Assessment of Commercial Off-the-Shelf Tissue Adhesives for Sealing Military-Relevant Corneal Perforation Injuries.

INTRODUCTION: Open-globe ocular injuries have increased in frequency in recent combat operations due to increased use of explosive weaponry. Unfortunately, open-globe injuries have one of the worst visual outcomes for the injured warfighter, often resulting in permanent loss of vision. To improve visual recovery, injuries need to be stabilized quickly following trauma, in order to restore intraocular pressure and create a watertight seal. Here, we assess four off-the-shelf (OTS), commercially available tissue adhesives for their ability to seal military-relevant corneal perforation injuries (CPIs). MATERIALS AND METHODS: Adhesives were assessed using an anterior segment inflation platform and a previously developed high-speed benchtop corneal puncture model, to create injuries in porcine eyes. After injury, adhesives were applied and injury stabilization was assessed by measuring outflow rate, ocular compliance, and burst pressure, followed by histological analysis. RESULTS: Tegaderm dressings and Dermabond skin adhesive most successfully sealed injuries in preliminary testing. Across a range of injury sizes and shapes, Tegaderm performed well in smaller injury sizes, less than 2 mm in diameter, but inadequately sealed large or complex injuries. Dermabond created a watertight seal capable of maintaining ocular tissue at physiological intraocular pressure for almost all injury shapes and sizes. However, application of the adhesive was inconsistent. Histologically, after removal of the Dermabond skin adhesive, the corneal epithelium was removed and oftentimes the epithelium surface penetrated into the wound and was adhered to inner stromal tissue. CONCLUSIONS: Dermabond can stabilize a wide range of CPIs; however, application is variable, which may adversely impact the corneal tissue. Without addressing these limitations, no OTS adhesive tested herein can be directly translated to CPIs. This highlights the need for development of a biomaterial product to stabilize these injuries without causing ocular damage upon removal, thus improving the poor vision prognosis for the injured warfighter.

Surgical applications of intracorporal tissue adhesive agents: current evidence and future development.

Introduction: Traditional mechanical closure techniques pose many challenges including the risk of infection, tissue reaction, and injury to both patients and clinicians. There is an urgent need to develop tissue adhesive agents to reform closure technique. This review examined a variety of tissue adhesive agents available in the market in an attempt to gain a better understanding of intracorporal tissue adhesive agents as medical devices.Areas covered: Fundamental principles and clinical determinants of the tissue adhesives were summarized. The available tissue adhesives for intracorporal use and their relevant clinical evidence were then presented. Lastly, the perspective of future development for intracorporal tissue adhesive were discussed. Clinical evidence shows current agents are efficacious as adjunctive measures to mechanical closure and these agents have been trialed outside of clinical indications with varied results.Expert opinion: Despite some advancements in the development of tissue adhesives, there is still a demand to develop novel technologies in order to address unmet clinical needs, including low tensile strength in wet conditions, non-controllable polimerization and sub-optimal biocompatibility. Research trends focus on producing novel adhesive agents to remit these challenges. Examples include the development of biomimetic adhesives, externally activated adhesives, and multiple crosslinking strategies. Economic feasibility and biosafety are limiting factors for clinical implementation.

Exploring the mucoadhesive behavior of sucrose acetate isobutyrate: a novel excipient for oral delivery of biopharmaceuticals.

Oral drug delivery is an attractive noninvasive alternative to injectables. However, oral delivery of biopharmaceuticals is highly challenging due to low stability during transit in the gastrointestinal tract (GIT), resulting in low systemic bioavailability. Thus, novel formulation strategies are essential to overcome this challenge. An interesting approach is increasing retention in the GIT by utilizing mucoadhesive biomaterials as excipients. Here, we explored the potential of the GRAS excipient sucrose acetate isobutyrate (SAIB) to obtain mucoadhesion in vivo. Mucoadhesive properties of a 90% SAIB/10% EtOH (w/w) drug delivery system (DDS) were assessed using a biosimilar mucus model and evaluation of rheological behavior after immersion in biosimilar intestinal fluid. To ease readability of this manuscript, we will refer to this as SAIB DDS. The effect of SAIB DDS on cell viability and epithelial membrane integrity was tested in vitro prior to in vivo studies that were conducted using SPECT/CT imaging in rats. When combining SAIB DDS with biosimilar mucus, increased viscosity was observed due to secondary interactions between biosimilar mucus and sucrose ester predicting considerable mucoadhesion. Mucoadhesion was confirmed in vivo, as radiolabeled insulin entrapped in SAIB DDS, remained in the small intestine for up to 22 h after administration. Moreover, the integrity of the system was investigated using the dynamic gastric model under conditions simulating the chemical composition of stomach fluid and physical shear stress in the antrum under fasted conditions. In conclusion, SAIB is an interesting and safe biomaterial to promote high mucoadhesion in the GIT after oral administration.

