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Biomimetic mineralization of high-strength apatite structure essentially relies on mimicking the inorganic building blocks of naturally occurring bones. However, conventional routes still have substantial function gaps in providing precision control over the geometrical dimensions and crystalline morphology of biomineralized apatite. Herein, we conceived the concept of microwave-assisted biomineralization (MAB) to customize 1D hydroxyapatite nanowhiskers (HANWs) at graphene templates, rendering the formation of graphene-hydroxyapatite (Gr-HA) nanohybrids. The HANWs essentially resembled bone apatite in elemental composition (Ca/P = 1.74), diameter (~20 nm), crystallinity (63 %), and rodlike geometry (aspect ratio of ~6). The Gr-HA nanohybrids were uniformly incorporated into poly(lactic acid) (PLA) microfibers (~1 μm) by electrospinning, engendering fibrous membranes with a set of Gr-HA loadings (10, 20 and 30 wt%). Intimate interactions were generated between Gr-HA and PLA matrix, contributing to significant promotion of the mechanical properties for PLA composite membranes. For example, the yield strength and elastic modulus of the PLA composite membranes loaded with 30 wt% Gr-HA achieved 5.4 and 66.4 MPa, increasing nearly 182 % and over 94 % compared to those of pure PLA, respectively. Moreover, the bone-like HANWs endowed PLA membranes with excellent cytocompatibility and good bioactivity, as demonstrated by over 38 % increase in cell viability and rapid apatite formation in mineral solution. The impressive combination of mechanical properties and biological characteristics make the PLA/Gr-HA scaffolds promising for guided tissue/bone regeneration therapy.

As a kind of bio-based polymer, poly (lactic acid) has potential application in fibers fields. Due to the weak nucleation ability, PLA crystallizes slowly and forms large spherulites during the forming process, which deteriorates the properties of PLA fibers. In this work, melt-spun method is employed for the fabrication of PLA/T composite fibers using succinate diphenyl dihydrazide (TMC-306) as the nucleating agent, and then the hot-drawing and heat setting is performed to the as-spun fibers. Compared with pure PLA fibers, PLA/T fibers show faster crystallization rate and improved performance due to the synergistic effect of heterogeneous nucleation and stress-induced crystallization. The characterization of non-isothermal crystallization behavior indicates that the peak crystallization temperature as well as crystallinity of PLA composites is increased to 121.5 °C and 36.78 % respectively by blending 0.3 wt% TMC-306. Meanwhile, the obtained PLA/0.3T composite fibers are highly crystallized and oriented at hot-drawing ratio of 2.4 folds and heat setting temperature of 100 °C, and the conformational stability is noticeably enhanced. Further, the tensile strength and storage modulus of PLA/0.3T composite fiber are 3.46 cN/dtex and 46,953 MPa respectively, which are increased by 42 % and 41 % compared with neat PLA fibers.

Thermophilic members of the genus Aneurinibacillus constitute a remarkable group of microorganisms that exhibit extraordinary flexibility in terms of polyhydroxyalkanoates (PHA) synthesis. In this study, we demonstrate that these Gram-positive bacteria are capable of the utilization of selected lactones, namely, γ-valerolactone (GVL), γ-hexalactone (GHL), and δ-valerolactone (DVL) as the structural precursors of related PHA monomers. In the presence of GVL, a PHA copolymer consisting of 3-hydroxybutyrate, 3-hydroxyvalerate, and also 4-hydroxyvalerate was synthesized, with a 4 HV fraction as high as 53.1 mol%. Similarly, the application of GHL resulted in the synthesis of PHA copolymer containing 4-hydroxyhexanaote (4HHx) (4HHx fraction reached up to 11.5 mol%) and DVL was incorporated into PHA in form of 5-hydroxyvalerate (5 HV) (maximal 5 HV content was 44.2 mol%). The produced materials were characterized by thermoanalytical and spectroscopic methods; the results confirmed extremely appealing material properties of produced copolymers. Further, due to their unique metabolic features and capability of incorporating various PHA monomers into the PHA chain, thermophilic Aneurinibacillus spp. can be considered not only promising chassis for PHA production but also potential donors of PHA-relevant genes to improve PHA production in other thermophiles by using approaches of synthetic biology.

Phasin is a surface-binding protein of polyhydroxyalkanoate (PHA) granules that is encoded by the phaP gene. As its expression increases, PHA granules become smaller, to increase their surface area, and are densely packed inside the cell, thereby increasing the PHA content. A wide range of PHA-producing bacteria have phaP genes; however, their PHA productivity differs, although they are derived from the cognate bacterial host cell. Modulating phasin expression could be a new strategy to enhance PHA production. This study aimed to characterize the effect of heterologous phasins on the reconstitution of E. coli BL21(DE3) and determine the best synergistic phaP gene combination to produce polyhydroxybutyrate (PHB). We identified novel phasins from a PHB high-producer strain, Halomonas sp. YLGW01, and introduced a combination of phaP genes into Escherichia coli. The resulting E. coli phaP1,3 strain had enhanced PHB production by 2.9-fold, leading to increased cell mass and increased PHB content from 48 % to 65 %. This strain also showed increased tolerance to inhibitors, such as furfural and vanillin, enabling the utilization of lignocellulose biosugar as a carbon source. These results suggested that the combination of phaP1 and phaP3 genes from H. sp. YLGW01 could increase PHB production and robustness.

Repair of periodontal and maxillofacial bone defects is a major challenge in clinical. Guided bone regeneration (GBR) is considered one of the most effective methods. However, the efficacy of currently available GBR membranes for repair is frequently limited by their poor osteogenic potential and lack of antibacterial activity. The first step in this investigation was to construct a zinc-based zeolite-imidazolate framework loaded with copper ions (Cu@ZIF-8). Following that, a novel polycaprolactone/polylactic acid/nano-hydroxyapatite/Cu@ZIF-8 (PCL/PLA/n-HA/Cu@ZIF-8) GBR membrane was developed using a simple porogen with nonsolvent-induced phase separation (NIPS) approach. The produced membrane with asymmetric porous structure (one smooth side and one rough side) possesses hydrophilicity corresponding to the roughness of its two sides. The superior mechanical property, stability of degradation, and ion release capability of the membrane all contribute to the clinical feasibility. Additionally, in vitro biological experiments demonstrated that the PCL/PLA/n-HA/Cu@ZIF-8 membrane had favorable osteogenic and antibacterial properties, which suggests the high potential for application in the GBR procedure.

