Long-term effect of biodegradable vs durable polymer everolimus-eluting stents on neoatherosclerosis in ST-segment elevation myocardial infarction: the CONNECT trial.

BACKGROUND AND AIMS: Neoatherosclerosis is a leading cause of late (>1 year) stent failure following drug-eluting stent implantation. The role of biodegradable (BP) versus durable polymer (DP) drug-eluting stents on long-term occurrence of neoatherosclerosis remains unclear. Superiority of biodegradable against durable polymer current generation thin-strut everolimus-eluting stent (EES) was tested by assessing the frequency of neoatherosclerosis 3 years after primary percutaneous coronary intervention (pPCI) among patients with ST-segment elevation myocardial infarction (STEMI). METHODS: The randomized controlled, multicentre (Japan and Switzerland) CONNECT trial (NCT03440801) randomly (1:1) assigned 239 STEMI patients to pPCI with BP-EES or DP-EES. The primary endpoint was the frequency of neoatherosclerosis assessed by optical coherence tomography (OCT) at 3 years. Neoatherosclerosis was defined as fibroatheroma or fibrocalcific plaque or macrophage accumulation within the neointima. RESULTS: Among 239 STEMI patients randomized, 236 received pPCI with stent implantation (119 BP-EES; 117 DP-EES). A total of 178 patients (75%; 88 in the BP-EES group and 90 in the DP-EES group) underwent OCT assessment at 3 years. Neoatherosclerosis did not differ between the BP-EES (11.4%) and DP-EES (13.3%; odds ratio 0.83, 95% confidence interval 0.33-2.04, p=0.69). There were no differences in the frequency of fibroatheroma (BP-EES 9.1% vs DP-EES 11.1%, p=0.66) or macrophage accumulation (BP-EES 4.5% vs DP-EES 3.3%, p=0.68), and no fibrocalcific neoatherosclerosis was observed. Rates of target lesion failure did not differ between groups (BP-EES 5.9% vs DP-EES 6.0%, p=0.97). CONCLUSIONS: Use of BP-EES for primary PCI in patients presenting with STEMI was not superior to DP-EES regarding frequency of neoatherosclerosis at 3 years.

One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation　- The REIWA Region-Wide Registry.

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain. METHODS AND RESULTS: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Astaxanthin-loaded alginate-chitosan gel beads activate Nrf2 and pro-apoptotic signalling pathways against oxidative stress.

Oxidative stress (OS) plays a crucial role in disease development. Astaxanthin (ATX), a valuable natural compound, may reduce OS and serve as a treatment for diseases like neurodegenerative disorders and cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates antioxidant enzymes and OS management. We evaluated ATX's antioxidant activity via Alg-CS/ATX gel beads in vitro. ATX-encapsulated alginate-chitosan (Alg-CS/ATX) gel beads were synthesized and structurally/morphologically characterized by SEM, FT-IR, and XRD. Their biological effects were examined in human umbilical vein endothelial cells (HUVECs) treated with H2O2 through MTT assay, Annexin V/PI, cell cycle studies, and western blotting. Alg-CS effectively carried ATX, with high capacity and reduced pore size. Alg-CS/ATX displayed an 84% encapsulation efficiency, maintaining stability for 30 days. In vitro studies showed a 1.4-fold faster release at pH 5.4 than at neutral pH, improving ATX's therapeutic potential. HUVECs treated with Alg-CS/ATX showed enhanced viability via increased Nrf2 expression. Alg-CS gel beads exhibit significant potential as a biocompatible vehicle for delivering ATX to combat OS with considerable opportunity for clinical applications.

Green synthesis of chitosan gum acacia based biodegradable polymeric nanoparticles to enhance curcumin's antioxidant property: an in vivo zebrafish (Danio rerio) study.

