The biointegration profile of fiber-reinforced plates following tibial implantation in sheep.

Biointegrative, mineral fiber-reinforced bone fixation implants recently introduced in orthopedic surgery have expanded available treatment options for fractures and bone deformities. This new technology aims to address the disadvantages of permanent metallic implants while overcoming inherent concerns of adverse inflammatory reactions when using polymer-based orthopedic implants. The purpose of this double-arm preclinical study was to evaluate the safety, biocompatibility, and biointegration of fiber-reinforced plates, following implantation on the tibias of eight sheep. Left tibias underwent periosteal elevation, allowing for implant attachment directly onto the cortical surface; right tibia plates were implanted over intact periosteum. Microcomputed tomography and histopathology were performed at 13, 26, 52, 78, 104, and 134 weeks postimplantation. All animals were evaluated clinically at each time point, with no evidence of local adverse reactions. Histopathology demonstrated anti-inflammatory M2-like macrophages and multinucleated giant cells corresponding to implant bioabsorption, similar for both groups at each time point, and indicating expected implant biocompatibility. Inflammatory cells (i.e., eosinophils, lymphophyctes, plasma cells, and M1-like macrophages) were absent throughout the study. The bioabsorption process had started at 13 W, with the highest rate at 52-78 W. At 104 W, only residual polymer material was left (∼5% of implant area). Low amounts of mineral fibers were evident at 78 W and were absent (fully remodeled) by 104 W. At 134 W, implants at both sites were fully bioabsorbed. In conclusion, these new fiber-reinforced implants demonstrated bone remodeling and complete biointegration, with no adverse tissue response. Clinical significance: In this double-arm, 2.5-year study, a biointegrative, fiber-reinforced plate implanted on the tibias of sheep was fully absorbed within 134 weeks, with no adverse tissue reaction. Bioabsorption was similar, with or without periosteal elevation, mimicking conditions like those observed in traumatic injuries disrupting the periosteum, open reduction and internal fixation, or minimally invasive surgeries. These results demonstrate the feasibility, versatility, and safety of this new class of biointegrative bone implants. This newly developed technology avoids the complications of the removal of metal implants.

Preclinical In-Vivo Safety and Toxicokinetics of D-PLEX100 in an Abdominal Surgery Incision Model in Juvenile Miniature Swine.

D-PLEX100 (D-PLEX) is a novel product candidate made of a polymer-lipid-based matrix (PLEX platform) which contains doxycycline that is being released at a constant rate for 30 days. D-PLEX was developed to prevent surgical site infections, which are a major global health challenge. Previous studies have shown its safety in adult humans, adult swine, and adult rabbits. The aim of this study was to assess the toxicity and safety of D-PLEX also in juvenile animals to support future clinical trials in pediatric patients. Yucatan miniature swine were selected as a model, primarily due to their relatively larger mass. D-PLEX or placebo (formulation without doxycycline) was administered locally to abdominal incisions, and the animal's safety parameters were followed for 9 months and compared to sham-control swine. There was no evidence of any systemic safety concern or local toxicity at the incision site in D-PLEX-treated animals. D-PLEX was detected after 1 month and was fully resorbed at the 3-month time point. The surgical incision sites were fully healed at the 6-month time point in all D-PLEX-treated animals. Toxicokinetic (TK) assessments revealed that doxycycline exhibited low Cmax and therefore minimal systemic exposure following a single dose of local administration. This study provides evidence for the safety of D-PLEX and PLEX-based formulation in juvenile miniature swine and supports its further testing in clinical pediatric population. In addition, it can be used as a reference for future preclinical studies aiming to evaluate the safety of other PLEX-based product candidates for the pediatric population.

Assessment of Bioprotect's Biodegradable Balloon System as a Rectal Spacer in Radiotherapy: An Animal Study on Tissue Response and Biocompatibility.

