Surgical Sealant Research Articles

Air leak and intraoperative bleeding in thoracic surgery: a Delphi consensus among the members of Italian society of thoracic surgery.

Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.

BioGlue® is not associated with polypropylene suture breakage after aortic surgery.

ObjectiveWe have encountered broken or damaged polypropylene sutures (Prolene®) at the anastomotic sites during aortic reoperations. Because a surgical sealant, bovine serum albumin-glutaraldehyde (BioGlue®), was used in previous aortic surgery in some of these cases, we undertook this in vitro study to evaluate whether the use of BioGlue® was associated with breakage of polypropylene sutures at the aortic anastomosis.Materials and methodsThe broken polypropylene sutures, anastomotic sites and aortic tissue at the location of suture breakage were visually inspected and evaluated intraoperatively. Six human cadaveric aortic samples were incised circumferentially and anastomosed proximally to a valved conduit with running 4–0 polypropylene sutures (Prolene®). In the test group (n = 3), BioGlue® was applied directly to the Prolene® sutures at the anastomotic sites, while in the control group (n = 3) the anastomoses were not sealed with any surgical adhesive. The six samples were immersed in Dulbecco's phosphate buffered saline solution and mounted on a M-6 Six Position Heart Valve Durability Testing System and tested up to 120 million cycles for a 2-year period. During and upon completion of the testing, the integrity of Prolene® sutures, the anastomosis and aortic tissues was regularly assessed by visual inspection.ResultsIntraoperative findings included a stretched and thin aortic wall (some with thrombus), a small cleft between the aortic tissue and the Dacron vascular graft. An excessive amount of BioGlue® was often found around the anastomosis, with cracking material, but no signs of mechanical damage were observed in these cases. Upon visual inspection during and after in vitro testing, there was no apparent damage to the polypropylene sutures on the interior or exterior of the aortic anastomoses in any of the samples. No difference was observed in the physical integrity of the polypropylene sutures at anastomotic lines, the anastomoses and aortic tissues between the test and control samples.ConclusionsThe results of this study suggest that the use of BioGlue® was not associated with breakage of the polypropylene sutures at the anastomotic sites after aortic dissection repair.

Mussel adhesive proteins as surgical sealants in post-extraction: Literature review

Background and objective: Tooth extraction is a dental procedure of removing a tooth from its socket, causing an injury. Dental socket wounds that are directlyexposed to the oral environment allow the entry of pathogenic micro-organisms that can cause post-extraction bleeding, alveolar osteitis, oroantral fistula, and others. Recent studies have shown that the use of mussel adhe-sive proteins (MAPs) without sutures or staples can accelerate socket wound closure or stopbleeding after tooth extraction. Con-clusion: MAPs that have been synthesized into injectable citrate-based mussel-inspired bioadhesive have the potential assurgical sealants after tooth extraction because they have strong adhesive properties in wet environments, good esthetics, atraumatic, and short operating time.

Safety and performance of surgical adhesives.

BackgroundTissue adhesives are an alternative to conventional surgical sutures to reduce the time and cost of wound closure and to improve patient comfort. The use of tissue adhesives does not require any subsequent intervention and significantly lowers the volume and rate of blood loss, and reduces the need for transfusions during and after surgery. However, based on their formulation, tissue adhesives’ safety profile and functional properties may differ. Therefore, this study aimed to evaluate the basic safety and performance of NE’X Glue® Surgical Sealant, BioGlue® Surgical Sealant, and PREVELEAKTM Surgical Sealant in vitro.MethodsThe basic safety of commercially available tissue adhesives was evaluated using MEM elution assay according to ISO 10993–5 and endotoxin level according to 85. USP. The in vitro performance was evaluated using lap-shear by tension loading test, burst strength test, degradation, and swelling assays.ResultsNE’X Glue®, BioGlue®, and PREVELEAKTM did not cause cytotoxicity in MEM elution assay. All surgical adhesives are below the general limit of endotoxin contamination of 20 EU/device. NE’X Glue® and BioGlue® showed the highest and comparable strength properties in lap shear and burst strength tests compared to PREVELEAKTM. NE’X Glue® and PREVELEAKTM are characterized by lower degradation potential than BioGlue®. PREVELEAKTM is characterized by the highest swelling when compared to NE’X Glue® and BioGlue®.ConclusionsNE’X Glue® is most versatile in terms of functional properties while maintaining the same safety profile as BioGlue® and PREVELEAKTM.

Mussel-inspired biomaterials: From chemistry to clinic.

After several billions of years, nature still makes decisions on its own to identify, develop, and direct the most effective material for phenomena/challenges faced. Likewise, and inspired by the nature, we learned how to take steps in developing new technologies and materials innovations. Wet and strong adhesion by Mytilidae mussels (among which Mytilus edulis —blue mussel and Mytilus californianus —California mussel are the most well‐known species) has been an inspiration in developing advanced adhesives for the moist condition. The wet adhesion phenomenon is significant in designing tissue adhesives and surgical sealants. However, a deep understanding of engaged chemical moieties, microenvironmental conditions of secreted proteins, and other contributing mechanisms for outstanding wet adhesion mussels are essential for the optimal design of wet glues. In this review, all aspects of wet adhesion of Mytilidae mussels, as well as different strategies needed for designing and fabricating wet adhesives are discussed from a chemistry point of view. Developed muscle‐inspired chemistry is a versatile technique when designing not only wet adhesive, but also, in several more applications, especially in the bioengineering area. The applications of muscle‐inspired biomaterials in various medical applications are summarized for future developments in the field.

Biocompatibility of novel albumin-aldehyde surgical adhesive

Many medical procedures could benefit from the use of tissue sealants which allow for reduced surgery time, limited blood loss, easier tissue handling, and fewer postoperative complications. The safety and biocompatibility of surgical sealants are of paramount importance therefore, the aim of this study is to investigate the biocompatibility of NE’X Glue Surgical Adhesive. Chemical characterization (VOC and elements), cytotoxicity (MEM elution), genotoxicity (AMES and MLA), endotoxin contamination, sensitization potential, intracutaneous reactivity, acute and subchronic systemic toxicity with implantation as well as pyrogenicity were evaluated to investigate the biocompatibility of the NE’X Glue Surgical Adhesive. Studies were conducted according to ISO 10993 standards. The biocompatibility requirements with accordance to ISO 10993-1 for NE'X Glue were met. In vitro studies showed that NE'X Glue surgical adhesive is non-cytotoxic and non-mutagenic. Also, in vivo studies demonstrated that NE'X Glue shows no signs of toxicity, has no pyrogenic potential, and is non-sensitizing and non-irritating. The chemical characterization showed that no compounds were identified above Analytical Evaluation Threshold (AET), and no elements with concentrations higher than element-specific PDE (µg/day) were detected. NE'X Glue Surgical Adhesive is a versatile and promising new surgical sealant with a wide range of potential applications and very good*0* biocompatibility.

Silk Fibroin-Based Biomaterials for Hemostatic Applications.

Hemostasis plays an essential role in all surgical procedures. Uncontrolled hemorrhage is the primary cause of death during surgeries, and effective blood loss control can significantly reduce mortality. For modern surgeons to select the right agent at the right time, they must understand the mechanisms of action, the effectiveness, and the possible adverse effects of each agent. Over the past decade, various hemostatic agents have grown intensely. These agents vary from absorbable topical hemostats, including collagen, gelatins, microfibrillar, and regenerated oxidized cellulose, to biologically active topical hemostats such as thrombin, biological adhesives, and other combined agents. Commercially available products have since expanded to include topical hemostats, surgical sealants, and adhesives. Silk is a natural protein consisting of fibroin and sericin. Silk fibroin (SF), derived from silkworm Bombyx mori, is a fibrous protein that has been used mostly in fashion textiles and surgical sutures. Additionally, SF has been widely applied as a potential biomaterial in several biomedical and biotechnological fields. Furthermore, SF has been employed as a hemostatic agent in several studies. In this review, we summarize the several morphologic forms of SF and the latest technological advances on the use of SF-based hemostatic agents.

Novel Surgical Sealant Using Pollock Gelatin

Novel Surgical Sealant Using Pollock Gelatin

A hydrogel spinal dural patch with potential anti-inflammatory, pain relieving and antibacterial effects

CSFL caused by spinal dural defect is a common complication of spinal surgery, which need repair such as suture or sealants. However, low intracranial pressure symptoms, wound infection and prolonged hospital associated with pin-hole leakage or loose seal effect were often occurred after surgical suture or sealants repair. Stable, pressure resistance and high viscosity spinal dural repair patch in wet environment without suture or sealants was highly needed. Herein, a bioactive patch composed of alginate and polyacrylamide hydrogel matrix cross-linked by calcium ions, and chitosan adhesive was proposed. This fabricated patch exhibits the capabilities of promoting defect closure and good tight seal ability with the bursting pressure is more than 790 mm H2O in wet environment. In addition, the chitosan adhesive layer of the patch could inhibit the growth of bacterial in vitro, which is meaningful for the postoperative infection. Furthermore, the patch also significantly reduced the expression of GFAP, IBA-1, MBP, TNF-α, and COX-2 in early postoperative period in vivo study, exerting the effects of anti-inflammatory, analgesic and adhesion prevention. Thus, the bioactive patch expected to be applied in spinal dural repair with the good properties of withstanding high pressure, promoting defect closure and inhibiting postoperative infection.

Complications associated with Dermabond® during head and neck surgery: MAUDE and literature review

IntroductionDermabond® is a liquid surgical sealant containing 2-octyl-cyanoacrylate that has been widely used during head and neck surgeries. This study aims to provide a summary of adverse events related to Dermabond® in head and neck procedures as reported in the MAUDE database, and to report a complete overview of all documented adverse events related to Dermabond® use in current literature. MethodsThe US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database was queried for reports of adverse events related to Dermabond® use from January 1, 2010, to February 1, 2020. Data were extracted from reports pertaining to head and neck procedures. In addition, literature review was performed from January 1970 to January 2021. Various adverse events related to Dermabond® were included in the study. ResultsWe identified 32 adverse events, from which 29 (90.6%) were patient-related events and 3 (9.4%) were operator-related events. Of the patient-related events, contact dermatitis (CD) (20 [69.0%]) was the most common, followed by wound dehiscence (4 [13.8%]). All of the operator-related events were from inadvertent cut injury (3 [100%]). Following the literature review, adverse events of Dermabond® were categorized into CD, wound dehiscence, infection, and cut injury. ConclusionDermabond® demonstrated utility in various surgical procedures including head and neck surgeries but are associated with risks. This study identified adverse events associated with Dermabond®. Further studies are needed to establish the causation of contact dermatitis in certain populations.

Liquid Copolymers as Biodegradable Surgical Sealant (Adv. Healthcare Mater. 19/2021)

Tissue Sealants In article number 2100803 by Boaz Mizrahi and co-workers, an elastic biodegradable sealant is designed by mixing two complementary neat (solvent-free) star shape prepolymers. This mixture, which hardens in several seconds, offers several advantages over existing tissue sealants, including excellent mechanical properties and degradation behavior, minimal cytotoxicity in vitro and biocompatibility in vivo.

Liquid Copolymers as Biodegradable Surgical Sealant.

Surgical sealants are widely used to prevent seepage of fluids and liquids, promote hemostasis, and close incisions. Despite the remarkable progress the field of biomaterials has undergone, the clinical uses of surgical sealants are limited because of their short persistence time in vivo, toxicity, and high production costs. Here, the development of two complementary neat (solvent-free) prepolymers, PEG4 -PLGA-NHS and PEG4 -NH2 , that harden upon mixing to yield an elastic biodegradable sealant is presented. The mechanical and rheological properties and cross-linking rate can be controlled by varying the ratio between the two prepolymers. The tested sealants show a longer persistence time compared with fibrin glue, minimal cytotoxicity in vitro, and excellent biocompatibility in vivo. The neat, multiarmed approach demonstrated here improves the mechanical and biocompatibility properties and provides a promising tissue sealant solution for wound closure in future surgical procedures.

Multifaceted Design and Emerging Applications of Tissue Adhesives.

Tissue adhesives can form appreciable adhesion with tissues and have found clinical use in a variety of medical settings such as wound closure, surgical sealants, regenerative medicine, and device attachment. The advantages of tissue adhesives include ease of implementation, rapid application, mitigation of tissue damage, and compatibility with minimally invasive procedures. The field of tissue adhesives is rapidly evolving, leading to tissue adhesives with superior mechanical properties and advanced functionality. Such adhesives enable new applications ranging from mobile health to cancer treatment. To provide guidelines for the rational design of tissue adhesives, here, existing strategies for tissue adhesives are synthesized into a multifaceted design, which comprises three design elements: the tissue, the adhesive surface, and the adhesive matrix. The mechanical, chemical, and biological considerations associated with each design element are reviewed. Throughout the report, the limitations of existing tissue adhesives and immediate opportunities for improvement are discussed. The recent progress of tissue adhesives in topical and implantable applications is highlighted, and then future directions toward next-generation tissue adhesives are outlined. The development of tissue adhesives will fuse disciplines and make broad impacts in engineering and medicine.

Formulation - Properties effects of novel dual composite hydrogels for use as medical sealants

Use of sealants for wound closure and healing applications is being widely investigated due to their many advantages. However, currently available surgical sealants do not combine high strength with biocompatibility and other desired properties. We recently developed and studied hydrogels based on the natural polymers gelatin and alginate. In the current study, two functional fillers, the hemostatic agent montmorillonite and cellulose fibers, were incorporated into a basic formulation to create novel “dual composite” medical hydrogel sealants.The effects of both functional fillers on the mechanical and physical properties of the hydrogels as well as their microstructure and cytotoxicity were studied. Moreover, a qualitative model on the mechanical and physical properties of the hydrogels was developed. Incorporation of montmorillonite and cellulose fibers resulted in a significant increase in the tensile strength and modulus, better sealing ability, higher viscosity and lower gelation time and swelling degree. These changes were mainly due to dispersion of montmorillonite into nanoparticles within the hydrogel and physical crosslinking of the gelatin molecules. The cellulose fibers contributed by their reinforcing effect and ability to absorb water, and probably also by entanglements of the polymeric structure. Understanding the effects of each functional filler on the mechanical and physical properties in both liquid and solid states enables fitting desired formulations to specific medical applications. Together with the excellent biocompatibility of these dual composite hydrogels, they are expected to successfully be used as bioadhesives and medical sealants in various applications.

Cerrahi doku yapıştırıcılar akciğer kanseri rezeksiyonu sonrası takip pozitron emisyon tomografisinde yanlış pozitifliğe neden olur mu?

Postoperative complications following thoracic procedures are a major cause of morbidity and mortality. Alveolar air leaks and/or bronchopleural fistulas are associated with increased risk of infection, prolonged chest tube, and hospital stay duration and therefore generate economical concern for health care providers. A variety of surgical sealants or adhesives have been introduced to overcome this complication. Since intraoperative BioGlue® application can also cause an inflammatory reaction and mimic tumor recurrence on FDG PET-CT, in the present study we aimed to investigate its potential role in false-positive PET-CT results in patients operated for NSCLC. Data of six patients who underwent resection for primary NSCLC at our institution (Department of Thoracic Surgery, Hacettepe University Medical Faculty) between January 2015 and December 2018 and had false positivity, due to BioGlue® application, at the bronchial stump in follow-up FDG PET-CT were retrospectively analyzed from a prospectively collected database. One of the 6 patients was female and 5 were male. The mean age was 68 years (range, 56-79 years). The average time interval between operation and postoperative FDG-PET imaging was 4.3 months (range, 4-6 months). Follow-up FDG-PET imaging SUVmax values ranged between 3.0 and 9.0 (median: 5.33). All patients have been evaluated by FDG-PET scan following the detection of soft tissue densities at the surgical site suspicious for recurrence at their follow-up chest CT scans. Four patients underwent a bronchoscopic examination, bronchial stumps were examined and multiple biopsies were taken from suspicious nodules or tissues and sent for pathologic examination. Histopathological results revealed inflammation which is compatible with foreign body granuloma, without any suspicion for malignancy, in all cases. Two patients were solely followed-up and subsequent FDG-PET imaging after 3 months revealed complete resolution of FDG uptake. To avoid unnecessary biopsies or surgical procedures, the possibility of false-positive results due to surgical adhesive product use should be taken into account while interpreting follow-up FDG-PET imaging results and the operative reports should be written in detail, describing which surgical materials used and their exact application sites.