Green-synthesis of biodegradable polymeric curcumin-nanoparticles using affordable biodegradable polymers to enhance curcumin's solubility and anti-oxidative potential. The curcumin-nanoparticle was prepared based on the ionic-interaction method without using any chemical surfactants, and the particle-size, zeta-potential, surface-morphology, entrapmentefficiency, and in-vitro drug release study were used to optimise the formulation. The antioxidant activity was investigated using H2DCFDA staining in the zebrafish (Danio rerio) model. The mean-diameter of blank nanoparticles was 178.2 nm (±4.69), and that of curcuminnanoparticles was about 227.7 nm (±10.4), with a PDI value of 0.312 (±0.023) and 0.360 (±0.02). The encapsulation-efficacy was found to be 34% (±1.8), with significantly reduced oxidative-stress and toxicity (∼5 times) in the zebrafish model compared to standard curcumin. The results suggested that the current way of encapsulating curcumin using affordable, biodegradable, natural polymers could be a better approach to enhancing curcumin's water solubility and bioactivity, which could further be translated into potential therapeutics.

Sustainable Polymers with High Performance and Infinite Scalability.

Our society has been pursuing high-performance biodegradable polymers made from facile methods and readily available monomers. Here, we demonstrate a library of enzyme-degradable polymers with desirable properties from the first reported step polyaddition of diamines, COS, and diacrylates. The polymers contain in-chain ester and thiourethane groups, which can serve as lipase-degradation and hydrogen-bonding physical crosslinking points, respectively, resulting in possible biodegradability as well as upgraded mechanical and thermal properties. Also, the properties of the polymers are scalable due to the versatile method and the wide variety of monomers. We obtain 46 polymers with tunable performance covering high-Tm crystalline plastics, thermoplastic elastomers, and amorphous plastics by regulating polymer structure. Additionally, the polymerization method is highly efficient, atom-economical, quantitatively yield, metal- and even catalyst-free. Overall, the polymers are promising green materials given their degradability, simple and modular synthesis, remarkable and tunable properties, and readily available monomers.

Long-term cardiovascular outcomes of biodegradable polymer drug eluting stents in patients with diabetes versus non-diabetes mellitus: a meta-analysis.

BACKGROUND: Today, diabetes mellitus (DM) has become a worldwide concern. DM is a major risk factor for the development of cardiovascular diseases (CVD). Eligible patients with CVD are treated invasively by percutaneous coronary intervention (PCI) whereby a stent is implanted inside the coronary vessel with the particular lesion to allow sufficient blood flow. Newer scientific research have shown that even though associated with a lower rate of re-stenosis, first-generation drug eluting stents (DES) were associated with a higher rate of late stent thrombosis. Recently, newer stents, namely biodegradable polymer DES (BP-DES) have been developed to overcome the safety issues of earlier generation DES. In this analysis we aimed to systematically compare the long term (≥ 12 months) adverse cardiovascular outcomes observed in DM versus non-DM patients who were implanted with BP-DES. METHODS: Cochrane central, MEDLINE (Subset PubMed), EMBASE, Web of Science, http://www. CLINICALTRIALS: gov and Google scholar were searched for relevant publications involving BP-DES in patients with DM versus non-DM and their associated adverse cardiovascular outcomes. The mean follow-up time period ranged from 12 to 120 months. Data analysis was carried out with the latest version of the RevMan software (version 5.4). Based on the Mantel-Haenszel test, risk ratios (RR) with 95% confidence intervals (CI) were calculated and used to represent the results following analysis. RESULTS: Seven (7) studies with a total number of 10,246 participants were included in this analysis. Stents which were implanted during PCI were BP-DES. Participants were enrolled from the year 2006 to 2013. Our current results showed that in patients who were implanted with BP-DES, the risks of major adverse cardiac events (RR: 1.30, 95% CI: 1.18-1.43; P = 0.00001), myocardial infarction (RR: 1.48, 95% CI: 1.14-1.93; P = 0.003), all-cause mortality (RR: 1.70, 95% CI: 1.29-2.23; P = 0.0002), cardiac death (RR: 1.93, 95% CI: 1.28-2.93; P = 0.002), target vessel revascularization (RR: 1.35, 95% CI: 1.03-1.77; P = 0.03), target lesion revascularization (RR: 1.28, 95% CI: 1.07-1.54; P = 0.007) and target lesion failure (RR: 1.79, 95% CI: 1.52-2.12; P = 0.00001) were significantly higher in the DM group. Definite and probable stent thrombosis (RR: 1.80, 95% CI: 1.28-2.55; P = 0.0009) were also significantly higher in the DM group. CONCLUSIONS: Diabetes mellitus was an independent risk factor associated with long term adverse cardiovascular outcomes following PCI with BP-DES.

