Biodegradable Polydioxanone Microspheres for Transcatheter Arterial Embolization: Proof of Principle.

PURPOSE: To evaluate feasibility, embolization success, biodegradability, reperfusion, and biocompatibility of biodegradable microspheres (MS) made from polydioxanone (PDO) for transcatheter arterial embolization. MATERIALS AND METHODS: Unilateral selective renal embolization of a segmental artery was performed in 16 New Zealand White rabbits with PDO-MS (100-150 µm and 90-315 µm). Animals were randomly assigned to different observation periods and underwent control digital subtraction angiography (DSA) and MR imaging immediately (n = 3), 1 week (n = 2), 4 weeks (n = 2), 8 weeks (n = 2), 12 weeks (n = 5), and 16 weeks (n = 2) after embolization. Kidneys were harvested for macroscopic and histologic analysis of embolization success, biodegradability, and biocompatibility. RESULTS: Embolization was technically successful in 15 of 16 animals. One animal died of anesthesia-related circulatory failure. The 100-150 µm MS were injected easily through 3-F catheters; the 90-315 µm MS tended to clog with intermittent catheter obstruction. DSA and MR imaging showed successful target embolization in 13 of 15 animals. In 2 animals, the entire kidney was affected owing to catheter clogging, including a reflux of MS while flushing. Control DSA and MR imaging showed increasing vascular reperfusion with time. Macroscopic and histologic analysis revealed necrosis/infarction in areas in which embolization was achieved. MS were extensively degraded after 16 weeks, and overall inflammatory reaction was mild. CONCLUSIONS: Biodegradable PDO-MS induced effective embolization of target vessels while demonstrating good biocompatibility. MS increasingly dissolved at 16 weeks, partial reperfusion started at week 1, and complete reperfusion started at week 8, thus offering possible advantages as a temporary embolic agent.

Effectiveness and safety of polydioxanone thread-embedding acupuncture (TEA) and electroacupuncture (EA) treatment for knee osteoarthritis (KOA) patients with postoperative pain: An assessor-blinded, randomized, controlled pilot trial.

BACKGROUND: Degenerative knee osteoarthritis (KOA) shows an increase in morbidity with improvement in the living conditions and extended lifespans. Treatment for degenerative KOA has been gaining attention since it significantly affects the life of the elderly population and is also associated with increased expenses for medical services and high socioeconomic costs. Treatments for degenerative KOA include nondrug therapy, drug therapy, and surgical treatment. For cases that show little response to conservative treatment but have not involved severe deformation of the knee, procedures such as arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation can be performed. However, effective treatment is required for patients experiencing sustained knee pain after surgery. Although studies confirming the therapeutic effects of acupuncture or thread-embedding acupuncture (TEA) treatment for degenerative KOA have been reported, clinical studies on a combination of TEA and electroacupuncture (EA) in patients complaining of knee pain after arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation have not yet been reported. Therefore, this study aimed to evaluate the effectiveness and safety of this combination treatment in patients with persistent knee pain after arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation. METHODS/DESIGN: This study has been designed as a 2-group, parallel, single-center, randomized, controlled, assessor-blinded trial. Thirty-six patients with degenerative KOA who complained of pain even after arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation will be randomized to either the (TEA + EA + Usual care) group or the (Usual care only) group in a 1:1 ratio. The patients in the (TEA + EA + Usual care) group will receive TEA treatment once a week for 4 weeks for a total of 4 sessions and EA twice a week for a total of 8 sessions while continuing usual care. The (Usual care only) group will only receive usual care for 4 weeks. To assess the efficacy of the TEA and EA combination treatment, the visual analogue scale, the Korean version of the Western Ontario and McMaster Universities Osteoarthritis Index, the EuroQol 5-Dimension 5-Level, and the doses of the rescue drug taken will be evaluated at baseline (1W) and weeks 2 (2W), 4 (4W), 6 (6W), and 8 (8W). The primary efficacy endpoint is the mean change in visual analogue scale at week 4 (4W) compared to baseline. Adverse events will be assessed at every visit. DISCUSSION: This study will provide useful data for evaluating the clinical efficacy and safety of TEA and electroacupuncture combination treatment for improving pain and quality of life after surgery for degenerative KOA. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea (CRIS- KCT0004804), March 6, 2020.

Repair of the sellar floor using bioresorbable polydioxanone foils after endoscopic endonasal pituitary surgery.