Prostate cancer is a significant health concern for men, emphasizing the need for effective treatment strategies. Dose-escalated external beam radiotherapy shows promise in improving outcomes but presents challenges due to radiation effects on nearby structures, such as the rectum. Innovative techniques, including rectal spacers, have emerged to mitigate these effects. This study comprehensively assessed tissue responses following the implantation of the Bioprotect biodegradable fillable balloon as a rectal spacer in a rat model. Evaluation occurred at multiple time points (4, 26, and 52 weeks) post-implantation. Results revealed localized tissue responses consistent with the expected reaction to biodegradable materials, characterized by mild to moderate fibrotic reactions and encapsulation, underscoring the safety and biocompatibility of the balloon. Importantly, no other adverse events occurred, and the animals remained healthy throughout the study. These findings support its potential clinical utility in radiotherapy treatments to enhance patient outcomes and minimize long-term implant-related complications, serving as a benchmark for future similar studies and offering valuable insights for researchers in the field. In conclusion, the findings from this study highlight the safety, biocompatibility, and potential clinical applicability of the Bioprotect biodegradable fillable balloon as a promising rectal spacer in mitigating radiation-induced complications during prostate cancer radiotherapy.

Chronic toxicity and carcinogenicity study of dietary gardenia blue in Sprague Dawley rats.

In this combined chronic toxicity/carcinogenicity study of gardenia blue as a natural food color additive, Sprague Dawley rats were administered 0.5%, 2.5%, or 5.0% gardenia blue via the feed or carrier diet (0.0% gardenia blue) for 12 (chronic toxicity cohort) or 24 (carcinogenicity cohort) months. No abnormal clinical, ophthalmological, neurotoxicity or clinical pathology changes were attributed to treatment, and there was no increase in mortality due to gardenia blue exposure. The only treatment-related change was grossly observed blue discoloration of the stomach, intestines, and mesenteric lymph nodes as well as reversible dark discoloration of the kidneys all without associated histopathology. The no-observed-adverse-effect level (NOAEL) for gardenia blue exposure via the diet for one or two years was determined to be 5.0% (2175.3 mg/kg body weight/day in male rats and 3075.4 mg/kg body weight/day in female rats).

Oral chronic toxicity and carcinogenicity study of alpha-glycosyl isoquercitrin (AGIQ) in Sprague Dawley rats.

alpha-Glycosyl isoquercitrin (AGIQ) is a flavonoid that possesses antioxidant and tumor suppressive capabilities and is marketed as a food additive in Japan. The aim of this study was to assess the potential for oral chronic toxicity and carcinogenicity of AGIQ in male and female Sprague Dawley rats following up to 5.0% dietary exposure. In the chronic toxicity study, rats were exposed to AGIQ or vehicle for one year with a 6-month interim termination point; for the carcinogenicity study, rats were treated for 24 months. No signs of AGIQ-related toxicity clinically or histologically were observed for up to one year except for yellow discoloration of bone. In the carcinogenicity study, a statistically significant increase in the incidence of malignant glioma of the brain or spinal cord was observed in female rats exposed to 5.0% AGIQ compared to those exposed to control feed. A Scientific Advisory Panel of experienced neuropathologists reviewed the gliomas (routine stains and glial cell markers) and concluded that the gliomas were a rare, spontaneous, rat-specific neoplasm: malignant microglial tumor. The lesions could not definitively be attributed to AGIQ exposure and have limited implications with respect to predicting human cancer risk.

Saroglitazar suppresses the hepatocellular carcinoma induced by intraperitoneal injection of diethylnitrosamine in C57BL/6 mice fed on choline deficient, l-amino acid- defined, high-fat diet.

