Bioresorbable Polymer Research Articles

Morphological and Functional Characteristics of the Microenvironment After Pleural Implantation of Biosynthetic Materials

The objective: to study morphological changes in tissues after implantation of a bioresorbable material synthesized on the basis of polylactide (PLA) and polycaprolactone (PCL) in various ratios.Subjects and Methods. Laboratory animals Chinchilla lanigera (n = 12) underwent intrapleural implantation with 2% PLA/PCL 1/1 and 4% PLA/PCL 1/3 materials. Morphometric assessment was carried out in14 and 28 weeks, the animals were withdrawn from the experiment by an anesthetic overdosing.Results. When studying tissues adjacent to the implant regardless of differences in its composition, similar morphological signs were observed. A fibrous capsule formed around the implants, and it was more pronounced in 4% of PLA/PCL 1/3. In the structure of the implants, we noted the growth of loose and dense unformed fibrous connective tissue with blood vessels with a significant replacement of the bioresorbable polymer material (by 2/3). Lymphocytes, plasma cells, single macrophages, and multinucleated cells were predominantly located at the implant/tissue interface. In all studied samples, no necrosis was observed in the implantation bed and surrounding tissue.Conclusion. The data obtained confirm the biosafety of biomaterials and demonstrate the potential for their use in surgical treatment of humans.

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.

Industry update, December 2022.

Industry update, December 2022.

Additive Manufacturing of Polyhydroxyalkanoate-Based Blends Using Fused Deposition Modelling for the Development of Biomedical Devices.

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes. We highlight issues with current CAD design and slicing and suggest optimisations of more complex designs targeted towards biomedical applications. We demonstrate the ability to print patient specific implants from real CT scans and reconstruct missing structures by means of mirroring and mesh mixing. A blend of Polyhydroxyalkanoates (PHAs), a family of biocompatible and bioresorbable natural polymers and Poly(L-lactic acid) (PLLA), a known bioresorbable medical polymer is used. Our characterisation of the PLA/PHA filament suggest that its tensile properties might be useful to applications such as stents, NGCs, and bone scaffolds. In addition to this, the proof-of-concept work for other applications shows that FDM is very useful for a large variety of other soft tissue applications, however other more elastomeric MCL-PHAs need to be used.

Новые гибридные покрытия для контроля скорости деградации магниевого сплава МА8

The method for modifying the surface of a bioresorbable magnesium alloy (MA8 – Mg-Mn-Ce system) using formation of the hybrid coatings containing an organic biocompatible corrosion inhibitor and a bioresorbable polymer material was developed. The anticorrosion properties of the formed coatings were studied in physiological solution (0.9 wt.% NaCl and HBSS). Such layers reduce the rate of alloy degradation due to the active protection function.

Получение скаффолдов на основе железа с антибактериальным покрытием на основе полимолочной кислоты и ванкомицина

Bioresorption of implants is a widely studied phenomenon today. Complete degradation of the implant after performing its mechanical function is the safest outcome for the patient. It also excludes revision prosthetics. Promising materials include metals and composites based on them. Currently, research on the development of biorezorable nanocomposite structures based on iron is actively underway. Often during orthopedic surgery, infections can enter the patient’s body. Therefore, various ways of modifying the implants with antibiotics are being developed. One of the modification options suggests that an antibacterial coating on the surface of the scaffold can be obtained by impregnating it with solutions of bioresorbable polymers filled with drugs. Variation in polymer composition, antibiotic concentration, and impregnation cycles makes it possible to obtain the necessary drug release parameters to achieve an optimal therapeutic effect. Since the object of our study, iron, does not have antimicrobial properties, in this work we considered the possibility of modifying Fe scaffolds with vancomycin by impregnation with antibiotic solution and polylactic acid (PLA) solution containing vancomycin. The process of drug release in physiological solution (0.9 % NaCl) and antibacterial properties of the obtained materials were studied. The structure and composition of the scaffolds and mechanical characteristics were also investigated. It was shown that modification of the surface of the scaffolds with polylactic acid leads to an increase in the ultimate strength by 40 % and to an overall smoothing of the deformation curve. The study showed that the introduction of vancomycin into the polymer allows obtaining an antibacterial coating on the surface of the scaffold with a prolonged release of the drug.