Fabrication of ultra-strong, ultra-tough, sustainable, and degradable bio-based composites is urgently needed but remains challenging. Here, a biomimetic sustainable, degradable, and multi-stimuli responsive cellulose/PCL/Fe

Crystallinity and flame retardancy are two key properties for poly(lactic acid)(PLA) in applications. In this paper, a quaternary phosphonium salt poly(ionic liquid) (PIL) and a phosphamide (POFA) were prepared. The PIL, POFA and their blend were used to regulate the flame retardancy and crystallization behaviors of PLA using the limiting oxygen index, UL-94 vertical burning, and thermogravimetric analysis, and differential scanning calorimetry etc. The results showed that a synergistic effect exists between PIL and POFA on flame retardancy. When 6 wt% PIL/POFA (2/1) was added into PLA, its LOI value is 28.0 vol%, and achieves the UL-94 V-0 rating while the PLA composites containing 6 wt% PIL or POFA just achieve the UL-94 V2. The PIL/POFA improves the flame retardancy of PLA by melting-away mode. In addition, the crystallization rate of PLA containing PIL/POFA is faster than that of PLA/PIL and PLA/POFA. The degradation of PLA induced by PIL/POFA produces some small molecular oligomers, which enhances the molecular chain mobility and rearrangement, thus contributes to better flame retardancy and faster crystallization.

Poly (L-lactic acid) (PLLA) based copolymers modified with δ-valerolactone (DVL) through random copolymerization (PVLA-R) and block copolymerization (PVLA-B) with various DVL content were prepared to investigate their degradation regulation and mechanism. Chemical structure, thermal properties, hydrophilicity, crystallization as well as the crystal defects of the obtained copolymers were respectively confirmed. Degradation regulation of both PVLA-R and PVLA-B, such molecular weight and pH value changes of PLLA based copolymers were investigated via vitro degradation method. In order to further explore the degradation principle of the two copolymers, their degradation residues at different stages were systematically studied. The addition and increasing content of DVL disturbs the regularity of original PLLA molecular structure, resulting in accelerating degradation of copolymers. Compared with amorphous region, the crystalline region of both two copolymers has better corrosion resistance, which could be confirmed by increased melting point and crystallinity of both PVLA-R and PVLA-B degradation residues. PVLA-B copolymers show relatively superior degradation resistance mainly due to their higher molecular weight, crystallinity and hydrophobic index than PVLA-R copolymers.

In this work, a facile and efficient strategy known as 'dynamic self-vulcanization of dual difunctional monomers' was reported to toughen poly(lactic acid) (PLA) with in-situ formed crosslinked bio-polyurethane (PCPUE) phase from plant oil-derived hydrogenated dimer diol (Pripol) and hexamethylene diisocyanate (HDI). By simply adjusting equivalent ratios (n

Volatile fatty acids (VFAs) derived from biomass are considered to be economical and environmentally friendly feedstocks for microbial fermentation. Converting VFAs to polyhydroxyalkanoate (PHA) could reduce the substrate cost and provide an economically viable route for the commercialization of PHA. The halophilic bacteria Salinivibrio spp. TGB4 and TGB19, newly isolated from salt fields, were found to accumulate poly-3-hydroxybutyrate (PHB) using acetate or butyrate as the substrate. Both strains exhibited considerable cell growth (OD

The meniscus is a fibrocartilaginous tissue that is very important for the stability of the knee joint. However, it has a low ability to heal itself, so damage to it will always lead to articular cartilage degeneration. The goal of this study was to make a new type of meniscus scaffold made of chitosan, loofah mat, and PHBV nanofibers, as well as to describe hydrogel composite scaffolds in terms of their shape, chemical composition, mechanical properties, and temperature. Three different concentrations of genipin (0.1, 0.3, and 0.5 %) were used and the optimal crosslinker concentration was 0.3 % for Chitosan/loofah (CL) and Chitosan/loofah/PHBV fiber (CLF). Scaffolds were seeded using undifferentiated MSCs and incubated for 21 days to investigate the chondrogenic potential of hydrogel scaffolds. Cell proliferation analyses were performed using WST-1 assay, GAG content was analyzed, SEM and fluorescence imaging observed morphologies and cell attachment, and histological and immunohistochemical studies were performed. The in vitro analysis showed no cytotoxic effect and enabled cells to attach, proliferate, and migrate inside the scaffold. In conclusion, the hydrogel composite scaffold is a promising material for engineering meniscus tissue.

Despite a growing understanding of exertional heatstroke (EHS), there is a paucity of clinical evidence for risk-stratification of patients with EHS. The objective of this study was to identify an appropriate scoring system for prognostic assessment of EHS.This was a retrospective cohort study of all patients with EHS admitted to intensive care unit (ICU) of the General Hospital of Southern Theatre Command of PLA between October 2008 and May 2019. Inflammatory indices and organ function parameters at admission, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores, and Glasgow Coma Scale (GCS) score were collected. Risk factors for 90-day mortality were identified using multivariate Cox proportional hazard risk regression model.189 patients (all male) were finally included, with a median age of 21.0 years (IQR 19.0-27.0), median APACHE II score of 11.0 (IQR 8.0-16.0), median SOFA score of 3.0 (IQR 2.0-6.0), and median GCS score of 12.0 (IQR 7.0-14.0). There were 166 survivors (87.8%) and 23 non-survivors (12.2%). Compared with survivor group, non-survivors had higher incidence of severe organ damage, including rhabdomyolysis (46.1% vs 63.6%), disseminated intravascular coagulation (25.6% vs 90.0%), acute liver injury (69.4% vs 95.7%), and acute kidney injury (36.6% vs 95.7%). Multivariate Cox risk regression model showed that SOFA score was an independent risk factor for 90-day mortality, with an optimal cutoff score of 7.5.SOFA score may be a clinically useful predictor of death in EHS. Prospective studies are required to confirm the effectiveness of SOFA score and the optimal cutoff level.

The fully degradable poly (lactic acid) foam with green environmental protection characteristics can alleviate the shortage of petroleum resources caused by the application of plastics. However, due to the inherent low melt strength and slow crystallization rate of linear PLA. It is difficult to obtain PLA microcellular foam with good morphology. In order to obtain PLA microcellular foam with ultra-high expansion ratio and small cell size, PTFE (polytetrafluoroethylene) nanofibers with excellent CO

A facile and high yield centrifugal spinning technique known as Forcespinning® (FS) was used to develop unique microstructures consisting of PLA microbeads along alginate fibers. Morphological variation and structural features appeared in the field-emission scanning electron micrographs for the PLA-alginate composites and dried PLA-alginate films from precursor emulsions at constant PLA and varied alginate contents. Shrunk and deflated microbeads were observed for composites whilst spherical beads were evident for the PLA control. Furthermore, PLA was found surrounding the alginate when the alginate was present at 0.24 wt% or lower, while alginate (mushroom-like structures), were seen protruding through the PLA layer at ≥0.34 wt% alginate. Rheological characterization of the composite emulsions revealed that the filler (alginate) provided shear thinning properties including pseudoplasticity, desirable for printing and other related applications in contrast to the Newtonian flow shown by the PLA control. Along with infra-red spectroscopy, the nanocomposites were further characterized using thermal gravimetry and differential scanning calorimetry featuring reversible events influenced by heat capacity and irreversible kinetic/thermodynamic counterparts. The work provides a comprehensive investigation of biocompatible networks of PLA-alginate microbeads embedded in nano-sized fibers and the prospective application of these microbeads as a drug delivery system.

