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Anthracyclines have a profound effect on breast cancer. However, at higher dosages, there are many toxic side effects associated with their use; these include bone marrow suppression, alopecia, gastrointestinal reactions and cardiotoxicity. Pegylated liposomal doxorubicin (PEG-LG) has been demonstrated to achieve equivalent efficacy to conventional doxorubicin, with significantly lower cardiotoxicity. We conducted an open-label, multicenter, single-armed clinical trial useing an NAC regimen based on four cycles of PEG-LD 40 mg/m 2 plus cyclophosphamide (CPM) 600 mg/m 2 on day 1 of a 21 day schedule, followed by four cycles of docetaxel (DTX) 85 mg/m 2 on day 1 of a 21 day schedule. The primary endpoint analysed was the pathological complete response rate (pCR) in the breast, while treatment toxicities and safety were also assessed. The results showed that the breast pCR rate was 18.75% (95% CI 11.5–26.0%). Among the different molecular cancer types, the triple negative breast cancer patients had the highest pCR, at 43.75%. No significant decrease in left ventricular ejection fraction was observed. Our data tends to draw the conclusion that this regimen is a viable option for the neoadjuvant treatment of patients with LABC, especially in the triple-negative subtype and patients with heart abnormalities. We believe the efficacy and the safety of this regimen is likely to be the same based on published data from other studies but that this cannot be certain without a randomized trial.

It is now widely accepted that a therapeutic strategy for spinal cord injury (SCI) demands a multi-target approach. Here we propose the use of an easily implantable bilayer polymeric patch based on poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) that combines physical guidance cues provided by electrospun aligned fibres and the delivery of ibuprofen, as a mean to reduce the inhibitory environment at the lesion site by taming RhoA activation. Bilayer patches comprised a solvent cast film onto which electrospun aligned fibres have been deposited. Both layers were loaded with ibuprofen. In vitro release (37°C, in phosphate buffered saline) of the drug from the loaded scaffolds under sink condition was found to occur in the first 24 h. The released ibuprofen was shown to retain its bioactivity, as indicated by the reduction of RhoA activation when the neuronal-like cell line ND7/23 was challenged with lysophosphatidic acid. Ibuprofen-loaded P(TMC-CL) bilayer scaffolds were successfully implanted in vivo in a dorsal hemisection rat SCI model mediating the reduction of RhoA activation after 5 days of implantation in comparison to plain P(TMC-CL) scaffolds. Immunohistochemical analysis of the tissue shows βIII tubulin positive cells close to the ibuprofen-loaded patches further supporting the use of this strategy in the context of regeneration after a lesion in the spinal cord.

Objective To compare the effect of polycaprolactone impregnated 3D printed nano‐hydroxyapatite (3DPHA‐PCL) with bovine bone substitute material (BB) in lateral maxillary sinus floor elevation (MSFE). Materials and Methods Lateral MSFE with two bone substitute materials was randomly performed in two centers: group BB (n = 11 sinuses) or group 3DPHA‐PCL (n = 11 sinuses). Lateral MSFE with two bone substitute materials was performed on 21 participants across two centers, resulting in a total of 22 sinuses analyzed. The sinuses were randomly allocated into two groups: group BB (11 sinuses) and group 3DPHA‐PCL (11 sinuses). Cone beam computed tomography (CBCT) was taken before (T0) and immediately after MSFE (T1), at 6 months (implant placement; T2), and 1 year (T3). Dimensional stability of the augmentation was analyzed using serial CBCT scans. At the time of implant placement, bone core biopsy was performed, followed by microcomputed tomographic (micro‐CT) and histomorphometric analyses. Results Based on the superimposed CBCT images between T1 and T2, the augmented height and volume decreased in both groups without a statistically significant difference between the groups (−0.48 ± 1.01 mm, −53.9 ± 117.8 mm3 in group BB vs. −0.39 ± 0.44 mm, −40.8 ± 101.2 mm3 in group 3DPHA‐PCL, p > 0.05). The percentage of newly formed bone was statistically significantly lower in group 3DPHA‐PCL (15.7 ± 7.5% histomorphometrically, 16.7 ± 7.5% in micro‐CT) than group BB (25.6 ± 7.2%, 26.3 ± 4.1%) (p < 0.05 in both methods). Two implants failed in the 3DPHA‐PCL group, while no failures in the BB group. Conclusions Dimensional stability of the augmented bone was comparable between the groups. However, group 3DPHA‐PCL demonstrated inferior new bone formation and implant survival compared to group BB. Long‐term follow‐up is warranted to monitor the behavior of 3DPHA‐PCL.

