Liquid antiadhesive agents for intraperitoneal hernia repair procedures: Artiss® compared to CoSeal® and Adept® in an IPOM rat model.

BACKGROUND: Adhesion formation remains an important issue in hernia surgery. Liquid agents were developed for easy and versatile application, especially in laparoscopy. The aim of this study was to compare the antiadhesive effect of fibrin sealant (FS, Artiss®), Icodextrin (ID, Adept®) and Polyethylene glycol (PEG, CoSeal®) alone and in combination and to evaluate the resulting effect on tissue integration of the mesh. METHODS: A total of 56 Sprague-Dawley rats were operated in open IPOM technique. A middleweight polypropylene mesh of 2 × 2 cm size was implanted and covered with 1: FS, 2: ID, 3: PEG, 4: FS + ID, 5: FS + PEG, 6: PEG + ID, 7: control group, uncovered mesh (n = 8 per treatment/control). Observation period was 30 days. Macroscopic and histological evaluation was performed. RESULTS: Severe adhesions were found in group 2 (ID), group 6 (PEG + ID) and the controls. Best results were achieved with FS alone or FS + ID. Mesh integration in the treatment groups was reduced in comparison with the control group. This is a new finding possibly relevant for the outcome of intraperitoneal mesh repair. Group 6 (PEG + ID) showed an impairment of tissue integration with <50 % of the mesh surface in seven samples. CONCLUSION: FS alone and in combination with ID yielded excellent adhesion prevention. ID alone did not show significant adhesion prevention after 30 days. Tissue integration of FS-covered meshes was superior to ID or PEG alone or combined. PEG did show adhesion prevention comparable to FS but evoked impaired tissue integration. So Artiss® is among the most potent antiadhesive agents in IPOM repair.

A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: results of a multicentre analysis.

New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines.

Fabrication of silk mesh with enhanced cytocompatibility: preliminary in vitro investigation toward cell-based therapy for hernia repair.

Recent studies have demonstrated that combining cells with meshes prior to implantation successfully enhanced hernia repair. The idea is to create a biologic coating surrounding the mesh with autologous cells, before transplantation into the patient. However, due to the lack of a prompt and robust cell adhesion to the meshes, extensive in vitro cultivation is required to obtain a homogenous cell layer covering the mesh. In this context, the objective of this publication is to manufacture meshes made of silk fibres and to enhance the cytoadhesion and cytocompatibility of the biomaterial by surface immobilization of a pro-adhesive wheat germ agglutinin (lectin WGA). We first investigated the affinity between the glycoprotein WGA and cells, in solution and then after covalent immobilization of WGA on silk films. Then, we manufactured meshes made of silk fibres, tailored them with WGA grafting and finally evaluated the cytocompatibility and the inflammatory response of silk and silk-lectin meshes compared to common polypropylene mesh, using fibroblasts and peripheral blood mononuclear cells, respectively. The in vitro experiments revealed that the cytocompatibility of silk can be enhanced by surface immobilization with lectin WGA without exhibiting negative response in terms of pro-inflammatory reaction. Grafting lectin to silk meshes could bring advantages to facilitate cell-coating of meshes prior to implantation, which is an imperative prerequisite for abdominal wall tissue regeneration using cell-based therapy.

The impact of atraumatic fibrin sealant vs. staple mesh fixation in TAPP hernia repair on chronic pain and quality of life: results of a randomized controlled study.

