Effect of poly-L-lactic acid and polydioxanone biostimulators on type I and III collagen biosynthesis.

OBJECTIVE: Safe, effective, and biocompatible minimally invasive procedures with the potential to stimulate collagen production have been made to recover dermal thickness and skin quality. The main of this animal model experiment was to observe the effect of poly-L-lactic acid (PLLA) and polydioxanone (PDO) biostimulators in collagen I and III after hypodermal injection. METHODOLOGY: Sixteen adult female rats (Wistar) were randomized into four groups and had dorsal treatment with: G1: hypodermic subcision (HS) only; G2: HS and PLLA hypodermic injection (HI), G3: HS and PDO HI; G4: Control, with no treatment. RESULTS: In histochemical, it was observed hypodermal and dermal tissue in more organized thickness in G3 and in G4 when compared to G1 and G2. There was few difference in G1 compared to G4. The tissue of G2 showed irregularities in the arrangement of collagen fibers, less defined structure and lower distribution of type I collagen compared to the other groups. There is a greater tendency for the proportions of type III collagen among tissues treated with both biostimulators (G2 and G3). PLLA and PDO had relatively similar percentages of collagen when compared to G4. The amount of type I collagen was higher in tissues treated with subcision, while type III collagen was higher in tissues treated with both biostimulators. CONCLUSION: G3 showed better performance in collagen production, although small, when compared with G2.

Resorbable electrospun polydioxanone fibres modify the behaviour of cells from both healthy and diseased human tendons.

Chronic tendinopathy in an active and ageing population represents an increasing burden to healthcare systems. Rotator cuff tendinopathy alone accounts for approximately 70 % of all shoulder pain. Tendinopathic tissue has a disorganised extracellular matrix, altered vasculature, and infiltration of fibroblasts and inflammatory cells. This altered biology may contribute to the limited success of surgical repair strategies. Electrospun resorbable scaffolds can potentially enhance endogenous repair mechanisms by influencing the tissue microenvironment. Polydioxanone (PDO) has an established safety profile in patients. We compared the response of healthy and diseased human tendon cells to electrospun PDO fibres using live cell imaging, proliferation, flow cytometry, and gene expression studies. Within 4 h of initial contact with electrospun PDO, healthy tendon cells underwent a marked transformation; elongating along the fibres in a fibre density dependent manner. Diseased tendon cells initially responded at a slower rate, but ultimately underwent a similar morphological change. Electrospun fibres increased the proliferation rate of diseased tendon cells and increased the ratio of type I:IIIcollagenmRNA expression. Flow cytometry revealed decreased expression of CD106, a marker of mesenchymal stem cells, and increased expression of CD10 on healthy versus diseased tendon cells. PDO electrospun scaffolds further promoted CD106negCD10pos expression of healthy tendon cells. Despite their behavioural differences, both healthy and diseased human tendon cells responded to electrospun PDO fibres. This encourages further work establishing their efficacy in augmenting surgical repair of diseased tendons.

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.

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.

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.

Mechanical characterization and neutrophil NETs response of a novel hybrid geometry polydioxanone near-field electrospun scaffold.

Near-field electrospinning (NFES) is a direct fiber writing sub-technique derived from traditional electrospinning (TES) by reducing the air gap distance to the magnitude of millimeters. In this paper, we demonstrate a NFES device designed from a commercial 3D printer to semi-stably write polydioxanone (PDO) microfibers. The print head was then programmed to translate in a stacking grid pattern, which resulted in a scaffold with highly aligned grid fibers that were intercalated with low density, random fibers. As the switching process can be considered random, increasing the grid size results in both a lower density of fibers in the center of each grid cell as well as a lower density of 'rebar-like' stacked fibers. These scaffolds resulted in tailorable as well as greater surface pore sizes as given by scanning electron micrographs and 3D permeability as indicated by fluorescent microsphere filtration compared to TES scaffolds of the same fiber diameter. Furthermore, ultimate tensile strength, percent elongation, yield stress, yield elongation, and Young's modulus were all tailorable compared to the static TES scaffold characterization. Lastly, the innate immune response of neutrophil extracellular traps was attenuated on NFES scaffolds compared to TES scaffolds. These results suggest that this novel NFES scaffold architecture of PDO can be highly tailored as a function of programming for a variety of biomedical and tissue engineering applications.

