Electrospun polydioxanone/fucoidan blend nanofibers loaded with anti-cancer precipitate from Jaspis diastra and paclitaxel: Physico-chemical characterization and in-vitro screening.

Nanofibers for drug delivery systems have gained much attention during the past years. This paper describes for the first time the loading of a bioactive precipitate (JAD) from the marine sponge Jaspis diastra in PDX and fucoidan-PDX. JAD was characterized by LC-MS/MS and the major component was jaspamide (1) with a purity of 62.66 %. The cytotoxicity of JAD was compared with paclitaxel (PTX). JAD and PTX displayed IC50 values of 1.10 ± 0.7 µg/mL and 0.21 ± 0.12 µg/mL on skin fibroblasts L929 cells whilst their IC50 values on uveal MP41 cancer cells, were 2.10 ± 0.55 µg/mL and 1.38 ± 0.68 µg/mL, respectively. JAD was found to be less cytotoxic to healthy fibroblasts compared to PTX. JAD and PTX loaded scaffolds showed sustained release over 96 h in physiological medium which is likely to reduce the secondary cytotoxic effect induced by JAD and PTX alone. The physico-chemical properties of the loaded and unloaded scaffolds together with their degradation and action on tumor microenvironment by using L929 and MP41 cells were investigated. JAD and PTX at a concentration of 0.5 % (drug/polymer, w/w) in the electrospun mats prevented growth and proliferation of L929 and MP41 cells. Co-culture of L929 and MP41 showed that the JAD and PTX loaded mats inhibited the growth of both cells and caused cell death.

Design and development of polydioxanone scaffolds for skin tissue engineering manufactured via green process.

Fiber spinning technologies attracted a great interest since the beginning of the last century. Among these, electrospinning is a widely diffuse technique; however, it presents some drawbacks such as low fiber yield, high energy demand and the use of organic solvents. On the contrary, centrifugal spinning is a more sustainable method and allows to obtain fiber using centrifugal force and melted materials. The aim of the present work was the design and the development of polydioxanone (PDO) microfibers intended for tissue engineering, using centrifugal spinning. PDO, a bioresorbable polymer currently used for sutures, was selected as low melting polyester and DES (deep eutectic solvents), either choline chloride/citric acid (ChCl/CA) or betaine/citric acid (Bet/CA) 1:1 M ratio, were used to improve PDO spinnability. Physical mixtures of DES and PDO were prepared using different weight ratios. These were then poured into the spinneret and melted at 140 °C for 5 min. After the complete melting, the blends were spun for 1 min at 700 rpm. The fibers were characterized for physico chemical properties (morphology; dimensions; chemical structure; thermal behavior; mechanical properties). Moreover, the preclinical investigation was performed in vitro (biocompatibility, adhesion and proliferation of fibroblasts) and in vivo (murine burn/excisional model to assess safety and efficacy). The multidisciplinary approach allowed to obtain an extensive characterization to develop PDO based microfibers as medical device for implant to treat full thickness skin wounds.

Histological and structural effects of biodegradable polydioxanone stents in the rabbit trachea.

OBJECTIVES: The aim of this study was to evaluate the potential biologic effects caused by the successive placement of biodegradable polydioxanone (PDO) stents in the rabbit trachea. PDO stents could eventually induce a fibroproliferative reaction in the submucosa that could be beneficial in the treatment of malacia due to an increase in its consistency without impairing the tracheal lumen. METHODS: Sixteen adult NZ rabbits were distributed into 3 groups with different survival times according to the number of stents placed: 1 stent (14 weeks), 2 stents (28 weeks) and 3 stents (42 weeks). Stent insertion was performed endoscopically in the cervical trachea of the animal. Histopathological studies included Masson's trichrome staining for submucosal fibrosis and Safranin O to assess the structural integrity of cartilage. Potential inflammatory changes were analysed by means of immunohistochemistry determining the number of CD45-positive cells. RESULTS: Stent placement was successful in every case. Histological studies did not show a statistically significant increase in tracheal wall collagen area and cartilage structure was not modified in those rabbits with 1 or more PDO stents inserted compared to non-stented tracheal sections. Furthermore, no statistically significant changes in the number of CD45+ cells were observed in stented tracheal segments compared to normal tracheal tissues. CONCLUSIONS: According to our data, successive PDO stenting caused mild inflammatory changes in the tracheal wall and no increase in the collagen matrix, and the cartilaginous support was not modified during a long follow-up period (up to 42 weeks). These findings suggest that they may be safe and show good biocompatibility in the long term.