BACKGROUND: Mesh reinforcement has become the standard of care in the open and laparoscopic repair of inguinal hernia. Chronic pain after inguinal hernia repair is often due to nerve injury by penetrating mesh fixation devices such as staples (ST), tacks, or sutures. In several studies on hernioplasty, atraumatic mesh fixation with fibrin sealant (FS) proved to be efficient in terms of fixation strength and elasticity. Unfortunately, most of these studies did not provide a standardized follow-up and assessment of the development of chronic pain (CP) and the quality of life (QoL). Therefore, a randomized controlled trial comparing CP and QoL after FS fixation of mesh with ST in transabdominal preperitoneal hernioplasty (TAPP) was performed at our department. The primary end point of our study was to assess the patient outcome by using a visual analog scale (VAS) and the short form 36 (SF-36). The evaluation of recurrence rates was the secondary aim. METHODS: According to the randomization, a macroporous mesh (TiMESH(®)) was fixed in group A (44 patients with 54 inguinal hernias) with FS (TISSEEL) or in group B (45 patients with 56 inguinal hernias) with ST (EMS(®) Stapler). The observation period was 1 year with regular clinical check ups and assessment of VAS and SF-36. RESULTS: Patient characteristics expressed by BMI, ASA scores, and Schumpelick hernia classification were similar in both treatment groups. In each group there was one recurrence within 8 (FS) and 9 months (ST) postsurgery. The mean preoperative pain values scored by VAS were 1.7 (range = 0-7.5) in the FS group and 2.2 (range = 0-6) in the ST group. Postoperative mean VAS scores measured at 1 year postsurgery were 0.4 (range = 0-3) in the FS group and 0.9 (range = 0-7.5) in the ST group. One year postsurgery there was no significant difference between the two groups with respect to the parameter pain in the SF-36 and VAS. CONCLUSION: Fibrin sealant fixation leads to a low rate of hernia recurrence and avoids tissue trauma. ST provide similar results in the hand of the expert but bear inherent risks of complications due to tissue perforation.

Comparison of three separate antiadhesive barriers for intraperitoneal onlay mesh hernia repair in an experimental model.

BACKGROUND: Adhesion formation is a common adverse effect in intraperitoneal onlay mesh (IPOM) surgery. Different methods of adhesion prevention have been developed, including coated meshes and separate antiadhesive barriers (SABs). In this study one type of mesh was tested with different SABs, which were fixed to the sutured mesh using fibrin sealant. The primary aim was to compare adhesion prevention between different SABs. Secondary aims were the assessment of tissue integration and evaluation of SAB fixation with fibrin sealant. METHODS: Thirty-two rats were randomized to one of three treatment groups (SurgiWrap, Prevadh and Seprafilm) or a control group (no SAB). Animals were operated on with an open IPOM technique (8 per group). One macroporous polypropylene mesh per animal (2 × 2 cm) was fixed with four non-absorbable sutures. An antiadhesive barrier of 2·5 × 2·5 cm was fixed with fibrin sealant. After 30 days, adhesion formation, tissue integration, seroma formation, inflammation and vascularization were evaluated macroscopically and by histology. RESULTS: Prevadh and Seprafilm groups showed a significant reduction in adhesion formation compared with the control group. Tissue integration of the mesh was reduced in these groups. Fibrin sealant fixed the SAB to the mesh securely in all groups. CONCLUSION: Prevadh and Seprafilm are potent materials for the reduction of adhesion formation. A potential relationship between effective adhesion prevention and impaired tissue integration of the implant was observed. Fibrin sealant proved an excellent agent for SAB fixation.

Human vital amniotic membrane reduces adhesions in experimental intraperitoneal onlay mesh repair.

BACKGROUND: Various antiadhesive coatings have been proposed for intraperitoneal onlay meshes (IPOM). However, adhesions, mesh infections, and impaired integration remain clinically relevant problems. In this experiment, human vital amniotic membrane (AM) was tested as antiadhesive mesh coating. Vital AM complies with clinical standards of product safety. METHODS: In this study, 24 rats were randomized to one control or two treatment groups (n=8). An uncoated polypropylene mesh (Vitamesh) was implanted using open IPOM technique and fixed with four sutures. In the treatment groups, vital AM was attached to Vitamesh by fibrin sealant fixation. The observation period was 7 and 17 days. Vitamesh fixed by suture only served as the control condition (17 days). Adhesion formation, tissue integration, and neovascularization were assessed macroscopically and histologically. RESULTS: All the meshes in the control group elicited severe adhesions. Vital AM was highly efficient in reducing adhesions to mesh and sutures. No foreign body reaction or unfavorable immunologic response to vital AM occurred. Tissue integration and neovascularization of coated meshes were good. Fibrin sealant yielded a reliable fixation. CONCLUSION: Human vital AM was highly effective in reducing adhesions to polypropylene mesh and sutures in experimental IPOM. No adverse effects were detected, and tissue integration of the mesh was good.

