Toward optimal tissue sealants for neurosurgery: use of a novel hydrogel sealant in a canine durotomy repair model

OBJECTIVE: Watertight dural repairs are difficult to achieve, and cerebrospinal fluid leakage causes complications and extends hospital stays. Therefore, a novel synthetic hydrogel film was evaluated as an adjunct to dural closure in a canine model. METHODS: The self-polymerizing, absorbable, and biocompatible hydrogel was sprayed onto tissue and formed a flexible, adherent sealant. A 2-cm incision of cranial dura and arachnoid was created in 26 adult dogs and loosely repaired. Hydrogel was applied over the 2-mm dural gap in 13 dogs; 13 control dogs received no hydrogel application. RESULTS: All dogs remained neurologically intact. Valsalva tests conducted at 1, 4, 7, and 56 days were associated with mean leakage pressures (+/- standard error of the mean) of 5 +/- 0, 5 +/- 0, 7 +/- 2, and 13 +/- 8 cm H(2)O in the controls and of 53 +/- 2, 37 +/- 11, 42 +/- 6, and 48 +/- 4 in the treated animals (P = 0.001, 0.053, 0.010, 0.035, respectively, at each time point; one-tailed t test). Histopathological analysis revealed minimal changes. CONCLUSION: The hydrogel-treated animals exhibited normal progression of dural healing, no dural adhesions, and no underlying effects on the brain. Although dural healing progressed normally, the control animals displayed marked peridural adhesions. The results of this in vivo study suggest that hydrogels, such as that used here, may significantly decrease cerebrospinal fluid leakage, thereby increasing the safety and effectiveness of dural closure in patients and facilitating surgical reexploration.     

Intestinal lengthening in an innovative rodent surgical model

PurposeCurrent animal models of mechanical lengthening separate intestinal segments from enteric continuity. Such models are difficult to use for repeated lengthening procedures and result in intestinal tissue loss during restoration into continuity. We sought to create a novel surgical model to allow multiple lengthening procedures for the purpose of maximizing the net increase in tissue after intestinal lengthening.MethodsA Roux-en-y jejunojejunostomy with a 6-cm blind-ended Roux limb was created in the proximal jejunum of rats. Encapsulated 1-cm polycaprolactone springs were placed into the closed end of the roux limb and secured with a vessel loop. After 4 weeks, lengthened segments and normal jejunum were retrieved for histologic analysis.ResultsJejunal segments were lengthened from 1.0 cm to 3.0 cm. Lengthened segments had increased smooth muscle thickness, fewer submucosal ganglia, and similar numbers of myenteric ganglia compared to normal intestine. When compared to normal jejunal mucosa, lengthened segments demonstrated unchanged villus height and increased crypt depth.ConclusionsWe created an innovative surgical model for intestinal lengthening and successfully lengthened jejunal segments with a degradable spring. The Roux-en-y model may allow the use of a degradable spring for the treatment of short bowel syndrome.     

Robotic microsurgical vasovasostomy and vasoepididymostomy: a prospective randomized study in a rat model

PURPOSE: Microsurgical vasovasostomy and vasoepididymostomy remain technically challenging procedures. Refinements in technique have continually improved patency and pregnancy rates for the 2 procedures in experienced hands. Advances in surgical robotics produced the Da Vinci robot (Intuitive Surgical, Inc., Sunnyvale, California) with motion reduction and no tremor, features that may improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using the Da Vinci robot in rats. MATERIALS AND METHODS: A total of 24 adult male Wistar rats underwent vasectomy through a midline abdominal incision. Two weeks later the animals were randomized to microsurgical multilayer vasovasostomy, longitudinal vasoepididymostomy or robotic vasovasostomy and vasoepididymostomy groups. Outcomes measured included surgical time, complications, patency and sperm granuloma formation at 9 weeks. RESULTS: Animals were sacrificed 9 weeks after microsurgery. There were no significant differences in complications among the groups. Robotic vasovasostomy was significantly faster than the conventional microsurgical technique (68.5 vs 102.5 minutes, p = 0.002). The robotic and microsurgical vasoepididymostomy groups did not differ significantly in time. Patency rates were 100% for the robotic vasovasostomy and vasoepididymostomy groups, and 90% in the microsurgical vasovasostomy and vasoepididymostomy groups. These differences were not significant. Sperm granulomas were found in 70% of microsurgical vasovasostomy anastomoses and 27% of robotic vasovasostomy anastomoses (p = 0.001). No significant difference in the sperm granuloma rate was found between the robotic or microsurgical vasoepididymostomy groups (42% and 50%, respectively, p = 0.37). CONCLUSIONS: To our knowledge we report the first randomized prospective study using the Da Vinci robot for microsurgery. We believe that the improved stability and motion reduction during microsurgical suturing with the robot helped achieve excellent patency rates for vasovasostomy and vasoepididymostomy. The robot may also allow experienced microsurgeons to perform microsurgical procedures in patients at remote locations where no experienced microsurgeons are available.     

