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The fast-progressing landscape of the bioprocessing industry emphasizes innovation and efficiency enhancement, propelled by the integration of advanced solutions. Additive manufacturing technologies, particularly laserbased powder bed fusion with polypropylene, are pivotal in this industrial metamorphosis. However, despite the substantial scientific effort in the field, a significant gap exists in comprehending the surface characteristics of new surfaces and their implications for bacterial attachment and biofilm formation. This arises, in part, due to the absence of comprehensive and universally applicable topographical characterization analysis specifically designed for additively manufactured-fabricated surfaces. Typically, researchers tend to rely on the commonly used roughness parameter, Sa, that primarily quantifies the average height variation across a surface. Addressing this limitation is crucial for understanding the connection between surface characteristics and bacterial attachment dynamics. Here, we propose an innovative approach using surface analysis including confocal microscopy, advanced roughness measurements, and multivariate statistical analysis to uncover the connections between bacterial attachment for Gram negative Escherichia coli and Gram positive Staphylococcus aureus in early biofilm formation with surfaces produced by standardized and additively manufactured techniques. Finally, we advocate for the adoption of a set of roughness parameters that specifically describe the dale region of the surfaces. By doing so, we intend to establish direct links between surface texture and bacterial adhesion, thus contributing significantly to the advancement of both bioprocessing and additive manufacturing research domains.

The fast-progressing landscape of the bioprocessing industry emphasizes innovation and efficiency enhancement, propelled by the integration of advanced solutions. Additive manufacturing technologies, particularly laserbased powder bed fusion with polypropylene, are pivotal in this industrial metamorphosis. However, despite the substantial scientific effort in the field, a significant gap exists in comprehending the surface characteristics of new surfaces and their implications for bacterial attachment and biofilm formation. This arises, in part, due to the absence of comprehensive and universally applicable topographical characterization analysis specifically designed for additively manufactured-fabricated surfaces. Typically, researchers tend to rely on the commonly used roughness parameter, Sa, that primarily quantifies the average height variation across a surface. Addressing this limitation is crucial for understanding the connection between surface characteristics and bacterial attachment dynamics. Here, we propose an innovative approach using surface analysis including confocal microscopy, advanced roughness measurements, and multivariate statistical analysis to uncover the connections between bacterial attachment for Gram negative Escherichia coli and Gram positive Staphylococcus aureus in early biofilm formation with surfaces produced by standardized and additively manufactured techniques. Finally, we advocate for the adoption of a set of roughness parameters that specifically describe the dale region of the surfaces. By doing so, we intend to establish direct links between surface texture and bacterial adhesion, thus contributing significantly to the advancement of both bioprocessing and additive manufacturing research domains.

The fast-progressing landscape of the bioprocessing industry emphasizes innovation and efficiency enhancement, propelled by the integration of advanced solutions. Additive manufacturing technologies, particularly laser-based powder bed fusion with polypropylene, are pivotal in this industrial metamorphosis. However, despite the substantial scientific effort in the field, a significant gap exists in comprehending the surface characteristics of new surfaces and their implications for bacterial attachment and biofilm formation. This arises, in part, due to the absence of comprehensive and universally applicable topographical characterization analysis specifically designed for additively manufactured-fabricated surfaces. Typically, researchers tend to rely on the commonly used roughness parameter, Sa, that primarily quantifies the average height variation across a surface. Addressing this limitation is crucial for understanding the connection between surface characteristics and bacterial attachment dynamics. Here, we propose an innovative approach using surface analysis including confocal microscopy, advanced roughness measurements, and multivariate statistical analysis to uncover the connections between bacterial attachment for Gram negative Escherichia coli and Gram positive Staphylococcus aureus in early biofilm formation with surfaces produced by standardized and additively manufactured techniques. Finally, we advocate for the adoption of a set of roughness parameters that specifically describe the dale region of the surfaces. By doing so, we intend to establish direct links between surface texture and bacterial adhesion, thus contributing significantly to the advancement of both bioprocessing and additive manufacturing research domains., This work is conducted within the Additive Manufacturing for the Life Sciences Competence Center (AM4Life). The authors gratefully acknowledge financial support from Sweden's Innovation Agency VINNOVA (Grant no: 2019-00029). The authors acknowledge financial support from the Swedish Foundation for Strategic Research (RMA15-0010).

The fast-progressing landscape of the bioprocessing industry emphasizes innovation and efficiency enhancement, propelled by the integration of advanced solutions. Additive manufacturing technologies, particularly laserbased powder bed fusion with polypropylene, are pivotal in this industrial metamorphosis. However, despite the substantial scientific effort in the field, a significant gap exists in comprehending the surface characteristics of new surfaces and their implications for bacterial attachment and biofilm formation. This arises, in part, due to the absence of comprehensive and universally applicable topographical characterization analysis specifically designed for additively manufactured-fabricated surfaces. Typically, researchers tend to rely on the commonly used roughness parameter, Sa, that primarily quantifies the average height variation across a surface. Addressing this limitation is crucial for understanding the connection between surface characteristics and bacterial attachment dynamics. Here, we propose an innovative approach using surface analysis including confocal microscopy, advanced roughness measurements, and multivariate statistical analysis to uncover the connections between bacterial attachment for Gram negative Escherichia coli and Gram positive Staphylococcus aureus in early biofilm formation with surfaces produced by standardized and additively manufactured techniques. Finally, we advocate for the adoption of a set of roughness parameters that specifically describe the dale region of the surfaces. By doing so, we intend to establish direct links between surface texture and bacterial adhesion, thus contributing significantly to the advancement of both bioprocessing and additive manufacturing research domains., QC 20240722

QC 20240906

The dynamic interplay between cells and their native extracellular matrix (ECM) influences cellular behavior, imposing a challenge in biomaterial design. Dynamic covalent hydrogels are viscoelastic and show self-healing ability, making them a potential scaffold for recapitulating native ECM properties. We aimed to implement kinetically and thermodynamically distinct crosslinkers to prepare self-healing dynamic hydrogels to explore the arising properties and their effects on cellular behavior. To do so, aldehyde-substituted hyaluronic acid (HA) was synthesized to generate imine, hydrazone, and oxime crosslinked dynamic covalent hydrogels. Differences in equilibrium constants of these bonds yielded distinct properties including stiffness, stress relaxation, and self-healing ability. The effects of degree of substitution (DS), polymer concentration, crosslinker to aldehyde ratio, and crosslinker functionality on hydrogel properties were evaluated. The self-healing ability of hydrogels was investigated on samples of the same and different crosslinkers and DS to obtain hydrogels with gradient properties. Subsequently, human dermal fibroblasts were cultured in 2D and 3D to assess the cellular response considering the dynamic properties of the hydrogels. Moreover, assessing cell spreading and morphology on hydrogels having similar modulus but different stress relaxation rates showed the effects of matrix viscoelasticity with higher cell spreading in slower relaxing hydrogels., QC 20240520