•Anionic biodegradable nanoparticles are coated by venom fraction: AahG50, BotG50.•We demonstrate innocuity of BotG50-coated PLA after injections to mice.•We demonstrate effective toxicity decrease of AahG50-coated PLA in mice.•Immune sera neutralized LD50 doses of AahG50 and BotG50 by a factor of 12.75 and 14.•Mice are fully protected against 1.8×LD50 of AahG50 dose given at the 6th month. Scorpion envenoming represents a public health issue in subtropical regions of the world. Treatment and prevention need to promote antitoxin immunity. Preserving antigenic presentation while removing toxin effect remains a major challenge in toxin vaccine development. Among particulate adjuvant, particles prepared with poly (d,l-lactide) polymer are the most extensively investigated due to their excellent biocompatibility and biodegradability. The aim of this study is to develop surfactant-free PLA nanoparticles that safely deliver venom toxic fraction to enhance specific immune response. PLA nanoparticles are coated with AahG50 (AahG50/PLA) and BotG50 (BotG50/PLA): a toxic fraction purified from Androctonus australis hector and Buthus occitanus tunetanus venoms, respectively. Residual toxicities are evaluated following injections of PLA-containing high doses of AahG50 (or BotG50). Immunization trials are performed with the detoxified fraction administered alone without adjuvant. A comparative study of the effect of Freund is also included. The neutralizing capacity of sera is determined in naive mice. Six months later, immunized mice are challenged subcutaneously with increased doses of AahG50. Subcutaneous lethal dose 50 (LD50) of AahG50 and BotG50 is of 575μg/kg and 1300μg/kg respectively. By comparison, BotG50/PLA is totally innocuous while 50% of tested mice survive 2875μg AahG50/kg. Alhydrogel and Freund are not able to detoxify such a high dose. Cross-antigenicity between particulate and soluble fraction is also, ensured. AahG50/PLA and BotG50/PLA induce high antibody levels in mice serum. The neutralizing capacity per mL of anti-venom was 258μg/mL and 186μg/mL calculated for anti-AahG50/PLA and anti-BotG50/PLA sera, respectively. Animals immunized with AahG50/PLA are protected against AahG50 injected dose of 3162μg/kg as opposed all non-immunized mice died at this dose. We find that the detoxification approach based PLA nanoparticles, benefit the immunogenicity and protective efficacy of venom immunogen.

Successfully interfacing enzymes and biomachinery with polymers affords on-demand modification and/or programmable degradation during the manufacture, utilization and disposal of plastics, but requires controlled biocatalysis in solid matrices with macromolecular substrates 1 – 7 . Embedding enzyme microparticles speeds up polyester degradation, but compromises host properties and unintentionally accelerates the formation of microplastics with partial polymer degradation 6 , 8 , 9 . Here we show that by nanoscopically dispersing enzymes with deep active sites, semi-crystalline polyesters can be degraded primarily via chain-end-mediated processive depolymerization with programmable latency and material integrity, akin to polyadenylation-induced messenger RNA decay 10 . It is also feasible to achieve processivity with enzymes that have surface-exposed active sites by engineering enzyme–protectant–polymer complexes. Poly(caprolactone) and poly(lactic acid) containing less than 2 weight per cent enzymes are depolymerized in days, with up to 98 per cent polymer-to-small-molecule conversion in standard soil composts and household tap water, completely eliminating current needs to separate and landfill their products in compost facilities. Furthermore, oxidases embedded in polyolefins retain their activities. However, hydrocarbon polymers do not closely associate with enzymes, as their polyester counterparts do, and the reactive radicals that are generated cannot chemically modify the macromolecular host. This study provides molecular guidance towards enzyme–polymer pairing and the selection of enzyme protectants to modulate substrate selectivity and optimize biocatalytic pathways. The results also highlight the need for in-depth research in solid-state enzymology, especially in multi-step enzymatic cascades, to tackle chemically dormant substrates without creating secondary environmental contamination and/or biosafety concerns. Nanoscopic dispersion of enzymes with deep active sites enables chain-end-mediated processive biodegradation of semi-crystalline polyesters with programmable latency and material integrity.