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.

In vivo and in vitro antibacterial efficacy of PDS plus (polidioxanone with triclosan) suture.

BACKGROUND: This study evaluated the efficacy of polydioxanone suture with and without triclosan against gram-positive and gram-negative bacteria in vitro and in vivo. METHODS: Polydioxanone suture with and without triclosan was tested against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis, methicillin-resistant S. epidermidis (MRSE), Klebsiella pneumoniae, and Escherichia coli by a zone of inhibition assay. In vivo evaluations were conducted in guinea pigs and mice in which test and control sutures (3-4 cm long) were implanted subcutaneously in the dorsal-lateral regions (control on left, test on right, 3-5 cm apart) through a 20 gauge catheter. Each implantation site was then challenged directly through the catheter with 4 x 10(5) colony-forming units (CFU) of S. aureus (guinea pigs) or 7 x 10(6) CFU of E. coli (mice). At 48 h post-implantation, the control and test sutures were explanted, and adherent bacteria were counted. RESULTS: Polydioxanone suture with triclosan demonstrated activity against all test organisms in vitro. The antibacterial activity was maintained until the sutures dissolved after 17 to 23 days when tested against E. coli and S. aureus, respectively. Evaluation in animal models demonstrated a 99.9% reduction in S. aureus and a 90% reduction in E. coli relative to controls. CONCLUSION: Polydioxanone suture with triclosan had activity in vitro against S. aureus, MRSA, E. coli, S. epidermidis, MRSE, and K. pneumoniae that persisted for as long as three weeks. In animal models, polydioxanone suture with triclosan inhibited in vivo colonization by S. aureus and E. coli.

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.

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.

Evaluation of expanded polytetrafluoroethylene (ePTFE) versus polydioxanone (PDS) for the repair of dura mater defects.

A comparative animal experimental study was performed to test the potential application of expanded polytetrafluoroethylene (ePTFE) vs. polydioxanone (PDS) as dural substitutes. Sixty male Sprague-Dawley rats underwent a right frontoparietal craniotomy, opening of the dura mater, and a small cortical lesion. The dural defect was covered with a piece of ePTFE or PDS. Animals were sacrificed at 30 days or 90 days. Following decalcification, heads including scalp, skull, and underlying brain were sectioned, stained with hematoxylin-eosin, and histologically analyzed. Dural defects repaired with ePTFE, showed minimal reactive changes and no adhesions to the brain surface. No foreign body type giant cell reaction was seen, and the graft became enclosed in a thin sheet of connective tissue. Dural defects repaired with PDS, showed some giant cell infiltration and ingrowth of collagen fibers. Both substitutes provided satisfactory biological function and biocompatibility. Expanded PTFE advantages included relative suppression of tissue ingrowth, ensheathment by connective tissue, and a high tearing strength. Although both materials show promise for use in dural grafting, further clinical studies are necessary to determine their potential applications as a human dural substitute.

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).

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).

Biodegradable weft-knitted intestinal stents: fabrication and physical changes investigation in vitro degradation.

Biodegradable stents can alleviate intestinal obstruction and stenosis in patients. The objective of this study was to develop a biodegradable polydioxanone (PDO) stent using weft-knitting technology and then investigate its biodegradation behaviors in vitro. PDO monofilament with linear density of 100 ± 10 tex was knitted into a tubular stent using a tubular weft-knitting machine. The physical and mechanical properties were evaluated according to the British standard BS EN 13895:2003 and ISO 7198:1998. The biodegradation behaviors of PDO weft-knitted stent in a phosphate buffer solution (pH = 6.8 ± 0.2, 37 ± 0.5 °C) were then investigated. The results showed that the stent maintained more than 60% of its original radial force above 12 weeks. During the 16 weeks of degradation, weight, crystallization, and pH change indicated the degradation medium was diffused into the chain segments of low molecular weight due to the rupture of ester bonds in the monofilament. Fourier transform infrared spectroscopy results demonstrated that the chemical structure of PDO polymer is stable during the in vitro degradation. In conclusion, this biodegradable stent can find valuable applications in treatment of intestinal obstruction and stenosis clinically.

In vivo monitoring of structural and mechanical changes of tissue scaffolds by multi-modality imaging.

Degradable tissue scaffolds are implanted to serve a mechanical role while healing processes occur and putatively assume the physiological load as the scaffold degrades. Mechanical failure during this period can be unpredictable as monitoring of structural degradation and mechanical strength changes at the implant site is not readily achieved in vivo, and non-invasively. To address this need, a multi-modality approach using ultrasound shear wave imaging (USWI) and photoacoustic imaging (PAI) for both mechanical and structural assessment in vivo was demonstrated with degradable poly(ester urethane)urea (PEUU) and polydioxanone (PDO) scaffolds. The fibrous scaffolds were fabricated with wet electrospinning, dyed with indocyanine green (ICG) for optical contrast in PAI, and implanted in the abdominal wall of 36 rats. The scaffolds were monitored monthly using USWI and PAI and were extracted at 0, 4, 8 and 12 wk for mechanical and histological assessment. The change in shear modulus of the constructs in vivo obtained by USWI correlated with the change in average Young's modulus of the constructs ex vivo obtained by compression measurements. The PEUU and PDO scaffolds exhibited distinctly different degradation rates and average PAI signal intensity. The distribution of PAI signal intensity also corresponded well to the remaining scaffolds as seen in explant histology. This evidence using a small animal abdominal wall repair model demonstrates that multi-modality imaging of USWI and PAI may allow tissue engineers to noninvasively evaluate concurrent mechanical stiffness and structural changes of tissue constructs in vivo for a variety of applications.

Implantation of a novel biologic and hybridized tissue engineered bioimplant in large tendon defect: an in vivo investigation.

Surgical reconstruction of large Achilles tendon defects is technically demanding. There is no standard method, and tissue engineering may be a valuable option. We investigated the effects of 3D collagen and collagen-polydioxanone sheath (PDS) implants on a large tendon defect model in rabbits. Ninety rabbits were divided into three groups: control, collagen, and collagen-PDS. In all groups, 2 cm of the left Achilles tendon were excised and discarded. A modified Kessler suture was applied to all injured tendons to retain the gap length. The control group received no graft, the treated groups were repaired using the collagen only or the collagen-PDS prostheses. The bioelectrical characteristics of the injured areas were measured at weekly intervals. The animals were euthanized at 60 days after the procedure. Gross, histopathological and ultrastructural morphology and biophysical characteristics of the injured and intact tendons were investigated. Another 90 pilot animals were also used to investigate the inflammatory response and mechanism of graft incorporation during tendon healing. The control tendons showed severe hyperemia and peritendinous adhesion, and the gastrocnemius muscle of the control animals showed severe atrophy and fibrosis, with a loose areolar connective tissue filling the injured area. The tendons receiving either collagen or collagen-PDS implants showed lower amounts of peritendinous adhesion, hyperemia and muscle atrophy, and a dense tendon filled the defect area. Compared to the control tendons, application of collagen and collagen-PDS implants significantly improved water uptake, water delivery, direct transitional electrical current and tissue resistance to direct transitional electrical current. Compared to the control tendons, both prostheses showed significantly increased diameter, density and alignment of the collagen fibrils and maturity of the tenoblasts at ultrastructure level. Both prostheses influenced favorably tendon healing compared to the control tendons, with no significant differences between collagen and collagen-PDS groups. Implantation of the 3D collagen and collagen-PDS implants accelerated the production of a new tendon in the defect area, and may become a valuable option in clinical practice.

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.