Complex primary percutaneous coronary intervention with ultrathin-strut biodegradable versus thin-strut durable polymer drug-eluting stents in patients with ST-segment elevation myocardial infarction: A subgroup analysis from the BIOSTEMI randomized trial.

BACKGROUND: Ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) are superior to thin-strut durable polymer everolimus-eluting stents (DP-EES) with respect to target lesion failure (TLF) at 2 years among patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the impact of primary percutaneous coronary intervention (pPCI) complexity on long-term clinical outcomes with BP-SES versus DP-EES in STEMI patients. METHODS: We performed a post hoc subgroup analysis from the BIOSTEMI (NCT02579031) randomized trial, which included individual data from 407 STEMI patients enrolled in the BIOSCIENCE trial (NCT01443104). STEMI patients were randomly assigned to treatment with ultrathin-strut BP-SES or thin-strut DP-EES, and further categorized into those undergoing complex versus noncomplex pPCI. Complex pPCI was defined by the presence of ≥1 of the following criteria: 3 vessel treatment, ≥3 stents implanted, ≥3 lesions treated, bifurcation lesion with ≥2 stents implanted, total stent length ≥60 mm, and/or chronic total occlusion treatment. The primary endpoint was TLF, a composite of cardiac death, target-vessel myocardial reinfarction, or clinically indicated target lesion revascularization, within 2 years. RESULTS: Among a total of 1707 STEMI patients, 421 (24.7%) underwent complex pPCI. Baseline characteristics were similar between groups. At 2 years, TLF occurred in 14 patients (7.1%) treated with BP-SES and 25 patients (11.6%) treated with DP-EES (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.32-1.19; p = 0.15) in the complex pPCI group, and in 28 patients (4.4%) treated with BP-SES and 49 patients (8.2%) treated with DP-EES (HR: 0.54; 95% CI: 0.34-0.86; p = 0.008; p for interaction = 0.74) in the noncomplex pPCI group. Individual TLF components and stent thrombosis rates did not significantly differ between groups. CONCLUSION: In a post hoc subgroup analysis from the BIOSTEMI randomized trial, ultrathin-strut BP-SES were superior to thin-strut DP-EES with respect to TLF at 2 years among STEMI patients undergoing both complex and noncomplex pPCI.

Angioscopic Comparison of Early- and Mid-Term Vascular Responses Following Treatment of ST-Elevation Acute Myocardial Infarction With Biodegradable vs. Durable Polymer Everolimus-Eluting Stents　- A Prespecified Subanalysis of the MECHANISM AMI RCT.

BACKGROUND: The vessel healing process after implantation of biodegradable polymer (BP) and durable polymer (DP) everolimus-eluting stent (EES) in ST-elevation myocardial infarction (STEMI) lesions remains unclear.Methods and Results: We conducted a multicenter prospective randomized controlled trial to compare early (2 weeks) and mid-term (12 months) vascular responses after implantation of BP-EES vs. DP-EES in STEMI patients. In this prespecified subanalysis, serial coronary angioscopy (CAS) analysis was performed in 15 stents in the BP-EES arm (n=10 patients) and 14 stents in the DP-EES arm (n=10 patients). At the 2-week follow-up, there was no significant difference in the estimated marginal means of the neointimal coverage grade (primary endpoint) between the 2 arms (mean [±SE] 0.00±0.00 in both arms; P>0.999). There were no significant differences between the BP-EES and DP-EES groups in the yellow color grade (1.046±0.106 vs. 0.844±0.114, respectively; P=0.201) or the presence of thrombus (77.8% vs. 88.8%, respectively; P=0.205). At 12 months, competent strut coverage, defined as yellow color grade ≤1, no thrombus, and a neointimal coverage grade ≥1 was achieved more frequently in the BP-EES than DP-EES arm (85.2% vs. 53.1%; adjusted odds ratio 2.11 [95% confidence interval 1.26-3.53]; P=0.023). CONCLUSIONS: Neointimal coverage 2 weeks after implantation of BP-EES and DP-EES in STEMI lesions was comparable on CAS evaluation. However, at 1 year, BP-EES was independently associated with competent strut coverage.