The challenge of dispersing nanocellulose in hydrophobic polymers such as polylactic acid (PLA) still obstacles the further application of cellulose nanocomposites. An environment-friendly and facile wet-shearing pretreatment strategy without using any organic solvent was developed in this work. Silane modified lignocellulose nanofiber (SLCNF) was pre-dispersed into PLA by wet-shearing pretreatment, followed by extrusion process and the SLCNF could be dispersed extremely well in PLA matrices. SLCNF formed a crosslinked network and had an improved compatibility, which improved the mechanical and thermal properties of PLA composites. The tensile strength, elongation at break and thermal deformation temperature of the composites were increased by 12.6 %, 32.4 % and 9.1 °C, respectively. Moreover, SLCNF promoted the crystallization of PLA as a heterogeneous nucleating agent and the crystallinity was increased by about 40 %. This study provides an effective way to disperse nanocellulose in polymer matrix with high efficiency to enhance polymer-based composites.

The application of poly(lactic acid) (PLA) in the packaging area is frequently dwarfed by the inadequate gas/water barrier properties, low heat resistance and high UV transmittance. Herein, an environmentally friendly and high-efficiency microwave-assisted functionalization (MAF) approach was proposed to aqueous grafting waste bamboo fibers with the bridging agent. It permitted significant promotion of interfacial interactions between the MAF bamboo fibers (MAFBs) and neighboring PLA chains, contributing to uniform dispersion and intimate interphase. Featuring the morphological features, the MAFB-reinforced (5, 10 and 20 wt%) PLA biocomposites achieved an unexpected combination of high mechanical properties, exceptional resistance to heat deflection and UV irradiation, and excellent water barrier performance. Upon addition of only 5 wt% MAFBs, the tensile strength and toughness of PLA composite films were increased to 46.5 MPa and 0.6 MJ/m

Polymeric micelle is a promising vehicle to improve the bioavailability and clinical outcomes of paclitaxel (PTX) which has been proven effective in the treatment of a wide range of cancers. However, conventional PTX formulation with the amphiphilic PEG-b-PLA usually suffers from insufficient PTX loading, low stability of PTX-micelles, and rapid PTX release due to low compatibility between PTX and PLA, limiting its clinical application. In this study, a novel nanoparticle platform was developed to improve the stability of PTX-loaded nanoparticles (NPs) and the delivery efficacy of PTX by integrating the flash nanoprecipitation (FNP) technique and a combination of amphiphilic PEG-PLA and super hydrophobic zein. The incorporation of zein led to the formation of distinct hydrophobic interiors of NPs which enhanced the interaction between PTX and NPs, therefore improving the encapsulation efficiency of PTX and sustained drug release compared with PEG-PLA micelles without zein. In addition, FNP allowed facile fabrication of PTX-NPs with smaller sizes and higher stability. These PTX-NPs showed superior sustained release of PTX and good cancer cell-killing in vitro. Among them, PTX-5k-16k-1Z NPs exhibited excellent biosafety and anti-tumor efficacy in a xenograft tumor model in mice, suggesting great potential in the delivery of hydrophobic drugs for cancer therapy.

With the rapid development of the packaging industry, people have high requirements for the functionality of packaging materials. As a representative biodegradable packaging material, polylactic acid (PLA) still has some problems. Multifunctional additives in PLA are an effective modification method. In this paper, cerium lactate (Ce-LA) was synthesized by a precipitation method and integrated into PLA to prepare a functional PLA composite. The results showed that Ce-LA not only significantly improved the crystallinity but also imparted antibacterial ability to PLA. When the concentration of Ce-LA was 0.9 %, the crystallinity of PLA reached 39.35 %, which was 77 % higher than that of pure PLA. When the addition of Ce-LA was 1.8 %, the antibacterial rates of PLA against Staphylococcus aureus and Escherichia coli reached 93 % and 85 %, respectively. This study provides a beneficial solution for the development of PLA packaging materials with high crystallinity and antibacterial properties.

One of the challenges in critical size bone defect repairing is the use of a porous degradable scaffold with appropriate properties to the host tissue. Nowadays, the three-dimensional (3D) printing method can produce custom and personalized scaffolds and overcome the problems of traditional methods by controlling the porosity and dimensions of biomaterial scaffolds. In this study, polylactic acid/polyethylene glycol (PLA/PEG) scaffolds were prepared with different PEG percentages (0, 5, 10, 15 and 20 wt%) by fused deposition modeling (FDM) to optimize printability and achieve suitable physico-mechanical properties and also enhance cellular behavior for bone tissue engineering and actually, this study complements previous studies. Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were employed for chemical, morphological and thermal evaluations, respectively. It was shown that the adding of 20 wt% PEG to PLA 3D printed scaffolds reduced water contact angle (from 78.16 ± 3.27 to 60.00 ± 2.16), and increased surface wettability. The results also showed that the mechanical properties of the printed scaffolds were not significantly reduced by adding 5 and 10 wt% of PEG. The addition of PEG increased the degradability of scaffolds during immersion in phosphate buffer saline (PBS) solution for 8 weeks and PLA/PEG20 scaffold with 50.96 % had the highest rate of degradation. MTT assay showed that none of the studied scaffolds had cytotoxicity against MG-63 cells and increasing the PEG levels to 20 wt%, increased cell viability and adhesion and osteogenic differentiation. According to the obtained physical, mechanical and biological results, PLA/PEG scaffold printed by the FDM method can be an appropriate candidate for use in bone repair applications.

Bone defects caused by tumors section, traffic accidents, and surgery remain a challenge in clinical. The drawbacks of traditional autografts and allografts limit their clinical application. 3D printed porous scaffolds have monumental potential to repair bone defects but still cannot effectively promote bone formation. Nano tantalum (Ta) has been reported with effective osteogenesis capability. Herein, we fabricated 3D printed PLA/β-TCP scaffold by using the fused deposition modeling (FDM) technique. Ta was doped on the surface of scaffolds utilizing the surface adhesion ability of polydopamine to improve its properties. The constructed PLA/β-TCP/PDA/Ta had good physical properties. In vitro studies demonstrated that the PLA/β-TCP/PDA/Ta scaffolds considerably promote cell proliferation and migration, and it additionally has osteogenic properties. Therefore, Ta doped 3D printed PLA/β-TCP/PDA/Ta scaffold could incontestably improve surface bioactivity and lead to better osteogenesis, which may provide a unique strategy to develop bioactive bespoke implants in orthopedic applications.

Bioceramics, particularly calcium phosphates, bioactive glasses, and crystalline silicates, are a principal group of biomaterials employed for the regeneration of damaged tissues and therapeutic delivery. The development of ceramic tissue engineering scaffolds with an appropriate combination of mechanical and biological properties is still one of the key challenges in this field. In this regard, the deposition of polymeric coatings on the scaffolds is a simple and effective approach to reinforce their functions. Among different polymers, the influences of biodegradable aliphatic polyester coatings, especially polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA), over the performance of the scaffolds have been investigated in numerous research. This review paper provides a comprehensive comparison of PLA- and PLGA-coated bioceramic scaffolds which are mainly employed in bone tissue engineering. It is concluded that both the polymers enhance the mechanical behaviors of the scaffolds, but control their biodegradability, bioactivity, and delivery kinetics, where PLA acts almost more influentially than PLGA in comparison. However, the response of biocompatibility to this surface treatment is condition-dependent and requires case-by-case experiments to be determined accurately.