Biologic hernia implants in experimental intraperitoneal onlay mesh plasty repair: the impact of proprietary collagen processing methods and fibrin sealant application on tissue integration.

BACKGROUND: Biologic implants have been recommended for reinforcement in routine and challenging hernia repair. However, experimental and clinical studies have reported adverse effects (e.g., slow implant integration and pronounced foreign body reaction). To evaluate the impact of different material processing methods (cross-linking vs. non-cross-linking of collagen) and implant design, four different biologic hernia implants were compared directly in experimental intraperitoneal onlay mesh plasty (IPOM). Tissue integration, shrinkage, and foreign body reaction were primary outcome parameters. METHODS: In this study, 48 Sprague-Dawley rats were randomized to four treatment groups. Open IPOM repair was performed. One peritoneal defect per animal was covered with 2 × 2 cm patches of cross-linked or non-cross-linked implants including CollaMend (n = 12), Peripatch (n = 12), Surgisis (n = 12), and Tutomesh (n = 12). In half of the animals, fibrin sealant was applied for additional fixation and to cover sutures. The observation period was 60 days. The primary outcome parameters were implant integration, shrinkage, and foreign body reaction. Macroscopic and histologic assessments were performed. RESULTS: The integration of implants was insufficient in all the groups. The implants could be detached easily from the underlying tissue, and the penetration of fibroblasts and vessels was limited to the perforations. Foreign body reaction was pronounced with CollaMend and Surgisis, leading to persistent granulomatous inflammation. Shrinkage was excessive with Surgisis, whereas Tutomesh and Peripatch yielded sufficient anti-adhesion and elicited no foreign body reaction. CONCLUSION: At 2 months, cross-linked and non-cross-linked biologic hernia implants were poorly integrated. Cross-linking led to a more pronounced foreign body reaction. Less inflammatory response may reduce local complications, but did not enhance implant integration in this study.

Repopulation of decellularised articular cartilage by laser-based matrix engraving.

BACKGROUND: In spite of advances in the treatment of cartilage defects using cell and scaffold-based therapeutic strategies, the long-term outcome is still not satisfying since clinical scores decline years after treatment. Scaffold materials currently used in clinical settings have shown limitations in providing suitable biomechanical properties and an authentic and protective environment for regenerative cells. To tackle this problem, we developed a scaffold material based on decellularised human articular cartilage. METHODS: Human articular cartilage matrix was engraved using a CO2 laser and treated for decellularisation and glycosaminoglycan removal. Characterisation of the resulting scaffold was performed via mechanical testing, DNA and GAG quantification and in vitro cultivation with adipose-derived stromal cells (ASC). Cell vitality, adhesion and chondrogenic differentiation were assessed. An ectopic, unloaded mouse model was used for the assessment of the in vivo performance of the scaffold in combination with ASC and human as well as bovine chondrocytes. The novel scaffold was compared to a commercial collagen type I/III scaffold. FINDINGS: Crossed line engravings of the matrix allowed for a most regular and ubiquitous distribution of cells and chemical as well as enzymatic matrix treatment was performed to increase cell adhesion. The biomechanical characteristics of this novel scaffold that we term CartiScaff were found to be superior to those of commercially available materials. Neo-tissue was integrated excellently into the scaffold matrix and new collagen fibres were guided by the laser incisions towards a vertical alignment, a typical feature of native cartilage important for nutrition and biomechanics. In an ectopic, unloaded in vivo model, chondrocytes and mesenchymal stromal cells differentiated within the incisions despite the lack of growth factors and load, indicating a strong chondrogenic microenvironment within the scaffold incisions. Cells, most noticeably bone marrow-derived cells, were able to repopulate the empty chondrocyte lacunae inside the scaffold matrix. INTERPRETATION: Due to the better load-bearing, its chondrogenic effect and the ability to guide matrix-deposition, CartiScaff is a promising biomaterial to accelerate rehabilitation and to improve long term clinical success of cartilage defect treatment. FUNDING: Austrian Research Promotion Agency FFG ("CartiScaff" #842455), Lorenz Böhler Fonds (16/13), City of Vienna Competence Team Project Signaltissue (MA23, #18-08).