Organic carbon release, denitrification performance and microbial community of solid-phase denitrification reactors using the blends of agricultural wastes and artificial polymers for the treatment of mariculture wastewater.

This paper explored the possibility of heterotrophic denitrification driven by composite solid carbon sources in low carbon/nitrogen ratio marine recirculating aquaculture wastewater. In this study, two agricultural wastes, reed straw (RS), corn cob (CC) and two artificial polymers, polycaprolactone (PCL), poly3-hydroxybutyrate-hydroxypropionate (PHBV) were mixed in a 1:1 ratio to compare the carbon release characteristics of the four composite carbon sources (RS+PCL, RS+PHBV, CC+PCL, and CC+PHBV) and their effects on improving the mariculture wastewater for denitrification. Dissolved organic carbon (DOC) after carbon source release (4.96-1.07 mg/g), total organic carbon/chemical oxygen demand (1.9-0.79) and short-chain fatty acids (SCFAs) (4.23-0.21 mg/g) showed that all the four composite solid carbon sources had excellent organic carbon release ability, and the CC+PCL group had the highest release of DOC and SCFAs. Energy-dispersive X-ray spectroscopy, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to observe the changes in the surface characteristics of the composite carbon source before and after application. And results showed that the stable internal structure enabled CC+PCL group to have continuous carbon release performance and achieved the maximum denitrification efficiency (93.32 %). The NRE results were supported by the abundance of the Proteobacteria microbial community at the phylum level and Marinobacter at the genus level. Quantitative real-time PCR (q-PCR) indicated CC-containing composite carbon source groups have good nitrate reduction ability, while PCL-containing composite carbon source groups have better nitrite reduction level. In conclusion, the carbon source for agricultural wastes and artificial polymers can be used as an economic and effective solid carbon source for denitrification and treatment of marine recirculating aquaculture wastewater.

Comparison of the Patency and Regenerative Potential of Biodegradable Vascular Prostheses of Different Polymer Compositions in an Ovine Model.

The lack of suitable autologous grafts and the impossibility of using synthetic prostheses for small artery reconstruction make it necessary to develop alternative efficient vascular grafts. In this study, we fabricated an electrospun biodegradable poly(ε-caprolactone) (PCL) prosthesis and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) prosthesis loaded with iloprost (a prostacyclin analog) as an antithrombotic drug and cationic amphiphile with antibacterial activity. The prostheses were characterized in terms of their drug release, mechanical properties, and hemocompatibility. We then compared the long-term patency and remodeling features of PCL and PHBV/PCL prostheses in a sheep carotid artery interposition model. The research findings verified that the drug coating of both types of prostheses improved their hemocompatibility and tensile strength. The 6-month primary patency of the PCL/Ilo/A prostheses was 50%, while all PHBV/PCL/Ilo/A implants were occluded at the same time point. The PCL/Ilo/A prostheses were completely endothelialized, in contrast to the PHBV/PCL/Ilo/A conduits, which had no endothelial cells on the inner layer. The polymeric material of both prostheses degraded and was replaced with neotissue containing smooth-muscle cells; macrophages; proteins of the extracellular matrix such as type I, III, and IV collagens; and vasa vasorum. Thus, the biodegradable PCL/Ilo/A prostheses demonstrate better regenerative potential than PHBV/PCL-based implants and are more suitable for clinical use.

An integrated multi-criteria decision-making framework for the selection of sustainable biodegradable polymer for food packaging applications.