The use of surgical sealants in the repair of dural tears during non-instrumented spinal surgery

Purpose

To compare the success in repair of dural tears (DTs) using two different surgical sealants in non-instrumented lumbar spinal surgery and evaluate the incidence of associated short- and long-term complications.

Methods

Twenty-three patients undergoing non-instrumented spinal surgery with intraoperative DTs were included both retrospectively and prospectively in this study. External signs of CSF leakage, neurological deficits, and infection-related complications were investigated postoperatively. The persistence of low-back pain was also evaluated and postoperative MRI was performed in all patients. DTs were repaired intraoperatively using suture with or without a dural patch. Eleven patients received an application of fibrin glue (Tissucol^®; Baxter, Inc., IL, USA) and 12 patients received an application of bovine serum albumin glutaraldehyde surgical adhesive (BioGlue^® Surgical Adhesive; CryoLife, GA, USA). These patients were followed up at 3 months and 1 year postoperatively.

Results

Successful intraoperative DT repair was obtained in all cases. Three patients in the Tissucol group presented with CSF leakage in the early postoperative period. There were no complications observed in the patients treated with BioGlue. At 3-month follow-up, no incidences of neurological or infection-related complications were observed in either group. There was no statistically significant difference in VAS between the two treatment groups.

Conclusions

Intraoperative DTs can be easily repaired by many effective techniques. However, in our experience, the use of BioGlue is an effective adjunct to immediate dural repair, being comparable in terms of efficacy and safety to the use of fibrin glue, potentially decreasing the incidence of associated short- and long-term complications.     

The use of tissue sealants to deliver antibiotics to an orthopaedic surgical site with a titanium implant

BackgroundOrthopaedic surgery is associated with unacceptable infection rates that respond poorly to systemic antibiotics. The objective of this study was to use an animal model for orthopaedic implant infection to examine the ability of a new-generation fibrin tissue sealant to effectively deliver antibiotics to the surgical site.MethodsThe antibiotics cefazolin, fusidic acid or 5-fluorouracil were blended into Vitagel? tissue sealant. The release rate of the drugs was measured using HPLC methods and bioactivity was measured by the zone of inhibition method with pathogenic Staphylococcus aureus. The antibiotic activity of the drug-loaded sealant was then tested in rats using infected orthopaedic surgical sites (titanium clip on spine). Efficacy was evaluated by residual bacterial counts on clips, clinical observations of infection, and histological findings.ResultsThe drugs were released in a controlled manner over 2–4 days. All three antibiotics demonstrated strong antibacterial activity when released from the sealants. None of the treated animals demonstrated systemic illness. Post mortem dissection revealed a well-encapsulated abscess surrounding the titanium clip with erosion of the bony process. Using an inoculum of 1–5 × 10³ CFU, treatment with antibiotic-loaded fibrin sealant demonstrated reduced infective swelling and reduced bacterial counts on surgical clip swabs compared to control rats or rats treated with antibiotic only. This model allowed for almost 100 % infectivity with a 0 % mortality rate due to infection, mimicking the clinical features of human implant infection.ConclusionThe results support the use of antibiotic-loaded commercially available fibrin sealants to prevent infection after implant surgery.     