New Polycaprolactone-Containing Self-Healing Coating Design for Enhance Corrosion Resistance of the Magnesium and Its Alloys

The method of hybrid coating formation on the surface of a bioresorbable wrought magnesium alloy and magnesium obtained by additive technology was proposed. Plasma electrolytic oxidation (PEO) with subsequent treatment of the material using an organic biocompatible corrosion inhibitor and a bioresorbable polymer material was used to obtain the protective layers. The optimal method of surface treatment was suggested. Using SEM/EDX analysis, XRD, XPS, and confocal Raman microspectroscopy, the composition of the formed surface layers was determined. The corrosion protection performance of the formed coatings was studied by potentiodynamic polarization and electrochemical impedance spectroscopy techniques in 0.9 wt.% NaCl and HBSS. Hydrogen evolution and mass loss tests were performed to study the corrosion rate of samples with different types of protective coatings. Sealing the pores of PEO coating with a polymeric material contributes to a significant reduction in the amount of the inhibitor diffusing into a corrosive medium. The best barrier properties were established for the hybrid coating formed with a one-stage application of benzotriazole and polycaprolactone. Such layers reduce the rate of alloy degradation due to active protection.

Magnesium Bioresorbable Scaffold (BRS) Magmaris vs Biodegradable Polymer DES Ultimaster in NSTE-ACS Population-12-Month Clinical Outcome.

Percutaneous coronary intervention (PCI) in the acute coronary syndrome (ACS) setting is associated with a greater probability of device failure. The currently ongoing development of new scaffold technologies has concentrated an effort on improving the PCI outcomes, including the use of new biodegradable materials. This pilot study evaluates the performance of a magnesium bioresorbable scaffold (Magmaris, Biotronik, Germany) in comparison to the sirolimus-eluting bioresorbable polymer stents (BP-SES) (Ultimaster, Terumo, Japan) in the NSTE-ACS setting. The population of this pilot comprised 362 patients assigned to one of two arms (193-Magmaris vs 169-Ultimaster). The data regarding the primary outcome comprised of death from cardiac causes, myocardial infarction, and stent thrombosis, along with target-lesion failure (TLF) and other clinical events was collected in the 1-yearfollow-up. There were no statistically significant differences in clinical outcomes in the short term (30 days) or in the 1-yearfollow-up between both groups. At 12 months, there were no statistically significant differences between the Magmaris and Ultimaster for composed endpoints or the TLF.

Bioresorbable PPDO sliding-lock stents with optimized FDM parameters for congenital heart disease treatment

Stent implantation has been a promising therapy for congenital heart disease (CHD) due to better efficacy. Compared to permanent metal stents, bioresorbable polymer stents have shown a great advantage in accommodating the vascular growth of pediatric patients, but the application is still limited due to inferior radial strength. Here, bioresorbable poly(p-dioxanone) (PPDO) sliding-lock stents for CHD treatment were fabricated by fused deposition modeling (FDM). The effects of FDM processing parameters, including nozzle temperature, bed temperature, layer thickness, and printing speed, on the mechanical properties of PPDO parts were investigated to optimize the processing condition to enhance the radial strength of stents. Finite element analysis (FEA) was also used to evaluate the mechanical properties of stents. PPDO sliding-lock stents fabricated under optimized FDM parameters showed radial strength of 3.315 ± 0.590 N/mm, superior to benchmark commercial metal stents. Radial strength curve and compression behavior of PPDO sliding-lock stents were investigated. Results of FEA exhibited that strut width, shape of the mesh cell and surface coverage ratio had an impact on the compression force of PPDO sliding-lock stents. PPDO sliding-lock stents fabricated with optimized FDM parameters show favorable mechanical performance and meet the requirement of CHD treatment.

Dense, porous, and fibrous scaffolds composed of PHBV, PCL, and their 75:25 blend: an in vitro morphological and cytochemical characterization

In tissue engineering bioresorbable polymers are commonly used to mimetize a damaged tissue characteristics. In spite of that, we did not find a comparative study of the response of the same cell to dense, porous, and fibrous biomaterials. The present work aimed to study the in vitro of pure polymers [poly (ε-caprolactone) (PCL) and poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV)] and their 75:25 blend in dense, porous, and fibrous forms in Vero cells, a fibroblast cell line. The biomaterials were characterized morphologically by scanning electron microscopy (SEM). The MTT assay was used for analysis of possible cytotoxicity. Vero cells were cultured on biomaterials for 120 h and submitted to SEM, morphological and cytochemical analyses. The dyes used were crystal violet (morphology), toluidine blue at pH 4.0 (for nucleic acids and glycosaminoglycans) and 2.5 (for glycosaminoglycans only), periodic acid-Schiff reactive (for neutral sugars), xylidine ponceau at pH 2.5 (for total proteins), and picrosirius/hematoxylin (for selective collagen analysis). The biomaterials studied were not considered citocytotoxic. The cells were able to adhere to and proliferate on the substrates. The cytochemical data indicate that the cells have high functional activity, with high protein synthesis on the scaffolds but do not accumulate acid or neutral sugars. The cells on the fibrous polymers appear to be more elongated, following the shape of the fibers. Regarding the scaffold form (porous or fibrous), the in vitro data do not show great superiority of one type to the other. Then, all the polymers tested are suitable for tissue engineering.

Development of 3D printable bioresorbable drug eluting coronary stents: An experimental and computational investigation

Over the last few years, the development of bioresorbable polymeric stents for the treatment of coronary artery diseases has attracted strong interest. In this study we introduced a computational modelling approach via a virtual testbed to investigate and predict the behaviour of 3D printed stents by applying inflation, hold and deflation sequences of loading. Bespoke designs – racetrack-cell and diamond-cell shaped stents were printed in a layer-by-layer manner using Fusion Deposition Modelling (FDM) where printable filaments comprised of bioresorbable polymers namely polydioxanone (PDO) and polylactic acid (PLA) blends at 60:40 and 70:30 ratios. The structural response of the stents was investigated by extracting from the numerical study the elastic recoil, foreshortening, longitudinal retraction, and dog-boning of the stents. Damage assessment indices were used to assess if a specific stent design failed during the deployment process and hence unsuitable for stent printing. The study revealed that racetrack designs are marginally better than the diamond stent designs. The study has shown the potential of computational modelling for the in-silico evaluation of 3D printed bioresorbable coronary artery stents.

3D-Printed Radiopaque Bioresorbable Stents to Improve Device Visualization.

Bioresorbable stents (BRS) hold great promise for the treatment of many life-threatening luminal diseases. Tracking and monitoring of stents in vivo is critical for avoiding their malposition and inadequate expansion, which often leads to complications and stent failure. However, obtaining high X-ray visibility of polymeric BRS has been challenging because of their intrinsic radiolucency. This study demonstrates the use of photopolymerization-based 3D printing technique to fabricate radiopaque BRS by incorporating iodixanol, a clinical contrast agent, into a bioresorbable citrate-based polymer ink. The successful volumetric dispersion of the iodixanol through the 3D-printing process confers strong X-ray visibility of the produced BRS. Following in vitro degradation, the 3D-printed BRS embedded in chicken muscle maintains high X-ray visibility for at least 4 weeks. Importantly, the 3D-printed radiopaque BRS demonstrates good cytocompatibility and strong mechanical competence in crimping and expansion, which is essential for minimally invasive stent deployment. In addition, it is found that higher loading concentrations of iodixanol, e.g. 10 wt.%, results in more strut fractures in stent crimping and expansion. To conclude, this study introduces a facile strategy to fabricate radiopaque BRS through the incorporation of iodixanol in the 3D printing process, which could potentially increase the clinical success of BRS.

Characterization and in vitro release of minocycline hydrochloride microspheres prepared via coacervation

Coacervation is a commonly used method for protein and peptide drug microencapsulation using biodegradable or bioresorbable polymers. However, there is a lack of literature focused on microencapsulation of small molecule drugs using coacervation techniques. In addition, the apparatus used for this microencapsulation method has not been well-described. The objectives of the present work were to: (1) establish a reliable apparatus for coacervation microencapsulation; (2) investigate the impact of the viscosity of the silicone oil used in processing on microsphere performance; and (3) develop a reproducible in vitro release testing method for minocycline hydrochloride microspheres. Minocycline hydrochloride was chosen as the model drug and two compositionally equivalent microsphere formulations were prepared via coacervation using an in-house designed glass vessel assembly with a novel in-house customized paddle to achieve a relatively homogeneous particle size distribution. The critical physicochemical properties including drug loading, particle size, and morphology of the prepared microspheres and the commercial microspheres product (Arestin) were determined. In vitro release testing of the prepared microspheres as well as of Arestin was performed using a sample-and-separate method. The method showed good reproducibility and discriminatory ability. The physicochemical properties (such as particle size) as well as the in vitro release characteristics of the prepared microspheres were determined to be sensitive to the viscosity of the silicone oil used in coacervation processing. The silicone oil with higher viscosity (1000 cSt) used during the coacervation process resulted in smaller particle sized microspheres and consequently caused a higher initial burst release. Whereas, the silicone oil with lower viscosity resulted in larger sized microspheres with low burst release and a slower drug release rate.

Additive Manufacturing of Drug-Eluting Multilayer Biodegradable Films.

Drug-eluting films made of bioresorbable polymers are a widely used tool of modern personalized medicine. However, most currently existing methods of producing coatings do not go beyond the laboratory, as they have low encapsulation efficiency and/or difficulties in scaling up. The PLACE (Printed Layered Adjustable Cargo Encapsulation) technology proposed in this article uses an additive approach for film manufacturing. PLACE technology is accessible, scalable, and reproducible in any laboratory. As a demonstration of the technology capabilities, we fabricated layered drug-eluting polyglycolic acid films containing different concentrations of Cefazolin antibiotic. The influence of the amount of loaded drug component on the film production process and the release kinetics was studied. The specific loading of drugs was significantly increased to 200–400 µg/cm2 while maintaining the uniform release of Cefazolin antibiotic in a dosage sufficient for local antimicrobial therapy for 14 days. The fact that the further increase in the drug amount results in the crystallization of a substance, which can lead to specific defects in the cover film formation and accelerated one-week cargo release, was also shown, and options for further technology development were proposed.

Coronary bioresorbable stents: Non-invasive quantitative evaluation of intra- and juxta-stent plaque composition-A computed tomography longitudinal study.

PurposeCoronary bioresorbable stents (BRS) do not produce blooming artifacts on computed tomography (CT), in contrast to metallic stents, as they are made of a bioresorbable polymer and are radiolucent. They allow to evaluate the coronary plaque beneath. The low-attenuation plaque (LAP) suggests plaque vulnerability and is CT assessable. The aim of our study was to show the possibility of a non-invasive CT evaluation of the volume and the LAP composition of the intra- and juxta-stent plaque.MethodologyIn our prospective longitudinal study, we recruited 27 consecutive patients (35 BRS stents total; mean age 60 +/- 9 years) with bioresorbable stents for a 256-slice ECG-synchronized CT evaluation at 1- and 12-months post stent implantation. Total plaque volume (mm3), absolute and relative (%) LAP volume per block in the pre- intra- and post-stent zones were analyzed; comparison 1- and 12-months post-implantation of BRS. Changes in the previously mentioned variables were assessed by the mixed effects models with and without spline, which also accounted for the correlation between repeated measurements.ResultsOur block or spline model analysis has shown no significant difference in plaque or absolute LAP volumes in pre- intra- and post-stent zones between 1 and 12 months. Interestingly, % LAP volume increases near-significantly in the distal block of the intrastent at 12-mo follow-up (from 23.38 ± 1.80% to 26.90 ± 2.22% (increase of 15%), p = 0.052).ConclusionOur study demonstrates the feasibility of the repeated non-invasive quantitative analysis of the intrastent coronary plaque and of the in-stent lumen by CT scan.

Natural and Synthetic Polymer Scaffolds Comprising Upconversion Nanoparticles as a Bioimaging Platform for Tissue Engineering.

Modern biocompatible materials of both natural and synthetic origin, in combination with advanced techniques for their processing and functionalization, provide the basis for tissue engineering constructs (TECs) for the effective replacement of specific body defects and guided tissue regeneration. Here we describe TECs fabricated using electrospinning and 3D printing techniques on a base of synthetic (polylactic-co-glycolic acids, PLGA) and natural (collagen, COL, and hyaluronic acid, HA) polymers impregnated with core/shell β-NaYF4:Yb3+,Er3+/NaYF4 upconversion nanoparticles (UCNPs) for in vitro control of the tissue/scaffold interaction. Polymeric structures impregnated with core/shell β-NaYF4:Yb3+,Er3+/NaYF4 nanoparticles were visualized with high optical contrast using laser irradiation at 976 nm. We found that the photoluminescence spectra of impregnated scaffolds differ from the spectrum of free UCNPs that could be used to control the scaffold microenvironment, polymer biodegradation, and cargo release. We proved the absence of UCNP-impregnated scaffold cytotoxicity and demonstrated their high efficiency for cell attachment, proliferation, and colonization. We also modified the COL-based scaffold fabrication technology to increase their tensile strength and structural stability within the living body. The proposed approach is a technological platform for “smart scaffold” development and fabrication based on bioresorbable polymer structures impregnated with UCNPs, providing the desired photoluminescent, biochemical, and mechanical properties for intravital visualization and monitoring of their behavior and tissue/scaffold interaction in real time.

A kinetic scission model for molecular weight evolution in bioresorbable polymers

AbstractFurther development of bioresorbable devices for use in clinical applications, where they can reduce long term risks, has been hindered by the complex degradation mechanisms that bioresorbable polymers exhibit and the difficulty this causes in designing suitable devices. Furthermore, experimental degradation studies often take years to complete, and small changes to the design of the test sample may significantly alter the degradation behavior. Motivated by existing degradation models, we present a kinetic scission model to predict how the molecular weight distribution evolves as a function of degradation time for bioresorbable polymers. Here, a refined kinetic model has been developed to capture the autocatalytic effect of carboxylic acid ends created via chain scissions, and our framework accounts for reduction in molecular weight via the cleavage of monomers from chain ends and from scissions in the middle of the polymer chain. These developments allow for a more complete representation of the molecular weight distribution during degradation. Young's modulus is estimated by approximating the changes in entropy for the molecular weight distributions following previous so‐called “entropy spring” models. The results obtained are quantitatively compared to and calibrated with existing experimental data for PLGA films. Finally, the effect of the initial carboxylic acid end on the degradation behavior is explored.

The Influence of Graphene Content on the Antibacterial Properties of Polycaprolactone.

This work contains an analysis of the impact of modifying a bioresorbable polymer—polycaprolactone (PCL)—with various additives on its antibacterial properties. To this end, samples of PCL filament containing various content levels of graphene (GNP), 0.5%, 5%, 10%, were obtained using injection molding. Polymer samples without additives were used for comparison. The next step was to assess the antimicrobial impact of the preparations under study against the following microorganisms: Staphylococcus aureus ATCC 25293, Escherichia coli ATCC 25922, Candida albicans ATCC 10231. Effective bactericidal activity of PCL with small amount of GNP, especially against C. albicans and S. aureus was confirmed. A decrease in this property or even multiplication of microorganisms was observed in direct proportion to the graphene content in the samples.

Business Roundup

BUSINESS Business Roundup ShareShare onFacebookTwitterWechatLinked InRedditEmail C&EN, 2022, 100 (32), p 11September 12, 2022Cite this:C&EN 100, 32, 11AbstractSeatex has acquired fellow Texas contract chemical manufacturer ChemQuest Chemicals. The combined firm will serve specialty chemical customers including oil and gas, cleaning, agriculture, and water treatment firms. Ashland will double the footprint and staffing of its bioresorbable polymer plant in Mullingar, Ireland. Various slow-release medications and dissolving medical devices use the lactide-glycolide-caprolactone copolymers made at the site. Balchem , which makes food ingredients and animal feed supplements, has acquired the methylsulfonylmethane (MSM) maker Bergstrom Nutrition. MSM is a food ingredient that supports joint and skin health and that can also be used in pet foods, Balchem says. BASF has agreed to purchase pyrolysis oil from Arcus Greencycling Technology, which operates a plastics pyrolysis recycling demonstration plant in Frankfurt, Germany. BASF plans to use the oil as feedstock at its chemical complex in Ludwigshafen, Germany. Lonza has formed a pact with Touchlight that allows it to offer Touchlight’s enzymatically madeView: PDF | Full Text HTML

Abbreviated Antiplatelet Therapy After Coronary Stenting in Patients With Myocardial Infarction at High Bleeding Risk

BackgroundThe optimal duration of antiplatelet therapy (APT) after coronary stenting in patients at high bleeding risk (HBR) presenting with an acute coronary syndrome remains unclear. ObjectivesThe objective of this study was to investigate the safety and efficacy of an abbreviated APT regimen after coronary stenting in an HBR population presenting with acute or recent myocardial infarction. MethodsIn the MASTER DAPT trial, 4,579 patients at HBR were randomized after 1 month of dual APT (DAPT) to abbreviated (DAPT stopped and 11 months single APT or 5 months in patients with oral anticoagulants) or nonabbreviated APT (DAPT for minimum 3 months) strategies. Randomization was stratified by acute or recent myocardial infarction at index procedure. Coprimary outcomes at 335 days after randomization were net adverse clinical outcomes events (NACE); major adverse cardiac and cerebral events (MACCE); and type 2, 3, or 5 Bleeding Academic Research Consortium bleeding. ResultsNACE and MACCE did not differ with abbreviated vs nonabbreviated APT regimens in patients with an acute or recent myocardial infarction (n = 1,780; HR: 0.83; 95% CI: 0.61-1.12 and HR: 0.86; 95% CI: 0.62-1.19, respectively) or without an acute or recent myocardial infarction (n = 2,799; HR: 1.03; 95% CI: 0.77-1.38 and HR: 1.13; 95% CI: 0.80-1.59; Pinteraction = 0.31 and 0.25, respectively). Bleeding Academic Research Consortium 2, 3, or 5 bleeding was significantly reduced in patients with or without an acute or recent myocardial infarction (HR: 0.65; 95% CI: 0.46-0.91 and HR: 0.71; 95% CI: 0.54-0.92; Pinteraction = 0.72) with abbreviated APT. ConclusionsA 1-month DAPT strategy in patients with HBR presenting with an acute or recent myocardial infarction results in similar NACE and MACCE rates and reduces bleedings compared with a nonabbreviated DAPT strategy. (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020)