BACKGROUND: Saroglitazar is a novel PPAR-α/γ agonist with predominant PPAR-α activity. In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. In view of these observations, and the fact that NASH is a progressive disease leading to HCC, we hypothesized that saroglitazar may prevent the development of HCC in rodents. METHODS: HCC was induced in C57BL/6 mice by a single intraperitoneal injection of 25 mg/kg diethylnitrosamine (DEN) at the age of 4 weeks and then feeding the animal a choline-deficient, L-amino acid- defined, high-fat diet (CDAHFD) for the entire study duration. Eight weeks after initiation of CDAHFD, saroglitazar (1 and 3 mg/kg) treatment was started and continued for another 27 weeks. RESULTS: Saroglitazar treatment significantly reduced the liver injury markers (serum ALT and AST), reversed hepatic steatosis and decreased the levels of pro-inflammatory cytokines like TNF-α in liver. It also resulted in a marked increase in serum adiponectin and osteopontin levels. All disease control animals showed hepatic tumors, which was absent in saroglitazar (3 mg/kg)- treatment group indicating 100% prevention of hepatic tumorigenesis. This is the first study demonstrating a potent PPARα agonist causing suppression of liver tumors in rodents, perhaps due to a strong anti-NASH activity of Saroglitazar that overrides its rodent-specific peroxisome proliferation activity. CONCLUSION: The data reveals potential of saroglitazar for chemoprevention of hepatocellular carcinoma in patients with NAFLD/NASH.

Safety and efficacy of a novel robotic, fractional micro-coring device in a swine model.

Laser resurfacing may be accompanied by unwanted side effects. The micro coring technology, designed to remove small skin columns, was developed to avoid the thermal injury associated with lasers. However, very limited data are available on its pre-clinical efficacy and safety. The novel robotic, fractional micro-coring device, AimeTM, was tested on four pigs, each treated in 12 sites, at 6 time-points, over the course of 28 days. Macroscopic and microscopic evaluation was performed at each of the 6 time-points during the 28-day follow-up. Macroscopically, treatment resulted in erythema and mild edema that quickly resolved. Microscopically, there was progressive re-coverage of the tested sites with complete, well differentiated, newly formed epidermis, associated with efficient elimination of the underlying excised dermis, which was replaced by maturing fibroplasia. Some of the sites demonstrated complete healing already after 7 days. No significant adverse events were noted with the use of the device. The use of the micro-coring device AimeTM in a porcine model for skin fractional micro-excision and resurfacing was effective and safe. The comprehensive gradual healing process shown in this study with detailed histopathological images can also serve as a basis for future pre-clinical studies of fractional ablative devices.

Preclinical In-Vivo Safety of a Novel Thyrotropin-Releasing Hormone-Loaded Biodegradable Nanoparticles After Intranasal Administration in Rats and Primates.

Thyrotropin-releasing hormone (TRH) and TRH-like peptides carry a therapeutic potential for neurological conditions. Nanoparticles (NP) made of the biodegradable polymer, Poly(Sebacic Anhydride) (PSA), have been developed to carry TRH, intended for intranasal administration to patients. There is limited information on the safety of biodegradable polymers when given intranasally, and therefore, we have performed two preclinical safety and toxicity studies in cynomolgus monkeys and rats using TRH-PSA nanoparticles. The rats and monkeys were dosed intranasally for 42 days or 28 days, respectively, and several animals were followed for additional 14 days. Animals received either placebo, vehicle (PSA), or different concentrations of TRH-PSA. No systemic adverse effects were seen. Changes in T3 or T4 concentrations were observed in some TRH-PSA-treated animals, which did not have clinical or microscopic correlates. No effect was seen on TSH or prolactin concentrations. In the monkey study, microscopic changes in the nasal turbinates were observed, which were attributed to incidental mechanical trauma caused during administration. Taken together, the TRH-loaded PSA NPs have proven to be safe, with no local or systemic adverse effects attributed to the drug loaded nanoparticles. These findings provide additional support to the growing evidence of the safety of peptide-loaded NPs for intranasal delivery and pave the way for future clinical trials in humans.

Self-regulating novel iron oxide nanoparticle-based magnetic hyperthermia in swine: biocompatibility, biodistribution, and safety assessments.

