Liquid resorbable nanofibrous surgical mesh: a proof of a concept.

BACKGROUND: Surgical mesh is widely used not only to treat but also to prevent incisional hernia formation. Despite much effort by material engineers, the 'ideal' mesh mechanically, biologically and surgically easy to use remains elusive. Advances in tissue engineering and nanomedicine have allowed new concepts to be tested with promising results in both small and large animals. Abandoning the concept of a pre-formed mesh completely for a 'pour in liquid mesh' has never been tested before. MATERIALS AND METHODS: Thirty rabbits underwent midline laparotomy with closure using an absorbable suture and small stitch small bites technique. In addition, their abdominal wall closure was reinforced by a liquid nanofibrous scaffold composed of a fibrin sealant and nanofibres of poly-ε-caprolactone with or without hyaluronic acid or the sealant alone, poured in as an 'onlay' over the closed abdominal wall. The animals were killed at 6 weeks and their abdominal wall was subjected to histological and biomechanical evaluations. RESULTS: All the animals survived the study period with no major complication. Histological evaluation showed an eosinophilic infiltration in all groups and foreign body reaction more pronounced in the groups with nanofibres. Biomechanical testing demonstrated that groups treated with nanofibres developed a scar with higher tensile yield strength. CONCLUSION: The use of nanofibres in a liquid form applied to the closed abdominal wall is easy to use and improves the biomechanical properties of healing fascia at 6 weeks after midline laparotomy in a rabbit model.

Differential Urinary Proteomic Analysis of Endometrial Cancer.

Endometrial cancer is one of the most frequent gynecological malignancies present in more than 95 % of all uterine cancers. In spite of that, screening of such disease is not commonly performed in clinical practice due to enormous costs and relatively low sensitivity. Therefore, developing an effective screening test to diagnose endometrial cancer at early stages is of great importance for the clinical area of investigation. In this work, we applied urinary proteomics (i.e., bottom-up proteomic approach followed by nano HPLC-ESI-MS/MS) in patients with endometrial cancer, with respect to find proteins aimed for the early diagnostics and screening. According to the results, the significant semi-quantitative changes were observed in urinary proteome of treated patients. The proteins that may be pivotal in pathogenesis of endometrial cancer, like cadherin-1 (CDH1), vitronectin (VTN) and basement membrane specific-heparan sulphate proteoglycan core protein (HSPG2) were down-regulated, when compared to the control group. Ultimately, it can be stated that urinary proteomics has a potential for the searching of cancer protein biomarkers based on their altered concentration.

PVA and PCL nanofibers are suitable for tissue covering and regeneration.

The aim of the study was to evaluate the safety and efficacy of a new therapeutic approach to skin defects resulting from split thickness grafting. Within the study, nanofiber-based dressings fabricated using polyvinyl alcohol (PVA) and poly-ε-caprolactone (PCL) were used, with different mass density. The study was performed in 1 female minipig. Nine defects (approx. 4x4 cm) were made in the superficial skin layer. The tested materials were applied to the squared skin defect and covered by a Jelonet paraffin gauze, sutured in the corners of the defects. The animal was monitored daily during the healing process (21 days). On day 5, 12, and 27, the healing of the wound was evaluated, and a biopsy was performed for further histologic testing. At the end of the study (on day 27 after the procedure), the animal was euthanized, and a standard pathologic evaluation was performed. We can conclude that the nanofiber scaffold which was well tolerated, could be used as a smart skin cover which could be functionalized with another bioactive substances directly on the surgeon table, among potential bioactive substances belong platelet derivatives, antibiotics, etc.

[Use of the Peptigel with Nanofibres in the Bone Defects Healing]. / Vyuzití peptigelu s nanovlákny k lécbe defektu kostní tkáne.

INTRODUCTION Traumatic bone injuries or pathological processes may sometimes result in very extensive bone defects. Currently, the standard procedure applied in clinical humane as well as veterinary medicine to fill a bone defect is the autogenous bone graft which, however, necessitates a more invasive procedure for the patient and in the cases of extensive defects it fails to provide adequate amount of graft. Synthetic bone replacements can be used with no further burden for the patient and can simultaneously be used as the carriers for bioactive molecules or therapeutic drugs. For clinical use, an easy and simple application is one of the requirements that have to be taken into consideration. These requirements are best satisfied by preparations in the form of gel, which may be injected into the defects of various shapes even through minimal surgical approach. MATERIAL AND METHODS Synthetic transparent PGD-AlphaProA hydro-peptide-gel was used as a basis to develop a composite hydrogel scaffold. This gel was enriched by cryogenically ground poly- -caprolactone nanofibers (PCL) in a ratio of 1 ml of gel to 16 µg of nanofibres. In experimental animals (laboratory rat Wistar, n=20), a single regular circular defect of 1.5 mm in diameter was drilled by a low speed drill machine across the whole width of distal femur diaphysis, identically in both the hind legs. In the right hindleg, this defect was filled by injection of 0.05 ml of the composite peptide gel with nanofibers (experimental defect). In the contralateral limb a similar defect was left untreated, without filling (control defect), for spontaneous healing. The group of experimental animals was subsequently divided into four sub-groups (A, B, C, D) for the purpose of further follow-up. One week after the surgical implantation, in the first group of experimental animals (Group A; n = 5) lege artis euthanasia was performed, a radiological examination of both the hind legs was carried out and a sample of the bone from both the control and experimental defect was collected for histologic examination. The other groups of experimental animals were evaluated similarly at 2, 4 and 6 weeks after the surgical procedure (Group B, C, D; n = 5). These groups of experimental animals were assessed using various histological techniques by two independent pathologists. RESULTS A difference between the control and the experimental bone defect was observed only at the healing stage at two weeks after the implantation, when a tendency for greater formation of new bone trabeculas was seen in the defect treated with the composite hydro-peptide-gel with PCL nanofibers. The results show a slightly higher angiogenesis and cellularity at the bone defect site with an increase of newly formed bone tissue and faster colonisation of lamellar bone structures by bone marrow cells at early stages of the healing process (1-2 weeks old defect). In the experimental and control groups, at the later stage of healing (4-6 weeks old defect), the process of healing and bone modelling at the defect site shows no detectable morphological differences. CONCLUSIONS The experimental use of hydro-peptide-gel with PCL nanofibers in vivo in laboratory rats shows very good applicability into the defect site and, compared to the untreated defect within two weeks after the implantation, accelerates the bone healing. This fact could be an advantage especially at the early stage of healing, and thus accelerate the healing of more extensive defects. Key words: peptide gel, polycaprolactone, PCL, replacement, bone, healing, scaffold, nanofibers, biomaterial.