Pre-clinical evaluation of liposomal gene transfer to improve dermal and epidermal regeneration.

Liposomal gene transfer effectively enhances dermal and epidermal regeneration in burned rodents. To advance this treatment to clinical studies, we investigated the efficacy of liposomal gene transfer in a clinically relevant porcine wound model. Mimicking the clinical scenario, six female Yorkshire pigs (40-50 kg) received up to 12 burns of 50 cm(2) area that were fully excised and covered with skin autograft meshed at 4:1 ratio 24 h post-burn. Animals received control injections (empty liposomes), liposomes (DMRIE-C) containing 1 mg LacZ-cDNA, or liposomes (DMRIE-C) with 1 mg of platelet-derived growth factor (PDGF)-cDNA, or the naked PDGF gene. Serial biopsies were taken from different wound sites at multiple time points up to 12 days post-wounding. Transfection efficacy and transfection rate of LacZ and localization of beta-gal were determined by immunohistochemical and immunofluorescent techniques. RT-PCR and multiplex protein analysis (ELISA) were used to measure levels of growth factor mRNA transcribed and growth factor protein translated. Wound re-epithelialization and graft adhesion was evaluated using planimetric analysis and clinical scores. We found that peak transfection of liposomal beta-galactosidase occurred on day 2, with a fluorescence increase of 154% to baseline (P<0.001). Transfection intensity dropped to 115% above baseline on day 4 (P<0.001) and 109% on day 7. Immunohistochemistry showed a maximum transfection rate of 34% of cells in wound tissue. Gene transfer of liposomal PDGF-cDNA resulted in increased PDGF-mRNA and protein expression on days 2 and 4, and accelerated wound re-epithlialization as well as graft adhesion on day 9 (P<0.05). In this study, we showed that liposomal cDNA gene transfer is possible in a porcine wound model, and by using PDGF-cDNA we further showed that dermal and epidermal regeneration can be improved. These data indicate that liposomal gene transfer can be a new therapeutic approach to improve wound healing in humans.

A comparison of a bovine albumin/glutaraldehyde glue versus fibrin sealant for hernia mesh fixation in experimental onlay and IPOM repair in rats.

BACKGROUND: Research in hernia repair has targeted new atraumatic mesh fixation to reduce major complications such as chronic pain and adhesion formation. The efficacy and safety of two surgical adhesives, viz. Artiss® (FS, fibrin sealant containing 4 IU thrombin) and Bioglue® (AGG, bovine serum albumin/glutaraldehyde glue), were evaluated in this study. Primary study endpoints were tissue integration, dislocation, and adhesion formation. Foreign-body reaction formed the secondary study endpoint. METHODS: Twenty-four polypropylene meshes (VM, Vitamesh®) were randomized to four groups (n = 6): two groups of onlay hernia repair (two meshes per animal) with mesh fixation by FS (O-FS) or by AGG (O-AGG), and two groups of IPOM repair (one mesh per animal) with mesh fixation by four sutures and FS (I-FS) or AGG (I-AGG). Eighteen rats underwent surgery. Follow-up was 30 days. Tissue integration, dislocation, seroma formation, inflammation, adhesion formation, and foreign-body reaction were assessed. RESULTS: Meshes fixed with FS (O-FS, I-FS) showed good tissue integration. No dislocation, seroma formation, or macroscopic signs of inflammation were detectable. Adhesion formation of I-FS was significantly milder compared with I-AGG (P = 0.024). A moderate foreign-body reaction without active inflammation was seen histologically in O-FS and I-FS groups. Samples fixed with AGG (O-AGG, I-AGG) showed extensive scar formation. No dislocation and no seroma formation were observed. All of these samples showed moderate to severe signs of inflammation with abscess formation in the six meshes of O-AGG. Histology underlined these findings. CONCLUSIONS: The fibrin sealant adhesive showed very good overall results of the primary and secondary outcome parameters. FS is a recommendable atraumatic fixation tool for the surgical onlay technique. AGG provides high adhesive strength, but shows low biocompatibility. Persisting active inflammation was seen in both the O-AGG and I-AGG groups, not favoring its use for these indications.

