ksharasutra), also known as window technique, where the Guggulu based Apamarg Ksharasutra is placed. This method shortens the healing time and allows repairing such a complicated fistula-in-ano with little tissue injury. Infected anal crypt, secondary extension and related conditions are the key factors that lead to the recurrence of complex anal fistulas. Surgery in complex anal fistula aims to prevent recurrence, avoid incontinence and avoid damaging the sphincter muscles (the ring of muscles that open and close the anus).

296. FIBRIN SEALANT FOR THE PREVENTION OF ANASTOMOTIC LEAKAGE AFTER ESOPHAGECTOMY: INTERIM REPORT OF A PROSPECTIVE, PHASE III, RANDOMIZED CONTROLLED STUDY

Abstract Purpose Anastomotic leakage (AL) is one of the most pernicious complications after esophagectomy for patients with esophageal or esophagogastric junction cancer (EC or EJC). The application of fibrin sealant (FS) may be advantageous for reducing the incidence of AL. This study aims to evaluate the safety and effectiveness of FS in preventing AL in patients undergoing McKeown esophagectomy. Methods In this multicenter, prospective, randomized controlled trial, we planned to recruit 360 patients aged 18–75 years with resectable EC or EJC and the interim analysis was performed when the number of participants reaches 180. Patients assigned to the FS group received McKeown esophagectomy with 2.5 mL Bioseal applied to the cervical anastomosis, while patients in the control group received surgery alone. The primary endpoint was the incidence of cervical AL within the first 3 months postoperatively. Result From February 2019 to November 2021, 180 patients were recruited, with 89 in the FS group and 91 in the control group. There was no statistically difference between the incidence of AL between the two groups [6.7% (6/89) in the FS vs. 14.3% (13/91) in the control group, P = 0.16]. Complications was comparable (P = 0.76) between the FS group (42 of 89, 47.2%) and the control group (45 of 91, 49.5%). No adverse events related to FS or deaths occurred postoperatively. Conclusion The application of Bioseal intraoperatively is feasible and does not increase the risk of complications, and its effectiveness for the prevention of AL needs to be revalidated after the completion of patient enrollment.

813 Management of Massive Air Leak with Persistent Pneumothorax and Pneumoperitoneum in a 1.2kg Preterm Neonate – a Case Report

Abstract Pneumothorax is a life-threatening condition with potential iatrogenic causes which can extend to pneumomediastinum and pneumoperitoneum. Risk factors of spontaneous pneumothorax include prematurity, low birthweight, low APGAR scores and caesarean-section delivery. A 1255 grams preterm boy (Twin-2) was born at 28+3 weeks of gestation by emergency lower segment caesarean section. He showed signs of respiratory distress after uncomplicated endotracheal tube insertion which was required due to apnoeic episodes during continuous positive airway pressure ventilation. Recurring tube thoracocentesis and high frequency oscillatory ventilation (HFOV) treated persistent right-sided pneumothorax and nonsurgical pneumoperitoneum, with improvement on day-10, gradual removal of five chest drains by day-19 and extubation on day-24. Transillumination and chest radiography were main diagnostic investigations. Laryngotracheobronchoscopy on day-16 identified erythema and possible old injury at the carina. He was also treated for hypotension, suspected sepsis and pulmonary hypertension and was discharged home on day-66. Identifying pneumothorax promptly is essential to reduce morbidity and mortality. Lung ultrasound would improve diagnosis and monitoring. Management is patient-specific and includes needle and tube thoracocentesis and HFOV. Use of blood patch, fibrin glue or chemical agents, selective bronchial ventilation have been reported. Surgery is usually applied in unstable patients where bridging the defect is not feasible. nonsurgical pneumoperitoneum should be considered in ventilated neonates and those with airway injury to avoid exploratory laparotomy. Our case demonstrates challenges of managing a massive air leak in a premature newborn, who with adequate tube thoracocentesis and HFOV, successfully recovered from presumed iatrogenic persistent pneumothorax and pneumoperitoneum with conservative management.

NHS-POx-loaded patch versus fibrin sealant patch in a porcine robotic liver bleeding model

BackgroundThe management of bleeding is paramount to any surgical procedure. With the increased use of less invasive laparoscopic and robotic methods, achieving hemostasis can be challenging since the surgeons cannot manually apply hemostatic agents directly onto bleeding tissue. In this study, we assessed the use of a pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with poly(2-oxazoline) (NHS-POx) for hemostasis in robotic liver resection in a porcine bleeding model.MethodsThe NHS-POx-loaded patch (GATT-Patch), was first evaluated in a Feasibility Study to treat surgical bleeding in 10 lesions, followed by a Comparative Study in which the NHS-POx patch was compared to a standard-of-care fibrin sealant patch (TachoSil), in 36 lesions (superficial, resection, or deep injuries mimicking metastasectomies). For each lesion type, the NHS-POx and fibrin sealant patches were used in an alternating fashion with 18 lesions treated with NHS-POx and 18 with the fibrin patch. Animal preparation and surgical procedures were consistent across studies. The primary outcome was time to hemostasis (TTH) within 3 min for the Feasibility Study and within 5 min for the Comparative Study.ResultsIn the Feasibility Study, 8 of the 10 NHS-POx-treated lesions achieved hemostasis at 30 s and 3 min. In the Comparative Study, all 18 NHS-POx patch-treated lesions and 9 of the 18 fibrin sealant patch-treated lesions achieved hemostasis at 5 min. Median TTH with NHS-POx vs fibrin sealant patch was 30 vs 300 s (P < 0.001).ConclusionsIn this animal study, hemostasis during robotic liver surgery was achieved faster and more often with the NHS-POx loaded vs fibrin sealant patch.

Application of polyglycolic acid sheets and basic fibroblast growth factor to prevent esophageal stricture after endoscopic submucosal dissection in pigs.

Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly has anti-scarring effects during cutaneous wound healing. We hypothesized that suppressing myofibroblast activation will prevent stricture after esophageal ESD. We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked poly-glycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA + bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). After removing the esophagus on day 22, we evaluated the mucosal constriction rate. Compared with those in the control group, esophageal stricture was significantly reduced in the PGA + bFGF group, and the areas stained with α-SMA and calponin-1 antibodies were significantly inhibited in the PGA + bFGF and PGA groups. The thickness of the fibrous layer in the PGA + bFGF group was uniform compared to that of the other groups. Thus, PGA + bFGF inhibited the development of unregulated fibroblasts in the acute phase, leading to uniform wound healing. Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.

Up-to-date meta-analysis of long-term evaluations of mesenchymal stem cell therapy for complex perianal fistula.

Local mesenchymal stem cell (MSC) therapy for complex perianal fistulas (PFs) has shown considerable promise. But, the long-term safety and efficacy of MSC therapy in complex PFs remain unknown. To explore the long-term effectiveness and safety of local MSC therapy for complex PFs. Sources included the PubMed, EMBASE, and Cochrane Library databases. A standard meta-analysis was performed using RevMan 5.3. After screening, 6 studies met the inclusion criteria. MSC therapy was associated with an improved long-term healing rate (HR) compared with the control condition [odds ratio (OR) = 2.13; 95% confidence interval (95%CI): 1.34 to 3.38; P = 0.001]. Compared with fibrin glue (FG) therapy alone, MSC plus FG therapy was associated with an improved long-term HR (OR = 2.30; 95%CI: 1.21 to 4.36; P = 0.01). When magnetic resonance imaging was used to evaluate fistula healing, MSC therapy was found to achieve a higher long-term HR than the control treatment (OR = 2.79; 95%CI: 1.37 to 5.67; P = 0.005). There were no significant differences in long-term safety (OR = 0.77; 95%CI: 0.27 to 2.24; P = 0.64). Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.

Interesting surgical cases of mesenteric cystic lymphangioma

Mesenteric cystic lymphangioma involving the gastrointestinal tract is uncommon in infants and children. It is a benign tumor due to abnormal formation lymphatic system. These tumors exhibit symptoms varying in site and size of localization. Usually, symptoms are manifested by acute abdominal pain, intestinal obstruction, rising body temperature, and diarrhea. Lymphangioma can easily misdiagnose with other conditions like intestinal obstruction, acute appendicitis, or ovarian cyst in a female child. Therapeutic interventions such as fibrin glue, steroids, bleomycin, OK-432, and laparoscopic-assisted surgery are available. From 2018 to 2022, the Regional Paediatrics Hospital of Grodno, Belarus has recorded two cases of mesenteric lymphangioma. Both were emergency cases. In this scientific paper, we have described a surgical approach with improved outcomes. In both cases, surgical resection of lymphangioma that was rooted alongside the ileum was done. We used laparotomy in our surgical procedure, however, the approach was different, one being lower median laparotomy and another being a transrectal approach. Post-operatively patients were in satisfactory condition. Even though mesenteric lymphangioma is a benign condition, it should be immediately diagnosed and surgically managed to avoid morbidity, and mortality due to an increase in size that can fatally compress the adjacent organs impairing the function of an organ and complications like intestinal obstruction and bleeding. Our approaches with case-1 and case-2, both resulted in effective surgical and post-surgical outcomes. But more data is required to make a population-based influence depending on our approach.

Role of Laser Ablation of Fistula Tract in High Perianal Fistula

Abstract Background Complex anal fistula has been a hot topic in clinic. Many surgical techniques have been described for the treatment of such anal fistula, including the use of seton, fibrin glue, collagen plugs, rectal advancement flaps, fistulotomy with sphincter repair, and rerouting the fistula tract. However, the results have been variable, and no one procedure is superior to the others absolutely. It is worth our concern that the goal of any treatment procedure is to obliterate the tract and to have low recurrence rates while maintaining full continence. A fistulotomy lays open the fistulous tract, thus leaving smaller unepithelized wounds, which hastens the wound healing. Until now, fistulotomy is still the most widely used. But, the high cure rate is limited by the fact that laying open a transsphincteric fistula tract and cutting both the internal and the external sphincter has the risk of fecal incontinence ranging up to 40%. Aim of the Work To assess and evaluate the efficacy and safety of LASER ablation of high perianal fistula. Patients and Methods This study is a randomized prospective study which will be conducted at Ain Shams University hospitals recruiting (20) patients and will be operated upon between January 2021 and July 2021 with minimal follow up to 3 months postoperatively. Results From these studies, it emerges that this procedure has some advantages. It doesn’t affect continence, administers controlled hyperthermic effect to the tissues, has a short learning-curve and reduces postoperative hospital stay as compared to endorectal advancement flap or LIFT. However, it has also some drawbacks. It is a blind procedure, as it’s not possible a direct visualization of the fistula tract or any secondary tracts and this may lead to recurrence. It requires expensive equipment, particularly if compared to other sphincter-saving techniques. Conclusion LASER ablation is a technique that has a promising results regarding complex perianal fistula preserving anal continence and short healing period and low recurrence rate as regarding classic and other techniques.

Compartive Study between Conventional Laying-Open Technique with Sphincter Repair and Ligation of Intersphincteric Fistula Tract (LIFT) in Treatment of High Trans-Sphincteric Perianal Fistula

Abstract Background Complex anal fistula has been a hot topic in clinic. Many surgical techniques have been described for the treatment of such anal fistula, including the use of seton, fibrin glue, collagen plugs, rectal advancement flaps, fistulotomy with sphincter repair, and rerouting the fistula tract. However, the results have been variable, and no one procedure is superior to the others absolutely. It is worth our concern that the goal of any treatment procedure is to obliterate the tract and to have low recurrence rates while maintaining full continence. A fistulotomy lays open the fistulous tract, thus leaving smaller unepithelized wounds, which hastens the wound healing. Until now, fistulotomy is still the most widely used. But, the high cure rate is limited by the fact that laying open a transsphincteric fistula tract and cutting both the internal and the external sphincter has the risk of fecal incontinence ranging up to 40%. Objective To retrospectively evaluate the success rate, the recurrence and incontinence when using the Conventional laying-open and sphincter Repair technique in comparison to Ligation of Intersphincteric Fistula Tract (LIFT) for treating high trans-shpincteric perianal fistula. Patients and Methods This was a cohort retrospective, comparative study that was conducted on cases of fistula in the anus, who were subjected to surgery in Ain Shams University Hospitals and Ain shams specialized hospitals in the period from October 2021 to March 2022 (at least 30 cases) to evaluate the success rate, the recurrence rate, and incontinence rate when using the conventional laying open with sphincter repair technique compared to ligation of inter-sphincteric fistula tract (LIFT) For High trans-sphincteric perianal fistula. Results Regarding Relation of recurrence with demographic data of the studied patients, de novo/recurrent, Wexner score before and after operation and complications. that there was no statistically significant relation found recurrence with demographic data of the studied patients, de novo/recurrent, Wexner score before and after operation while there was statistically significant relation found with complications. Conclusion LIFT procedure is an effective and preferred sphincter-saving technique for fistula-inano with shorter healing time and lower incidence of postoperative anal incontinence, but have higher incidence of recurrence as compared to conventional layopen with sphincter repair which have a lower incidence of recurrence but have a relatively longer Healing time and higher incidence of postoperative anal incontinence. Both techniques are effective, have post operative good results and safe in treatment of high transsphincteric perianal fistula but Further research work is still warranted to confirm the long term outcome of these 2 techniques with a larger sample size and a longer follow up period. To know which technique is superior over the other.

Revolutionizing Fistula Treatment: A Case Series on the Application of Kshara Sutra Therapy

A chronic, abnormal contact between the epithelialized anal canal surface and the perianal skin is known as an anal fistula (fistula-in-ano), which can cause serious morbidity and lower quality of life. Traditional surgical procedures as well as more contemporary ones, like the application of fibrin glue, a plug, or closure of the intersphincteric fistula tract, are available as treatment options (LIFT). These conventional techniques, however, may have varying degrees of efficacy, and some may be connected to the risk of incontinence. The Kshara Sutra, an antiquated Ayurvedic parasurgical procedure, was used to treat a case series of 10 patients with a range of anal fistulas, ranging in complexity from simple to complex presentations. Patients in the cases range in age from 22 to 55, both male and female. Despite variations in their particular circumstances, all patients had completely healed fistulas following Kshara Sutra treatment. Additionally, this treatment showed promise in simplifying complicated fistulas. These results add to the expanding body of research that supports the use of Kshara Sutra therapy for the repair of anal fistulas, offering a promising, secure, and maybe more effective option than traditional surgical procedures.

Injectable, self-healing hydrogel adhesives with firm tissue adhesion and on-demand biodegradation for sutureless wound closure.

Tissue adhesives have garnered extensive interest as alternatives and supplements to sutures, whereas major challenges still remain, including weak tissue adhesion, inadequate biocompatibility, and uncontrolled biodegradation. Here, injectable and biocompatible hydrogel adhesives are developed via catalyst-free o-phthalaldehyde/amine (hydrazide) cross-linking reaction. The hydrogels demonstrate rapid and firm adhesion to various tissues, and an o-phthalaldehyde-mediated tissue adhesion mechanism is established. The hydrogel adhesives show controlled degradation profiles of 6 to 22 weeks in vivo through the incorporation of disulfide bonds into hydrogel network. In liver and blood vessel injury, the hydrogels effectively seal the incisions and rapidly stop bleeding. In rat and rabbit models of full-thickness skin incision, the hydrogel adhesives quickly close the incisions and accelerate wound healing, which exhibit efficacies superior to those of commercially available fibrin glue and cyanoacrylate glue. Thus, the hydrogel adhesives show great potential for sutureless wound closure, hemostasis sealing, and prevention of leakage in surgical applications.

Developing the supraparticle technology for round window-mediated drug administration into the cochlea

The semi-permeable round window membrane (RWM) is the gateway to the cochlea. Although the RWM is considered a minimally invasive and clinically accepted route for localised drug delivery to the cochlea, overcoming this barrier is challenging, hindering development of effective therapies for hearing loss. Neurotrophin 3 (NT3) is an emerging treatment option for hearing loss, but its therapeutic effect relies on sustained delivery across the RWM into the cochlea. Silica supraparticles (SPs) are drug delivery carriers capable of providing long-term NT3 delivery, when injected directly into the guinea pig cochlea. However, for clinical translation, a RWM delivery approach is desirable. Here, we aimed to test approaches to improve the longevity and biodistribution of NT3 inside the cochlea after RWM implantation of SPs in guinea pigs and cats. Three approaches were tested (i) coating the SPs to slow drug release (ii) improving the retention of SPs on the RWM using a clinically approved gel formulation and (iii) permeabilising the RWM with hyaluronic acid. A radioactive tracer (iodine 125: 125I) tagged to NT3 (125I NT3) was loaded into the SPs to characterise drug pharmacokinetics in vitro and in vivo. The neurotrophin-loaded SPs were coated using a chitosan and alginate layer-by-layer coating strategy, named as ‘(Chi/Alg)SPs’, to promote long term drug release. The guinea pigs were implanted with 5× 125I NT3 loaded (Chi/Alg) SPs on the RWM, while cats were implanted with 30× (Chi/Alg) SPs. A cohort of animals were also implanted with SPs (controls). We found that the NT3 loaded (Chi/Alg)SPs exhibited a more linear release profile compared to NT3 loaded SPs alone. The 125I NT3 loaded (Chi/Alg)SPs in fibrin sealant had efficient drug loading (~5 μg of NT3 loaded per SP that weights ~50 μg) and elution capacities (~49% over one month) in vitro. Compared to the SPs in fibrin sealant, the (Chi/Alg)SPs in fibrin sealant had a significantly slower 125I NT3 drug release profile over the first 7 days in vitro (~12% for (Chi/Alg) SPs in fibrin sealant vs ~43% for SPs in fibrin sealant). One-month post-implantation of (Chi/Alg) SPs, gamma count measurements revealed an average of 0.3 μg NT3 remained in the guinea pig cochlea, while for the cat, 1.3 μg remained. Histological analysis of cochlear tissue revealed presence of a 125I NT3 signal localised in the basilar membrane of the lower basal turn in some cochleae after 4 weeks in guinea pigs and 8 weeks in cats. Comparatively, and in contrast to the in vitro release data, implantation of the SPs presented better NT3 retention and distribution inside the cochlea in both the guinea pigs and cats. No significant difference in drug entry was observed upon acute treatment of the RWM with hyaluronic acid. Collectively, our findings indicate that SPs and (Chi/Alg)SPs can facilitate drug transfer across the RWM, with detectable levels inside the cat cochlea even after 8 weeks with the intracochlear approach. This is the first study to examine neurotrophin pharmacokinetics in the cochlea for such an extended period of times in these two animal species. Whilst promising, we note that outcomes between animals were variable, and opposing results were found between in vitro and in vivo release studies. These findings have important clinical ramifications, emphasising the need to understand the physical properties and mechanics of this complex barrier in parallel with the development of therapies for hearing loss.

Effect of Kartogenin combined with adipose-derived stem cells on tendon-bone healing after anterior cruciate ligament reconstruction

To investigate the effect of Kartogenin (KGN) combined with adipose-derived stem cells (ADSCs) on tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in rabbits. After the primary ADSCs were cultured by passaging, the 3rd generation cells were cultured with 10 μmol/L KGN solution for 72 hours. The supernatant of KGN-ADSCs was harvested and mixed with fibrin glue at a ratio of 1∶1; the 3rd generation ADSCs were mixed with fibrin glue as a control. Eighty adult New Zealand white rabbits were taken and randomly divided into 4 groups: saline group (group A), ADSCs group (group B), KGN-ADSCs group (group C), and sham-operated group (group D). After the ACL reconstruction model was prepared in groups A-C, the saline, the mixture of ADSCs and fibrin glue, and the mixture of supernatant of KGN-ADSCs and fibrin glue were injected into the tendon-bone interface and tendon gap, respectively. ACL was only exposed without other treatment in group D. The general conditions of the animals were observed after operation. At 6 and 12 weeks, the tendon-bone interface tissues and ACL specimens were taken and the tendon-bone healing was observed by HE staining, c-Jun N-terminal kinase (JNK) immunohistochemical staining, and TUNEL apoptosis assay. The fibroblasts were counted, and the positive expression rate of JNK protein and apoptosis index (AI) were measured. At the same time point, the tensile strength test was performed to measure the maximum load and the maximum tensile distance to observe the biomechanical properties. Twenty-eight rabbits were excluded from the study due to incision infection or death, and finally 12, 12, 12, and 16 rabbits in groups A-D were included in the study, respectively. After operation, the tendon-bone interface of groups A and B healed poorly, while group C healed well. At 6 and 12 weeks, the number of fibroblasts and positive expression rate of JNK protein in group C were significantly higher than those of groups A, B, and D (P<0.05). Compared with 6 weeks, the number of fibroblasts gradually decreased and the positive expression rate of JNK protein and AI decreased in group C at 12 weeks after operation, with significant differences (P<0.05). Biomechanical tests showed that the maximum loads at 6 and 12 weeks after operation in group C were higher than in groups A and B, but lower than those in group D, while the maximum tensile distance results were opposite, but the differences between groups were significant (P<0.05). After ACL reconstruction, local injection of a mixture of KGN-ADSCs and fibrin glue can promote the tendon-bone healing and enhance the mechanical strength and tensile resistance of the tendon-bone interface.