Manifold aspects, such as the booming market for superior quality food items with increased shelf life and the escalating concern to mitigate plastic trash due to plastic packaging have motivated researchers and food industrialists to explore sustainable eco-friendly packaging solutions extensively. Biodegradable polymers are being rigorously investigated to replace conventional plastics that are toxic, non-biodegradable, and detrimental to the marine ecosystem. The scientific methodology for the prudent selection of biodegradable polymer among the frequently used biopolymers for food packaging is being reported here. The data were extracted from the available literature. A hybrid multi-criteria decision-making framework has been developed to address the problem of material selection owing to the multiple conflicting criteria involved. Assignment of equal weights to primary criteria was selected to establish the criteria weights. Different decision-making techniques (weighted sum method (WSM), weighted product method (WPM), weighted aggregated sum product assessment method (WASPAS), and technique for order of preference by similarity to ideal solution (TOPSIS)) were used for the comparative analysis. Thereon, the different ranks obtained for each alternative were aggregated using the degree of membership technique. The robustness of the solution was checked using sensitivity analysis which was conducted by varying weights of importance using the entropy method, the CRITIC method, and the equal weights to secondary criteria. The analysis reported polylactic acid (PLA) as the most reliable polymer for food packaging applications. The sensitivity analysis concluded that the solution was without prejudice, and water vapor permeation rating was the most critical decision criterion in deciding the optimal polymer.

Thermal degradation and combustion properties of most popular synthetic biodegradable polymers.

Various products made from biodegradable polymers have been increasing rapidly in the market since the use of non-biodegradable materials has been banned, particularly for the disabled packaging materials. Burning remains the most popular method that is increasingly used in treating city wastes. The impact of these polymers on environmental during thermal degradation and combustion is an important issue for city waste management. In this work, the thermal degradation and combustion behaviours of the most popular synthetic biodegradable polymers in the market, poly(lactide acid) (PLA), poly(e-caprolactone) (PCL), poly(butylene succinate) (PBS), poly(butylene adipate-co-terephthalate) (PBAT) and polyhydroxyalkenoates (PHA), are investigated. Both isothermal and non-isothermal thermal decomposition in oxygen and nitrogen environment were studied using thermogravimetric analysis combining with differential scanning calorimeter and coupled with Fourier transform infrared spectroscopy and gas chromatograph/mass spectroscopy. The combustion behaviour was investigated by a combustion colorimeter. The study results show that thermal degradation temperatures are PCL > PBS > PLA > PBAT > PHA. The thermal decomposition of all the polyesters started from scission reaction (cis-elimination), and then a stereoselective cis-elimination, which resulted in the formation of trans-crotonic acid and its oligomers. They all decomposed into CO2 and water in excess oxygen environment above 800°C. Various chemical products with smaller molecules were detected under oxygen-free conditions, including oligomers and unsaturated carboxylic acid. The order of the total heat release of the materials from high to low is as follows: PHA > PCL > PBAT > PBS > PLA. The combustion values of these polyesters are lower than those of polyolefins; thus, they will not damage furnace used currently. The results provide some important and useful data for managing these new city waste.

Toughening Brittle Bio-P3HB with Synthetic P3HB of Engineered Stereomicrostructures.

Poly(3-hydroxybutyrate) (P3HB), a biologically produced, biodegradable natural polyester, exhibits excellent thermal and barrier properties but suffers from mechanical brittleness, largely limiting its applications. Here we report a mono-material product design strategy to toughen stereoperfect, brittle bio or synthetic P3HB by blending it with stereomicrostructurally engineered P3HB. Through tacticity ([mm] from 0 to 100 %) and molecular weight (Mn to 788 kDa) tuning, high-performance synthetic P3HB materials with tensile strength to ≈30 MPa, fracture strain to ≈800 %, and toughness to 126 MJ m-3 (>110× tougher than bio-P3HB) have been produced. Physical blending of the brittle P3HB with such P3HB in 10 to 90 wt % dramatically enhances its ductility from ≈5 % to 95-450 % and optical clarity from 19 % to 85 % visible light transmittance while maintaining desirably high elastic modulus (>1 GPa), tensile strength (>35 MPa), and melting temperature (160-170 °C). This P3HB-toughening-P3HB methodology departs from the traditional approach of incorporating chemically distinct components to toughen P3HB, which hinders chemical or mechanical recycling, highlighting the potential of the mono-material product design solely based on biodegradable P3HB to deliver P3HB materials with diverse performance properties.

Poly-Alanine-ε-Caprolacton-Methacrylate as Scaffold Material with Tuneable Biomechanical Properties for Osteochondral Implants.