Biphasic calcium phosphate ceramics in small bone defects: potential influence of carrier substances and bone marrow on bone regeneration.

OBJECTIVES: Synthetic calcium phosphate bone substitutes such as hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP) or mixtures are alternatives to autogenous bone grafts. TricOs T((R)) and Collagraft((R)) are resorbable bone substitutes consisting of biphasic calcium phosphate and a bioactive matrix. Both products have a similar HA to beta-TCP ratio, but differ by their matrix. It was the aim of this study to determine the influence of matrix and autologous bone marrow on bone regeneration in a rabbit femoral condyle model. MATERIAL AND METHODS: A critical-sized bicortical channel with a diameter of 4.5 mm was drilled through the femoral condyles in male New Zealand rabbits. Collagraft((R)) with bone marrow harvested from the posterior iliac crest or TricOs T((R)) with and without bone marrow was introduced into the defect. Rabbits were euthanized 8 weeks later. The percentage of newly formed bone was determined by micro-computed tomography. RESULTS: There was no significant difference between bone ingrowth at 8 weeks. Thus, TricOs T((R)) without bone marrow showed similar bone ingrowth as Collagraft((R)) with bone marrow. Furthermore, no increase of bone ingrowth could be achieved by adding bone marrow to TricOs T((R)) in the present setting. CONCLUSION: Both bone substitutes showed similar bone ingrowth in this investigation. Using TricOs T((R)) without bone marrow could avoid donor site morbidity due to harvesting of bone marrow. Further prospective clinical trials will be needed to investigate this approach.

The assessment of quality of life in a trial on lightweight mesh fixation with fibrin sealant in transabdominal preperitoneal hernia repair.

BACKGROUND: Chronic pain is a major concern in open and laparoscopic hernia repair. Study groups have adopted a variety of tools to assess postoperative (postOP) pain and quality of life (QoL). Unfortunately, modifications of existing tests and self-designed questionnaires are common, yielding unvalidated results and making comparison of data difficult. The aim of this study was to assess the QoL in transabdominal preperitoneal mesh repair (TAPP) with fibrin sealant (FS) for lightweight mesh fixation, applying the standardised Short Form 36 (SF36) questionnaire in its unmodified design. The SF36 has already been validated and implemented in a large number of studies. In this trial the physical-health-component summary measure (PHM), summarising the physical health-related scales, served as the primary outcome parameter. MATERIALS AND METHODS: After informed written consent was obtained, TAPP with fibrin mesh sealing was performed in 11 non-selected consecutive patients by a single surgeon. A direct control group (e.g. TAPP with staples) was not enrolled, because a favourable change in the QoL in patients subjected to the mesh sealing approach was the tested hypothesis and not the comparison of techniques. The macroporous mesh (TI-Mesh, GfE, Germany) was fixed with 1 ml of FS (FS, Tisseel, Tissucol, Baxter Biosciences, Austria), and the QoL and pain were assessed preoperatively and 1 year postOP using the SF36 survey and the visual analogue score (VAS). RESULTS: After 12 months, recurrences or complications were observed. The analysis of the unmodifed SF36 revealed a highly significant improvement in the PHM, based on significant changes of all physical-health-related scales. The scale 'social functioning' (SOCIAL), which belongs to the mental-health-related scale, had also significantly improved. The VAS was significantly reduced after 1 year. CONCLUSIONS: Despite a small number of patients (n = 11), a strikingly significant improvement in physical health and reduction of pain was detected with the unmodified SF36 and the VAS 1 year after TAPP repair with fibrin-sealed lightweight meshes. We suggest the use of the unmodified SF36 for QoL in hernia repair in order to assess all aspects of recovery (physical and mental) and to facilitate comparison of data.

Assessment of different screw augmentation techniques and screw designs in osteoporotic spines.

This is an experimental study on human cadaver spines. The objective of this study is to compare the pullout forces between three screw augmentation methods and two different screw designs. Surgical interventions of patients with osteoporosis increase following the epidemiological development. Biomechanically the pedicle provides the strongest screw fixation in healthy bone, whereas in osteoporosis all areas of the vertebra are affected by the disease. This explains the high screw failure rates in those patients. Therefore PMMA augmentation of screws is often mandatory. This study involved investigation of the pullout forces of augmented transpedicular screws in five human lumbar spines (L1-L4). Each spine was treated with four different methods: non-augmented unperforated (solid) screw, perforated screw with vertebroplasty augmentation, solid screw with vertebroplasty augmentation and solid screw with balloon kyphoplasty augmentation. Screws were augmented with Polymethylmethacrylate (PMMA). The pullout forces were measured for each treatment with an Instron testing device. The bone mineral density was measured for each vertebra with Micro-CT. The statistical analysis was performed with a two-sided independent student t test. Forty screws (10 per group and level) were inserted. The vertebroplasty-augmented screws showed a significant higher pullout force (mean 918.5 N, P = 0.001) than control (mean 51 N), the balloon kyphoplasty group did not improve the pullout force significantly (mean 781 N, P > 0.05). However, leakage occurred in some cases treated with perforated screws. All spines showed osteoporosis on Micro-CT. Vertebroplasty-augmented screws, augmentation of perforated screws and balloon kyphoplasty augmented screws show higher pullout resistance than non-augmented screws. Significant higher pullout forces were only reached in the vertebroplasty augmented vertebra. The perforated screw design led to epidural leakage due to the position of the perforation in the screw. The position of the most proximal perforation is critical, depending on screw design and proper insertion depth. Nevertheless, using a properly designed perforated screw will facilitate augmentation and instrumentation in osteoporotic spines.

Infections associated with mesh repairs of abdominal wall hernias: Are antimicrobial biomaterials the longed-for solution?

The incidence of mesh-related infection after abdominal wall hernia repair is low, generally between 1 and 4%; however, worldwide, this corresponds to tens of thousands of difficult cases to treat annually. Adopting best practices in prevention is one of the keys to reduce the incidence of mesh-related infection. Once the infection is established, however, only a limited number of options are available that provides an efficient and successful treatment outcome. Over the past few years, there has been a tremendous amount of research dedicated to the functionalization of prosthetic meshes with antimicrobial properties, with some receiving regulatory approval and are currently available for clinical use. In this context, it is important to review the clinical importance of mesh infection, its risk factors, prophylaxis and pathogenicity. In addition, we give an overview of the main functionalization approaches that have been applied on meshes to confer anti-bacterial protection, the respective benefits and limitations, and finally some relevant future directions.

Cyanoacrylate tissue sealant impairs tissue integration of macroporous mesh in experimental hernia repair.

BACKGROUND: Tissue sealants have been proposed as an alternative to permanent fixation devices in hernia repair with the aim of reducing perforation-associated complications and chronic pain. Sealants can be divided into three main categories: synthetic glues (e.g., cyanoacrylate based), biologic products (e.g., fibrin sealant), and genetically engineered polymer protein glues. The beneficial effects of fibrin sealant have been reported in both experimental and clinical hernia repair. However, data on cyanoacrylate glues for mesh sealing are limited. METHODS: In 20 Sprague-Dawley rats, two hernia defects (1.5 cm in diameter) per animal were created bilaterally in the midline of the abdominal wall. The peritoneum was spared. The lesions were left untreated for 10 days to achieve a chronic condition. Defects then were covered with TI-Mesh xl (2 x 2 cm), which was glued with Glubran-II. The time points of sacrifice were 17 days, 28 days, and 3 months. At autopsy, meshes were biomechanically tested, and histology was performed. RESULTS: Tissue integration of the meshes was impaired at all time points by impenetrable glue plaques. At application sites, the elasticity of the abdominal wall was significantly reduced because of nonresorbed, rigid glue residues. CONCLUSIONS: Mesh fixation by Glubran-II impairs tissue integration, elicits inflammation, and unfavorably alters the biomechanics of macroporous mesh and the abdominal wall.