The fast-progressing landscape of the bioprocessing industry emphasizes innovation and efficiency enhancement, propelled by the integration of advanced solutions. Additive manufacturing technologies, particularly laserbased powder bed fusion with polypropylene, are pivotal in this industrial metamorphosis. However, despite the substantial scientific effort in the field, a significant gap exists in comprehending the surface characteristics of new surfaces and their implications for bacterial attachment and biofilm formation. This arises, in part, due to the absence of comprehensive and universally applicable topographical characterization analysis specifically designed for additively manufactured-fabricated surfaces. Typically, researchers tend to rely on the commonly used roughness parameter, Sa, that primarily quantifies the average height variation across a surface. Addressing this limitation is crucial for understanding the connection between surface characteristics and bacterial attachment dynamics. Here, we propose an innovative approach using surface analysis including confocal microscopy, advanced roughness measurements, and multivariate statistical analysis to uncover the connections between bacterial attachment for Gram negative Escherichia coli and Gram positive Staphylococcus aureus in early biofilm formation with surfaces produced by standardized and additively manufactured techniques. Finally, we advocate for the adoption of a set of roughness parameters that specifically describe the dale region of the surfaces. By doing so, we intend to establish direct links between surface texture and bacterial adhesion, thus contributing significantly to the advancement of both bioprocessing and additive manufacturing research domains.

The fast-progressing landscape of the bioprocessing industry emphasizes innovation and efficiency enhancement, propelled by the integration of advanced solutions. Additive manufacturing technologies, particularly laserbased powder bed fusion with polypropylene, are pivotal in this industrial metamorphosis. However, despite the substantial scientific effort in the field, a significant gap exists in comprehending the surface characteristics of new surfaces and their implications for bacterial attachment and biofilm formation. This arises, in part, due to the absence of comprehensive and universally applicable topographical characterization analysis specifically designed for additively manufactured-fabricated surfaces. Typically, researchers tend to rely on the commonly used roughness parameter, Sa, that primarily quantifies the average height variation across a surface. Addressing this limitation is crucial for understanding the connection between surface characteristics and bacterial attachment dynamics. Here, we propose an innovative approach using surface analysis including confocal microscopy, advanced roughness measurements, and multivariate statistical analysis to uncover the connections between bacterial attachment for Gram negative Escherichia coli and Gram positive Staphylococcus aureus in early biofilm formation with surfaces produced by standardized and additively manufactured techniques. Finally, we advocate for the adoption of a set of roughness parameters that specifically describe the dale region of the surfaces. By doing so, we intend to establish direct links between surface texture and bacterial adhesion, thus contributing significantly to the advancement of both bioprocessing and additive manufacturing research domains.

The fast-progressing landscape of the bioprocessing industry emphasizes innovation and efficiency enhancement, propelled by the integration of advanced solutions. Additive manufacturing technologies, particularly laser-based powder bed fusion with polypropylene, are pivotal in this industrial metamorphosis. However, despite the substantial scientific effort in the field, a significant gap exists in comprehending the surface characteristics of new surfaces and their implications for bacterial attachment and biofilm formation. This arises, in part, due to the absence of comprehensive and universally applicable topographical characterization analysis specifically designed for additively manufactured-fabricated surfaces. Typically, researchers tend to rely on the commonly used roughness parameter, Sa, that primarily quantifies the average height variation across a surface. Addressing this limitation is crucial for understanding the connection between surface characteristics and bacterial attachment dynamics. Here, we propose an innovative approach using surface analysis including confocal microscopy, advanced roughness measurements, and multivariate statistical analysis to uncover the connections between bacterial attachment for Gram negative Escherichia coli and Gram positive Staphylococcus aureus in early biofilm formation with surfaces produced by standardized and additively manufactured techniques. Finally, we advocate for the adoption of a set of roughness parameters that specifically describe the dale region of the surfaces. By doing so, we intend to establish direct links between surface texture and bacterial adhesion, thus contributing significantly to the advancement of both bioprocessing and additive manufacturing research domains., This work is conducted within the Additive Manufacturing for the Life Sciences Competence Center (AM4Life). The authors gratefully acknowledge financial support from Sweden's Innovation Agency VINNOVA (Grant no: 2019-00029). The authors acknowledge financial support from the Swedish Foundation for Strategic Research (RMA15-0010).

The fast-progressing landscape of the bioprocessing industry emphasizes innovation and efficiency enhancement, propelled by the integration of advanced solutions. Additive manufacturing technologies, particularly laserbased powder bed fusion with polypropylene, are pivotal in this industrial metamorphosis. However, despite the substantial scientific effort in the field, a significant gap exists in comprehending the surface characteristics of new surfaces and their implications for bacterial attachment and biofilm formation. This arises, in part, due to the absence of comprehensive and universally applicable topographical characterization analysis specifically designed for additively manufactured-fabricated surfaces. Typically, researchers tend to rely on the commonly used roughness parameter, Sa, that primarily quantifies the average height variation across a surface. Addressing this limitation is crucial for understanding the connection between surface characteristics and bacterial attachment dynamics. Here, we propose an innovative approach using surface analysis including confocal microscopy, advanced roughness measurements, and multivariate statistical analysis to uncover the connections between bacterial attachment for Gram negative Escherichia coli and Gram positive Staphylococcus aureus in early biofilm formation with surfaces produced by standardized and additively manufactured techniques. Finally, we advocate for the adoption of a set of roughness parameters that specifically describe the dale region of the surfaces. By doing so, we intend to establish direct links between surface texture and bacterial adhesion, thus contributing significantly to the advancement of both bioprocessing and additive manufacturing research domains.

QC 20240906

Light responsive polymeric materials are of great interest for several applications; in particular, the NIR spectrum is considered an ideal light source for e.g. biomedical applications. Here, we have designed light sensitive poly (epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) triblock copolymer, end-capped with modified coumarin. When dialyzed against water, the coumarin-functionalized triblock copolymers self -assembled into core-shell nanoparticles, characterized by DLS, SEM, and NMR. The hydrophobic Nile Red, used as a model guest molecule, was loaded in the nanoparticles and its release by light irradiation of selected wavelength was demonstrated by fluorescence spectroscopy. When irradiated with UV or NIR light, coumarin end-groups of the copolymer were photolyzed, converting the end groups to carboxylic acids, thus provoking the disruption of the preassembled nanoparticles, and the release of the encapsulated guest molecule., QC 20230201

Polypropylene (PP) powder bed fusion (PBF) with subsequent mechanical postprocessing can enable the development of more efficient and effective surfaces for bioprocessing equipment. However, there is still a lack of knowledge regarding the most relevant surface differences when compared to standardized surfaces. Herein, we present a new systematic methodology, including the evaluation of relevant roughness parameters and surface wettability, which has been implemented to assess the potential of AM to produce biopharmaceutical components. Surfaces of PP components produced by PBF and mechanically postprocessed by tumble surface finishing at 5, 10 and 15 h were compared to reference surfaces produced by computer numerical control (CNC) milling manufacturing. Thirteen roughness parameters were found to be relevant, of which the arithmetic mean peak curvature (Spc) and the density of peaks (Spd) were the most significant. The results demonstrate that the reference surfaces had Spc and Spd values of 1029 ± 36 mm−1 and 67739 ± 5440 mm−2, respectively, and moderate wettability with advancing (ACA) and receding (RCA) contact angles of 89 ± 3° and 68 ± 2°, respectively. The as-printed PBF surfaces were hydrophobic, with ACA of 119 ± 2° and RCA of 107 ± 4°, and with Spc and Spd values of 1089 ± 110 mm−1 and 30078 ± 4325 mm−2, respectively. PBF surfaces switched to a hydrophilic surface of 67 ± 3° and 44 ± 4° when the tumble surface finishing time was increased to 15 h. By taking advantage of this knowledge, we could produce surfaces using PBF and 5 h of mechanical postprocessing, which mimicked surface wetting and had Spc of 1100 ± 68 mm−1 and Spd of 55702 ± 9477 mm−2, similar to that of the CNC milling manufacturing. The developed comparative method and the results are important to better understand AM surfaces and can be used to transfer manufacturing from subtractive to additive technologies., QC 20230711