Fibrin tissue sealant and minor skin grafts in burn surgery: A systematic review and meta-analysis.

BACKGROUND: The indications for use of fibrin glue in skin grafting burn patients remains understudied. The purpose of this study is to review the efficacy of fibrin tissue sealant in skin graft adherence, establish guidelines for use of fibrin tissue sealant, and review the cost effectiveness of fibrin glue. METHODS: Publications with the following criteria were included: comparative human studies, autologous skin grafts, and autologous or commercial fibrin sealant. Outcomes assessed included evidence of engraftment, wound closure, rates of hematoma/seroma, graft loss and infection. Meta-analysis obtained pooled odds ratios for outcomes of interest. Cost analysis was performed using data available in the literature. RESULTS: 7 studies and 751 interventions (fibrin) and controls (staples) were included in the final analysis. 67.6% grafts with fibrin were 100% adherent by one week, vs. 55.5% (OR 1.45, p = 0.086). Complete wound closure by one month was 80.2% with fibrin, vs. 73.3% (OR 1.34, p = 0.187). Hematoma/seroma occurred 38.2% with fibrin, vs. 64.7% (OR 0.487, p = 0.122). Graft loss was higher in the control group, 21% vs. 12.6% (OR 0.891, p = 0.604). Average cost of fibrin glue was $50 per ml, and averaged costs of stapler and staple remover was $30 USD ($10-50). CONCLUSION: Fibrin glue is as effective as staples for adhering skin grafts, and trends towards lower rates of hematoma/seroma. In topographically complex regions, fibrin glue may be a better choice for adherence of skin grafts.

Prospective randomised study to evaluate the use of DERMABOND ProPen (2-octylcyanoacrylate) in the closure of abdominal wounds versus closure with skin staples in patients undergoing elective colectomy.

BACKGROUND: Topical 2-octylcyanoacrylate tissue (OCA) adhesive has been used as an alternative to close wounds with a comparable cosmetic outcome. The use of 2-OCA in the closure of abdominal laparotomy wounds has not been thoroughly evaluated. Our aim was to compare 2-OCA with conventional skin stapling devices in colorectal surgery. METHODS: A prospective randomised study was conducted in which 74 consecutive patients above the age of 21 undergoing open elective colectomies for benign or malignant indications were allocated to skin closure with 2-OCA or skin staples. Cosmetic outcome as assessed with the Hollander Cosmesis Scale with a single assessor, complication rates, and patient satisfaction were recorded at discharge (4-10POD) 2 weeks after discharge and then at 3 months. RESULTS: Of the 74 patients, 38 were randomised to skin staples and 36 to 2-OCA. There was no significant difference in cosmetic outcomes between the two groups as assessed with a visual analogue scale or the Hollander Cosmesis Scale but showed a trend to better cosmetic outcomes in the 2-OCA group. Patient satisfaction scores were higher but did not reach statistical significance. The time taken to close a wound with 2-OCA was significantly longer than with skin staples. There was no statistical difference in rates of wound infection. CONCLUSION: 2-OCA is a safe and effective means of skin closure in patients undergoing elective colectomies with a good and at least equivalent outcome to traditional methods of closure.

Phototoxicity is not associated with photochemical tissue bonding of skin.

BACKGROUND AND OBJECTIVE: We have developed a light-activated method called photochemical tissue bonding (PTB) for closing wounds using green light and a photosensitizing dye (Rose Bengal-RB) to initiate photochemical crosslinking of wound surface proteins. These studies were designed to determine whether RB causes phototoxicity during closure of skin incisions with PTB. STUDY DESIGN/MATERIALS AND METHODS: RB phototoxicity was evaluated after sealing incisions in porcine skin ex vivo and rabbit skin in vivo using PTB (1 mM RB, 100 J/cm(2), 532 nm, 0.3 or 0.5 W/cm(2).) Dead cells were identified by pyknotic nuclei and eosinophilic cytoplasm on H&E-stained sections. The influence on RB phototoxicity of penetration of RB into the wound wall (by confocal microscopy), RB concentration in the tissue (by extraction), and fluence of 532 nm reaching depths in skin (calculated from skin optical properties) were investigated. RESULTS: No significant differences were found in the percent dead cells in PTB-treated and control incisions in porcine skin at 24 hours or in rabbit skin at 2 hours and 3 and 7 days after surgery. RB was retained in a approximately 100 microm wide band next to the wound wall. The mean RB concentration within this band was 0.42+/-0.03 mM. Monte Carlo modeling of light distribution indicated that the fluence rate decreased from the subsurface peak to 0.5 W/cm(2) in the mid-dermis (approximately 350 microm.) In vitro RB phototoxicity to dermal fibroblasts yielded an LD(50) of 0.50+/-0.09 J/cm(2) when the cells contained 0.46 mM RB. CONCLUSIONS: PTB does not cause phototoxicity when used to repair skin wounds even though the RB concentration and 532 nm fluence in the mid-dermis during PTB are much greater than the LD(50) for RB phototoxicity in vitro. These results indicate that phototoxicity is not a concern when using PTB for tissue repair.

Assessment of bioactive and bio-adhesive therapies to enhance stem cell attachment to root surface dentine.

AIM: To compare bioactive and bio-adhesive therapies to enhance stem cell attachment to the root dentine of human teeth. METHODOLOGY: Dentine slabs (n = 72) were cut from the lower 3 mm of the roots of extracted human permanent teeth. The root dentine slabs were untreated, or coated with bio-adhesive, or human recombinant transforming growth factor-beta1 (hrTGF-B1), or human recombinant bone morphogenic protein-2 (hrBMP-2). The dentine slabs were placed with the root surface in contact with confluent periodontal stem cell (PSC) cultures using aseptic techniques. The cells and dentine slabs were submerged in culture media for 4, 24 and 72 h. The specimens were fixed in formalin, dehydrated and processed for scanning electron microscopy (SEM). RESULTS: SEM micrographs at x2000 magnification revealed PSC extensive adherence to root dentine for all of the bio-adhesive and bioactive treatments. The addition of bioactive molecules did not improve PSC attachment. Few cells attached to the negative control treatments. CONCLUSIONS: Bio-adhesive and bioactive growth factors were not needed to promote PSC attachment to the root dentine of human teeth, because it already appears to have good natural properties to promote PSC attachment. This suggests PSC can be used for the clinical replantation of avulsed teeth without the need for bio-adhesive and bioactive treatments.

Assessment of the thrombogenic effect of fibrin sealant dressing in a vascular surgery model in rabbits.

This study's objective was to investigate the potential thrombogenic effects of thrombin-containing fibrin sealant dressings (FSD) in a vascular repair model. Oval-shaped pieces of the rabbit abdominal aorta and vena cava were excised, the injuries were repaired with FSD, and animals were allowed to recover. Thrombus formation was examined by (1) an infusion of indium-labeled platelets into the rabbits following FSD application and estimation of total number of platelets attached to the wounds at 2, 4, and 6 h later (short-term effect, n = 12); and by (2) morphological and histological examinations of the vessels and dressings on days 1, 3, and 7 after repair operation in another group of rabbits (long-term effect, n = 12). Application of FSD sealed the vascular injures and produced immediate hemostasis that was stable up to 1 week. The highest numbers of platelets (both native and labeled) adhered to the arterial and venous repair sites were 6.5 x 106 and 4.4 x 107, respectively, 6 h after operation. The adhered platelets, however, did not form a visible and clinically significant thrombus. In long-term experiments, no evidence of thrombus was found in the lumens of the repaired vessels or on the dressings, and no microthrombi were detected histologically in other tissues at any time point. Although vena caval injuries showed signs of healing at day 7 postoperatively, the aortic wounds expanded progressively (pseudoaneurysm) and were prone to rupture at later times. Thus, direct exposure of FSD does not cause intravascular thrombosis or thrombotic events in rabbits. The dressing appears to be safe and effective for short-term repair of vascular injuries. It may also allow healing of minor venous defects, but cannot replace conventional surgical techniques (suturing) for permanent repair of arterial damages.