Fibrin sealants in supporting surgical techniques: strength in factor XIII

Factor XIII has a well-established role in natural coagulation and clot stabilization. It is often added back to fibrin sealants that are used in a wide range of surgical settings to achieve successful hemostasis, tissue adhesion and wound healing. Factor XIII is the final enzyme to be activated in the blood coagulation cascade. It plays an important role in maintaining the balance between coagulation and fibrinolysis. Factor XIII facilitates the formation of covalent cross-links within the fibrin network, forming a loose mesh after activation by thrombin. It adds significant resilience to fibrin clots, augmenting strength by as much as 5-fold. Both fibrin cross-linking and the factor XIII-catalyzed ligation of the fibrinolysis inhibitor alpha(2)-antiplasmin to the fibrin clot contribute to the increased proteolytic resistance of factor XIII-stabilized clots. Preclinical studies indicate that the inclusion of factor XIII in fibrin sealants used for vascular grafting significantly reduces suture-hole blood loss. This has important implications for the successful control of bleeding in comparable clinical situations. The advantages of factor XIII stabilized clots (increased strength, resistance to proteolysis, promotion of wound healing) suggest that the presence of factor XIII in fibrin sealants may optimize their performance in the clinical setting. The aim of this paper is to review preclinical data that provide evidence for a potentially positive role for factor XIII in fibrin sealants.     

Fibrin sealants in supporting surgical techniques: The importance of individual components

Fibrin sealants have many different uses across a broad range of surgeries, where they have proved successful in controlling bleeding, providing suture support and tissue sealing. The action of all fibrin sealants depends on the thrombin-catalyzed formation of a fibrin clot. However, neither the purity nor the concentration of the main components of fibrin sealants (thrombin and fibrinogen) is uniform across all commercial products and this will affect performance. In addition, the optional inclusion of other components such as factor XIII and antiproteolytic inhibitors may also influence the quality of clot formation. Properties that vary among different fibrin sealants, such as the clotting rate, viscosity, adhesiveness, clot strength and resistance to proteolysis, are all-important considerations for the surgeon. The application of fibrin sealants in a very wide spectrum of surgical procedures means that some fibrin sealants may be more suitable for a particular procedure than others. One of the advantages of commercial fibrin sealants is that the high level of quality control ensures that their composition is extremely consistent between batches. On the other hand, blood bank-derived fibrin sealants may vary in their composition from one preparation to the next and hence be less predictable in their performance. This paper discusses how individual components contribute to the overall performance of fibrin sealants, thereby providing to the surgeon the necessary information to select the optimal fibrin sealant for a specific procedure.     

Fetal surgical repair with placenta-derived mesenchymal stromal cell engineered patch in a rodent model of myelomeningocele

Purpose

The purpose of this study is to determine the feasibility of fetal surgical repair of myelomeningocele (MMC) in a rodent model using human placental mesenchymal stromal cells (PMSCs) seeded onto extracellular matrix (ECM) and to characterize the resulting changes in spinal cord tissue.

Study of subchondral bone adaptations in a rodent surgical model of OA using in vivo micro-computed tomography

OBJECTIVE: To non-invasively investigate the changes to epiphyseal bone occurring in a longitudinal pre-clinical model of osteoarthritis (OA) using in vivo micro-computed tomography (micro-CT). DESIGN: In vivo micro-CT images were acquired using a bench-top micro-CT scanner, which produces three-dimensional data with isotropic voxel spacing of 0.046 mm. Male rodents were scanned prior to surgical destabilization, consisting of anterior cruciate ligament transection and partial medial menisectomy (ACLX). Subsequent scans were performed every 4 weeks post-ACLX, for up to 5 months. Volumetric bone mineral density (vBMD) was measured in specific, anatomically segmented regions within each image. The ACLX rodent data were compared with the contralateral non-operated hind limb of the same animal, as well as a sham-operated group (SHAM) of animals, for each time point. End-point histology compared changes to cartilage and bone between the ACLX and control animals. RESULTS: The micro-CT protocol produced sufficient spatial resolution and signal-to-noise ratio (SNR=19) to quantify subchondral bone pathology, with an acceptable entrance exposure to radiation (0.36 Gy). Significantly lower vBMD was measured in the ACLX group, vs SHAM rodents, at 1, 4, and 5 months post-surgery (P<0.05). Qualitative observations of ACLX joints revealed significant loss of cartilage, subchondral bone cysts, and calcification of tendon similar to changes found in humans. CONCLUSIONS: This study demonstrates in vivo micro-CT as an effective method for investigating the development of rodent knee OA longitudinally. This method can be applied, in future pre-clinical trials, to non-destructively monitor the efficacy of pharmacological interventions.     