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.

A Simple Solution for Infractured Lateral Nasal Osteotomy Lines During Revision or Primary Rhinoplasty: Osseos Stabilization With Polydioxanone Sutures.

ABSTRACT: In addition to precautions taken with perioperative surgical techniques, nasal packing and external nasal splinting are frequently employed to ensure the stability of the nasal bones following osteotomies performed during rhinoplasty. However, despite these precautions, nasal bone fragments, generally caused by trauma or healing problems, can approach the midline, progress in a posterior direction and heal with malunion in an infractured manner. Since cavities on the infractured side can result in asymmetries and/or airway narrowing, revision osteotomy is required to correct these problems. Subsequent potential recurrent infractures caused by nasal fragments can easily be prevented with late-absorbed sutures passing through the neighboring holes and opening near the osteotomy lines. This technique would be useful for both primary and secondary rhinoplasty, but especially in secondary rhinoplasty operations. (Level of Evidence: Level IV).

In Vitro and in Vivo Biocompatibility and Degradability Evaluation of Modified Polydioxanone Plate.

BACKGROUND: Polydioxanone (PDS) has been widely used in the medical field over the past 30 years. In the 2000s, PDS plate began to be used for rhinoplasty and septoplasty. However, in Asia PDS plates are not widely used due to lack of awareness and high prices. The authors devised a method of producing a modified PDS (m-PDS; Rhinoblock Material & Design Co., Gyeonggi-do, Sothh Korea) at low cost, and compared the biocompatibilities and degradabilities of plates produced with m-PDS and commercial PDS plates (Ethicon, Somerville, NJ) in vivo and in vitro. METHODS: The melting point and decomposition rate of m-PDS were determined by differential scanning calorimetry and thermogravimetric analysis and its tensile strength was also measured. Implants (1 cm × 1 cm × 0.15 mm sized) were inserted subcutaneously into mice and harvested en bloc 2, 5, 10, 15, or 25 weeks later. Tissues were stained with hematoxylin and eosin or Masson's trichrome to evaluate inflammation, extracellular matrix deposition, and vascularization, and plate degradability was also assessed. RESULTS: No significant difference was observed between the thermal analysis and tensile test results of m-PDS and PDS plates. m-PDS started to degrade in vivo from around 10 weeks, and commercial PDS plates from around 15 weeks. After 25 weeks in vivo, both products were completely degraded and not observed in tissue slides. Histologic analysis of excised specimens showed m-PDS and PDS were similar in terms of inflammation, extracellular matrix deposition, and vascularization. CONCLUSION: In vivo and in vitro experiments detected no significant difference between the biocompatibilities and degradabilities of modified and commercial PDS plates. The results of this study suggest that the modified PDS can be used to produce versatile, low cost, absorbable graft materials for rhinoplasty and septoplasty.

First-in-Human Study with Eight Patients Using an Absorbable Vena Cava Filter for the Prevention of Pulmonary Embolism.