OBJECTIVE: Postoperative CSF leakage is the most common unwanted sequela of transnasal pituitary surgery. The individual anatomy, the extent of the sellar opening, and the occurrence of an intraoperative CSF leak add to the risk of postoperative rhinorrhea. Despite the current sophistication and recent developments in pituitary surgery, watertight closure of the sellar floor remains a matter of concern. Improvements and additions to the technical armamentarium of sellar reconstruction are therefore still desirable. METHODS: The authors present a closure technique of the sellar floor using a bioresorbable polydioxanone foil, which is placed between the dura and the bony margins of the open sellar floor to keep the intrasellar implants in place and to withstand the pressure arising from the intracranial compartment. RESULTS: The technique was used in a technical case series of 30 patients, and in all patients the floor could be sufficiently reconstructed. CSF flow intraoperatively was documented in 10 cases (33.3%). Postoperative CSF rhinorrhea was detected in one patient (3.3%). No complications could be attributed to the technique or the material during a mean follow-up period of 477 days. The foils can easily be identified on MR images and CT scans and therefore do not affect the postoperative radiological assessment. CONCLUSIONS: The described technique is an easy, inexpensive, and reliable method for sellar floor reconstruction and has a low CSF leakage rate. It is recommended when the risk of a postoperative CSF leak is high and there is still enough bony margin of the sellar floor left that enables a sufficient fixation of the foil.

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.

Clinical outcome after orbital floor fracture reduction with special regard to patient's satisfaction.

PURPOSE: Primary reconstruction via transconjunctival approach is a standardized treatment option for orbital floor fractures. The aim of this study was to compare the findings of specific ophthalmologic assessment with the patient's complaints after fracture reduction. METHODS: A retrospective medical chart analysis was performed on patients who had undergone transconjunctival orbital floor fracture reduction for fracture therapy with resorbable foil (ethisorb sheet or polydioxanone foil). A follow-up assessment including ophthalmological evaluation regarding visual acuity (eye chart projector), binocular visual field screening (Bagolini striated glasses test) and diplopia (cover test, Hess screen test) was conducted. Additionally, a questionnaire was performed to assess patients' satisfaction. RESULTS: A total of 53 patients with a mean follow-up of 23 months (ranging from 11 to 72) after surgical therapy were included. Diplopia was present preoperatively in 23 (43.4%) and reduced in follow-up examination (n = 12, 22.6%). Limitations in ocular motility reduced from 37.7% to 7.5%. The questionnaire about the patient's satisfaction revealed excellent outcomes in relation to the functional and esthetical parameters. CONCLUSION: Transconjunctival approach is a safe approach for orbital fracture therapy. Postoperative diplopia is nearly never perceptible for the individual and differs to pathologic findings in the ophthalmic assessment.

Biostimulatory effects of polydioxanone, poly-d, l lactic acid, and polycaprolactone fillers in mouse model.

BACKGROUND: Numerous fillers are increasingly used for augmentation of volume loss and relaxation of facial wrinkles. Collagen stimulators are the latest next-generation dermal fillers that can induce neocollagenesis. To investigate biophysical characteristics, safety, and efficacy of newly developed polydioxanone (PDO) filler in comparison with poly-l lactic acid (PLLA) and polycaprolactone (PCL) fillers. METHODS: In vitro assay, morphology of particles, and rheological property of fillers were measured. A total of 24 female hairless mice (SKH1-Hrhr ) were randomly divided into three groups and injected with PDO, PLLA, or PCL fillers. Durability of fillers was assessed at 0, 3 days, and 1, 4, 8, 12 weeks after injection using folliscope and PRIMOS. To determine biocompatibility and neocollagenesis, histologic evaluation was performed at 1, 4, 8, and 12 weeks after injection. Efficacy was also evaluated based on skin surface roughness changes using PRIMOS in a hairless mouse photoaging model. RESULTS: In the particle morphology test, PDO microspheres had an irregular surface and were spherical and uniformly sized. PDO filler demonstrated similar neocollagenesis and inflammatory response to other collagen stimulators. PDO filler showed better biodegradability than PLLA and PCL fillers. In the hairless mouse photoaging model, there was a statistically significant decrease in skin surface roughness after PDO filler injection. CONCLUSIONS: Our data suggest that newly developed collagen stimulating PDO filler might be a safe and effective option for correction of volume loss and rejuvenation of photoaging skin.

Tissue changes over time after polydioxanone thread insertion: An animal study with pigs.