An aging population and injury-related damage of the bone substance lead to an increasing need of innovative materials for the regeneration of osteochondral defects. Biodegradable polymers form the basis for suitable artificial implants intended for bone replacement or bone augmentation. The great advantage of these structures is the site-specific implant design, which leads to a considerable improvement in patient outcomes and significantly reduced post-operative regeneration times. Thus, biomechanical and biochemical parameters as well as the rate of degradation can be set by the selection of the polymer system and the processing technology. Within this study, we developed a polymer platform based on the amino acid Alanine and ε-Caprolacton for use as raw material for osteochondral implants. The biomechanical and degradation properties of these Poly-(Alanine-co-ε-Caprolacton)-Methacrylate (ACM) copolymers can be adjusted by changing the ratio of the monomers. Fabrication of artificial structures for musculo-skeletal tissue engineering was done by Two-Photon-Polymerization (2PP), which represents an innovative technique for generating defined scaffolds with tailor-made mechanical and structural properties. Here we show the synthesis, physicochemical characterization, as well as first results for structuring ACM using 2PP technology. The data demonstrate the high potential of ACM copolymers as precursors for the fabrication of biomimetic implants for bone-cartilage reconstruction.

Dry Powder Inhalers for Proteins Using Cryo-Milled Electrospun Polyvinyl Alcohol Nanofiber Mats.

To enable the efficient delivery of drugs to the lungs, the drug particle design for most dry powder inhalers (DPIs) involves reducing the aerodynamic particle size to a few microns using methods such as spray-drying or jet-milling. Stresses, including heat and the shear forces generated by the preparation processes, may result in the degradation and denaturation of drugs such as those based on peptides and proteins. Here, we showed that cryo-milled polyvinyl alcohol nanofiber mats loaded with α-chymotrypsin by electrospinning exhibited suitable inhalation properties for use in DPIs, while maintaining enzymatic activity. The cryo-milled nanofiber mats were porous to fine particles, and the particle size and drug stability depended on the freezing and milling times. The median diameter of the milled fiber mats was 12.6 µm, whereas the mass median aerodynamic diameter was 5.9 µm. The milled nanofiber mats were successfully prepared, while retaining the enzymatic activity of α-chymotrypsin; furthermore, the activity of milled fiber mats that had been stored for 6 months was comparable to the activity of those that were freshly prepared. This novel method may be suitable for the DPI preparation of various drugs because it avoids the heating step during the DPI preparation process.

Features of Cell Reactions during Implantation of Biodegradable Polymer and Polypropylene in the Experiment.

Quantitative and qualitative characteristics of cell infiltrates in male Wistar rats were studied from 14 days to 12 months after implantation of polypropylene and a biodegradable polymer obtained by electrospinning and consisting of 65% polycaprolactone and 35% polytrimethylene carbonate. It was found that a predominantly macrophage-giant cell reaction developed around the biodegradable polymer; it spread into the matrix and the number of cells in the infiltrate decreased, as the degradation progressed. Around polypropylene, mainly lymphocytic and leukocytic reaction was seen; it also decreased with time, but was characterized by a reverse increase in the number of lymphocytes. Immunohistochemical analysis showed that the proportion of CD38+ cells 12 months after implantation increased around polypropylene to a greater extent than around the biodegradable polymer, while the proportion of CD68+ cells decreased. These findings suggest that implantation of a biodegradable polymer caused no prolonged lymphocytic and plasma cell reaction in animals as in the case of polypropylene, which indicates that biodegradable polymer is a promising material for tissue engineering.

Advanced Materials in Wireless, Implantable Electrical Stimulators That Offer Rapid Rates of Bioresorption for Peripheral Axon Regeneration.

Injured peripheral nerves typically exhibit unsatisfactory and incomplete functional outcomes, and there are no clinically approved therapies for improving regeneration. Post-operative electrical stimulation (ES) increases axon regrowth, but practical challenges from the cost of extended operating room time to the risks and pitfalls associated with transcutaneous wire placement have prevented broad clinical adoption. This study presents a possible solution in the form of advanced bioresorbable materials for thin, flexible, wireless implant that provides precisely controlled ES of the injured nerve for a brief time in the immediate post-operative period. Afterward, rapid, complete and safe modes of bioresorption naturally and quickly eliminate all of the constituent materials in their entirety, without the need for surgical extraction. The unusually high rate of bioresorption follows from the use of a unique, bilayer enclosure that combines two distinct formulations of a biocompatible form of polyanhydride as an encapsulating structure, to accelerate the resorption of active components and confine fragments until complete resorption. Results from mouse models of tibial nerve transection with re-anastomosis indicate that this system offers levels of performance and efficacy that match those of conventional wired stimulators, but without the need to extend the operative period or to extract the device hardware.