Tissue engineering is an emerging method for replacing damaged tissues. In this study, the potential application of electrospun polycaprolactone/chitosan/ the internal layer of oak fruit (Jaft) as skin scaffolds was investigated. A combination of Polycaprolactone (PCL), chitosan (CH), and the internal layer of oak fruit (Jaft) was used to incorporate mechanical properties of synthetic polymers, biological properties of natural polymers, and antibacterial activity of Jaft. Physical and morphological characteristics of prepared scaffolds were investigated using a scanning electron microscope (SEM), mechanical analysis, swelling ratio, and contact angle. Moreover, chemical and biological properties were evaluated by Fourier-transform infrared spectroscopy (FTIR), chromatography, flow cytometry, DAPI staining, MTT assay, and trypan blue exclusion assay. Obtained results demonstrated that the fabricated scaffolds have good mechanical properties. Moreover, the addition of chitosan and Jaft to the PCL scaffolds improved their water absorption capacity as well as surface hydrophilicity. MTT results showed the fabricated nanofibrous scaffolds have adequate cell viability, which is higher than the cell culture plate at each time point of culture. Furthermore, SEM images of cultured scaffolds, trypan blue exclusion assay, and DAPI staining confirmed that fibroblast cells could be well-attached and proliferate on the PCL/CH/Jaft scaffolds. Results have proven that this novel bioactive scaffold has promising mechanical properties, suitable biocompatibility in vitro, and in vivo. Consequently, it could be a promising candidate for skin tissue engineering applications.

The CFTR modulator elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) leads to significant improvement in the symptoms and spirometry of people with cystic fibrosis (pwCF), but little evidence exists to understand its effect on respiratory pump function. Dynamic chest radiography (DCR) is a novel cineradiographic tool that identifies and tracks the chest wall and diaphragm throughout the breathing cycle, alongside fluoroscopic images of the chest of diagnostic quality.In this observational work, we examined the spirometry and DCR of 24 pwCF before and after starting ELX/TEZ/IVA. DCR automatically tracked the hemidiaphragm midpoints and projected lung area (PLA) during tidal and deep breathing manoeuvres.ppFEVDCR demonstrated significant improvements in hemidiaphragm excursion and ΔPLA in pwCF started on ELX/TEZ/IVA. These changes likely reflect a reduction in air trapping and improved elastic recoil of the chest, and are consistent with improvements seen in spirometry. The changes seen with DCR are physiologically plausible and correlate well with spirometry. DCR warrants further investigation as a tool for assessing the impact of CFTR-modulating therapies.

An atmosphere within a package affects the metabolic process of food and the microbial growth of fresh products and has a vital role in preserving food. It depends on the membrane's specific gas permeability and selectivity to generate a desirable atmosphere for storage. In this study, triblock poly(l-lactic acid‑d-ɛ-caprolactone) (PLDC) copolymers and three-arm poly(l-lactic acid-g-ɛ-caprolactone) (PLGC) star copolymers were synthesized, in which a microphase-separated morphology of sea-island structure was established in PLGC membrane as a gas "fast permeation channel" for regulating CO

Two kinds of phosphoramide derivatives containing one (POFA) or two (BPOFA) phosphoramide bonds were synthesized using diphenylphosphinic chloride, phenylphosphonic dichloride and furfurylamine, respectively. The flame retardancy, thermal degradation and crystallization behaviors of polylactic acid (PLA)/POFA and PLA/BPOFA blends were investigated using the limiting oxygen index (LOI), UL-94 vertical burning tests, cone calorimeter tests, thermogravimetric analysis and differential scanning calorimetry. A small amount of 1.0 wt% BPOFA increases the LOI of PLA from 20.4 vol% to 28.0 vol% and achieves the UL-94 V0 rating, while 7.0 wt% POFA is needed to achieve the UL-94 V0 rating indicating that the PLA/BPOFA has better flame retardancy than that of PLA/POFA. Both POFA and BPOFA decrease the amount of flammable gaseous compounds and play positive roles in transesterification of PLA. More importantly, BPOFA is easier to catalyze the degradation of PLA and improve UL-94 rating by melting-away mode. Moreover, the BPOFA accelerates the crystallization rate and thus improves the crystallinity of PLA, while POFA does not show a positive effect on crystallization behaviors of PLA.

The aim of this study is the development of a methodology for manufacturing 3D printed anthropomorphic structures, which mimic the X-ray properties of the human bone tissue.A mixing approach of two different materials is proposed for the fabrication of a radiologically equivalent hip bone for an anthropomorphic abdominal phantom. The materials employed for the phantom were polylactic acid (PLA) and Stonefil, while a custom-made dual motor filament extrusion setup and a custom-made software associating medical images directly with the 3D printing process were employed.Three phantoms representing the hip bone were 3D printed utilizing two filaments under three different printing scenarios. The phantoms are based on a patient's abdominal CT scan images. Histograms of CT scans of the printed hip bone phantoms were calculated and compared to the original patient's hip bone histogram, demonstrating that a constant mixing composition of 30% Stonefil and 70% PLA with 0.0375 extrusion rate per voxel (93.75% flow for fulfilling a single voxel) for the cancellous bone, and using 100% Stonefil with 0.04 extrusion rate per voxel (100% flow) for the cortical bone results in a realistic anatomy replication of the hip bone. Reproduced HU varied between 700 and 800, which are close to those of the hip bone.The study demonstrated that it is possible to mix two different filaments in real-time during the printing process to obtain phantoms with realistic and radiographically bone tissue equivalent attenuation. The results will be explored for manufacturing a CT-compatible abdominal phantom.

A new biodegradable semi-interpenetrated polymer network (semi-IPN) of two US Food and Drug Administration approved materials, poly(3-hydroxybutyrate-co-3-valerate) (PHBV) and calcium alginate (CA) was engineered to provide an alternative strategy to enhance the poor adhesion properties of CA. The synthesis procedure allows the additional incorporation of 10 % w/w of graphene nanoplatelets (GNPs), which have no cytotoxic effect on human keratinocytes. This quantity of multilayer graphene provides superior antiviral activity to the novel semi-IPN against a surrogate virus of SARS-CoV-2. Adding GNPs hardly affects the water absorption or electrical conductivity of the pure components of CA and PHBV. However, the semi-IPN's electrical conductivity increases dramatically after adding GNP due to molecular rearrangements of the intertwined polymer chains that continuously distribute the GNP nanosheets, This new hydrophilic composite biomaterial film shows great promise for skin biomedical applications, especially those that require antiviral and/or biodegradable electroconductive materials.

The incorporation of poly(d-lactide) (PDLA) to form stereocomplex crystallites (SCs) within a poly(l-lactide) (PLLA) matrix is among the most effective strategies in overcoming PLLA's numerous drawbacks. However, high concentrations of PDLA (3 wt%) are required to improve PLLA's crystallization kinetics and melt strength, which is undesirable owing to PDLA's high cost. In this study, we use chain alignment as a levier to tune stereocomplex superstructure morphology to overcome these limitations. Herein, PLLA/PDLA blends were manufactured using an environmentally friendly and low-cost single step spunbond fibrillation process, yielding microfibers stretched to diameters of 5-20 μm. During this stretching process, PLLA and PDLA chains are aligned along the flow direction. SCs subsequently formed in situ upon heating, dramatically improving crystallization kinetics, melt elasticity, and tensile performance compared with neat PLLA and non-stretched blend analogues, even with low PDLA content (3 wt%). These improvements were attributed to topological variations in SC superstructures caused by alignment of PLLA and PDLA chains. The application of chain alignment in tuning SC superstructure morphology is ubiquitous in fibrillation processes.

Bone tissue engineering is a field to manufacture scaffolds for bone defects that cannot repair without medical interventions. Ceramic nanoparticles such as bredigite have importance roles in bone regeneration. We synthesized a novel strontium (Sr) doped bredigite (Bre) nanoparticles (BreSr) and then developed new nanocomposite scaffolds using polycaprolactone (PCL), poly lactic acid (PLA) by the 3D-printing technique. Novel functional nanoparticles were synthesized and characterized using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and energy dispersive spectroscopy (EDS: map). The nanoparticles were uniformly distributed in the polymer matrix composites. The 3D- printed scaffolds were investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), attenuated total reflection-fourier transform infrared (ATR-FTIR), degradation rate porosity, mechanical tests, apatite formation and cell culture. Degradation rate and mechanical strength were increased in the PLA/PCL/Bre-5%Sr nanocopmposite scaffolds. Hydroxyapatite crystals were also created on the scaffold surface in the bioactivity test. The scaffolds supported viability and proliferation of human osteoblasts. Gene expression and calcium deposition in the samples containing nanoparticles indicated statistical different than the scaffolds without nanoparticles. The nanocomposite scaffolds were implanted into the critical-sized calvarial defects in rat for 3 months. The scaffolds containing Bre-Sr ceramic nanoparticles exhibited the best potential to regenerate bone tissue.

Electrical stimulation is conducive to neural regeneration. Different types of stimuli propagation patterns are required for regenerating cells in peripheral and central nervous systems. Modulation of the pattern of stimuli propagation cannot be achieved through external means. Reinforcing scaffolds, with suitably shaped conductive second phase materials, is a promising option in this regard. The present study has taken the effort of modulating the pattern (arrangement) of reinforced phase, namely multiwalled carbon nanotubes (MWCNT), in a biodegradable scaffold made of PCL-collagen mixture, by applying an external electric field during curing. Because of their extraordinary physical properties, MWCNTs have been selected as nano-reinforcement for this study. The nature of reinforcement affects the electrical conductivity of the scaffold and also determines the type of cell it can support for regeneration. Further, electrical stimulation, applied during incubation, was observed to have a positive influence on differentiating neural cells in vitro. However, the structure of the nano-reinforcement determined the differentiated morphology of the cells. Reinforced MWCNTs being tubes, imparted bipolarity to the cells. Therefore, these scaffolds, coupled with electrical stimulation possess significant potential to be used for directional regeneration of the nerves.

Poly (L-lactic acid) (PLLA)-based biocomposites have been used in tissue engineering applications because of their reasonable biocompatibility and mechanical properties. However, the imperfect bioactive and mechanical properties of the composite make it difficult to be used in the region of bone defects that require high load-bearing. Therefore, this study introduced two fabricating strategies to induce mechanically and biologically enhanced hydroxyapatite (HA)/PLLA biocomposites. By introducing an in situ plasma treatment, which was simultaneously applied during the 3D-printing process, followed by the thermal annealing process, the flexural modulus of the composite was increased by 2.1-fold compared to the normal HA/PLLA composite. Furthermore, using the combinational process, efficient coating of bioactive material [decellularized extracellular matrix (dECM) derived from porcine bones] was possible. The fabricated biocomposite scaffold was assessed for various in vitro cellular activities such as cell proliferation and osteogenic activity. Based on the mechanical and biological studies, the HA/PLLA/dECM biocomposite scaffold is one of the promising scaffolds that can be applied in bone tissue regeneration.

Poly(L-lactic acid) (PLLA) braided stents have superior biocompatibility and flexibility, substituting metal stents in peripheral blood vessels. However, the radial supporting capacity of PLLA braided stent should be improved to bear the dynamic load from the peripheral artery. This paper evaluated the radial support performance of PLLA braided stents with different braiding angles after the radial cyclic loads test. The results indicate that braiding angle of stents is an important parameter affecting its ability to resist radial cyclic loads. The stent with a smaller braiding angle has better initial radial support but insufficient durability, while the stent with a larger braiding angle could maintain adequate radial support and suitable ability to resist radial cyclic loads. The theoretical analysis, verified by observing the surface morphology of filament crossover points, found that filaments of the stents with smaller braiding angles have more significant axial displacement and axial rotation angle during radial compression, which made the friction phenomenon more intense and led to insufficient ability to resist radial cyclic loads. This study could provide a meaningful idea for preparing biodegradable braided stents with suitable ability to resist radial cyclic loads.

The desire of producing marketable green bio-composites displaying good functional properties has increased. Biodegradable composites are a subject of interest as they respond to ecological concerns. In this study, an eco-friendly alkali-laccase modification was used to improve the interfacial adhesion of mukwa wood fiber and polylactic acid (PLA) matrix. The untreated and treated mukwa-PLA composites were fabricated via extrusion and compression molding technique and investigated. The mukwa wood fibers and mukwa-PLA composites were characterized by chemical composition, crystallite size, Fourier transform infrared spectroscope (FTIR), mechanical properties, and scanning electron microscope (SEM) respectively. The cellulose content was found to increase, while the hemicellulose, lignin, and extractives reduced after the surface modifications. The alkali-laccase, laccase, and alkali modifications increased the tensile strength of the untreated/PLA composites by 12.3 %, 5.2 %, and 3.8 % respectively. The flexural strength of the composites reached a maximum of 95.1 MPa following the alkali-laccase treatment. The alkali-laccase treated composites showed increased impact strength of 53.9 % on the untreated/PLA composites. Good correlations between the crystallite size and the mechanical properties were reported, with the highest R-square (R

The paper demonstrates curcumin/β-cyclodextrin-based inclusion complex (IC) loaded polyvinyl alcohol (PVA) dip-coated and copolymer-compatibilized polylactic acid (PLA)/poly(ε-caprolactone) (PCL) blend-based electrospun mats (EMs) as antibacterial, and suture-resistant constructs, to overcome the present challenges in developing structurally-stable, biocompatible, pliable, and stand-alone multifunctional-biomedical-devices. The thermal, microstructural, and viscoelastic characterization confirmed the presence of H-bonding interactions between IC and PVA moieties and between IC incorporated PVA matrix with the copolymer-mediated nanotextured PLA/PCL blend-based EMs. IC release and surface PVA erosion induced a decrease in modulus (4-fold) and strength (2-fold) of constructs (post-release). Mechanistically new and architectural-framework-defined PVA-gelation induced bi-axially diverted suture-failure (post-release) and resulted in a significant enhancement in suture-retention-strength (3-fold), energy (5-fold), and displacement (2-fold) for ~20 wt% IC-loaded-PVA-coated EM-constructs. The fabricated EM-constructs exhibited improvement in surface-hydrophilicity (contact angle ~45°), surface nano-roughness (~ 600 nm), surface area (~34 m

In this study, nanocomposites of polylactic acid (PLA) with clove essential oil (CEO) and alkali treated halloysite nanotubes (NHNT) as fillers were synthesized by using simple solvent casting method. The treatment of halloysite nanotubes with NaOH increased the surface area from 50.16 m

The chemolithotroph Cupriavidus necator H16 is known as a natural producer of the bioplastic-polymer PHB, as well as for its metabolic versatility to utilize different substrates, including formate as the sole carbon and energy source. Depending on the entry point of the substrate, this versatility requires adjustment of the thermodynamic landscape to maintain sufficiently high driving forces for biological processes. Here we employed a model of the core metabolism of C. necator H16 to analyze the thermodynamic driving forces and PHB yields from formate for different metabolic engineering strategies. For this, we enumerated elementary flux modes (EFMs) of the network and evaluated their PHB yields as well as thermodynamics via Max-min driving force (MDF) analysis and random sampling of driving forces. A heterologous ATP:citrate lyase reaction was predicted to increase driving force for producing acetyl-CoA. A heterologous phosphoketolase reaction was predicted to increase maximal PHB yields as well as driving forces. These enzymes were then verified experimentally to enhance PHB titers between 60 and 300% in select conditions. The EFM analysis also revealed that PHB production from formate may be limited by low driving forces through citrate lyase and aconitase, as well as cofactor balancing, and identified additional reactions associated with low and high PHB yield. Proteomics analysis of the engineered strains confirmed an increased abundance of aconitase and cofactor balancing. The findings of this study aid in understanding metabolic adaptation. Furthermore, the outlined approach will be useful in designing metabolic engineering strategies in other non-model bacteria.

It remains a great challenge to manufacture polylactic (PLA) with high strength, ductility, and heat resistance simultaneously. Herein, PLA/poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoribboned composites, the highly oriented PHBV nanoribbons decorated by the PLA lamella, are successfully achieved through the multistage stretching extrusion (MSE) system. SEM confirms that in-situ highly oriented PHBV nanoribbons are achieved by biaxial-stretching field during the MSE process. Through investigating crystalline architecture of PLA/PHBV nanoribboned composites, it is found that the stiff shish and sparse lamellae of PLA are obtained under the coupling effect of PHBV nanoribbons and biaxial-stretching field. DMA reveals partial compatibility between PLA and PHBV. Interestingly, during tensile test, PHBV nanoribbons show high flexibility and synergistically facilitate the stretch of semi-rigid chains of PLA by an effective interfacial interaction. Consequently, even they both are extremely brittle, PLA/PHBV nanoribboned composites exhibit excellent strength (82.9 MPa) and ductility (186.7 %), compared with pure PLA (71.4 MPa and 12.3 %). Additionally, due to the promotion of the crystallization of PLA, PLA/PHBV nanoribboned composites show excellent heat resistance (E'

Most small diameter vascular grafts (inner diameterlt;6 mm) evaluation studies are performed in healthy animals that cannot represent the clinical situation. Herein, an hypercholesterolemia (HC) rat model with thickened intima and elevated expression of pro-inflammatory intercellular adhesion molecular-1 (ICAM-1) in the carotid branch is established. Electrospun polycaprolactone (PCL) vascular grafts (length: 1 cm; inner diameter: 2 mm) are implanted into the HC rat abdominal aortas in an end to end fashion and followed up to 43 days, showing a relative lower patency accompanied by significant neointima hyperplasia, abundant collagen deposition, and slower endothelialization than those implanted into healthy ones. Moreover, the proliferation, migration, and adhesion behavior of endothelial cells (ECs) isolated from the HC aortas are impaired as evaluated under both static and pulsatile flow conditions. DNA microarray studies of the HC aortic endothelium suggest genes involved in EC proliferation (Egr2), apoptosis (Zbtb16 and Mt1), and metabolism (Slc7a11 and Hamp) are down regulated. These results suggest the impaired proliferative, migratory, and adhesive abilities of ECs are associated with the bad performances of grafts in HC rat. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications. STATEMENT OF SIGNIFICANCE: During the development of small diameter vascular grafts (Dlt;6 mm), young and healthy animal models from pigs, sheep, dogs, to rabbits and rats are preferred. However, it cannot represent the clinic situation, where most cardiovascular grafting procedures are performed in the elderly and age is the primary risk factor for disease development or death. Herein, the performance of electrospun polycaprolactone (PCL) vascular grafts implanted into hypercholesterolemia (HC) or healthy rats were evaluated. Results suggest the proliferative, migratory, and adhesive abilities of endothelial cells (ECs) are already impaired in HC rats, which contributes to the observed slower endothelialization of implanted PCL grafts. Future pre-clinical evaluation of small diameter vascular grafts may concern more disease animal models with clinical complications.

The limitations of non-biodegradable polymers have paved the way for biodegradable polymers in the pharmaceutical and biomedical sciences over the years. Poly (lactic-co-glycolic acid) (PLGA), also known as "Smart polymer", is one of the most successfully developed biodegradable polymers due to its favorable properties, such as biodegradability, biocompatibility, controllable drug release profile, and ability to alter surface with targeting agents for diagnosis and treatment. The release behavior of drugs from PLGA delivery devices is influenced by the physicochemical properties of PLGA. In this review, the current state of the art of PLGA, its synthesis, physicochemical properties, and degradation are discussed to enunciate the boundaries of future research in terms of its applicability with the optimized design in today's modern age. The fundamental objective of this review is to highlight the significance of PLGA as a polymer in the field of cancer, cardiovascular diseases, neurological disorders, dentistry, orthopedics, vaccine therapy, theranostics and lastly emerging epidemic diseases like COVID-19. Furthermore, the coverage of recent PLGA-based drug delivery systems including nanosystems, microsystems, scaffolds, hydrogels, etc. has been summarized. Overall, this review aims to disseminate the PLGA-driven revolution of the drug delivery arena in the pharmaceutical and biomedical industry and bridge the lacunae between material research, preclinical experimentation, and clinical reality.

Tracheal fistula (TF) treatments may involve temporary orthosis and further ablative procedures, which can lead to infection. Thus, TF requires other therapy alternatives development. The hypothesis of this work was to demonstrate the feasibility of a tissue-engineered alternative for small TF in a preclinical model. Also, its association with suture filaments enriched with adipose tissue-derived mesenchymal stromal stem cells (AT-MSCs) was assessed to determine whether it could optimize the regenerative process.Poly (L-Lactic acid) (PLLA) membranes were manufactured by electrospinning and had morphology analyzed by scanning electron microscopy. AT-MSCs were cultured in these scaffolds and in vitro assays were performed (cytotoxicity, cellular adhesion, and viability). Subsequently, these cellular constructs were implanted in an animal small TF model. The association with suture filaments containing attached AT-MSCs was present in one animal group. After 30 d, animals were sacrificed and regenerative potential was evaluated, mainly related to the extracellular matrix remodeling, by performing histopathological (Hematoxylin-Eosin and trichrome Masson) and immunohistochemistry (Collagen I/II/III, matrix metalloproteinases-2, matrix metalloproteinases-9, vascular endothelial growth factor, and interleukin-10) analyses.PLLA membranes presented porous fibers, randomly oriented. In vitro assays results showed that AT-MSCs attached were viable and maintained an active metabolism. Swine implanted with AT-MSCs attached to membranes and suture filaments showed aligned collagen fibers and a better regenerative progress in 30 d.PLLA membranes with AT-MSCs attached were useful to the extracellular matrix restoration and have a high potential for small TF treatment. Also, their association with suture filaments enriched with AT-MSCs was advantageous.

The high density and poor thermal insulation of traditional wood-plastic composites limited the application in the field of building materials. In this paper, wood fiber (WF) and PLA were used as raw materials and azodicarbonamide was used as the foaming agent. Lightweight WF/PLA composites were prepared by the hot-pressing foaming method, aiming to obtain renewable, low-density material with high strength-to-weight ratio and thermal insulation performance. The results showed that after adding 20 % WF into PLA, the cell morphology was excellent and the cell size was uniform. The magnification reached the minimum value of 0.36 g/cm

A large training dataset with high-quality annotations is necessary for building an accurate and generalisable deep learning system, which can be difficult and expensive to prepare in medical applications. We present a novel deep-learning-based system, requiring no annotator but weak annotation from a diagnosis report, for accurate and generalisable performance in detecting multiple head disorders from CT scans, including ischaemia, haemorrhage, tumours, and skull fractures.Our system was developed on 104 597 head CT scans from the Chinese PLA General Hospital, with associated textual diagnosis reports. Without expert annotation, we used keyword matching on the reports to automatically generate disorder labels for each scan. The labels were inaccurate because of the unreliable annotator-free strategy and inexact because of scan-level annotation. We proposed RoLo, a novel weakly supervised learning algorithm, with a noise-tolerant mechanism and a multi-instance learning strategy to address these issues. RoLo was tested on retrospective (2357 scans from the Chinese PLA General Hospital), prospective (650 scans from the Chinese PLA General Hospital), cross-centre (1525 scans from the Brain Hospital of Hunan Province), cross-equipment (1484 scans from the Chinese PLA General Hospital), and cross-nation (CQ500 public dataset from India) test datasets. Four radiologists were tested on the prospective test dataset before and after viewing system recommendations to assess whether the system could improve diagnostic performance.The area under the receiver operating characteristic curve for detecting the four disorder types was 0·976 (95% CI 0·976-0·976) for retrospective, 0·975 (0·974-0·976) for prospective, 0·965 (0·964-0·966) for cross-centre, and 0·971 (0·971-0·972) for cross-equipment test datasets, and 0·964 (0·964-0·966) for CQ500 (with only haemorrhage and fracture). The system achieved similar performance to four radiologists and helped to improve sensitivity and specificity by 0·109 (95% CI 0·086-0·131) and 0·022 (0·017-0·026), respectively.Without expert annotated data, our system achieved accurate and generalisable performance for head disorder detection. The system improved the diagnostic performance of radiologists. Because of its accuracy and generalisability, our computer-aided diganostic system could be used in clinical practice to improve the accuracy and efficiency of radiologists in different hospitals.National Key RD Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

There are complications in applying regenerative strategies at the interface of hard and soft tissues due to the limited designs of constructs that can accommodate different cell types in different sites. The problem originates from the challenges in the adhesion of dissimilar materials, such as polymers and hydrogels, that can be suitable for regenerating different tissues such as bone and soft tissues. This paper presents a design of a new hybrid construct in which a polymer (polycaprolactone (PCL)) membrane firmly adheres to a layer of hydrogen (gelatin).PCL membranes with defined size and porosity were fabricated using 3D printing. The gelatin layer was attached to the PCL membranes using the aminolysis procedure. We have examined this construct for the application of Guided Bone Regeneration (GBR) as a typical surgical regenerative procedure of the oral cavity at the interface of bone and soft tissue. Complete in vitro and in vivo investigations on canine tibia bone defects have been performed. Histological analyses for fibrosis morphometric and bone morphometric evaluation, as well as bone-fibrosis histological grading and CBCT imaging, were conducted.Chemical and morphological studies of the membrane proved that gelatin was uniformly attached to the aminolyzed PCL membranes. The in vitro and in vivo studies indicated the membrane's biocompatibility, mechanical stability, and barrier function for the GBR application. Furthermore, in vitro study showed that the membranes could improve osteogenesis and the regeneration of bone defects. The results illustrated that the mean bone density in the membrane groups was about three times more than that of the control group.The fabricated 3D-printed hybrid Gelatin/PCL bi-layered membrane can be a good candidate for interfacial tissue engineering and a promising membrane for GBR procedure.

In this study, the physicochemical properties of torrefied biomass (larch and yellow poplar) were investigated based on torrefaction temperature. The effect of torrefied biomass on the hydrophobicity and mechanical properties of a polylactic acid (PLA) composites was evaluated. Hemicellulose was removed from the biomass during torrefaction, whereas the cellulose and lignin contents increased slightly. The color of the biomass changed from brown to black. The grindability of the torrefied biomass improved as the torrefaction temperature increased, which contributed to the production of fine particles (100 mesh). A PLA composite was prepared using torrefied biomass (10 %) and polylactic acid. At 280 °C, water contact angle was the highest, regardless of the particle size and biomass species. Tensile strength of the PLA composite was slightly lower than that of PLA alone, regardless of the particle size of torrefied biomass. Nevertheless, the strength increased with the torrefaction temperature, except for larch with a relatively large particle size (100 mesh). The tensile strength of the control was 68.0 MPa, whereas that of the torrefied biomass ranged from 61.1 to 65.8 MPa.

Producción Científica, Biogas-based biopolymer production represents an alternative biogas valorization route with potential to cut down plastic pollution and greenhouse gas emissions. This study investigated for the first time the continuous bioconversion of methane, contained in biogas, into poly(3-hydroxybutyrate) (PHB) by a mixed methanotrophic culture using an innovative high mass-transfer Taylor flow bioreactor. Following a hydrodynamic flow regime mapping, the influence of the gas residence time and the internal gas recirculation on CH4 abatement was assessed under non nutrient limiting conditions. Under optimal operational conditions (gas residence time of 60 min and internal gas recycling ratio of 17), the bioreactor was able to support a CH4 removal efficiency of 63.3%, a robust CH4 elimination capacity (17.2 g-CH4 m-3h-1) and a stable biomass concentration (1.0 g L-1). The simultaneous CH4 abatement and PHB synthesis was investigated under 24-h:24-h nitrogen feast/famine continuous operation. The cyclic nitrogen starvation and the Taylor flow imposed in the bioreactor resulted in a relatively constant biomass concentration of 0.6 g L-1 with PHB contents ranging from 11 to 32% w w-1 (on a dry weight basis), entailing an average PHB productivity of 5.9 g-PHB m-3 d-1 with an associated PHB yield of 19.8 mg-PHB g-CH4-1. Finally, the molecular analysis of the microbial population structure indicated that type II methanotrophs outcompeted non-PHB accumulating type I methanotrophs, with a heterotrophic-methanotrophic consortium enriched in Methylocystis, Hyphomicrobium, Rubinisphaeraceae SH PL14 and Pseudonocardia., Ministerio de Ciencia, Innovación y Universidades (project RTI2018-0-096441-B-I00), Erasmus+ International Master of Science in Environmental Technology and Engineering (project 2017-1957/001-001-EMJMD), Junta de Castilla y Leon - Fondo Europeo de Desarrollo Regional (grants CLU 2017-09 and UIC 315)

3D printing represents a democratization of manufacturing processes, and inexpensive 3D printed parts for cell culture have been tested as replacements for single-use plastics currently unavailable due to worldwide supply chain issues. In addition, such distributed manufacturing of cell culture laboratory materials helps remote areas and developing countries with limited resources. HEK293 cells were used to test printed shake flasks for cell culture applications and their ease of manufacture. Recorded growth curves showed that renewable biodegradable poly(lactic acid) (PLA) thermoplastic is an excellent and economical replacement for single-use plastic shake flasks, which have shipment lead times during pandemic situations or other supply chain disruptions of over 6 months. With a price of 0.60 € in materials, and printing machines with prices lower than one box of single-use pre-sterilized plastic shake flasks (350€), the use of PLA is very affordable. Low-cost photopolymerization resins were also tested, but the inherent cytotoxicity of these materials prevented cell growth. This was also true for plant-based resins marketed as having low volatile organic compounds (VOC). Treatment of parts to reduce VOC content was partially successful, but not sufficient to sustain prolonged cell growth. A high-cost medical device IIa-class material showed no improved cell growth. Nevertheless, with PLA a low-cost printing material was identified and the use as cell culture compatible material was demonstrated, providing low-cost supply chain independence. In the future, the printing of pilot-scale bioreactors with PLA as a green sustainable material at the point of its use will be possible.

Temporomandibular disorder (TMD) remained a huge clinical challenge, with high prevalence but limited, unstable, and only palliative therapeutic methods available. As one of the most vulnerable sites implicated in TMD, the temporomandibular joint disc (TMJD) displayed a complicated microstructure, region-specific fibrocartilaginous distribution, and poor regenerative property, which all further hindered its functional regeneration. To address the problem, with versatile and relatively simple electrospinning (ELS) technique, our study successfully fabricated a biomimetic, three-dimensional poly (ϵ-caprolactone) (PCL)/polylactide (PLA)/carbon nanotubes (CNTs) disc scaffold, whose biconcave gross anatomy and regionally anisotropic microstructure recapitulating those of the native disc. As in vitro results validated the superior mechanical, bioactive, and regenerative properties of the biomimetic scaffolds with optimal CNTs reinforcement, we further performed in vivo experiments. After verifying its biocompatibility and ectopic fibrochondrogenicity in nude mice subcutaneous implantation models, the scaffolds guided disc regeneration and subchondral bone protection were also confirmed orthotopically in rabbits TMJD defected areas, implying the pivotal role of morphological cues in contact-guided tissue regeneration. In conclusion, our work represents a significant advancement in complex, inhomogeneous tissue engineering, providing promising clinical solutions to intractable TMD ailments. STATEMENT OF SIGNIFICANCE: Complex tissue regeneration remains a huge scientific and clinical challenge. Although frequently implicated in temporomandibular joint disorder (TMD), functional regeneration of injured temporomandibular joint disc (TMJD) is extremely hard to achieve, mainly because of the complex anatomy and microstructure with regionally variant, anisotropic fiber alignments in the native disc. In this study, we developed the biomimetic electrospun scaffold with optimal CNTs reinforcement and regionally anisotropic fiber orientations. The excellent mechanical and bioactive properties were confirmed both in vitro and in vivo, effectively promoting defected discs regeneration in rabbits. Besides demonstrating the crucial role of morphological biomimicry in tissue engineering, our work also presents a feasible clinical solution for complex tissue regeneration.

There is a tremendous need for simple-to-administer, long-acting contraception, which can increase access to improved family planning. Microneedle (MN) patches enable simple self-administration and have previously been formulated for 1-2 months' controlled release of contraceptive hormone using monolithic polymer/drug MN designs having first-order release kinetics. To achieve zero-order release, we developed a novel core-shell MN patch where the shell acts as a rate-controlling membrane to delay release of a contraceptive hormone, levonorgestrel (LNG), for 6 months. In this approach, LNG was encapsulated in a poly(lactide-co-glycolide) (PLGA) core surrounded by a poly(l-lactide) (PLLA) shell and a poly(D,L-lactide) (PLA) cap that were fabricated by sequential casting into a MN mold. Upon application to skin, the core-shell MNs utilized an effervescent interface to separate from the patch backing within 1 min. The core-shell design limited the initial 24 h burst release of LNG to 5.8 ± 0.5% and achieved roughly zero-order LNG release for 6.2 ± 0.1 months in vitro. A monolithic MN patch formulated with the same LNG and PLGA core, but without the rate-controlling PLLA shell and PLA cap had a larger LNG burst release of 22.6 ± 2.0% and achieved LNG release for just 2.1 ± 0.2 months. This study provides the first core-shell MN patch for controlled months-long drug release and supports the development of long-acting contraception using a simple-to-administer, twice-per-year MN patch.

Intended for food packaging, nanocomposites films based on poly (lactic acid) reinforced by polydopamine-wrapped carbon nanotubes (PLA/PDA-MWCNTs) or TiO

Active and pH-sensitive films of poly(lactic acid) (PLA)/nanofibrillated cellulose (NFC) have been fabricated and tested. The PLA and PLA/NFC films with 1.5% NFC were prepared via solvent casting method, with different loadings of essential oil (EO), including thymol and curry, being added at 5, 10, and 15%. The fixed content of anthocyanin powder (1%) was incorporated into the films as a pH indicator. The active PLA and PLA/NFC films were characterised on their physical, mechanical, thermal, and biodegradation properties. The addition of NFC reduced the tensile strength but increased the flexibility of films due to the plasticizing effect of EOs. The PLA/EO and PLA/NFC/EO films containing curry demonstrated a slightly higher strength than the films with thymol. The flexibility of films was increased at higher loading of EO regardless of the types of EO. The thermal profile demonstrated that the neat PLA film had a higher maximum degradation temperature than the active PLA/EO and PLA/NFC/EO films. The active PLA/EO and PLA/NFC/EO films containing anthocyanin successfully changed its colour in pH 2.0 and 14.0. The PLA/NFC films with thymol and anthocyanin formulation could inhibit fungus growth better in the cherry tomato sample than the PLA/NFC films with curry and anthocyanin.