Background Age-driven immune signals cause a state of chronic low-grade inflammation and in consequence affect bone healing and cause challenges for clinicians when repairing critical-sized bone defects in elderly patients. Methods Poly(l-lactide-co-e-caprolactone) (PLCA) scaffolds are functionalized with plant-derived nanoparticles from potato, rhamnogalacturonan-I (RG-I), to investigate their ability to modulate inflammation in vitro in neutrophils and macrophages at gene and protein levels. The scaffolds' early and late host response at gene, protein and histological levels is tested in vivo in a subcutaneous rat model and their potential to promote bone regeneration in an aged rodent was tested in a critical-sized calvaria bone defect. Significant differences were tested using one-way ANOVA, followed by a multiple-comparison Tukey's test with a p value <= 0.05 considered significant. Results Gene expressions revealed PLCA scaffold functionalized with plant-derived RG-I with a relatively higher amount of galactose than arabinose (potato dearabinated (PA)) to reduce the inflammatory state stimulated by bacterial LPS in neutrophils and macrophages in vitro. LPS-stimulated neutrophils show a significantly decreased intracellular accumulation of galectin-3 in the presence of PA functionalization compared to Control (unmodified PLCA scaffolds). The in vivo gene and protein expressions revealed comparable results to in vitro. The host response is modulated towards anti-inflammatory/ healing at early and late time points at gene and protein levels. A reduced foreign body reaction and fibrous capsule formation is observed when PLCA scaffolds functionalized with PA were implanted in vivo subcutaneously. PLCA scaffolds functionalized with PA modulated the cytokine and chemokine expressions in vivo during early and late inflammatory phases. PLCA scaffolds functionalized with PA implanted in calvaria defects of aged rats downregulating pro-inflammatory gene markers while, QC 20220421

Synthetic, degradable macromonomers have been developed to serve as ink for 3D printing technologies based on direct-ink-writing. The macromonomers are purposely designed to be cross-linkable under the radical mechanism, to impart hydrophilicity to the final material, and to have rheological properties matching the printer's requirements. The suitable viscosity enables the ink to be printed at room temperature, in absence of organic solvents, and to be cross-linked to manufacture soft 3D scaffolds that show no indirect cytotoxicity and have a hydration capacity of up to 100% their mass and a compressive modulus in the range of 0.4-2 MPa., QC 20220321

Central nervous system (CNS) injuries such as stroke or trauma can lead to long-lasting disability, and there is no currently accepted treatment to regenerate functional CNS tissue after injury. Hydrogels can mimic the neural extracellular matrix by providing a suitable 3D structure and mechanical properties and have shown great promise in CNS tissue regeneration. Here we present successful synthesis of a thermosensitive hyaluronic acid-RADA 16 (Puramatrix (TM)) peptide interpenetrating network (IPN) that can be applied in situ by injection. Thermosensitive hyaluronic acid (HA) was first synthesized by combining HA with poly(N-isopropylacrylamide). Then, the Puramatrix (TM) self-assembled peptide was combined with the thermosensitive HA to produce a series of injectable thermoresponsive IPNs. The HA-Puramatrix (TM) IPNs formed hydrogels successfully at physiological temperature. Characterization by SEM, rheological measurements, enzymatic degradation and swelling tests was performed to select the IPN optimized for neurologic use. SEM images of the optimized dry IPNs demonstrated an aligned porous structure, and the rheological measurements showed that the hydrogels were elastic, with an elastic modulus of approximately 500 Pa, similar to that of brain tissue. An evaluation of the cell-material interactions also showed that the IPN had biological characteristics required for tissue engineering, strongly suggesting that the IPN hydrogel possessed properties beneficial for regeneration of brain tissue., QC 20220222

Stimuli-responsive drug delivery systems (DDS) may overcome the drawbacks of conventional chemotherapy for cancer treatment. In particular, light-responsive polymer-based DDS may ensure spatio and temporal control in drug delivery. In this regard, near infrared (NIR) light triggered drug nanocarriers present several advantages when compared to UV–visible light triggered nanocarriers. This review surveys the recent development on the design, synthesis, functions, and applications of NIR photo-sensitive compounds in the development of long-wavelength light-responsive nanocarriers. Diverse NIR light responsive groups such as coumarin (CM), ortho-nitrobenzyl (ONB), 2-diazo-1,2-naphthoquinone (DNQ) and spiropyran (SP) derivatives and their photo-cleavage reaction mechanisms are discussed, as well as the use of indocyanine green (ICG) and its photo-thermal application. The loading into polymeric nanocarriers of up converting nanoparticles (UCNPs) which can convert NIR light into UV or visible light is also discussed. The described DDS are classified on the basis on the photo responsive groups. In details, the behavior of different polymeric materials such as micelles, hydrogels bearing photo responsive groups linked to bioactive molecules which are released under NIR light irradiation is reviewed and discussed. A section relative to commonly used instrument setup for drug release studies by NIR light irradiation is also presented for better understanding how the light has been used to irradiate in various experimental situations., QC 20230227

Polymethylmethacrylate is clinically used as a bone cement in various orthopedic and trauma surgeries. Post the surgery, such conventional acrylic bone cement has been reported to cause adjacent vertebral fractures; modifying it by adding linoleic acid in the formulation has shown potential in averting such fractures thanks to bone-compliant mechanical properties, besides providing convenient handling properties. Although the resulting properties are attractive, the understanding of how linoleic acid imparts such advantageous properties remain unclear. Linoleic acid is typically sterilized in an autoclave before being used in the bone cement formulation; however, there are apprehensions whether the sterilization causes degradation. In this research, sterilized and unsterilized linoleic acid were evaluated alone and with different components of bone cement, such as activator, initiator, monomer, and inhibitor, and the ensuing structural changes in linoleic acid were monitored through 1H NMR and UV–Vis. The results reveal that linoleic acid degrade due to sterilization. In addition, evidence for reactions of sterilized/unsterilized linoleic acid with activator and initiator have been collected. We hypothesize that these reactions can reduce the availability of the components for the in situ polymerization of methyl methacrylate monomer and cause the improvement in handling properties and decrease in mechanical properties., QC 20221214