Over the past few decades, with the development of science and technology, the field of biomedicine has rapidly developed, especially with respect to biomedical materials. Low toxicity and good biocompatibility have always been key targets in the development and application of biomedical materials. As a degradable and environmentally friendly polymer, polylactic acid, also known as polylactide, is favored by researchers and has been used as a commercial material in various studies. Lactic acid, as a synthetic raw material of polylactic acid, can only be obtained by sugar fermentation. Good biocompatibility and biodegradability have led it to be approved by the U.S. Food and Drug Administration (FDA) as a biomedical material. Polylactic acid has good physical properties, and its modification can optimize its properties to a certain extent. Polylactic acid blocks and blends play significant roles in drug delivery, implants, and tissue engineering to great effect. This article describes the synthesis of polylactic acid (PLA) and its raw materials, physical properties, degradation, modification, and applications in the field of biomedicine. It aims to contribute to the important knowledge and development of PLA in biomedical applications.

Poly-β-hydroxybutyrate (PHB) is a biodegradable polymer, synthesized as carbon and energy reserve by bacteria and archaea. To the best of our knowledge, this is the first report on PHB production by a rare actinomycete species, Rhodococcus pyridinivorans BSRT1-1. Response surface methodology (RSM) employing central composite design, was applied to enhance PHB production in a flask scale. A maximum yield of 3.6 ± 0.5 g/L in biomass and 43.1 ± 0.5 wt% of dry cell weight (DCW) of PHB were obtained when using RSM optimized medium, which was improved the production of biomass and PHB content by 2.5 and 2.3-fold, respectively. The optimized medium was applied to upscale PHB production in a 10 L stirred-tank bioreactor, maximum biomass of 5.2 ± 0.5 g/L, and PHB content of 46.8 ± 2 wt% DCW were achieved. Furthermore, the FTIR and 1 H NMR results confirmed the polymer as PHB. DSC and TGA analysis results revealed the melting, glass transition, and thermal decomposition temperature of 171.8, 4.03, and 288 °C, respectively. In conclusion, RSM can be a promising technique to improve PHB production by a newly isolated strain of R. pyridinivorans BSRT1-1 and the properties of produced PHB possessed similar properties compared to commercial PHB.

Biomaterial-based scaffolds are important cues in tissue engineering (TE) applications. Recent advances in TE have led to the development of suitable scaffold architecture for various tissue defects. In this narrative review on polycaprolactone (PCL), we have discussed in detail about the synthesis of PCL, various properties and most recent advances of using PCL and PCL blended with either natural or synthetic polymers and ceramic materials for TE applications. Further, various forms of PCL scaffolds such as porous, films and fibrous have been discussed along with the stem cells and their sources employed in various tissue repair strategies. Overall, the present review affords an insight into the properties and applications of PCL in various tissue engineering applications.

This review focuses on the polyesters such as polylactide and polyhydroxyalkonoates, as well as polyamides produced from renewable resources, which are currently among the most promising (bio)degradable polymers. Synthetic pathways, favourable properties and utilisation (most important applications) of these attractive polymer families are outlined. Environmental impact and in particular (bio)degradation of aliphatic polyesters, polyamides and related copolymer structures are described in view of the potential applications in various fields.

Polyhydroxyalkanoates (PHA) are bio-based microbial biopolyesters; their stiffness, elasticity, crystallinity and degradability are tunable by the monomeric composition, selection of microbial production strain, substrates, process parameters during production, and post-synthetic processing; they display biological alternatives for diverse technomers of petrochemical origin. This, together with the fact that their monomeric and oligomeric in vivo degradation products do not exert any toxic or elsewhere negative effect to living cells or tissue of humans or animals, makes them highly stimulating for various applications in the medical field. This article provides an overview of PHA application in the therapeutic, surgical and tissue engineering area, and reviews strategies to produce PHA at purity levels high enough to be used in vivo. Tested applications of differently composed PHA and advanced follow-up products as carrier materials for controlled in vivo release of anti-cancer drugs or antibiotics, as scaffolds for tissue engineering, as guidance conduits for nerve repair or as enhanced sutures, implants or meshes are discussed from both a biotechnological and a material-scientific perspective. The article also describes the use of traditional processing techniques for production of PHA-based medical devices, such as melt-spinning, melt extrusion, or solvent evaporation, and emerging processing techniques like 3D-printing, computer-aided wet-spinning, laser perforation, and electrospinning.