PURPOSE: To prospectively evaluate the initial human experience with an absorbable vena cava filter designed for transient protection from pulmonary embolism (PE). MATERIALS AND METHODS: This was a prospective, single-arm, first-in-human study of 8 patients with elevated risk of venous thromboembolism (VTE). Seven absorbable IVC filters (made of polydioxanone that breaks down into H2O and CO2 in 6 mo) were placed prophylactically before orthopedic (n = 5) and gynecologic (n = 2) surgeries, and 1 was placed in a case of deep vein thrombosis. Subjects underwent CT cavography and abdominal radiography before and 5, 11, and 36 weeks after filter placement to assess filter migration, embolization, perforation, and caval thrombosis and/or stenosis. Potential PE was assessed immediately before and 5 weeks after filter placement by pulmonary CT angiography. RESULTS: No symptomatic PE was reported throughout the study or detected at the planned 5-week follow-up. No filter migration was detected based on the fixed location of the radiopaque markers (attached to the stent section of the filter) relative to the vertebral bodies. No filter embolization or caval perforation was detected, and no caval stenosis was observed. Throughout the study, no filter-related adverse events were reported. CONCLUSIONS: Implantation of an absorbable vena cava filter in a limited number of human subjects resulted in 100% clinical success. One planned deployment was aborted as a result of stenotic pelvic veins, resulting in 89% technical success. No PE or filter-related adverse events were observed.

In vitro evaluation of the modified forwarder knot used to end a continuous suture pattern in large-gauge suture.

OBJECTIVE: To evaluate the strength and size of forwarder end (FE) knots modified to end continuous suture lines compared with Aberdeen (AB), square (SQ), and surgeon's (SU) knots. STUDY DESIGN: In vitro mechanical study. STUDY POPULATION: Knotted suture. METHODS: Knots were tied with 2 USP (United States Pharmacopeia) polydioxanone, 2 USP, and 3 USP polyglactin 910 and tested on a universal testing machine under linear tension. Mode of failure and knot holding capacity (KHC) were recorded, and relative knot security (RKS) was calculated. Knot volume and weight were determined by digital micrometer and balance. Knot holding capacity, RKS, size, and weight between knot type, number of throws, and suture type and size were compared by using analysis of variance testing, with P < .05 considered significant. RESULTS: In all suture types and number of throws, FE knot KHC/RKS was 28% to 66.99% (1.2-1.6 fold) stronger compared with SQ/SU knots (P < .001). For 2 USP polydioxanone, FE knots had 10% (1.1 fold) higher KHC/RKS compared with AB knots (P < .042). However, in 2 and 3 USP polyglactin 910, FE knot KHC/RKS values were not different from those of AB knots (P > .080). Forwarder end/AB knots failed by suture breakage at the knot, whereas some SQ/SU knots unraveled. Forwarder end knots in 2 and 3 USP polyglactin 910 were 21.1% to 44.4% (1.2-1.4 fold) smaller compared with SQ/SU knots (P < .028). Forwarder end knots in 2 and 3 USP polyglactin 910 were 40% to 99% (1.4-2.0 fold) larger compared with AB knots (P < .001). CONCLUSION: Forwarder end knots provided increased KHC/RKS compared with SQ/SU knots. CLINICAL RELEVANCE: Forwarder end knots should be considered for closures when suture is placed under tension.

Mechanical properties of a biodegradable self-expandable polydioxanone monofilament stent: In vitro force relaxation and its clinical relevance.

Biodegradable stents are promising treatments for many diseases, e.g., coronary artery disease, urethral diseases, tracheal diseases, and esophageal strictures. The mechanical properties of biodegradable stent materials play a key role in the safety and efficacy of treatment. In particular, insufficient creep resistance of the stent material could result in premature stent collapse or narrowing. Commercially available biodegradable self-expandable SX-ELLA stents made of polydioxanone monofilament were tested. A new, simple, and affordable method to measure the shear modulus of tiny viscoelastic wires is presented. The important mechanical parameters of the polydioxanone filament were obtained: the median Young's modulus was [Formula: see text] = 958 (922, 974) MPa and the shear modulus was [Formula: see text] = 357 (185, 387) MPa, resulting in a Poisson's ratio of ν = 0.34. The SX-ELLA stents exhibited significant force relaxation due to the stress relaxation of the polydioxanone monofilament, approximately 19% and 36% 10 min and 48 h after stent application, respectively. However, these results were expected, and the manufacturer and implanting clinician should be aware of the known behavior of these biodegradable materials. If possible, a biodegradable stent should be designed considering therapeutic force rather than initial force. Additionally, new and more advanced biodegradable shape-memory polymers should be considered for future study and use.