Enrichment of marine manganese-oxidizing microorganisms using polycaprolactone as a solid organic substrate.

OBJECTIVE: Heterotrophic manganese (Mn)-oxidizing microorganisms responsible for biogenic manganese oxide (Bio-MnOx) production are fastidious. Their enrichment is not easily accomplished by merely adding a soluble organic substrate to non-sterile mixed cultures. The objective of this study was to evaluate polycaprolactone (PCL), an aliphatic polyester, as an effective solid organic substrate for the enrichment of marine Mn-oxidizing microorganisms. RESULTS: We successfully obtained marine microbial enrichment with the capacity for dissolved Mn removal and MnOx production using PCL as a solid organic substrate. The removal of dissolved Mn by the Mn-oxidizing enrichment culture followed first-order kinetics with a rate constant of 0.014 h-1. 16S rRNA gene amplicon sequencing analysis revealed that the Mn-oxidizing enrichment culture was highly dominated by operational taxonomic units related to the bacterial phyla Cyanobacteria, Planctomycetes, and Proteobacteria. CONCLUSIONS: Our data demonstrate that PCL can serve as a potential substrate to enrich Mn-oxidizing microorganisms with the ability to produce MnOx under marine conditions.

Nanostructured scaffolds based on bioresorbable polymers and graphene oxide induce the aligned migration and accelerate the neuronal differentiation of neural stem cells.

Within the field of neural tissue engineering, there is a huge need for the development of materials that promote the adhesion, aligned migration and differentiation of stem cells into neuronal and supportive glial cells. In this study, we have fabricated bioresorbable elastomeric scaffolds combining an ordered nanopatterned topography together with a surface functionalization with graphene oxide (GO) in mild conditions. These scaffolds allowed the attachment of murine neural stem cells (NSCs) without the need of any further coating of its surface with extracellular matrix adhesion proteins. The NSCs were able to give rise to both immature neurons and supporting glial cells over the nanostructured scaffolds in vitro, promoting their aligned migration in cell clusters following the nanostructured grooves. This system has the potential to reestablish spatially oriented neural precursor cell connectivity, constituting a promising tool for future cellular therapy including nerve tissue regeneration.

Comparative Evaluation of Safety and Efficacy of a Novel Hyaluronic Acid-polynucleotide/Poly-L-lactic Acid Composite Dermal Filler.

BACKGROUND: Poly-L-lactic acid (PLLA) is widely used in tissue engineering. The natural polymer hyaluronic acid (HA) shows excellent biocompatibility and affects cell signaling, proliferation, and differentiation. In addition, a polynucleotide (PN) induces cell growth of human skin fibroblasts and osteoblasts. OBJECTIVE: In this study, we evaluated the properties, safety, and efficacy of a novel composite filler consisting of cross-linked HA with PN in combination with monodisperse PLLA microspheres manufactured using Inventage Lab Precision Particle Fabrication method. MATERIALS AND METHODS: The composition of the filler and characteristics of the microspheres were examined via scanning electron microscopy, particle size analysis, gel permeation chromatography, and rheology and osmolality measurement. Additionally, safety and efficacy of HA-PN/PLLA composite filler were conducted in in vitro and in vivo. RESULTS: Analysis of PLLA microspheres revealed spherical surfaces and a narrower particle size distribution than that in PLLA filler. HA-PN/PLLA composite filler had higher viscosity and elasticity values and similar osmolality as compared to those of HA and PN fillers. The nontoxicity in in vitro and in vivo tests reflected that the composite filler may be safe for human use. In addition, the composite filler maintained a more stable volume than did HA filler for 24 weeks after administration in HWY/Slc hairless rats. Furthermore, the results support the effect of HA-PN/PLLA in restoring skin structure. CONCLUSION: Altogether, these data suggest that the novel composite filler might be a safe and effective option in terms of tissue integration, clinical management during delivery and high esthetic durability. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .