Electrospun nanofibrous scaffolds as a platform to reduce melanoma tumour growth, recurrence, and promote post-resection wound repair.

Wound healing following skin tumour surgery still remains a major challenge. To address this issue, polysaccharide-loaded nanofibrous mats have been engineered as skin patches on the wound site to improve wound healing while simultaneously eliminating residual cancer cells which may cause cancer relapse. The marine derived polysaccharides kappa-carrageenan (KCG) and fucoidan (FUC) were blended with polydioxanone (PDX) nanofibers due to their inherent anti-cancer activity conferred by the sulphate groups as well as their immunomodulatory properties which can reduce inflammation resulting in accelerated wound healing. KCG and FUC were released sustainably from the blend nanofibers via the Korsmeyer-Peppas kinetics. MTT assays, live/dead staining and SEM images demonstrated the toxicity of KCG and FUC towards skin cancer MP 41 cells. In addition, MP 41 cells showed reduced metastatic potential when grown on KCG or FUC containing mats. Both KCG and FUC were non- cytotoxic to healthy L 929 fibroblast cells. In vivo studies on healthy Wistar rats confirmed the non-toxicity of the nanofibrous patches as well as their improved and scarless wound healing potential. In vivo studies on tumour xenograft model further showed a reduction of 7.15 % in tumour volume in only 4 days following application of the transdermal patch.

Polydioxanone Enhances Bone Regeneration After Resection and Reconstruction of Rat Femur with rhBMP2.

The aim of this study was to assess the bone regeneration potential of a polydioxanone (PDO) scaffold together with recombinant human bone morphogenetic protein-2 (rhBMP-2) for the reconstruction of large bone defect. In total, 24 male rats (6 months old) were subjected to bilateral femoral stabilization using titanium plates to create a 2 mm gap, and reconstruction using rhBMP-2 (Infuse®; 3.25 µg). The bone defects were covered with PDO (PDO group), or with titanium mesh (Ti group). Animals were euthanized on days 14 and 60. Simultaneously, 16 rats received PDO and Ti in their dorsum for the purpose of biocompatibility analysis at 3, 5, 7, and 10 days postoperatively. X-ray densitometry showed a higher density in the PDO group on day 14. On day 60, coverage of the bone defect with PDO showed a larger quantity of newly formed bone than that found for the Ti group, a lower inflammatory infiltrate value, and a more significant number of blood vessels on day 14. By immunohistochemical assessment, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) showed higher labeling on day 14 in the PDO group. On day 60, bone morphogenetic protein-2 (BMP-2) showed higher labeling in the PDO group, whereas Ti showed higher labeling for osteoprotegerin, nuclear factor kappa B ligand-activating receptor, RUNX2, and OCN. Furthermore, biocompatibility analysis showed a higher inflammatory response in the Ti group. The PDO scaffold enhanced bone regeneration when associated with rhBMP-2 in rat femur reconstruction. Impact statement Regeneration of segmental bone defects is a difficult task, and several techniques and materials have been used. Recent advances in the production of synthetic polymers, such as polydioxanone (PDO), produced by three-dimensional printing, have shown distinct characteristics that could improve tissue regeneration even in an important bone defect. The present preclinical study showed that PDO membranes used as scaffolds to carry recombinant human bone morphogenetic protein-2 (rhBMP-2) improved bone tissue regeneration by more than 8-fold when compared with titanium mesh, suggesting that PDO membranes could be a feasible and useful material for use in guided bone regeneration. (In English, viable is only used for living creatures capable of sustaining life.

The efficacy of powdered polydioxanone in terms of collagen production compared with poly-L-lactic acid in a murine model.

BACKGROUND: There are many collagen-stimulating fillers, including calcium hydroxyapatite, polycaprolactone (PCL), and poly-L-lactic acid (PLLA), and other materials have been tested. Polydioxanone (PDO) has recently been used as absorbable thread-lifting material due to its collagen-forming effects. PDO in powdered form is expected to be a good material for collagen-producing fillers. OBJECTIVES: To evaluate the collagen-producing effects of powdered PDO injection compared with PLLA injection in a murine model. MATERIALS AND METHODS: Powdered PDO mixed with sodium carboxymethyl cellulose, PLLA, and phosphate-buffered saline was injected on dorsal skin of 8-week-old rat. Tissue samples were obtained 1, 2, and 12 weeks after the procedures for histopathologic review and for real-time PCR to quantify collagen and tissue growth factors. RESULTS: Both PLLA and powdered PDO injections induced granulomatous reactions. Collagen type 1, collagen type 3, TGF-ß1, TGF-ß2, and TGF-ß3 showed increases 2 weeks after injection but decreased 12 weeks after injection for both powdered PDO and PLLA. CONCLUSION: Our results suggested that powdered PDO injection induces collagen formation more effectively than PLLA injection. Therefore, PDO can be a good option for forming collagen.

Galectin-1 promotes an M2 macrophage response to polydioxanone scaffolds.

Regulating soft tissue repair to prevent fibrosis and promote regeneration is central to creating a microenvironment conducive to soft tissue development. Macrophages play an important role in this process. The macrophage response can be modulated using biomaterials, altering cytokine and growth factor secretion to promote regeneration. Electrospun polydioxanone (PDO) fiber scaffolds promoted an M2 phenotype when macrophages were cultured on large diameter, highly porous scaffolds, but an M1 phenotype on smaller diameter fibers. In this study, we investigated whether incorporation of galectin-1, an immunosuppressive protein that enhances muscle regeneration, could promote the M2 response. Galectin-1 was incorporated into large and small fiber PDO scaffolds during electrospinning. Galectin-1 incorporation increased arginase-1 and reduced iNOS and IL-6 production in mouse bone-marrow derived macrophages compared with PDO alone for both scaffold types. Inhibition of ERK mitogen-activated protein kinase did not alter galectin-1 effects on arginase-1 and iNOS expression, but reversed IL-6 suppression, indicating that IL-6 is mediated by a different mechanism. Our results suggest that galectin-1 can be used to modulate macrophage commitment to a pro-regenerative M2 phenotype, which may positively impact tissue regeneration when using small diameter PDO scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2562-2571, 2017.

Assessment of Scaffolding Properties for Chondrogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells in Nasal Reconstruction.

IMPORTANCE: Nasal reconstruction in patients who are missing a significant amount of structural nasal support remains a difficult challenge. One challenge is the deficiency of cartilage left within the nose as a consequence of rhinectomy or a midline destructive disease. Historically, the standard donor source for large quantities of native cartilage has been costal cartilage. OBJECTIVE: To enable the development of protocols for new mesenchymal stem cell technologies as alternative procedures with reduced donor site morbidity, risk of infection and extrusion. DESIGN, SETTING, AND MATERIALS: We examined 6 popular scaffold materials in current practice in terms of their biodegradability in tissue culture, effect on adipose-derived mesenchymal stem cell growth, and chondrogenic fate commitment. Various biomaterials of matching size, porosity, and fiber alignment were synthesized by electrospinning and overlaid with rabbit adipose-derived mesenchymal cells in media supplemented or not with chondrogenic factors. Experiments were performed in vitro using as end points biomarkers for cell growth and chondrogenic differentiation. Polydioxanone (PDO), poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV), PHBV-polycaprolactone, poly(L-lactide-co-caprolactone), poly(lactic-co-glycolic acid), and polystyrene scaffolds of 60% to 70% porosity and random fiber alignment were coated with poly(L)-lysine/laminin to promote cell adhesion and incubated for 28 days with 2.5 to 3.5 × 105 rabbit adipose mesenchymal cells. MAIN OUTCOMES AND MEASURES: Cell growth was measured by fluorometric DNA quantitation and chondrogenic differentiation of stem cells by spectrophotometric sulfated glycosaminoglycan (sGAG) assay. Microscopic visualization of cell growth and matrix deposition on formalin-fixed, paraffin-embedded tissue sections was performed, respectively, with nuclear fast red and Alcian blue. RESULTS: Of 6 scaffold materials tested using rabbit apidose mesenchymal cells, uncoated scaffolds promoted limited cell adhesion but coating with poly(L)-lysine/laminin enabled efficient cell saturation of scaffold surfaces, albeit with limited involvement of scaffold interiors. Similar growth rates were observed under these conditions, based on DNA content analysis. However, PDO and PHBV/PCL scaffolds supported chondrogenic fate commitment better than other materials, based on soluble sGAG analysis and microscopic observation of chondrogenic matrix deposition. The mean (SD) sGAG scaffold values expressed as fold increase over control were PDO, 2.26 (0.88), PHBV/PCL, 2.09 (0.83), PLCL, 1.36 (0.39), PLGA, 1.34 (0.77), PHBV, 1.07 (0.31), and PS, 0.38 (0.14). CONCLUSIONS AND RELEVANCE: These results establish materials, reagents, and protocols for tissue engineering for nasal reconstruction using single-layer, chondrogenically differentiated, adipose-derived mesenchymal stem cells. Stackable, scaffold-supported, multisheet bioengineered tissue may be generated using these protocols. LEVEL OF EVIDENCE: NA.

Ex vivo evaluation of 7 polydioxanone for closure of equine ventral midline celiotomies.

The objective of this study was to compare the bursting strength (BS) and mode of failure (MF) of ventral midline (VM) celiotomies closed with USP 7 polydioxanone (7PD) in 1 or 2 simple continuous sections. A bursting strength model, consisting of inserting and inflating a 200-L polyurethane bladder through a 25-cm VM celiotomy, was used on 15 fresh equine cadavers. Celiotomies were closed using 7PD in 2 separate sections (4 knots), 2 continuous sections (3 knots), or a single section (2 knots) using a simple continuous pattern. The horses' signalment, body weight, number of total knots, MF, and BS were recorded and analyzed statistically for interactions. No difference was found between the BS of VM celiotomies closure types (P = 0.4). All celiotomy/ suture constructs failed at the abdominal wall. The celiotomy closure types evaluated in this study provided a secure method of closure in VM celiotomies in vivo.

L'objectif de la présente étude était de comparer la force d'éclatement (BS) et le mode d'échec (MF) de laparotomies par la ligne ventrale médiale (VM) refermées avec du 7 polydioxanone USP (7PD) en une ou 2 sections continues. Un modèle de force d'éclatement, consistant en l'insertion et le gonflement une vessie de 200 L en polyuréthane via une laparotomie de 25 cm fut utilisé sur 15 cadavres frais de cheval. Les laparotomies étaient refermées en utilisant le 7PD en deux sections séparées (4 nœuds), 2 sections continues (3 nœuds), ou une section simple (2 nœuds) au moyen d'un patron simple continu. L'historique des chevaux, leur poids corporel, le nombre total de nœuds, MF, et BS ont été enregistrés et analysés statistiquement pour les interactions. Aucune différence ne fut trouvée entre les BS et les types de fermetures de VM des laparotomies (P = 0,4). Toutes les laparotomies/modes de suture ont lâché au niveau de la paroi abdominale. Les types de fermeture des laparotomies évalués dans ce projet ont fourni une méthode sécuritaire de fermeture par la VM de laparotomies in vivo.(Traduit par Docteur Serge Messier).

Polymeric nanomicelles for sustained delivery of anti-cancer drugs.

In the first section of this paper, the existing and emerging nanotechnology-based cancer therapies--nanoparticles, drug conjugates, nanomicelles--are reviewed. In a second part, we present our original and unpublished findings on the sustained release of anti-cancer drugs such as paclitaxel, doxorubicin and camptothecin using block copolymer micelles [PEG-b-poly(dioxanone-co-methyl dioxanone)]. Copolymers with variable lengths of hydrophobic and hydrophilic blocks have been synthesized and successfully loaded with paclitaxel, doxorubicin and camptothecin anti-cancer drugs, with micelles size in the range 130-300 nm. Drug encapsulation efficiencies varied between 15% and 70% depending on drug and copolymer composition. The drug binding constants, which give a good insight into drug encapsulation and release, were evaluated from UV spectroscopy as we reported previously for anti-TB drugs. Through variation of the methyl dioxanone content of the copolymer, our systems can be tailored for sustained release of the different drugs.

Mechanism of inhibition on L929 rat fibroblasts proliferation induced by potential adhesion barrier material poly(p-dioxanone-co-L-phenylalanine) electrospun membranes.

Fibroblast plays an important role in the occurrence of postoperative tissue adhesion; materials that have particular "cell-material" interactions to inhibit proliferation of fibroblast will be excellent potential adhesion barriers. In the current study, we synthesized copolymers of p-dioxanone and L-phenylalanine (PDPA) and evaluated the mechanism of its particular inhibition effect on L929 fibroblast proliferation when used as a culture surface. PDPA electrospun membranes could induce apoptosis of L929 fibroblasts. We hypothesized there were two reasons for the apoptosis induction: one was the ability to facilitate cell adhesion of materials, and the other was production of the degradation product, L-phenylalanine. Ninhydrin colorimetric results revealed that L-phenylalanine was continuously released during the culture process and could induce apoptosis in L929 cells. Relatively poor cell adhesion and constant release of L-phenylalanine made PDPA-1 to be the most efficient polymer for the induction of apoptosis. Analysis of apoptosis-related genes revealed that PDPA-induced apoptosis might be performed in a mitochondrial-dependent pathway. But poly(p-dioxanone)-induced apoptosis might occur in a c-Myc independent pathway that was different from PDPA.

Bone morphogenetic proteins-immobilized polydioxanone porous particles as an artificial bone graft.

Bone morphogenetic proteins (BMPs)-immobilized polydioxanone (PDO)/Pluronic F127 porous particles were prepared as a bone graft using a melt-molding particulate-leaching method, and the sequential binding of heparin and BMPs (BMP-2 and BMP-7, single or dual) onto the porous particles. The prepared PDO/Pluronic F127 porous particles gradually degraded with time, with ∼30% of the initial particle weight remaining after 16 weeks. The degradation rate of the PDO/Pluronic F127 porous particles may parallel the bone-healing rate. The BMPs were easily immobilized onto the pore surfaces of PDO/Pluronic F127 particles via heparin binding and were released in a sustained manner for up to 21 days, regardless of BMP type. The BMPs (single BMP-2 or dual BMP-2/BMP-7)-immobilized porous particles were effective for in vitro osteogenesis of bone marrow stem cells (BMSCs), as analyzed by alkaline phosphatase activity, calcium content, time polymerase chain reaction using specific markers for osteogenesis (Type I collagen, osteocalcin, osteopotin, and RunX2), and immunohistochemical staining. The BMPs (single BMP-2 or dual BMP-2/BMP-7)-immobilized porous particles were also effective in promoting new bone formation, as analyzed by the preliminary animal study using a full-thickness skull defect model of Sprague-Dawley rats (microcomputed tomography). The synergistic effect of dual BMPs on the osteogenesis of BMSCs and bone regeneration was not significant in our system. The BMP-2 or dual BMPs (BMP-2/BMP-7)-immobilized PDO/Pluronic F127 porous particles may be a promising candidate as a bone graft for the delayed and insufficient bone healing in clinical fields.

Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds.

In this study, we investigated the effect of fiber and pore size of an electrospun scaffold on the polarization of mouse bone marrow-derived macrophages (BMMΦs) towards regenerative (M2) or inflammatory (M1) phenotypes. BMMΦs were seeded on Polydioxanone (PDO) scaffolds electrospun from varying polymer concentrations (60, 100, and 140 mg/ml). Higher polymer concentrations yielded larger diameter fibers with larger pore sizes and porosity. BMMΦ cultured on these scaffolds showed a correlation between increasing fiber/pore size and increased expression of the M2 marker Arginase 1 (Arg1), along with decreased expression of the M1 marker inducible nitric oxide synthase (iNOS). Secretion of the angiogenic cytokines VEGF, TGF-ß1 and bFGF was higher among cultures employing larger fiber/pore size scaffolds (140 mg/ml). Using a 3D in vitro angiogenesis bead assay, we have demonstrated that the M2-like profile of BMMΦ induced by the 140 mg/ml is functional. Furthermore, our results show that the pore size of a scaffold is a more critical regulator of the BMMΦ polarization compared to the fiber diameter. The study also shows a potential role for MyD88 in regulating M1 BMMΦ signaling on the large vs. small fiber/pore size PDO scaffold. These data are instructive for the rationale design of implantable prosthetics designed to promote in situ regeneration.

Generation of osteogenic construct using periosteal-derived osteoblasts and polydioxanone/pluronic F127 scaffold with periosteal-derived CD146 positive endothelial-like cells.

The purpose of this study was to generate tissue-engineered bone using human periosteal-derived osteoblasts (PO) and polydioxanone/pluronic F127 (PDO/pluronic F127) scaffold with preseeded human periosteal-derived CD146 positive endothelial-like cells (PE). PE were purified from the periosteal cell population by cell sorting. One of the important factors to consider in generating tissue-engineered bone using osteoprecursor and endothelial cells and a specific scaffold is whether the function of osteoprecursor and endothelial cells can be maintained in originally different culture medium conditions. After human PE were preseeded into PDO/pluronic F127 scaffold and cultured in endothelial cell basal medium-2 for 7 days, human PO were seeded into the PDO/pluronic F127 scaffold with PE, and then, this cell-scaffold construct was cultured in endothelial cell basal medium-2 with osteogenic induction factors, including ascorbic acid, dexamethasone, and ß-glycerophosphate, for a further 7 days. Then, this 2-week cultured construct was grafted into the mandibular defect of miniature pig. Twelve weeks after implantation, the animal was sacrificed. Clinical examination revealed that newly formed bone was seen more clearly in the defect with human PO and PDO/pluronic F127 scaffold with preseeded human PE. The experimental results suggest that tissue-engineered bone formation using human PO and PDO/pluronic F127 scaffold with preseeded human PE can be used to restore skeletal integrity to various bony defects when used in clinics.

Modulation of mast cell adhesion, proliferation, and cytokine secretion on electrospun bioresorbable vascular grafts.

Mast cells synthesize several potent angiogenic factors and can also stimulate fibroblasts, endothelial cells, and macrophages. An understanding of how they participate in wound healing and angiogenesis is important to further our knowledge about in situ vascular prosthetic regeneration. The adhesion, proliferation, and cytokine secretion of bone marrow-derived murine mast cells (BMMC) on electrospun polydioxanone, polycaprolactone, and silk scaffolds, as well as tissue culture plastic, has been investigated in the presence or absence of IL-3, stem cell factor, IgE and IgE with a crosslinking antigen, dinitrophenol-conjugated albumin (DNP). It was previously believed that only activated BMMCs exhibit adhesion and cytokine secretion. However, this study shows nonactivated BMMC adhesion to electrospun scaffolds. Silk scaffold was not found to be conducive for mast cell adhesion and cytokine secretion. Activation by IgE and DNP significantly enhanced mast cell adhesion, proliferation, migration, and secretion of tumor necrosis factor alpha, macrophage inflammatory protein-1α, and IL-13. This indicates that mast cells might play a role in the process of biomaterial integration into the host tissue, regeneration, and possibly angiogenesis.

Comparison of skin adhesive and absorbable intracutaneous suture for the implantation of cardiac rhythm devices.

AIMS: Wound healing is a major determent in the post-surgical course of patients (pts) after pacemaker (PM) and implantable cardioverter defibrillator (ICD) implantation. Insufficient closure may lead to serious complications with pocket infections leading to the device's explantation as the worst case scenario. In addition to the different types of suture and suture clips, a novel topical skin adhesive containing 2-octyl-cyanoacrylate is commercially available. METHODS AND RESULTS: Over a period of 18 months, we prospectively assigned all cases of PM, ICD, and loop recorder implants either to skin adhesive (Group 1) or to absorbable intracutaneous polydioxanon suture (Group 2). Data were analysed with respect to operation time, wound infections, and healing disorders. One hundred and eighty-three pts were randomized into Group 1 [71 PMs, 60 ICD, 15 cardiac resynchronization therapy (CRT), 11 loop recorders, and 26 generator replacements]. One hundred and eighty-five pts were assigned to Group 2 (62 PMs, 70 ICD, 30 CRT, 7 loop recorders, and 16 generator replacements). There were no differences regarding sex, diabetes, renal insufficiency, corticosteroid therapy, oral anticoagulants, and acetylsalicylic asa/clopidogrel (P = n.s.). For the significantly higher amount of CRT devices (P < 0.05) in Group 2, the procedure times are given for surgeries except CRT. It was 49.1 ± 27.7 min for Group 1 and 53.4 ± 31.9 min for Group 2 (P = n.s.). Adverse events as insufficient closure, major and minor bleeding, pocket haematoma, erythema, incrustation, dehiscence, keloid, and explantation due to infection occurred significantly more often in the adhesive group (P = 0.02). The greatest impact on this result had early adverse events as insufficient closure, wound incrustation, and inflammation (9.3 vs. 6.0%; P = 0.02). We did not find any difference in long-term adverse events, infections in particular (2.7 vs. 1.6%; P = 0.47). CONCLUSION: This study shows no benefit using skin adhesive in comparison to absorbable intracutaneous suture regarding surgery times for the implantation of cardiac rhythm devices. The rate of early adverse events after wound closure is higher after skin adhesive but no difference in long-term adverse events occurred.

A polydioxanone electrospun valved patch to replace the right ventricular outflow tract in a growing lamb model.

A major issue in congenital heart surgery is the lack of viable right ventricular outflow tract (RVOT) replacement materials. Several biomaterials have been used, with different scaffolds and cells, but they have failed to restore a tri-layered RVOT, and reoperations are often required. We investigated the function, histological changes and potential of growth and tissue regeneration of polydioxanone (PDO) electrospun bioabsorbable valved patches seeded with mesenchymal stem cells (MSCs) in the RVOT of growing lambs. Autologous blood-derived MSCs were labeled with quantum dots and seeded on PDO electrospun valved patches. Those were implanted into the RVOT of 6 growing lambs followed up until 8 months. Results were assessed by echocardiography, magnetic resonance imaging (MRI), histology, immunohistochemistry and biochemical assays. Tissue-engineered RVOT were neither stenotic nor aneurismal and displayed a growth potential, with less fibrosis, less calcifications and no thrombus compared with control polytetrafluoroethylene (PTFE)-pericardial patches. The PDO scaffold was completely degraded and replaced by a viable, three-layered, endothelialized tissue and an extracellular matrix with elastic fibers similar to that of native tissue. Detection of quantum dots at 1 month suggested that at least some of the cells were-derived from the grafted cells. A polydioxanone electrospun tissue-engineered valved transannular patch seems to be a promising device in restoring a living RVOT and could ultimately lead to applications in the treatment of congenital RVOT diseases.

Modulation of murine innate and acquired immune responses following in vitro exposure to electrospun blends of collagen and polydioxanone.

In light of cell sourcing issues and the lack of a bioreactor comparable to the body, many in the field of tissue engineering have focused their efforts on designing biomaterials capable of in situ regeneration. The theory is that, by using the body as both the bioreactor and the source for cell infiltration, scaffolds composed of bioresorbable materials can be remodeled into native tissue. Thus, research into the effects of such materials on the host immune response is increasingly important. This study applies an immunotoxicological approach to evaluate the effects of electrospun blends of polydioxanone (PDO) and collagen type I on murine innate and acquired immune responses. Results indicated that these materials had few effects on innate immune responses, yet they produced significant immunomodulatory effects in multiple endpoints evaluating both branches of acquired immunity (i.e., cell-mediated and humoral immunity). Specifically, collagen content appeared to be responsible for suppression of cell-mediated immunity, while blends of PDO and collagen appeared to be more suppressive of antibody-forming cell responses than either PDO or collagen alone. These results demonstrate the importance of completing evaluations into the immunotoxicological effects of biomaterials, and they suggest that such testing should become a primary focus when evaluating a material's potential foruse in tissue engineering applications.

In vitro evaluations of innate and acquired immune responses to electrospun polydioxanone-elastin blends.

Immune response testing of biomaterials is an essential component of biocompatibility assessment, particularly when the materials of interest are used to design bioresorbable scaffolds with the potential to promote in situ regeneration. Current trends in immune response testing of biomaterials typically examine few elements of the immune system, and they often undertake a mechanistic approach without first determining if material exposure results in physiologically relevant modulation of both innate and acquired immunity. Here, we present a comprehensive in vitro evaluation of biomaterial-induced modulation of acquired (i.e. cell-mediated and humoral) and innate immune responses following exposure to electrospun blends of polydioxanone (PDO) and elastin (ELAS). Results indicated that in vitro exposure of murine spleen cells to PDO-ELAS blends produced statistically significant immunosuppression in multiple cell-mediated and humoral endpoints. Results suggested that ELAS is the primary cause of cell-mediated immunosuppression. In contrast, PDO and ELAS were equally suppressive of humoral immune responses, while blends of the two were more immunosuppressive than either pure polymer alone. Evaluations of innate immune responses demonstrated few significant effects, with statistically significant immunosuppression observed in natural killer cell activity but not in macrophage functional assays. This work presents an approach for assessing potential modulation of immune responses resulting from exposure to biomaterials, and such evaluations are essential to obtaining comprehensive assessments of biocompatibility.

Tissue reactions of suture materials (polyglactine 910, chromed catgut and polydioxanone) on rat bladder wall and their role in bladder stone formation.

Suture materials are widely used in urological surgery especially in regions that are in contact with urine. In this study, we aimed to compare polyglactine 910, chromed catgut and polydioxanone sutures according to stone formation and inflammation, congestion and foreign body reaction that occur on bladder mucosa. Cystotomy procedure was performed, in three groups of Wistar female rats, with 4/0 polyglactine 910, 4/0 chromed catgut and 4/0 polydioxanone sutures. All groups were divided into two sub-groups with 4 and 8-week follow up periods. Rats were treated with 20 mg kg(-1) day(-1) Ofloxacin (i.p.) daily until the seventh post-operative day. Urinary pH, leucocyte esterase and nitrite levels were determined. All rats were killed at the end of the follow-up period and stone formation on sutures and degrees of tissue reactions (inflammation, congestion and foreign body reaction) on bladder mucosa were compared. Tissue reactions were evaluated by the same pathologist (S. K.). Chi-square and Student's t test were used in statistical analysis (p<0.05). There was no significant difference between the mean weights of the groups. Leucocyte esterase and nitrite were negative in urine analyses. There was no significant difference between urinary pH levels of the groups with 4 and 8 weeks follow-up (p>0.05). Although the difference between the degrees of congestion in groups was not statistically significant (p>0.05), there were statistically significant differences between the degrees of inflammation and foreign body reaction in groups. Although the duration of urinary contact of suture is the main factor in stone formation on suture material, tissue reaction on mucosa and the physical structure of suture also affect this formation. We observed lower degrees of inflammation and foreign body reaction with 4/0 polydioxanone and no stone formation. We believe that polydioxanone may be useful and reliable in urological surgery due to these properties.

External septal reconstruction with the use of polydioxanone foil: our experience.

We present our experience and results after using polydioxanone (PDS) foil in septal reconstruction. In a period of 2 years, 12 patients who were admitted in our department with severe septal deviation and breathing problems underwent septoplasty under general anaesthesia. The nasal septum was approached via an external approach. In all patients, after resecting and exposing the septum, the removable piece after being divided into straight pieces, was sutured onto an appropriate sized PDS foil and reimplanted together between the mucoperichondrium flaps. Sutures were placed to fixate the "new septum" to the nasal dorsum and to the anterior nasal spine. The immediate postoperative course was unremarkable and in a follow-up appointment 6 months and 1 year postoperatively, one complication occurred, with septum subluxation noted in one patient. Use of PDS foil in septal reconstruction is an important surgical option for the correction of the markedly deviated nasal septum. Fixation of the straightened and replanted septum at the nasal dorsal septum border with the upper lateral cartilages and at the nasal spine is essential.

Influence of polydioxanone foil on growing septal cartilage after surgery in an animal model: new aspects of cartilage healing and regeneration (preliminary results).

OBJECTIVE: To determine whether late complications after septoplasty in growing septal cartilage in children can be prevented by the use of a resorbable polydioxanone (PDS) foil in combination with the cartilage. DESIGN: Animal study with 45 young rabbits, operated on at the nasal septum. Four typical septoplasty procedures were carried out, including elevation of the mucoperichondrium, cartilage excision, and reimplantation of crushed and noncrushed cartilage; for each of the procedures, resorbable PDS foil was used in half of the animals. Observation time ranged from 2 weeks to 5 months, to observe the healing process until complete outgrowth of the septum and complete resorption of the foil were achieved. SETTING: Ear, Nose, and Throat Department at University of Pécs, Pécs, Hungary. MAIN OUTCOME MEASURE: Histomorphologic findings on specimens of septum stained with hematoxylin-eosin and periodic acid-Schiff stains. RESULTS: Depending on the surgical procedure, there were various degrees of differences between the groups with and without PDS. After elevation of the mucoperichondrium, there were almost no differences between the 2 groups. After cartilage resection, reimplantation, and crushing, however, there was a remarkable difference between groups. In the group without PDS, septal deviations and poorly regenerated cartilage were observed, but in the group with PDS no significant deviation after complete regeneration of septal cartilage was observed. CONCLUSIONS: The resorbable PDS foil prevented a secondary deviation in the surgically treated growing septal cartilage in young rabbits. Use of this foil could reduce late complications such as septal deviations and possibly prevent growth inhibition in the growing nasal septum after septoplasty.

The relationship between five kinds of laparoscopic knots and five types of suture materials and histological findings in tissues: an experimental study on rabbits.

The aim of the current study was to examine the slipping and the tightening of laparoscopic knots with various kinds of sutures, as well as the histologic alterations in tissues. Fifty rabbits and five kinds of sutures were used-silk, polyglactine-910 (Vicryl), Polydioxanone (PDS), Polyglycol (Dexon), and cat-gut chromic-and five laparoscopic knots were used-Tayside, Roeder, Melzer, Cross, and Blood. The knots were performed extracorporeally and were used to ligate a part of the omentum. Sliding and tightening of the knots were evaluated. The omentum, the suture, and the knots were checked 10 days and 1 month after operation. Histologic examination was performed 1 month after surgery. Polyglactine-910 (Vicryl) and silk were the most qualitative sutures used in Tayside, Roeder, and Blood knots and the least harmful for the tissues. Catgut chromic and Polydioxanone (PDS) were the most defective sutures. The most efficient laparoscopic slipknots are Tayside, Roeder, and Blood, especially when constructed with silk and polyglactine-910 (Vicryl).