Orbit in a Box: A Simplified Technique for Patient-Specific Virtually Planned Orbital Floor Reconstruction.

PURPOSE: Possibilities for the reconstruction of orbital floor fractures have been extensive for years with regard to materials, methods and differential indications and are inconsistent worldwide. With the spread of CAD/CAM techniques, new and mostly time-consuming possibilities for orbital floor reconstructions have been added. METHODS: The simple and time-efficient CT-to-patient-specific implant workflow presented here shows that a "form-box" can be created from a patient's computer tomography data set using planning software and a 3D printer. The box is then used to form a patient-specific implant for orbital floor reconstruction: here polydioxanone foil was used, for which stable thermoplastic deformability has been demonstrated for 3D reconstructions. RESULTS: Patient-specific thermoplastic shaping of polydioxanone is feasible in a theoretical clinical setting, though its thermoplastic shaping is not yet certified for clinical use. However, a flexible adaptation of the "form-box" design to other materials is possible by setting a single planning parameter. CONCLUSIONS: The simple structure of the box and its straightforward planning/fabrication process with widely available low-cost materials offer the possibility that a surgeon without a 3D specialist can produce a "form-box" for next day surgery if needed.

Tensile properties of synthetic, absorbable monofilament suture materials before and after incubation in phosphate-buffered saline.

OBJECTIVE: To compare tensile properties of synthetic, absorbable, monofilament suture material before and after incubation in phosphate-buffered saline (PBS). STUDY DESIGN: Two sizes (2-0 and 3-0) of Biosyn, Maxon, Monocryl, PDS II, Securocryl, and Securodox were tested. SAMPLE POPULATION: Ten suture loops per group. METHODS: Tensile strength, elongation, and modulus of suture loops were measured at baseline and after 7, 14, 21, or 28 days of incubation in PBS. RESULTS: Size, suture material, and size × suture material interaction influenced maximum breaking load, maximum elongation, and modulus of elasticity. At baseline, 2-0 and 3-0 Maxon had the highest breaking loads (111.67 N and 79.71 N, respectively) for their size, and 2-0 PDSII and 3-0 Securodox had the lowest (68.71 N and 48.73 N, respectively). Maxon 2-0 and 3-0 had the greatest elongations (9.68 mm and 8.45 mm, respectively) for their size, and 2-0 Biosyn and 3-0 Securocryl had the least (7.21 mm and 6.58 mm, respectively). Biosyn 2-0 and 3-0 had the highest modulus. With incubation, Maxon (2-0), PDS II (2-0, 3-0), and Securodox (2-0, 3-0) maintained or gained strength over 4 weeks. Strengths of 2-0 and 3-0 Biosyn and 3-0 Maxon were maintained for 2 weeks, while Monocryl and Securocryl lost 20% to 44% of baseline strength within 1 week and 60% to 72% within 2 weeks. Day 7 strengths of 2-0 Biosyn and 2-0 Monocryl were greater than baseline strength of 2-0 PDS II. Strength of 3-0 Biosyn at day 14 was greater than strength of Monocryl at days 7 and 14 and greater than strength of 3-0 PDS II, 3-0 Securodox, and 3-0 Securocryl at baseline and days 7 and 14. CONCLUSION: Suture tensile properties varied with suture size, composition, and brand. At baseline, Maxon suture had the greatest strength and elongation, and Biosyn had the greatest stiffness. CLINICAL SIGNIFICANCE: Tensile strength retention, when reported as a percentage of original strength, provides insufficient information for comparison of suture tensile properties.

Nanofibrous antibiotic-eluting matrices: Biocompatibility studies in a rat model.

This study evaluated the biocompatibility of degradable polydioxanone (PDS) electrospun drug delivery systems (hereafter referred as matrices) containing metronidazole (MET) or ciprofloxacin (CIP) after subcutaneous implantation in rats. Sixty adult male rats were randomized into six groups: SHAM (sham surgery); PDS (antibiotic-free matrix); 1MET (one 25 wt% MET matrix); 1CIP (one 25 wt% CIP matrix); 2MET (two 25 wt% MET matrices); and 2CIP (two 25 wt% CIP matrices). At 3 and 30 days, animals were assessed for inflammatory cell response (ICR), collagen fibers degradation, and oxidative profile (reactive oxygen species [ROS]; lipid peroxidation [LP]; and protein carbonyl [PC]). At 3 days, percentages of no/discrete ICR were 100, 93.3, 86.7, 76.7, 50, and 66.6 for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP, respectively. At 30 days, percentages of no/discrete ICR were 100% for SHAM, PDS, 1MET, and 1CIP and 93.3% for 2MET and 2CIP. Between 3 and 30 days, SHAM, 1CIP, and 2CIP produced collagen, while 1MET and 2MET were unchanged. At 30 days, the collagen fiber means percentages for SHAM, PDS, 1MET, 1CIP, 2MET, and 2CIP were 63.7, 60.7, 56.6, 62.6, 51.8, and 61.7, respectively. Antibiotic-eluting matrices showed similar or better oxidative behavior when compared to PDS, except for CIP-eluting matrices, which showed higher levels of PC compared to SHAM or PDS at 30 days. Collectively, our findings indicate that antibiotic-eluting matrices may be an attractive biocompatible drug delivery system to fight periodontopathogens. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2019.

Effectiveness and safety of polydioxanone thread embedding acupuncture compared to physical therapy in the treatment of patients with non-specific chronic neck pain: Study protocol for an assessor-blinded, randomized, controlled, clinical trial.

BACKGROUND: As the number of patients who suffer from non-specific chronic neck pain (CNP) is increasing in the Republic of Korea, conservative treatments for patients with CNP have been spotlighted. Although several studies on thread embedding acupuncture (TEA) treatment have been published for the treatment of such patients, no randomized controlled trial has been reported that investigates the effectiveness and safety of the TEA treatment compared with other conservative treatments for the treatment of patients with CNP. Therefore, the purpose of this trial is to compare the effectiveness and safety of TEA to those of physical therapy (PT) for the treatment of patients with CNP. METHODS/DESIGN: This study is planned as a parallel design, randomized, controlled, assessor-blinded, clinical study. One hundred twenty-eight patients diagnosed with CNP will be randomly assigned to either the TEA group or the PT group in a 1:1 ratio. Participants in the TEA group will receive 4 sessions of TEA treatment, while those in the PT group will receive 8 sessions of PT treatment over 4 weeks. An assessment of effectiveness based on the outcomes of the Neck Pain and Disability Scale (NPDS), cervical spinal angle, Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), Patient Global Impression of Change (PGIC), EuroQol-Five Dimension 3 level version (EQ-5D-3L), and Pressure Pain Threshold (PPT) will be conducted at baseline, and at 5, 9, and 13 weeks. The primary outcome is the mean change in the NPDS at 9 weeks. Adverse events (AEs) will be recorded at every visit. DISCUSSION: The results of this study will be expected to provide useful information for the effectiveness and safety of TEA treatment compared to PT treatment for patients with CNP. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea (CRIS- KCT0003720), April 5, 2019.

Nanofibrous Polydioxanone Depots for Prolonged Intraperitoneal Paclitaxel Delivery.