A knowledge on the pullout forces of degradable craniomaxillofacial screws is essential in designing pediatric cranial implants. Herein, four non-identical commercially available screws composed of different aliphatic polyesters were fixated to 3D-printed poly(L-lactide) screw hole test rig and onto a bone substitute material using manual tapping and ultrasonic welding fixation techniques. A method for mechanical testing was developed to determine and compare their quasi-static pullout strength. The degradation of the screws was followed for up to one year in three different degrading environments. While the screw size influences the initial pullout force, the degrading environment, size, and screw composition determine the degradation rate which in turn influences the pullout force over time. Given the limited availability of standard methods, the method developed herein can be used in determining the pullout forces of degradable craniomaxillofacial screws and comparing the effectiveness of various screw insertion techniques., QC 20220524

High molar mass poly(lactic acid) (PLA) is obtained by either the polycondensation of lactic acid or ring-opening polymerization (ROP) of the cyclic dimer 2,6-dimethyl-1,4-dioxane-2,5-dione, commonly referred to as dilactide or lactide (LA). This chapter describes preparation of polymers and copolymers of LAs with different structures, using polycondensation and ROP. Typical comonomers and polymers which are used for lactic acid or LA copolymerization include glycolic acid or glycolide, poly(ethylene glycol) or poly(ethylene oxide), and so on. PLAs having amino, carboxyl, or other functional groups are well reported in the literature. These functional groups can be utilized for chemical modification or as binding sites for biomolecules to impart selective binding and adhesion. PLA and its copolymers especially when used for biological applications, besides requirement of optimization of mechanical properties by engineering at the molecular level, also demands a fast degradation polymer rate., Part of ISBN 9781119767480, 9781119767442QC 20230907

Degradable polyester-based scaffolds are ideal for tissue engineering applications where long-term structural integrity and mechanical support are a requisite. However, their hydrophobic and unfunctionalized surfaces restrain their tissue-mimetic quality. Instead, hyaluronan (HA) hydrogels are able to act as cell-instructive materials with the ability to recapitulate native tissue, although HA is rapidly metabolized in vivo. Taking advantage of these distinctly diverse material properties, a degradable and concurrent hybrid hydrogel material was developed that combines the short-term tissue-relevant properties of bio-orthogonal crosslinked HA with the long-term structural and mechanical support of poly(L-lactide-co-trimethylene carbonate) (PLATMC) scaffolds. This method rendered the formulation of transparent, minimally swelling hydrogel compartments with a desirable cell-instructive “local” elastic modulus within the scaffold matrix without impeding key material properties of PLATMC. Long-term degradability over 180 days in vivo was realized by the integral PLATMC scaffold architecture obtained through either extrusion-based 3D printing or salt-particulate leaching. Intrinsic diffusion capacity within the hydrogel elicited unaffected degradation kinetics of PLATMC in vivo, despite its autocatalytic bulk degradation characteristics displayed when 3D-printed. The effect of the processing method on the material properties of PLATMC markedly extends to its in vivo degradation characteristics, and essential uniform degradation behavior can be advanced using salt-particulate leaching. Regardless of the scaffold fabrication method, the polymer exhibited a soft and flexible nature throughout the degradation period, governed by the rubbery state of the polymer. Our results demonstrate that the physicochemical properties of the hybrid hydrogel scaffold endow it with the potential to act as a cell instructive microenvironment while not affecting key material properties of PLA, QC 20230614

Background: Age-driven immune signals cause a state of chronic low-grade inflammation and in consequence affect bone healing and cause challenges for clinicians when repairing critical-sized bone defects in elderly patients. Methods: Poly(l-lactide-co-ɛ-caprolactone) (PLCA) scaffolds are functionalized with plant-derived nanoparticles from potato, rhamnogalacturonan-I (RG-I), to investigate their ability to modulate inflammation in vitro in neutrophils and macrophages at gene and protein levels. The scaffolds’ early and late host response at gene, protein and histological levels is tested in vivo in a subcutaneous rat model and their potential to promote bone regeneration in an aged rodent was tested in a critical-sized calvaria bone defect. Significant differences were tested using one-way ANOVA, followed by a multiple-comparison Tukey’s test with a p value ≤ 0.05 considered significant. Results: Gene expressions revealed PLCA scaffold functionalized with plant-derived RG-I with a relatively higher amount of galactose than arabinose (potato dearabinated (PA)) to reduce the inflammatory state stimulated by bacterial LPS in neutrophils and macrophages in vitro. LPS-stimulated neutrophils show a significantly decreased intracellular accumulation of galectin-3 in the presence of PA functionalization compared to Control (unmodified PLCA scaffolds). The in vivo gene and protein expressions revealed comparable results to in vitro. The host response is modulated towards anti-inflammatory/ healing at early and late time points at gene and protein levels. A reduced foreign body reaction and fibrous capsule formation is observed when PLCA scaffolds functionalized with PA were implanted in vivo subcutaneously. PLCA scaffolds functionalized with PA modulated the cytokine and chemokine expressions in vivo during early and late inflammatory phases. PLCA scaffolds functionalized with PA implanted in calvaria defects of aged rats downregulating pro-inflammatory gene markers whil

Background: Age-driven immune signals cause a state of chronic low-grade inflammation and in consequence affect bone healing and cause challenges for clinicians when repairing critical-sized bone defects in elderly patients. Methods: Poly(l-lactide-co-ɛ-caprolactone) (PLCA) scaffolds are functionalized with plant-derived nanoparticles from potato, rhamnogalacturonan-I (RG-I), to investigate their ability to modulate inflammation in vitro in neutrophils and macrophages at gene and protein levels. The scaffolds’ early and late host response at gene, protein and histological levels is tested in vivo in a subcutaneous rat model and their potential to promote bone regeneration in an aged rodent was tested in a critical-sized calvaria bone defect. Significant differences were tested using one-way ANOVA, followed by a multiple-comparison Tukey’s test with a p value ≤ 0.05 considered significant. Results: Gene expressions revealed PLCA scaffold functionalized with plant-derived RG-I with a relatively higher amount of galactose than arabinose (potato dearabinated (PA)) to reduce the inflammatory state stimulated by bacterial LPS in neutrophils and macrophages in vitro. LPS-stimulated neutrophils show a significantly decreased intracellular accumulation of galectin-3 in the presence of PA functionalization compared to Control (unmodified PLCA scaffolds). The in vivo gene and protein expressions revealed comparable results to in vitro. The host response is modulated towards anti-inflammatory/ healing at early and late time points at gene and protein levels. A reduced foreign body reaction and fibrous capsule formation is observed when PLCA scaffolds functionalized with PA were implanted in vivo subcutaneously. PLCA scaffolds functionalized with PA modulated the cytokine and chemokine expressions in vivo during early and late inflammatory phases. PLCA scaffolds functionalized with PA implanted in calvaria defects of aged rats downregulating pro-inflammatory gene markers whil

Adipose-derived stem cells (ASC) have been used as an alternative to bone marrow mesenchymal stem cells (BMSC) for bone tissue engineering. However, the efficacy of ASC in bone regeneration in comparison with BMSC remains debatable, since inconsistent results have been reported. Comparing ASC with BMSC obtained from different individuals might contribute to this inconsistency in results. Therefore, this study aimed to compare the bone regenerative capacity of donor-matched human ASC and BMSC seeded onto poly(l-lactide-co-ε-caprolactone) scaffolds using calvarial bone defects in nude rats. First, donor-matched ASC and BMSC were seeded onto the co-polymer scaffolds to evaluate their in vitro osteogenic differentiation. Seeded scaffolds and scaffolds without cells (control) were then implanted in calvarial defects in nude rats. The expression of osteogenesis-related genes was examined after 4 weeks. Cellular activity was investigated after 4 and 12 weeks. Bone formation was evaluated radiographically and histologically after 4, 12, and 24 weeks. In vitro, ASC and BMSC demonstrated mineralization. However, BMSC showed higher alkaline phosphatase activity than ASC. In vivo, human osteogenesis–related genes Runx2 and collagen type I were expressed in defects with scaffold/cells. Defects with scaffold/BMSC had higher cellular activity than defects with scaffold/ASC. Moreover, bone formation in defects with scaffold/BMSC was greater than in defects with scaffold/ASC, especially at the early time-point. These results suggest that although ASC have the potential to regenerate bone, the rate of bone regeneration with ASC may be slower than with BMSC. Accordingly, BMSC are more suitable for bone regenerative applications., QC 20210319

Aliphatic polyesters are the synthetic polymers most commonly used in the development of resorbable medical implants / devices. Various three-dimensional (3D) scaffolds have been fabricated from these polymers and used in adipose tissue engineering. However, their systematic evaluation altogether lacks, which makes it difficult to select a suitable degradable polymer to design 3D resorbable implants and / or devices able to effectively mimic the properties of adipose tissue. Additionally, the impact of sterilization methods on the medical devices, if any, must be taken into account. We evaluate and compare five different medical-grade resorbable polyesters with l-lactide content ranging from 50 to 100 mol% and exhibiting different physiochemical properties depending on the comonomer (d-lactide, ε-caprolactone, glycolide, and trimethylene carbonate). The salt-leaching technique was used to prepare 3D microporous scaffolds. A comprehensive assessment of the physical, chemical, and mechanical properties of the scaffolds was carried out in PBS at 37 ° C. The cell-material interactions and the ability of the scaffolds to promote adipogenesis of human adipose tissue-derived stem cells were assessed in vitro. The diverse physical and mechanical properties of the scaffolds, due to the different composition of the copolymers, influenced human adipose tissue-derived stem cells proliferation and differentiation. Scaffolds made from polymers which were above their glass transition temperature and with low degree of crystallinity showed better proliferation and adipogenic differentiation of stem cells. The effect of sterilization techniques (electron beam and ethylene oxide) on the polymer properties was also evaluated. Results showed that scaffolds sterilized with the ethylene oxide method better retained their physical and chemical properties. Overall, the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to au, QC 20210511

It has been recently reported that, in a rat calvarial defect model, adding endothelial cells (ECs) to a culture of bone marrow stromal cells (BMSCs) significantly enhanced bone formation. The aim of this study is to further investigate the ossification process of newly formed osteoid and host response to the poly(L-lactide-co-1,5-dioxepan-2-one) [poly(LLA-co-DXO)] scaffolds based on previous research. Several different histological methods and a PCR Array were applied to evaluate newly formed osteoid after 8 weeks after implantation. Histological results showed osteoid formed in rat calvarial defects and endochondral ossification-related genes, such as dentin matrix acidic phosphoprotein 1 (Dmp1) and collagen type II, and alpha 1 (Col2a1) exhibited greater expression in the CO (implantation with BMSC/EC/Scaffold constructs) than the BMSC group (implantation with BMSC/Scaffold constructs) as demonstrated by PCR Array. It was important to notice that cartilage-like tissue formed in the pores of the copolymer scaffolds. In addition, multinucleated giant cells (MNGCs) were observed surrounding the scaffold fragments. It was concluded that the mechanism of ossification might be an endochondral ossification process when the copolymer scaffolds loaded with co-cultured ECs/BMSCs were implanted into rat calvarial defects. MNGCs were induced by the poly(LLA-co-DXO) scaffolds after implantation, and more specific in vivo studies are needed to gain a better understanding of host response to copolymer scaffolds., QC 20210609

We have developed an innovative methodology to overcome the lack of techniques for real-time assessment of degradable biomedical polymers at physiological conditions. The methodology was established by combining polymer characterization techniques with electrochemical sensors. The in vitro hydrolytic degradation of a series of aliphatic polyesters was evaluated by following the molar mass decrease and the mass loss at different incubation times while tracing pH and L-lactate released into the incubation media with customized miniaturized electrochemical sensors. The combination of different analytical approaches provided new insights into the mechanistic and kinetics aspects of the degradation of these biomedical materials. Although molar mass had to reach threshold values for soluble oligomers to be formed and specimens' resorption to occur, the pH variation and L-lactate concentration were direct evidence of the resorption of the polymers and indicative of the extent of chain scission. Linear models were found for pH and released L-lactate as a function of mass loss for the Llactide-based copolymers. The methodology should enable the sequential screening of degradable polymers at physiological conditions and has potential to be used for preclinical material's evaluation aiming at reducing animal tests., QC 20210406

Additive manufacturing is suitable for producing complex geometries; however, variation in thermo-mechanical properties are observed during one batch cycle when degradable aliphatic polyesters of medical grade are used in melt extrusion-based methods. This is one important reason for why additive manufacturing has not yet been fully utilised to produce degradable medical implants. Herein, the internal variation has been minimised during one batch cycle by assessing the effect of different processing parameters when using commercially available medical grade copolymers. To minimise the molar mass, thermal and mechanical variation within one batch cycle, the rheological fingerprint of the commercially available medical grade poly(L-lactide-co-ε-caprolactone) and poly(L-lactide-co-trimethylene carbonate) has been correlated to the process parameters of the ARBURG Plastic Freeforming. An increase in the temperature up to 220°C and the associated increase in pressure are beneficial for the viscoelastic and thermally stable poly(L-lactide-co-ε-caprolactone). In contrast, a temperature below 220°C should be used for the poly(L-lactide-co-trimethylene carbonate) to reduce the variation in strain at break during one batch cycle. The residence time is decreased through the increase of the discharge parameter. An increase in temperature is however required to reduce the viscosity of the polymer and allow the pressure to stay within the machine limitations at higher discharge parameters. The results are highly relevant to the development of additive manufacturing for the production of degradable medical devices with identical properties. In fact, Food and Drug Administration guidelines for additive manufacturing of medical implants specify the need to control changes in material properties during the process., QC 20210203

Various 3D printing techniques currently use degradable polymers such as aliphatic polyesters to create well-defined scaffolds. Even though degradable polymers are influenced by the printing process, and this subsequently affects the mechanical properties and degradation profile, degradation of the polymer during the process is not often considered. Degradable scaffolds are today printed and cell-material interactions evaluated without considering the fact that the polymer change while printing the scaffold. Our methodology herein was to vary the printing parameters such as temperature, pressure, and speed to define the relationship between printability, polymer microstructure, composition, degradation profile during the process, and rheological behavior. We used high molecular weight medical-grade (co)polymers, poly(L-lactide-co-epsilon-caprolactone) (PCLA), poly(L-lactide-co-glycolide) (PLGA), and poly(D,L-lactide-co-glycolide) (PDLGA), with L-lactide content ranging from 25 to 100 mol %, for printing in an extrusion-based printer (3D Bioplotter). Optical microscopy confirmed that the polymers were printable at high resolution and good speed, until a certain degree of degradation. The results show also that printability can not be claimed just by optimizing printing parameters and highlight the importance of a careful analysis of how the polymer's structure and properties vary during printing. The polymers thermally decomposed from the first processing minute and caused a decrease in the average block length of the lactide blocks in the copolymers and generated lower crystallinity. Poly(L-lactide) (PLLA) and PCLA are printable at a higher molecular weight, less degradation before printing was possible, compared to PLGA and PDLGA, a result explained by the higher complex viscosity and more elastic polymeric melt of the copolymer containing glycolide (GA) and lactide (LA). In more detail, copolymers comprised of LA and epsilon-caprolactone (CL) formed lower molecula, QC 20200310

The advancement of 3D printing technologies in the fabrication of degradable scaffolds for tissue engineering includes, from the standpoint of the polymer chemists, an urgent need to develop new materials that can be used as ink and are suitable for medical applications. Here, we demonstrate that a copolymer of epsilon-caprolactone (CL) with low amounts of p-dioxanone (DX) (15 mol %) is a degradable and printable material that suits the requirements of melt extrusion 3D printing technologies, including negligible degradation during thermal processing. It is therefore a potential candidate for soft tissue regeneration. The semicrystalline CL/DX copolymer is processed at a lower temperature than a commercial polycaprolactone (PCL), shaped as a filament for melt extrusion 3D printing and as porous and pliable scaffolds with a gradient design. Scaffolds have Young's modulus in the range of 60-80 MPa, values suitable for provision of structural support for damaged soft tissue such as breast tissue. SEM and confocal microscope indicate that the CL/DX copolymer scaffolds support adipose stem cell attachment, spreading, and proliferation., QC 20200409

We present a solution to regenerate adipose tissue using degradable, soft, pliable 3D-printed scaffolds made of a medical-grade copolymer coated with polydopamine. The problem today is that while printing, the medical grade copolyesters degrade and the scaffolds become very stiff and brittle, being not optimal for adipose tissue defects. Herein, we have used high molar mass poly(L-lactide-co-trimethylene carbonate) (PLATMC) to engineer scaffolds using a direct extrusion-based 3D printer, the 3D Bioplotter (R). Our approach was first focused on how the printing influences the polymer and scaffold's mechanical properties, then on exploring different printing designs and, in the end, on assessing surface functionalization. Finite element analysis revealed that scaffold's mechanical properties vary according to the gradual degradation of the polymer as a consequence of the molar mass decrease during printing. Considering this, we defined optimal printing parameters to minimize material's degradation and printed scaffolds with different designs. We subsequently functionalized one scaffold design with polydopamine coating and conducted in vitro cell studies. Results showed that polydopamine augmented stem cell proliferation and adipogenic differentiation owing to increased surface hydrophilicity. Thus, the present research show that the medical grade PLATMC based scaffolds are a potential candidate towards the development of implantable, resorbable, medical devices for adipose tissue regeneration., QC 20201026

Background: Recent studies have suggested that both poly(l-lactide-co-1,5-dioxepan-2-one) (or poly(LLA-co-DXO)) and poly(l-lactide-co-epsilon-caprolactone) (or poly(LLA-co-CL)) porous scaffolds are good candidates for use as biodegradable scaffold materials in the field of tissue engineering; meanwhile, their surface properties, such as hydrophilicity, need to be further improved. Methods: We applied several different concentrations of the surfactant Tween 80 to tune the hydrophilicity of both materials. Moreover, the modification was applied not only in the form of solid scaffold as a film but also a porous scaffold. To investigate the potential application for tissue engineering, human bone marrow mesenchymal stem cells (hMSCs) were chosen to test the effect of hydrophilicity on cell attachment, proliferation, and differentiation. First, the cellular cytotoxicity of the extracted medium from modified scaffolds was investigated on HaCaT cells. Then, hMSCs were seeded on the scaffolds or films to evaluate cell attachment, proliferation, and osteogenic differentiation. The results indicated a significant increasing of wettability with the addition of Tween 80, and the hMSCs showed delayed attachment and spreading. PCR results indicated that the differentiation of hMSCs was stimulated, and several osteogenesis related genes were up-regulated in the 3% Tween 80 group. Poly(LLA-co-CL) with 3% Tween 80 showed an increased messenger Ribonucleic acid (mRNA) level of late-stage markers such as osteocalcin (OC) and key transcription factor as runt related gene 2 (Runx2). Conclusion: A high hydrophilic scaffold may speed up the osteogenic differentiation for bone tissue engineering., QC 20200818

Degradable porous polymeric structures are attractive candidates for biological tissue scaffolds, and adequate mechanical, transport, chemical and biological properties determine their functionality. Aside from the properties of polymer-based materials, the scaffold's meso-structure controls its elasticity at the organ length-scale. This study investigated the effect of the meso-structure on scaffolds' mechanical and transport properties using finite element analysis (FEA) and computational fluid dynamics (CFD). A number of poly (ε-caprolactone) (PCL) - based scaffolds were 3D printed, analyzed by microcomputed tomography (micro-CT) and mechanically tested. We found that the gradient (G) and gradient and staggered (GS) meso-structure designs led to a higher scaffold permeability, a more homogeneous flow inside the scaffold, and a lower wall shear stress (WSS) in comparison with the basic (B) meso-structure design. The GS design resulted in scaffold stiffness as low as 1.07/0.97 MPa under compression/tension, figures that are comparative with several soft tissues. Image processing of micro-CT data demonstrated that the imposed meso-structures could have been adequately realized through 3D printing, and experimental testing validated FEA analysis. Our results suggest that the properties of 3D-printed PCL-based scaffolds can be tuned via meso-structures toward soft tissue engineering applications. The biological function of designed scaffolds should be further explored in-situ studies., QC 20200220

Degradable polymers based on alpha-hydroxy acids and alpha-amino acids constitutes a potent class of biomaterials, combining high hydrolyzability with structural features that mimics peptides. Driven by the design criteria to construct isolated a-amino acid units along a main polylactide chain, a copolymer system was developed based on two monomers with distinctly different equilibrium behaviors. This was uncovered by detailed understanding on the kinetic and thermodynamic polymerizability of 3S,6S-dimethylmorpholine-2,5-dione (DMMD) and L-lactide (LLA) at low reaction temperatures. Under Bronsted base-promoted ring-opening copolymerization (ROCOP) conditions, the equilibrium nature of the copolymerization was shown susceptible to changes in the system, such as catalyst basicity, solvent polarity and initial monomer concentrations. Subsequently, high equilibrium conversions of both monomers with control over molecular weight and dispersity could be achieved within short reaction times by modulation of these factors. Thermodynamic elucidations of the copolymerization system revealed that DMMD behaved as an unstrained monomer with a large propagation barrier, favored by an increase in polymerization temperature. Ultimately, the high propagation barrier of DMMD in the system resulted in a kinetically controlled mechanism with the formation of completely isolated units of DMMD along the polylactide backbone. These results extend current ROCOP strategies of morpholine-2,5-diones and cyclic esters to a mild and selective copolymerization platform for the construction of sequence-controlled a-amino acid decorated polyesters for medical applications., QC 20200601

We consider optimal sensor scheduling with unknown communication channel statistics. We formulate two types of scheduling problems with the communication rate being a soft or hard constraint, respectively. We first present some structural results on the optimal scheduling policy using dynamic programming and assuming that the channel statistics is known. We prove that the Q-factor is monotonic and submodular, which leads to threshold-like structures in both problems. Then we develop a stochastic approximation and parameter learning frameworks to deal with the two scheduling problems with unknown channel statistics. We utilize their structures to design specialized learning algorithms. We prove the convergence of these algorithms. Performance improvement compared with the standard Q-learning algorithm is shown through numerical examples, which also discuss an alternative method based on recursive estimation of the channel quality., QC 20200409

Although additive manufacturing through melt extrusion has become increasingly popular as a route to design scaffolds with complex geometries the technique if often limited by the reduction in molecular weight and the viscoelastic response when degradable aliphatic polyesters of high molecular weight are used. Here we use a melt extruder and fused filament fabrication printer to produce a reliable nondegradative route for scaffold fabrication of medical grade copolymers of L-lactide, poly(epsilon-caprolactone-co-L-lactide), and poly(L-lactide-co-trimethylene carbonate). We show that degradation is avoided using filament extrusion and fused filament fabrication if the process parameters are deliberately chosen based upon the rheological behavior, mechanical properties, and polymer composition. Structural, mechanical, and thermal properties were assessed throughout the process to obtain comprehension of the relationship between the rheological properties and the behavior of the medical grade copolymers in the extruder and printer. Scaffolds with a controlled architecture were achieved using high-molecular-weight polyesters exhibiting a large range in the elastic response causing negligible degradation of the polymers., QC 20200217

Solutions of amorphous poly(d,l-lactide-co-trimethylene carbonate)s (PDLTMCs) in ethyl acetate work as solvent-based physical adhesives through diffusion mechanisms for a variety of aliphatic polyester-based adherents. The random PDLTMCs with a trimethylene carbonate content of 11, 16, and 20 mol% are synthesized in bulk, achieving high molecular weight, M-n, up to 128 kg mol(-1) and dispersity around 1.7. The PDLTMCs are amorphous and have a glass transition temperature in the range 34.7 to 43.6 degrees C and in agreement with the theoretical values calculated using the Fox equation. The mechanical and surface properties of the PDLTMCs are tested preparing solvent cast films, which are soft and tough and, although they have a higher contact angle than the parent homopolymer, they show higher water uptake capacity. The potential application as adhesives of the synthesized PDLTMCs is evaluated by preparing a 20 wt% solution in ethyl acetate and testing them by adhering films with different compositions as well as constructs having different geometries and surface roughness. The results demonstrate that the adhesion strength is higher on adherent films having similar chemical compositions as the adhesives and on surfaces having similar compositions to each other but different roughness. The similar chemical nature of the adhesive and adherent probably favors the diffusion mechanism through which adhesion takes place., QC 20210909

The present invention relates to a novel ester monomersusceptible to ring opening polymerization where the monomer comprise a functional group that may be transformedinto thiols or S S groups which allows further functionalization . The present invention also relates to polymers andco - polymers derived from said monomer ., QC 20210615

The present invention relates to a novel ester monomersusceptible to ring opening polymerization where the monomer comprise a functional group that may be transformedinto thiols or S S groups which allows further functionalization . The present invention also relates to polymers andco - polymers derived from said monomer ., QC 20210615

The present invention relates to a novel ester monomersusceptible to ring opening polymerization where the monomer comprise a functional group that may be transformedinto thiols or S S groups which allows further functionalization . The present invention also relates to polymers andco - polymers derived from said monomer ., QC 20210615

The present invention relates to a novel ester monomersusceptible to ring opening polymerization where the monomer comprise a functional group that may be transformedinto thiols or S S groups which allows further functionalization . The present invention also relates to polymers andco - polymers derived from said monomer ., QC 20210615

The present invention relates to a novel ester monomersusceptible to ring opening polymerization where the monomer comprise a functional group that may be transformedinto thiols or S S groups which allows further functionalization . The present invention also relates to polymers andco - polymers derived from said monomer ., QC 20210615

Apart from osteogenesis, neovascularization of the defect area is an important determinant for successful bone healing. Accordingly, several studies have employed the combined delivery of VEGFA and BMP2 for bone regeneration. Nevertheless, the outcomes of these studies are highly variable. The aim of our study was to compare the effectiveness of adenoviral mediated delivery of BMP2 alone and in combination with VEGFA in rat bone marrow stromal cells (rBMSC)seeded on a poly(LLA-co-CL)scaffold in angiogenesis and osteogenesis using a critical-sized rat calvarial defect model. Both mono delivery of BMP2 and the combined delivery of a lower ratio of VEGFA and BMP2 (1:4)led to up-regulation of osteogenic genes (Alpl and Runx2)and increased calcium deposition in vitro, compared with the GFP control. Micro computed tomography (microCT)analysis of the rat calvarial defect at 8 weeks showed that the mono delivery of BMP2 (43.37 ± 3.55% defect closure)was the most effective in healing the bone defect, followed by the combined delivery of BMP2 and VEGFA (27.86 ± 2.89%)and other controls. Histological and molecular analyses supported the microCT findings. Analysis of the angiogenesis, however, showed that both mono delivery of BMP2 and combined delivery of BMP2 and VEGFA had similar angiogenic effect in the calvarial defects. Examination of the key genes related to host response against the adenoviral vectors showed that the current model system was not associated with adverse immune response. Overall, the results show that the mono delivery of BMP2 was superior to the combined delivery of BMP2 and VEGFA in healing the critical-sized rat calvarial bone defect. These findings underscore the importance of appropriate growth factor combination for the successful outcome in bone regeneration., QC 20200921

Poly(L-lactide-co-epsilon-caprolactone) scaffolds were functionalised by 10 or 20 mu g/mL of human demineralised dentine matrix. Release kinetics up to 21 days and their osteogenic potential on human bone marrow stromal cells after 7 and 21 days were studied. A total of 390 proteins were identified by mass spectrometry. Bone regeneration proteins showed initial burst of release. Human bone marrow stromal cells were cultured on scaffolds physisorbed with 20 mu g/mL and cultured in basal medium (DDM group) or physisorbed and cultured in osteogenic medium or cultured on non-functionalised scaffolds in osteogenic medium. The human bone marrow stromal cells proliferated less in demineralised dentine matrix group and activated ERK/1/2 after both time points. Cells on DDM group showed highest expression of IL-6 and IL-8 at 7 days and expressed higher collagen type 1 alpha 2, SPP1 and bone morphogenetic protein-2 until 21 days. Extracellular protein revealed higher collagen type 1 and bone morphogenetic protein-2 at 21 days in demineralised dentine matrix group. Cells on DDM group showed signs of mineralisation. The functionalised scaffolds were able to stimulate osteogenic differentiation of human bone marrow stromal cells., QC 20190814

We have succeeded to modulated the degradation rate of poly(L-lactide) (PLLA) melt-spun multifilament fibers to extend the service lifetime and increase the resorption rate by using random copolymers of L-lactide and trimethylene carbonate (TMC). The presence of TMC units enabled an overall longer service lifetime but faster degradation kinetics than PLLA. By increasing the amount of TMC up to 18 mol%, multifilament fibers characterized by a homogenous degradation profile could be achieved. Such composition allowed, once the mechanical integrity was lost, a much longer retention of mechanical integrity and a faster rate of mass loss than samples containing less TMC. The degradation profile of multifilament fibers consisting of (co)polymers containing 0, 5, 10 and 18 mol% of TMC has been identified during 45 weeks in vitro hydrolysis following the molecular weight decrease, mass loss and changes in microstructure, crystallinity and mechanical properties. The fibers degraded by a two-step, autocatalyzed bulk hydrolysis mechanism. A high rate of molecular weight decrease and negligible mass loss, with a consequent drop of the mechanical properties, was observed in the early stage of degradation for fibers having TMC content up to 10 mol%. The later stage of degradation was, for these samples, characterized by a slight increase in the mass loss and a negligible molecular weight decrease. Fibers prepared with the 18 mol% TMC copolymer showed instead a more homogenous molecular weight decrease ensuring mechanical integrity for longer time and faster mass loss during the later stage of degradation., QC 20190329

We have developed a straightforward strategy to obtain semicrystalline and random copolymers of epsilon-caprolactone (CL) and p-dioxanone (DX) with thermal stabilities similar to poly(epsilon-caprolactone), PCL, but with a faster- hydrolytic degradation rate-CL/DX-copolymers-are promising inks when printing scaffolds aimed for tissue engineering. Such copolymers behave similar to PCL and resorb faster. The copolymers were synthesized by bulk ring-opening copolymerization, achieving a high yield; a molecular weight, M-n, of 57-176 kg mol(-1); and an inherent viscosity of 1.7-1.9 dL g(-1). The copolymer microstructure consisted of long CL blocks that are separated by isolated DX units. The block length and the melting point were a linear function of the DX content. The copolymers crystallize as an orthorhombic lattice that is typical for PCL, and they formed more elastic, softer, and less hydrophobic films with faster degradation rates than PCL. Relatively high thermal degradation temperatures (above 250 C), similar to PCL, were estimated by thermogravimetric analysis, and copolymer filaments for three-dimensional printing and scaffolds were produced without thermal degradation., QC 20190906

Polyester-based scaffolds covalently functionalized with arginine-glycine-aspartic acid-cysteine (RGDC) peptide sequences support the proliferation and osteogenic differentiation of stem cells. The aim is to create an optimized 3D niche to sustain human bone marrow stem cell (hBMSC) viability and osteogenic commitment, without reliance on differentiation media. Scaffolds consisting of poly(lactide-co-trimethylene carbonate), poly(LA-co-TMC), and functionalized poly(lactide) copolymers with pendant thiol groups are prepared by salt-leaching technique. The availability of functional groups on scaffold surfaces allows for an easy and straightforward method to covalently attach RGDC peptide motifs without affecting the polymerization degree. The strategy enables the chemical binding of bioactive motifs on the surfaces of 3D scaffolds and avoids conventional methods that require harsh conditions. Gene and protein levels and mineral deposition indicate the osteogenic commitment of hBMSC cultured on the RGDC functionalized surfaces. The osteogenic commitment of hBMSC is enhanced on functionalized surfaces compared with nonfunctionalized surfaces and without supplementing media with osteogenic factors. Poly(LA-co-TMC) scaffolds have potential as scaffolds for osteoblast culture and bone grafts. Furthermore, these results contribute to the development of biomimetic materials and allow a deeper comprehension of the importance of RGD peptides on stem cell transition toward osteoblastic lineage., QC 20190904

A challenge in the extrusion-based bioprinting is to find a bioink with optimal biological and physicochemical properties. The aim of this study was to evaluate the influence of wood-based cellulose nanofibrils (CNF) and bioactive glass (BaG) on the rheological properties of gelatin-alginate bioinks and the initial responses ofbone cells embedded in these inks. CNF modulated the flow behavior of the hydrogels, thus improving their printability. Chemical characterization by SEM-EDX and ion release analysis confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility of the hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells (Saos-2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-containing gels and crosslinked with CaCl2. Viability, proliferation and alkaline phosphatase activity (ALP) were monitored over 14 d. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG the viability and proliferation decreased in correlation with the increased viscosity. Still, there was a constant increase in the ALP activity in all the hydrogels. Further bioprinting experiments were conducted using human bone marrow-derived mesenchymal stem cells (hBMSCs), a clinically relevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and the ALP indicated BaG-stimulated early osteogenic commitment. The addition of CNF and BaG to gelatin-alginate bioinks holds great potential for bone tissue engineering applications., QC 20190520

l-Lactide/trimethylene carbonate copolymers have been produced as multifilament fibers by high-speed melt-spinning. The relationship existing between the composition, processing parameters and physical properties of the fibers has been disclosed by analyzing how the industrial process induced changes at the macromolecular level, i.e., the chain microstructure and crystallinity development. A poly(l-lactide) and three copolymers having trimethylene carbonate contents of 5, 10 and 18 mol % were synthesized with high molecular weight (M n ) up to 377 kDa and narrow dispersity. Their microstructure, crystallinity and thermal properties were dictated by the composition. The spinnability was then assessed for all the as-polymerized materials: four melt-spun multifilament fibers with increasing linear density were collected for each (co)polymer at a fixed take-up speed of 1800 m min -1 varying the mass throughput during the extrusion. A linear correlation resulted between the as-spun fiber properties and the linear density. The as-spun fibers could be further oriented, developing more crystallinity and improving their tensile properties by a second stage of hot-drawing. This ability was dependent on the composition and crystallinity achieved during the melt-spinning and the parameters selected for the hot-drawing, such as temperature, draw ratio and input speed. The crystalline structure evolved to a more stable form, and the degree of crystallinity increased from 0-52% to 25-66%. Values of tensile strength and Young's modulus up to 0.32-0.61 GPa and 4.9-8.4 GPa were respectively achieved., QC 20190429

The history of resorbable polymers containing glycolide, lactide, e-caprolactone and trimethylene carbonate, with a special emphasis being placed on the time frame of the 1960s-1990s is described. Reviewing the history is valuable when looking into the future perspectives regarding how and where these monomers should be used. This story includes scientific evaluations indicating that these polymers are safe to use in medical devices, while the design of the medical device is not considered in this report. In particular, we present the data regarding the tissue response to implanted polymers, as well as the toxicity and pharmacokinetics of their degradation products. In the translation of these polymers from "the bench to the bedside," various challenges have been faced by surgeons, medical doctors, biologists, material engineers and polymer chemists. This Perspective highlights the visionary role played by the pioneers, addressing the problems that occurred on a case by case basis in translational medicine., QC 20190524