BACKGROUND: Polydioxanone (PDO) sutures have been widely used to tighten and lift the face. However, why the complexion brightens and skin elasticity is maintained with a smaller facial outline after a PDO monofilament thread treatment remains unclear. AIMS: We aimed to determine what significant changes occur in the tissue over time when a PDO suture is inserted. METHODS: We selected four White Yucatan variety pygmy pigs with skin that most closely resembles the structure of human skin. 4-0 PDO thread was inserted into the subcutaneous fat. Tissue samples were obtained at 4, 12, 24, and 48 weeks. For the histologic analysis, H&E staining, Masson trichrome staining, and anti-smooth muscle actin immunohistochemical staining techniques were used. RESULTS: Nine histological findings appeared over time, and these findings are summarized as five tissue changes. CONCLUSIONS: PDO sutures cause specific changes to the surrounding tissues that result in neo-collagenesis, a fibrous merging effect, fat reduction, tissue contracture, and an improved vascular environment. The results of this study explain the positive changes described in previous clinical research.

Multipolydioxanone scaffold improves upper lip and forehead wrinkles: A 12-month outcome.

BACKGROUND: The safety and wrinkle-reducing effects of multipolydioxanone (PDO) scaffold have been confirmed in animal, and clinical tests for 3 months, but the 12-month outcomes, are unknown. OBJECTIVE: The safety and efficacy of multi-PDO scaffold were tested in animal models and in humans for 12 months. METHODS: In the animal study, a multi-PDO scaffold was implanted into the panniculus carnosus of rat dorsal skin (n = 18) and into the subcutaneous layer of minipig dorsal skin (n = 2) followed by histological staining and analysis. In a human study, a multi-PDO scaffold was implanted deep into the periosteal subcutaneous layer under the wrinkles on the upper lips and forehead, followed by evaluation of clinical changes using digital photography and PRIMOS. RESULTS: A multi-PDO scaffold was not observed after 6 months in rats and minipigs. However, the newly formed tissues within the hollow body of the scaffolds were maintained for up to 12 months. The enhanced effect on the upper lips and forehead wrinkles lasted up to 12 months without any side effects. CONCLUSION: A multi-PDO scaffold represents a new tool to improve upper lips and forehead wrinkles.

Multi-polydioxanone (PDO) scaffold for forehead wrinkle correction: A pilot study.

BACKGROUND: Forehead wrinkles are the result of contracture of the frontalis muscle and the skin aging process. Currently, hyaluronic acid filler and botulinum toxin are the main materials used for correction of these wrinkles. In addition, polydioxanone (PDO) thread has also been applied for this treatment. OBJECTIVE: In order to evaluate the efficacy and safety of multi-PDO scaffold in animal and human skin, we tested PDO insertion in rat and mini-pig models and human volunteers with forehead wrinkles. METHODS: A stent-shaped multi-PDO scaffold was inserted under the panniculus carnosus of rat dorsal skin and the subcutaneous layer of mini-pig dorsal skin and forehead wrinkles in three human volunteers. RESULTS: Histological analysis at 12 weeks revealed evidence of de novo collagen synthesis, which was consistent with clinical results on photo evaluation. CONCLUSION: Stent-shaped multi-PDO scaffolds may be another effective and safe treatment modality for reduction of forehead wrinkles.

[Chemical synthesis of biodegradable poly-para-dioxanone and its application for mandibular fracture fixation].

OBJECTIVE: To observe mandibular fracture healing after synthesized bioabsorable poly-para-dioxanone (PDS) ligature fixation. METHODS: Para-dioxanone monomer was prepared by chemical reactions of metallic sodium, ethylene glycol and other raw materials. PDS was synthesized by polymerizing the purified para-dioxanone in the presence of catalyst under the conditions of negative pressure and certain temperature. PDS ligature was obtained by processing the polymer into small granules, drying and melt-extruding through a spinnerette. Eighteen adult male New Zealand rabbits were assigned randomly into two groups. After mandibular fracture models were created, reductions of the artificial fractures were accomplished by means of transosseous PDS ligatures on each of 12 rabbits in experimental group. While the other six rabbits without any internal fixation were set as control. Schedules for killing were arranged to give postoperative samples at two-week interval till 12th week. RESULTS: Radiographical and histological examinations demonstrated that all fractures fixed with PDS ligatures healed without any complication. Periosteal and cartilaginous osteogenesis was observed in newly formed external callus. In contrast, bone fragment migration and the consequent nonunion occurred in the control group. PDS ligature degraded and absorbed without interference with osseous union and healing. The tensile strength reduction of PDS ligature was prior to its absorption in vivo. CONCLUSION: The synthesized PDS is a colorless, flexible, themoplastic and monofilament fiber, which can be sterilized by ethylene oxide embalmment without serious loss of tensile strength. It seems that the application of this macromolecular material in internal fixation is of great worth for further study.