BACKGROUND: Prolonged chemodrug delivery to the tumor site is a prerequisite to maintaining its localised therapeutic concentrations for effective treatment of malignant solid tumors. OBJECTIVE: The current study aims to develop implantable polymeric depots through conventional electrospinning for sustained drug delivery, specifically to the peritoneum. METHODS: Non-woven electrospun mats were fabricated by simple electrospinning of Polydioxanone solution loaded with the chemodrug, Paclitaxel. The implants were subjected to the analysis of morphology, mechanical properties, degradation and drug release in phosphate buffer and patient-derived peritoneal drain fluid samples. In vivo studies were conducted by surgical knotting of these implants to the peritoneal wall of healthy mice. RESULTS: Non-woven electrospun mats with a thickness of 0.65±0.07 mm, weighing ~ 20 mg were fabricated by electrospinning 15 w/v% polymer loaded with 10 w/w% drug. These implants possessing good mechanical integrity showed a drug entrapment efficiency of 87.82±2.54 %. In vitro drug release studies in phosphate buffer showed a sustained profile for ~4 weeks with a burst of 10 % of total drug content, whereas this amounted to >60% in patient samples. Mice implanted with these depots remained healthy during the study period. The biphasic drug release profile obtained in vivo showed a slow trend, with peritoneal lavage and tissues retaining good drug concentrations for a sustained period. CONCLUSION: The results indicate that non-woven electrospun mats developed from biodegradable Polydioxanone polymer can serve as ideal candidates for easily implantable drug depots to address the challenges of peritoneal metastasis in ovarian cancer.

Microscopic and clinical evidence of the degradation of polydioxanone lifting threads in the presence of hyaluronic acid: a case report. / Evidencia clínica y microscópica de la degradación de hilos de dermosustentación de polidioxanona en presencia de ácido hialurónico: reporte de caso.

We present the case of a female patient with complications from superficial implantation of polydioxanone spiculated threads in the facial middle third. The manifestations were edema, ecchymosis, superficial palpation of the thread and skin plication. For the treatment we propose a novel protocol of clinical degradation of polydioxanone threads, using hyaluronic acid injecting it into the implantation area of the polydioxanone threads. Non-cross linked hyaluronic acid was infiltrated along the path of the thread. The follow-up at seven, 21 and 45 days showed decreased edema, folds and skin irregularities due to wire traction and attenuation of secondary rhytides. A sample of the thread in hyaluronic acid was observed in a laminar flow campaign evidencing degradation at 72 hours. Administering hyaluronic acid was effective in inducing clinical biodegradation of the thread suggesting that non-crosslinked hyaluronic acid is a powerful catalyst for the hydrolytic degradation of polydioxanone.

Se expone el caso de una paciente remitida por complicaciones posteriores a la implantación superficial en el tercio medio facial de hilos de polidioxanona espiculados. Presentaba edema, equimosis, palpación superficial del hilo y plicación dérmica. Para el tratamiento planteamos un novedoso protocolo de degradación clínica de hilos de polidioxanona, empleando ácido hialurónico inyectándolo en el área de su implantación. Se infiltró ácido hialurónico no reticulado en el trayecto a lo largo del recorrido del hilo. El seguimiento a los siete, 21 y 45 días evidenció disminución del edema, de los pliegues e irregularidades dérmicas por la tracción del hilo y atenuación de rítides secundarias. Una muestra del hilo en ácido hialurónico fue observado en campana de flujo laminar evidenciándose degradación a las 72 horas. Administrar ácido hialurónico fue efectivo para inducir la biodegradación clínica del hilo. La hipótesis derivada sugiere que el ácido hialurónico no reticulado es un poderoso catalizador de la degradación hidrolítica de la polidioxanona.

Pyridine as an additive to improve the deposition of continuous electrospun filaments.

Electrospun filaments are leading to a new generation of medical yarns that have the ability to enhance tissue healing through their biophysical cues. We have recently developed a technology to fabricate continuous electrospun filaments by depositing the submicron fibres onto a thin wire. Here we investigate the influence of pyridine on the fibre deposition. We have added pyridine to polydioxanone solutions at concentrations ranging from 0 to 100 ppm, increasing the conductivity of the solutions almost linearly from 0.04 uS/cm to 7 uS/cm. Following electrospinning, this led to deposition length increasing from 1 cm to 14 cm. The samples containing pyridine easily underwent cold drawing. The strength of drawn filaments increased from 0.8 N to 1.5 N and this corresponded to a decrease in fibre diameter, with values dropping from 2.7 µm to 1 µm. Overall, these findings are useful to increase the reliability of the manufacturing process of continuous electrospun filaments and to vary their biophysical properties required for their application as medical yarns such as surgical sutures.

Polymer scaffold architecture is a key determinant in mast cell inflammatory and angiogenic responses.

Implanted polymer scaffolds can induce inflammation leading to the foreign body response (FBR), fibrosis, and implant failure. Thus, it is important to understand how immune cells interact with scaffolds to mitigate inflammation and promote a regenerative response. We previously demonstrated that macrophage phenotype is modulated by fiber and pore diameters of an electrospun scaffold. However, it is unclear if this effect is consistent among other innate immune cells. Mast cells are inflammatory sentinels that play a vital role in the FBR of implanted biomaterials, as well as angiogenesis. We determined if altering electrospun scaffold architecture modulates mast cell responses, with the goal of promoting regenerative cell-scaffold interactions. Polydioxanone (PDO) scaffolds were made from 60 mg/mL or 140 mg/mL PDO solutions, yielding structures with divergent fiber and pore diameters. Mouse mast cells plated on these scaffolds were activated with IL-33 or lipopolysaccharide (LPS). Relative to the 60 mg/mL scaffold, 140 mg/mL scaffolds yielded less IL-6 and TNF, and greater VEGF secretion. Pores >4-6 µm elicited less IL-6 and TNF secretion. IL-33-induced VEGF regulation was more complex, showing effects of both pore size and fiber diameter. These data indicate parameters that can predict mast cell responses to scaffolds, informing biomaterial design to increase wound healing and diminish implant rejection. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 884-892, 2019.

Improved Multicellular Response, Biomimetic Mineralization, Angiogenesis, and Reduced Foreign Body Response of Modified Polydioxanone Scaffolds for Skeletal Tissue Regeneration.

The potential of electrospun polydioxanone (PDX) mats as scaffolds for skeletal tissue regeneration was significantly enhanced through improvement of the cell-mediated biomimetic mineralization and multicellular response. This was achieved by blending PDX ( i) with poly(hydroxybutyrate- co-valerate) (PHBV) in the presence of hydroxyapatite (HA) and ( ii) with aloe vera (AV) extract containing a mixture of acemannan/glucomannan. In an exhaustive study, the behavior of the most relevant cell lines involved in the skeletal tissue healing cascade, i.e. fibroblasts, macrophages, endothelial cells and preosteoblasts, on the scaffolds was investigated. The scaffolds were shown to be nontoxic, to exhibit insignificant inflammatory responses in macrophages, and to be degradable by macrophage-secreted enzymes. As a result of different phase separation in PDX/PHBV/HA and PDX/AV blend mats, cells interacted differentially. Presumably due to varying tension states of cell-matrix interactions, thinner microtubules and significantly more cell adhesion sites and filopodia were formed on PDX/AV compared to PDX/PHBV/HA. While PDX/PHBV/HA supported micrometer-sized spherical particles, nanosized rod-like HA was observed to nucleate and grow on PDX/AV fibers, allowing the mineralized PDX/AV scaffold to retain its porosity over a longer time for cellular infiltration. Finally, PDX/AV exhibited better in vivo biocompatibility compared to PDX/PHBV/HA, as indicated by the reduced fibrous capsule thickness and enhanced blood vessel formation. Overall, PDX/AV blend mats showed a significantly enhanced potential for skeletal tissue regeneration compared to the already promising PDX/PHBV/HA blends.