An Intrinsically-Adhesive Family of Injectable and Photo-Curable Hydrogels with Functional Physicochemical Performance for Regenerative Medicine.

Attaching hydrogels to soft internal tissues is crucial for the development of various biomedical devices. Tough sticky hydrogel patches present high adhesion, yet with lack of injectability and the need for treatment of contacting surface. On the contrary, injectable and photo-curable hydrogels are highly attractive owing to their ease of use, flexibility of filling any shape, and their minimally invasive character, compared to their conventional preformed counterparts. Despite recent advances in material developments, a hydrogel that exhibits both proper injectability and sufficient intrinsic adhesion is yet to be demonstrated. Herein, a paradigm shift is proposed toward the design of intrinsically adhesive networks for injectable and photo-curable hydrogels. The bioinspired design strategy not only provides strong adhesive contact, but also results in a wide window of physicochemical properties. The adhesive networks are based on a family of polymeric backbones where chains are modified to be intrinsically adhesive to host tissue and simultaneously form a hydrogel network via a hybrid cross-linking mechanism. With this strategy, adhesion is achieved through a controlled synergy between the interfacial chemistry and bulk mechanical properties. The functionalities of the bioadhesives are demonstrated for various applications, such as tissue adhesives, surgical sealants, or injectable scaffolds.

Enhancing the regenerative potential of stem cell-laden, clinical-grade implants through laminin engineering

Protected delivery of neural stem cells (NSCs; a major transplant population) within bioscaffolds has the potential to improve regenerative outcomes in sites of spinal cord injury. Emergent research has indicated clinical grade bioscaffolds (e.g. those used as surgical sealants) may be repurposed for this strategy, bypassing the long approval processes and difficulties in scale-up faced by laboratory grade materials. While promising, clinical scaffolds are often not inherently regenerative. Extracellular molecule biofunctionalisation of scaffolds can enhance regenerative features such as encapsulated cell survival/distribution, cell differentiation into desired cell types and nerve fibre growth. However, this strategy is yet to be tested for clinical grade scaffolds. Here, we show for the first time that Hemopatch™, a widely used, clinically approved surgical matrix, supports NSC growth. Further, functionalisation of Hemopatch™ with laminin promoted homogenous distribution of NSCs and their daughter cells within the matrix, a key regenerative criterion for transplant cells.

Chemically Stable, Strongly Adhesive Sealant Patch for Intestinal Anastomotic Leakage Prevention

AbstractIntestinal anastomotic leaking, which involves the discharge of chemically aggressive, non‐sterile fluids into the abdomen, remains one of the most dreaded postoperative complications of abdominal surgery. Depending on the site and the patient condition, incidence ranging between 4% and 21% and mortality rates up to 27% are reported. Currently available surgical sealants only poorly address the issue, especially since most commonly used fibrin glues fail due to insufficient adhesion and chemical instability. Here, a chemically highly resistive, leak‐tight, and mucoadhesive hydrogel sealant, which is grafted on the surface of the intestinal wall using a mutually interpenetrating network that traverses hydrogel and tissue is presented. In contrast to clinically used fibrin‐based sealants (including Tachosil), the developed adhesive poly(acrylamide‐methyl acrylate‐acrylic acid) patch does not degrade and exhibits strong tissue adhesion even when exposed to intestinal fluid. The biocompatible hydrogel patch effectively seals anastomotic leaks in ex vivo intestinal models, greatly surpassing commercial sealants (time to patch‐failure >24 h compared to 5 min for commonly used Tachosil). Importantly, the developed adhesive patch paves the way for the application of both mechanically and chemically robust sealants suitable for the treatment and prevention of intestinal leaks.