Biodegradable nanomats produced by electrospinning: expanding multifunctionality and potential for tissue engineering.

With increasing interest in nanotechnology, development of nanofibers (n-fibers) by using the technique of electrospinning is gaining new momentum. Among important potential applications of n-fiber-based structures, scaffolds for tissue-engineering represent an advancing front. Nanoscaffolds (n-scaffolds) are closer to natural extracellular matrix (ECM) and its nanoscale fibrous structure. Although the technique of electrospinning is relatively old, various improvements have been made in the last decades to explore the spinning of submicron fibers from biodegradable polymers and to develop also multifunctional drug-releasing and bioactive scaffolds. Various factors can affect the properties of resulting nanostructures that can be classified into three main categories, namely: (1) Substrate related, (2) Apparatus related, and (3) Environment related factors. Developed n-scaffolds were tested for their cytocompatibility using different cell models and were seeded with cells for to develop tissue engineering constructs. Most importantly, studies have looked at the potential of using n-scaffolds for the development of blood vessels. There is a large area ahead for further applications and development of the field. For instance, multifunctional scaffolds that can be used as controlled delivery system do have a potential and have yet to be investigated for engineering of various tissues. So far, in vivo data on n-scaffolds are scarce, but in future reports are expected to emerge. With the convergence of the fields of nanotechnology, drug release and tissue engineering, new solutions could be found for the current limitations of tissue engineering scaffolds, which may enhance their functionality upon in vivo implantation. In this paper electrospinning process, factors affecting it, used polymers, developed n-scaffolds and their characterization are reviewed with focus on application in tissue engineering.

Nerve regeneration using tubular scaffolds from biodegradable polyurethane.

INTRODUCTION: In severe nerve lesion, nerve defects and in brachial plexus reconstruction, autologous nerve grafting is the golden standard. Although, nerve grafting technique is the best available approach a major disadvantages exists: there is a limited source of autologous nerve grafts. This study presents data on the use of tubular scaffolds with uniaxial pore orientation from experimental biodegradable polyurethanes coated with fibrin sealant to regenerate a 8 mm resected segment of rat sciatic nerve. METHODS: Tubular scaffolds: prepared by extrusion of the polymer solution in DMF into water coagulation bath. The polymer used for the preparation of tubular scaffolds was a biodegradable polyurethane based on hexamethylene diisocyanate, poly(epsilon-caprolactone) and dianhydro-D-sorbitol. EXPERIMENTAL MODEL: Eighteen Sprague Dawley rats underwent mid-thigh sciatic nerve transection and were randomly assigned to two experimental groups with immediate repair: (1) tubular scaffold, (2) 180 degrees rotated sciatic nerve segment (control). Serial functional measurements (toe spread test, placing tests) were performed weekly from 3rd to 12th week after nerve repair. On week 12, electrophysiological assessment was performed. Sciatic nerve and scaffold/nerve grafts were harvested for histomorphometric analysis. Collagenic connective tissue, Schwann cells and axons were evaluated in the proximal nerve stump, the scaffold/nerve graft and the distal nerve stump. The implants have uniaxially-oriented pore structure with a pore size in the range of 2 micorm (the pore wall) and 75 x 700 microm (elongated pores in the implant lumen). The skin of the tubular implants was nonporous. Animals which underwent repair with tubular scaffolds of biodegradable polyurethanes coated with diluted fibrin sealant had no significant functional differences compared with the nerve graft group. Control group resulted in a trend-wise better electrophysiological recovery but did not show statistically significant differences. There was a higher level of collagenic connective tissue within the scaffold and within the distal nerve stump. Schwann cells migrated into the polyurethane scaffold. There was no statistical difference to the nerve graft group although Schwann cell counts were lower especially within the middle of the polyurethane scaffold. Axon counts showed a trend-wise decrease within the scaffold. CONCLUSION: These results suggest that biodegradable polyurethane tubular scaffolds coated with diluted fibrin sealant support peripheral nerve regeneration in a standard gap model in the rat up to 3 months. Three months after surgery no sign of degradation could be seen.

Abdominal wall reinforcement: biologic vs. degradable synthetic devices.