Sutureless vasovasostomy: new technique using experimental microclip in rat model.

Standard microscopic suture vasovasostomy represents a challenge to many urologists. It is technically demanding, and requires two to five hours of operative time. In an attempt to decrease the technical demand and the time requirement, we report the use of a microvascular anastomotic clip and compare this microclip to a standard eight-suture nonstented technique and a six-suture stented technique using a hollow, absorbable 0.5-mm polyglycolic acid stent. The control group with suture required an average of 38.5 minutes per anastomosis for the nonstented group and twenty-two minutes for the stented group. The clip group required 7.6 minutes for the unstented vasovasostomy and 6.5 minutes for the stented vasovasostomy. We obtained a 91 percent patency rate for the stented clip group and 100 percent patency for the unstented clip group. In a rat vasovasostomy, the operative time as well as the inherent technical demand were significantly reduced.     

Autotransplantation of adrenal cortical tissue: a rodent model

Autotransplantation of human adrenal tissue has been attempted often, but results have been difficult to evaluate and success has been infrequent. Factors that may affect success include: volume of transplanted tissue, recipient site, inclusion of cortical capsule with the autograft, systemic or local growth factors, and the timing of evaluation. We have evaluated a model of autotransplantation in rats that will permit examination of these factors. Male Sprague-Dawley rats were assigned to (1) bilateral adrenalectomy (ADX), (2) bilateral adrenalectomy with immediate autotransplantation to a flank muscle pocket of one third of a single adrenal gland with its capsule attached (TX), or (3) sham operation. Animals were provided with 0.9% saline solution ad lib. At 2, 4, 6, and 12 weeks after surgery animals were stressed by brief exposure to ether and 15 minutes later had blood collected for determination of corticosterone concentration (C). ADX animals consistently weighed less than either TX or sham-operated animals; weights of sham-operated and TX animals were similar. Sham-operated animals uniformly had C levels higher than ADX or TX animals. At 2 and 4 weeks after surgery, C was similar in ADX and TX; but at 6 and 12 weeks, TX animals had higher values than had ADX animals. With this model, graft function can be demonstrated at 2 weeks by comparing body weight and at 6 weeks by comparing postether levels of C in TX animals to ADX animals. ADX animals can be maintained without steroid replacement on a regular diet with 0.9% saline solution ad lib. This model will permit examination of technical and physiologic influences on transplant success with both fresh and cryopreserved tissue and may lend itself to radionuclide or nuclear magnetic resonance assessment of graft function.     

Toward a common language: surgical wound bed preparation and debridement

Wound management encompasses a number of disciplines. As new concepts and innovative technologies develop within this exciting field, it is important to share them in spite of the divergence of clinical perspectives between the expert disciplines. One such divergence exists between surgeons and nonsurgical wound specialists. As a result, there is a need to develop a common language between these two groups. How can we develop a common language that unites surgical expertise within medical wound management? One route may be through the principles of wound bed preparation, which we believe have great potential for the communication of effective surgical techniques. Another is through sharing our concepts of surgical debridement as it is applied to different wounds by a variety of surgical disciplines. In this monograph, we try to bring these two themes together. We discuss how wound bed preparation has added to our understanding of the pathophysiology of the nonhealing wound and has provided us with some general clinical concepts. We discuss what role debridement, and then specifically surgical debridement, has to play within wound bed preparation, before analyzing the importance of surgical debridement in tissue preservation and the control of infection. We finally look at ongoing work that examines the cost of various surgical debridement techniques. We will also review a new hydrosurgery system (VERSAJET^®, Smith and Nephew, Hull, UK), which we believe has an important role to play in the surgical preparation of the wound. We also expect that this paper will remind our medical colleagues about the critical role played by surgery in wound management.