Safety and efficacy of currently available fibrin tissue adhesives.

PURPOSE: The purpose of this study is to review preparation methods, bonding power, preparation time, and costs associated with currently available autologous and homologous fibrin tissue adhesive preparations. METHODS: Two autologous fibrin tissue adhesive preparations (AFTA-A and AFTA-E), a single-donor homologous preparation, and 2 multiple-donor pooled homologous fibrin tissue adhesives, Vi-Guard and Tisseel, were evaluated and compared in relation to bonding power, preparation time, cost, bicompatibility, and biodegradability. RESULTS: Vi-Guard and Tisseel showed significantly greater bonding strengths than their single-donor counterparts. AFTA-C offers the quickest preparation time. All preparations were found to be similar in biocompatibility and biodegradability in soft tissue tests. Histology showed no infection or tissue reaction from adhesive exposure in any of the preparations. CONCLUSION: The optimal choice of a fibrin tissue adhesive is determined by the particular clinical indication. Currently available fibrin tissue adhesives vary appreciably in their bonding strength, cost, level of exposure risk, and preparation methods and times. Autologous preparations, which offer optimal safety, lack the strength and availability characteristics found with the multiple-donor preparations.

Female sterilization in current clinical practice.

PIP: The sterilization procedures most widely employed in the U.S. and newer methods which hold promise are reviewed. Abdominal Pomeroy tubal ligation, the most commonly used method, is usually done within 48 hours after delivery. A small incision ate. A knuckle of each fallopian tube is ligated and then resected. The cut ends of the tubes retract from each other when the suture absorbs and become sealed by a peritoneal covering. Local or general anesthesia may be used. nimally prolonged. Postoperative morbidity is 2-4% and a reported failure rate of less than 1%. Following Caesarean section, the Irving procedure is used most often. In this method the tubes are double ligated and bedded in the uterine musculature and the distal ends are buried beneath the broad ligament. As an interval procedure, the Pomeroy method or fimbriectomy may be done using the vaginal approach. Pelvic erus prevent this method from being used. igation is combined with first trimester abortion the morbidity is increased. Laparoscopy, culdoscopy, and hysteroscopy are recent advances. To use these methods, special training is needed and the required equipment is 2-puncture method and general anesthesia are preferred. An alternative to coagulation of the tubes is the application of clips. The new spring-loaded clips appear to be most promising. With culdoscopy each tube ligated, cut, and returned to its normal position. Tantalum clips may be used to occlude the tubes. This operation requires a good deal of time to learn but can be done as an outpatient procedure. Pelvic cult. Postoperative infection may follow in 2-10% of cases. In using the hysteroscopic technique, after dilatation of the cervix the hysteroscopic sleeve is introduced and the uterine cavity A cautery probe is introduced into each uterotubal junction and electrocoagulation done. Scar tissue later blocks the tubes. The equipment is expensive and special training is re are numerous contraindications to this method. Hysterectomy for sterilization is a drastic measure. Quinacrine hydrochloride instilled into the uterine cavity is 90% effective in preventing pregnancy. Other sclerosing agents cements, as gelatin-resorcinol-formilin have been used to promote tissue ingrowth to seal fallopian tubes. The choice of procedure for each woman varies according to her life situation and specific needs. seem to offer any advantages over the postpartum Pomeroy tubal ligation. Hysterotomy and tubal ligation are a combination which sometimes seems favorable. Counseling for sterilization is important and complications. problems.^ieng