Studies demonstrating the successful and safe application of magnetic hyperthermia in large animals are scarce. A therapeutic approach for advanced cancer comprising multicore encapsulated iron oxide (IO) Sarah Nanoparticles (SaNPs), that uniquely self-regulate their temperature, was developed thus overcoming the safety challenges of hyperthermia. SaNPs are intravenously injected and accumulate in tumor tissue, leading to selective heating upon exposure to an external alternating magnetic field (AMF). A series of studies were conducted in healthy swine to assess SaNPs' safety, alone or combined with AMF application. Administration of single high (up to 22 mg IO/kg) or low (3.6 mg IO/kg) SaNP doses had no adverse effects, including no infusion reactions. Vital signs remained stable with no significant clinical pathology changes, and no treatment-associated toxicities. Biodistribution analysis indicated that SaNPs predominantly accumulate in the lungs and clear in a dose- and time-dependent manner. In minipigs that received a single SaNP no-observed-adverse-effect-level (NOAEL)-based dose (3.6 mg IO/kg) with AMF, the average percentage remaining in vital organs after 90 days was 13.7%. No noticeable clinical signs were noted during the 87 to 92-day observation period following irradiation, and no inflammation, necrosis, nor thermal damage were found in the histopathology evaluation. In another minipig, ~ 90 days after three recurrent high doses (14 mg IO/kg), without AMF, almost half of the injected SaNPs were cleared with no residual detrimental effects. We demonstrate that the approach is safe and well tolerated in swine, opening potential avenues as a novel therapeutic modality for cancer patients.

Preliminary nonclinical safety and immunogenicity of an rVSV-ΔG-SARS-CoV-2-S vaccine in mice, hamsters, rabbits and pigs.

rVSV-ΔG-SARS-CoV-2-S is a clinical stage (Phase 2) replication competent recombinant vaccine against SARS-CoV-2. To evaluate the safety profile of the vaccine, a series of non-clinical safety, immunogenicity and efficacy studies were conducted in four animal species, using multiple doses (up to 108 Plaque Forming Units/animal) and dosing regimens. There were no treatment-related mortalities or any noticeable clinical signs in any of the studies. Compared to unvaccinated controls, hematology and biochemistry parameters were unremarkable and no adverse histopathological findings. There was no detectable viral shedding in urine, nor viral RNA detected in whole blood or serum samples seven days post vaccination. The rVSV-ΔG-SARS-CoV-2-S vaccination gave rise to neutralizing antibodies, cellular immune responses, and increased lymphocytic cellularity in the spleen germinal centers and regional lymph nodes. No evidence for neurovirulence was found in C57BL/6 immune competent mice or in highly sensitive type I interferon knock-out mice. Vaccine virus replication and distribution in K18-human Angiotensin-converting enzyme 2-transgenic mice showed a gradual clearance from the vaccination site with no vaccine virus recovered from the lungs. The nonclinical data suggest that the rVSV-ΔG-SARS-CoV-2-S vaccine is safe and immunogenic. These results supported the initiation of clinical trials, currently in Phase 2.

Safety and Performance Evaluation of Su2ura Approximation, a New Suturing Device, in Pigs.

One of the challenging aspects of minimal invasive surgery (MIS) is intracorporal suturing, which can be significantly time-consuming. Therefore, there is a rising need for devices that can facilitate the suturing procedure in MIS. Su2ura Approximation Device (Su2ura Approximation) is a novel device developed to utilize the insertion of anchors threaded with stitches to allow a single action placement of a suture. The objective of this study was to evaluate the long-term safety and tissue approximation of Su2ura Approximation in comparison to Endo Stitch + Surgidac sutures in female domestic pigs. All incision sites were successfully closed by both methods. Firm consolidation within and around the incision site was noted in several animals in both treatment groups, which corresponded histopathologically to islands of ectopic cartilage or bone spicules within the fibrotic scar. These changes reflect heterotopic ossification that is commonly seen in the healing of abdominal operation sites in pigs. No other abnormal findings were observed throughout the study period. In conclusion, the use of Su2ura Approximation under the present experimental conditions revealed no safety concerns.

Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model.

Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect, SaNPs need to accumulate in the tumor. Since the potential accumulation and associated toxicity in normal tissues are an important risk consideration, biodistribution and toxicity were assessed in naïve BALB/c mice. Therapeutic efficacy and the effect on survival were investigated in the 4T1 murine model of metastatic breast cancer. Toxicity evaluation at various timepoints did not reveal any abnormal clinical signs, evidence of alterations in organ function, nor histopathologic adverse target organ toxicity, even after a follow up period of 25 weeks, confirming the safety of SaNP use. The biodistribution evaluation, following SaNP administration, indicated that SaNPs accumulate mainly in the liver and spleen. A comprehensive pharmacokinetics evaluation, demonstrated that the total percentage of SaNPs that accumulated in the blood and vital organs was ~78%, 46%, and 36% after 4, 13, and 25 weeks, respectively, suggesting a time-dependent clearance from the body. Efficacy studies in mice bearing 4T1 metastatic tumors revealed a 49.6% and 70% reduction in the number of lung metastases and their relative size, respectively, in treated vs. control mice, accompanied by a decrease in tumor cell viability in response to treatment. Moreover, SaNP treatment followed by alternating magnetic field exposure significantly improved the survival rate of treated mice compared to the controls. The median survival time was 29 ± 3.8 days in the treated group vs. 21.6 ± 4.9 days in the control, p-value 0.029. These assessments open new avenues for generating SaNPs and alternating magnetic field application as a potential novel therapeutic modality for metastatic cancer patients.

The toxicologic pathology aspects of selected natural herbal products and related compounds.

Herbal products have been in use for many years, but they are becoming more and more popular in recent years, and they are currently in widespread use throughout the world. In this review article we describe the histopathologic findings found after exposure to 12 dietary herbals in studies conducted in rodent model systems. Clear or some evidence for carcinogenic activity was seen with 6 herbals, with the liver being the most common organ affected. The intestine was affected by two herbals (aloe vera nondecolorized extract and senna), three had no clear evidence for carcinogenic activity and one was cardiotoxic (Ephedrine and Ephedra in combination with caffeine). Information from these studies can help to better understand potential target organs for further evaluation from exposure to various herbal products.

alpha-Glycosyl Isoquercitrin (AGIQ) and its lack of carcinogenicity in rasH2 mice.

alpha-Glycosyl Isoquercitrin (AGIQ), is used in Japan as a food additive and was granted generally recognized as safe (GRAS) status in 2005 (FEMA) and 2007 (FDA). The safety and toxicity information for AGIQ is sparse and therefore, the carcinogenicity potential of AGIQ was examined in the CByB6F1-Tg(HRAS)2Jic (rasH2) model. One hundred female and male rasH2 mice, each, were allocated to one of four designated dose groups; 0 (control)%, 1.5%, 3.0% or 5.0% AGIQ. Animals were administered the diets for six months and an additional 10 females and 10 males, each, were administered a positive control, N-methyl-N-nitrosourea (MNU). Body weights and clinical observations were collected. A full screen necropsy, organ weights, clinical chemistry, urinalysis and histopathology were performed. The positive control animals elicited appropriate responses specific to this strain (rasH2) of mice. There were statistically significant sporadic non-dose-dependent changes in clinical chemistries without corresponding pathological correlation. No microscopic AGIQ-related findings were noted; the range of pathology observations were all considered background findings, either specific to rasH2 mice or common to inbred strains of mice. Therefore, under the study conditions, the no-observed-adverse-effect level (NOAEL) was determined to be more than 5.0% (7215.4 mg/kg BW/day in male mice and 14685.5 mg/kg/day in female mice).

Chemical-Induced Oral Squamous Cell Neoplasms in Rodents: An Overview of NTP 2-Year Cancer Studies.

Oral cancer is the seventh most common malignancy worldwide, and lifestyle factors participate in its development. Rodent studies can help identify substances that contribute to its development and provide information on the early stages of carcinogenicity. The National Toxicology Program (NTP) has conducted more than 500 short-term and 2-year toxicology and carcinogenicity studies in rodents, and some of the tested compounds resulted in oral cancer. Our goal was to review the NTP carcinogenic studies to describe those chemicals that have oral carcinogenic outcome in rodents. For this project, we reviewed the results from all NTP carcinogenicity studies and a board-certified veterinary pathologist reviewed the slides from all neoplasms in the oral cavity that were considered treatment related. We have identified 26 chemicals with an adverse effect in the oral cavity. Fourteen chemicals demonstrated clear evidence of carcinogenicity in the oral cavity. We provide information on the carcinogenic findings in rodents together with a detailed description of the morphologic aspects of the oral cancers and speculate that the carcinogenic effects can be induced by different pathological modes of action. The findings reviewed here provide indicators for potential oral carcinogenesis processes in rodent models, which can be further investigated in future mechanistic studies.

D-PLEX100 in an Abdominal Surgery Incision Model in Miniature Swine: Safety Study.

Surgical site infections (SSIs) are a common surgical-related complication. To avoid these complications, a new biodegradable polymer-lipid encapsulation matrix that provides controlled release of doxycycline (doxycycline/polymer-lipid encapsulation matrix [D-PLEX]) has been developed. The aim of this comprehensive study was to evaluate the potential safety of D-PLEX100 in abdominal surgical site. D-PLEX100 was administered into incisions of abdominal surgical site in Yucatan miniature swine, which were followed for up to 6 months and compared to sham-control swine. The D-PLEX100 mass did not migrate from the incisional site, and there was no evidence for systemic toxicity or other safety concerns. Surgical incision sites, including the peritoneal surface, were fully healed at 6 months in all animals. Most of the D-PLEX100 mass was absorbed during the first 3 months, and by 6 months, D-PLEX100 was fully absorbed. Toxicokinetic evaluation revealed that doxycycline concentrations were evident at 30 minutes and persisted to 8 days (71 mg/kg) or at least 15 days (284 mg/kg) and were no longer present in plasma by day 29. This study supports the safety of D-PLEX100 and its favorable degradability profile. A clinical study is being performed to assess the safety and the efficacy of D-PLEX100 to prevent human abdominal SSIs.

Local Tolerability and Performance Evaluation in Domestic Pigs of a Fractional Radiofrequency Device for Dermatologic Treatment.

Information on the safety of energy-based dermatological surgical devices in domestic pigs, and fractional radiofrequency (RF) devices in particular, is very limited. The aim of this study was to evaluate in a GLP-compliant study in domestic pigs the local reaction and performance of a novel fractional RF device. Five female domestic pigs were subjected to fractional RF pulses, using different energy and pulse durations and depth of penetration of the pulses. The animals were evaluated clinically and histologically at different time points (days 0, 1, 3, 7, and 14) postenergy exposure. There were no microscopic or macroscopic local adverse effects in any tested power settings, and there was time-related progressive healing, reaching complete macroscopic and microscopic healing by 7 days postapplication. As expected, there was power-related progressive increase in the incidence of ablation (destruction of skin tissue by vaporization) and coagulative necrosis of the dermis from low to high power setting. This comprehensive study, using multiple power settings (both ablative and coagulative) and several time points, will be of benefit for future studies evaluating new fractional RF devices.

Biodegradable Breast Tissue Marker Clip.

Biodegradable soft tissue biopsy clips have been developed as implants with the potential to serve as visual markers for regions suspected to contain tumor growth in the breast. These clips are multidimensional tissue markers with better biocompatibility and imaging features. The clips were prepared using biodegradable polymers, poly(l-lactide-co-ε-caprolactone) and methoxy polyethylene glycol-co-l-lactide, that contain iodixanol or barium sulfate as contrast agents; they are further coated with hyaluronic acid or sodium alginate hydrogels. The clips were visible by imaging modalities such as mammography, ultrasound, and magnetic resonance imaging after implantation in Sprague-Dawley rats. The clips stayed intact in the implantation cavity of the animal for more than 3 months with unpretentious changes in their lengths and morphology. The histopathological examination of implanted clips revealed no signs of systemic toxicity in the rats. Overall, the interpretation of the results reveals that the developed clips can be a potential replacement for metal-based markers.

Mesh fixation using novel bio-adhesive coating compared to tack fixation for IPOM hernia repair: in vivo evaluation in a porcine model.

BACKGROUND: Mesh fixation in hernia repair is currently based on penetrating sutures or anchors, with proven early and late complications such as pain, adhesions, erosions, and anchor migration. In an attempt to reduce these complications, a bio-adhesive-based self-fixation system was developed. The purpose of this study was to assess the performance and safety of this novel self-adhesive mesh (LifeMesh™) by comparing it with standard tack fixation. METHODS: A full-thickness abdominal wall defect was created bilaterally in 24 pigs. The defects were measured 14 days later, and laparoscopic intraperitoneal onlay mesh (IPOM) repairs were performed. In each animal, both LifeMesh and a titanium tack-fixed control, either uncoated polypropylene mesh (PP) or composite mesh (Symbotex™), were used. After 28 and 90 days, we performed macroscopic evaluation and analyzed the fixation strength, shrinkage, adhesion scores, and histopathology in all samples. RESULTS: Measurements at both time points revealed that LifeMesh had fully conformed to the abdominal wall, and that its fixation strength was superior to that of the tack-fixated Symbotex and comparable to that of the tack-fixated PP. Shrinkage in all groups was similar. Adhesion scores with LifeMesh were lower than with PP and comparable with Symbotex at both time points. Histology demonstrated similar tissue responses in LifeMesh and Symbotex. Lack of necrosis, mineralization, or exuberant inflammatory reaction in all three groups pointed to their good progressive integration of the mesh to the abdominal wall. By 28 days the bio-adhesive layer in LifeMesh was substantially degraded, allowing a gradual tissue ingrowth that became the main fixation mode of this mesh to the abdominal wall. CONCLUSIONS: The excellent incorporation of LifeMesh to the abdominal wall and its superior fixation strength, together with its low adhesion score, suggest that LifeMesh may become a preferred alternative for abdominal wall repair.

Biodegradability and Safety Study of LifeMesh™, a Novel Self-adhesive Mesh, in Sprague-Dawley Rats.

Self-adhesive meshes are being developed to avoid complications due to traumatic fixation methods. LifeMesh™ is a novel self-adhesive mesh with a biodegradable gelatin adhesive layer developed for hernia repair. The aim of this study was to assess the safety and biodegradability of LifeMesh in Sprague-Dawley (SD) rats for 6 weeks, in comparison to a bare polypropylene (BPP) mesh fixed with sutures. LifeMesh was tolerated well and its implantation did not result in any adverse local reaction, and its adhesive layer was substantially degraded after 4 weeks. Histopathological examination revealed that the presence of the adhesive contributed to a uniform thickness of the granulation tissue surrounding the mesh, in contrast to a nonuniform granulation tissue with BPP. Nonuniform granulation tissue suggests that there will be poorer integration of the mesh to the abdominal wall. The use of LifeMesh also resulted in less adhesions of internal organs with a smaller surface area of involvement. These findings lend support to the potential benefit of LifeMesh for hernia repair in humans and expand the available information on the typical histopathological findings expected with biodegradable implants in the peritoneal cavity of SD rats.