Application of prosthesis eversion method for ascending aorta replacement guarantees better clinical outcomes of type A acute aortic dissection surgery.

BackgroundThe advantages of prosthesis eversion method in patients diagnosed with Stanford type A acute aortic dissection (AAD) undergoing ascending aorta replacement (AAR) is unknown. This research is designed to explore it.MethodsWe retrospectively analyzed the data of a total of 283 patients diagnosed with type A aortic dissection that underwent surgery in Renmin Hospital of Wuhan University from March, 2006 to April, 2020. Eighty-eight patients underwent surgical repair with traditional continuous suture technique, and 195 patients received prosthesis eversion. Baseline data, intra-operative data and early-stage clinical results were collected and statistically analyzed.ResultsBaseline data were similar except for age, incidence of hyperlipidemia and taking ACEI/ARB drugs (P<0.05). Cardiopulmonary bypass time, cross-clamp time, circulation arrest time, hemostasis time and total operation time in the traditional method group were far longer than in the prothesis eversion group (P<0.01). The operative mortality was similar (P>0.01). Post-operatively, there was no statistically significant difference in the mean ventilation time, mortality, incidence of re-exploration, tracheostomy, paraplegia, long-term coma and stroke between the two groups (P>0.05). Patients in the traditional method group had a longer duration stay in ICU and hospital than patients in the prosthesis eversion group (P<0.05). Patients in the traditional method group received more red blood cells (RBC) (P<0.01), plasma (P<0.05), fibrinogen (P<0.01) and albumin (P<0.05) transfusions, and CoSeal™ surgical sealant (P<0.05) than patients in the prosthesis eversion group.ConclusionsOur experience and statistical analysis showed prosthesis eversion method to have some advantage in reducing blood loss and improving clinical results compared with repair with continuous suture. This technique is both simple to learn and perform.

TGF-β loaded exosome enhances ischemic wound healing in vitro and in vivo.

Rationale: With over seven million infections and $25 billion treatment cost, chronic ischemic wounds are one of the most serious complications in the United States. The controlled release of bioactive factor enriched exosome from finbrin gel was a promising strategy to promote wound healing.Methods: To address this unsolved problem, we developed clinical-grade platelets exosome product (PEP), which was incorporate with injectable surgical fibrin sealant (TISSEEL), to promote chronic wound healing and complete skin regeneration. The PEP characterization stimulated cellular activities and in vivo rabbit ischemic wound healing capacity of TISSEEL-PEP were performed and analyzed.Results: PEP, enriched with transforming growth factor beta (TGF-β), possessed exosomal characteristics including exosome size, morphology, and typical markers including CD63, CD9, and ALG-2-interacting protein X (Alix). In vitro, PEP significantly promoted cell proliferation, migration, tube formation, as well as skin organoid formation. Topical treatment of ischemic wounds with TISSEEL-PEP promoted full-thickness healing with the reacquisition of hair follicles and sebaceous glands. Superior to untreated and TISSEEL-only treated controls, TISSEEL-PEP drove cutaneous healing associated with collagen synthesis and restoration of dermal architecture. Furthermore, PEP promoted epithelial and vascular cell activity enhancing angiogenesis to restore blood flow and mature skin function. Transcriptome deconvolution of TISSEEL-PEP versus TISSEEL-only treated wounds prioritized regenerative pathways encompassing neovascularization, matrix remodeling and tissue growth.Conclusion: This room-temperature stable, lyophilized exosome product is thus capable of delivering a bioactive transforming growth factor beta to drive regenerative events.