BACKGROUND: New biodegradable synthetic and biologic hernia implants have been promoted for rapid integration and tissue reinforcement in challenging repairs, e.g. at the hiatus or in contaminated wound fields. Interestingly, experimental data to support or falsify this assumption is scarce. METHODS: Synthetic (BioA®) and biologic implants (porcine and bovine collagen matrices Strattice® and Veritas®) have been tested in experimental onlay hernia repair in rats in observation periods of 30 and 60 days. The key outcome parameters were mesh integration and reinforcement of the tissue at the implant site over sutured and sealed defects as well as comparison to native abdominal wall. Macroscopic assessment, biomechanical analysis and histology with haematoxylin/eosin staining, collagen staining and van Willebrand factor staining for detection of neovascularization were performed. RESULTS: BioA® was well integrated. Although the matrices were already fragmented at 60 days follow-up, hernia sites treated with synthetic scaffolds showed a significantly enhanced tissue deflection and resistance to burst force when compared to the native abdominal wall. In porcine and bovine matrices, tissue integration and shrinkage were significantly inferior to BioA®. Histology revealed a lack of fibroblast ingrowth through mesh interstices in biologic samples, whereas BioA® was tightly connected to the underlying tissue by reticular collagen fibres. CONCLUSIONS: Strattice® and Veritas® yielded reduced tissue integration and significant shrinkage, prohibiting further biomechanical tests. The synthetic BioA® provides little inherent strength but reticular collagen remodelling led to an augmentation of the scar due to significantly higher burst force resistance in comparison to native tissue.

The impact of hydrophobic hernia mesh coating by omega fatty acid on atraumatic fibrin sealant fixation.

BACKGROUND: Fibrin sealant (FS) is a safe and efficient fixation method in open intraperitoneal hernia repair. While favourable results have been achieved with hydrophilic meshes, hydrophobic (such as Omega fatty acid coated) meshes (OFM) have not been specifically assessed so far. Atrium C-qur lite(®) mesh was tested in rats in models of open onlay and intraperitoneal hernia repair. METHODS: 44 meshes (2 × 2 cm) were implanted in 30 male Sprague-Dawley rats in open (n = 2 meshes per animal) and intraperitoneal technique (IPOM; n = 1 mesh per animal). Animals were randomised to four groups: onlay and IPOM sutured vs. sealed. Follow-up was 6 weeks, sutured groups serving as controls. Evaluation criteria were mesh dislocation, adhesions and foreign body reaction. RESULTS: FS provided a reliable fixation in onlay technique, whereas OFM meshes dislocated in the IPOM position when sealed only. CONCLUSION: FS mesh fixation was safe with OFM meshes in open onlay repair. Intraperitoneal placement of hydrophobic meshes requires additional fixation and cannot be achieved with FS alone.

Convulsive seizures following subdural application of fibrin sealant containing tranexamic acid in a rat model.

OBJECTIVES: Tranexamic acid (t-AMCA) has been shown to cause severe convulsions in humans and cats when applied topically to the central nervous system. We wanted to determine whether pure t-AMCA or fibrin sealant (FS) containing t-AMCA would induce similar effects when applied to the spinal cord in a rat model. METHODS: Following low-thoracic laminectomy, the dura was incised to expose the dorsal surface of the lumbar enlargement. Rats were allocated to one of the following treatments: 1) t-AMCA (10 mg/ml), 2) vehicle (phosphate buffered saline), 3) FS containing t-AMCA, 4) FS containing aprotinin. The response of the rats was evaluated based on neurological and behavioral observations. Additionally, motor function was scored in the rats that had received FS. RESULTS: Application of either 10 mg/ml t-AMCA or FS containing t-AMCA caused severe hind limb spasms that developed into spontaneous generalized convulsions. Two of the three rats that had received FS containing t-AMCA died of respiratory failure. In contrast, application of vehicle or FS containing aprotinin did not cause any abnormal conditions of the animals. CONCLUSION: Tranexamic acid may cause severe complications when used in the central nervous system. Thus, fibrin sealants containing t-AMCA should not be used in neurosurgery.