Biodegradable Polymer Surfaces Research Articles

Enhancing biodegradable polymer surface wettability properties through atmospheric plasma treatmsurfaent and nanocellulose incorporation

This study investigates the effects of atmospheric plasma treatment on the surface properties of polylactic acid (PLA)/nanocrystalline cellulose (CNC) composites, aiming to improve their wettability and mechanical properties. The research utilizes a twin-screw extrusion process for fabricating PLA/CNC biocomposites, followed by surface modification using a custom-built, with a tenfold high-voltage atmospheric plasma system. The motivation of this treatment was to improved surface wettability and potential for enhanced adhesive bonding in ecological applications. These findings contribute to developing more sustainable composite materials by providing a method to improve the functionality of biodegradable polymers without compromising their environmental benefits.

Drug release control and anti-inflammatory effect of biodegradable polymer surface modified by gas phase chemical functional reaction

The plasma technique has been widely used to modify the surfaces of materials. The purpose of this study was to evaluate the probability of controlling the prednisolone delivery velocity on a polylactic acid (PLA) surface modified by plasma surface treatment. Surface modification of PLA was performed at a low-pressure radio frequency under conditions of 100 W power, 50 mTorr chamber pressure, 100–200 sccm of flow rate, and Ar, O2, and CH4 gases. The plasma surface-modified PLA was characterized using scanning emission microscope, x-ray photoelectron spectroscopy (XPS), and contact angle measurements. In vitro evaluations were performed to determine cellular response, drug release behavior, and anti-inflammatory effects. The PLA surface morphology was changed to a porous structure (with a depth of approximately 100 μm) and the surface roughness was also significantly increased. The XPS results demonstrated higher oxygenized carbon contents than those in the non-treated PLA group. The prednisolone holding capacity increased and the release was relatively prolonged in the surface-modified PLA group compared to that in the non-treated PLA group. In addition, cell migration and proliferation significantly increased after PLA treatment alone. The activity of cytokines such as cyclooxygenase-2 (COX-2), tumor necrosis factor-a (TNF-α), interleukin (IL-1β), and IL-6 were considerably reduced in the plasma-treated and prednisolone holding group. Taken together, surface-modified PLA by plasma can provide an alternative approach to conventional physicochemical approaches for sustained anti-inflammatory drug release.

Development of Antibacterial Protective Coatings Active against MSSA and MRSA on Biodegradable Polymers.

In this work the in vitro antimicrobial activity of colloidal solutions of nine different commercially available nanoparticles were investigated against Staphylococcus aureus strains, both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA). Research covered antimicrobial investigation of different metal and metal-oxide nanoparticles, including Ag 10 nm, Ag 40 nm, Al2O3 100 nm, Au 20 nm, Pt 4 nm, TiO2 100 nm, Y2O3 100 nm, ZnO 100 nm and ZrO2 100 nm nanoparticles. Such materials were foreseen to be applied as coatings on 3D-printed biodegradable polymers: i.e., catheters, disposable materials, hospital bedding items, disposable antimicrobial linings and bandages for chronic wounds. Therefore, the antimicrobial activity of the nanoparticles was determined by agar well diffusion assays and serial microdilution broth assays. In addition, the chromatographic characterization of elements present in trace amounts was performed as a method for tracing the nanoparticles. Moreover, the potential of preparing the rough surface of biodegradable polymers for coating with antimicrobial nanoparticles was tested by 3D-printing fused deposition methodology. The in vitro results have shown that particular nanoparticles provided powerful antimicrobial effects against MSSA and MRSA strains, and can be easily applied on different biopolymers.

Cellular attachment behavior on biodegradable polymer surface immobilizing endothelial cell-specific peptide

Small-caliber artificial blood vessels with inner diameters of smaller than 4 mm have not been put into practical use because of early thrombus formation and graft occlusion. To realize small-caliber artificial blood vessels with anti-thrombus property and long-term patency, one of the promising approaches is endothelialization of the lumen by tissue engineering approaches. Integrin α4β1 on the endothelial cell membrane is known to act as a receptor for Arg-Glu-Asp-Val (REDV) tetra-peptide, and this peptide can be used as a specific ligand to introduce endothelial cell attachment onto the surfaces of polymer scaffold. In this study, biodegradable polymer surface immobilizing REDV peptide were prepared, and the specific attachment of endothelial cells on it was investigated as a preliminary study for tissue-engineered small-caliber blood vessels in a future application. We synthesized copolymer of ε-caprolactone and depsipeptide having reactive carboxylic acid side-chain groups (PGDCL), and REDV peptide was attached to the copolymer to give PGDCL-REDV. The attachment of human umbilical vein endothelial cells (HUVECs) were investigated for the blend polymer film prepared by mixing PGDCL and PGDCL-REDV. The obtained blend polymer films exhibited sequence- and cell-specific HUVECs attachment through REDV peptide recognition. This technique should be useful not only to obtain artificial blood vessels which induce endothelialization and but also to provide biodegradable scaffolds with specific ligands immobilized surfaces for tissue regeneration.

Porous polybutylene succinate films enabling adhesion of human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE)

In the last decade, several studies have shown that polybutylene succinate (PBSu) has a high potential as a biomaterial enabling cell adhesion and growth. In this study, porous PBSu films have been prepared by the breath figure method (BF) and by particulate leaching (PL), and characterized in terms of thickness, surface properties, diffusion capacity and in vitro stability. Because porous films are of high interest for tissue engineering of retinal pigment epithelium (RPE), the initial viability and adhesion of human embryonic stem cell-derived RPE onto the PBSu films was then evaluated. To the best of our knowledge, this is the first study on the adhesion behavior of hESC-RPE onto porous and biodegradable polymer surfaces. The results clearly demonstrated that the two manufacturing methods produced materials with very distinct properties. Films produced by BF expressively demonstrated the highest roughness and surface area, and the lowest water contact angle. These features likely contributed to increase the biocompatibility of the surface, particularly when coated with laminin and collagen IV, as observed by the improved cell viability, cell morphology, adhesion and production of extracellular matrix proteins. Altogether, our results showed not only that PBSu holds high potential in retinal tissue engineering, but also that the physical properties and biocompatibility of the material are highly dependent on the adopted casting method.

Consensus QSPR modelling for the prediction of cellular response and fibrinogen adsorption to the surface of polymeric biomaterials

ABSTRACTIn the current study, we have developed predictive quantitative structure–activity relationship (QSAR) models for cellular response (foetal rate lung fibroblast proliferation) and protein adsorption (fibrinogen adsorption (FA)) on the surface of tyrosine-derived biodegradable polymers designed for tissue engineering purpose using a dataset of 66 and 40 biodegradable polymers, respectively, employing two-dimensional molecular descriptors. Best four individual models have been selected for each of the endpoints. These models are developed using partial least squares regression with a unique combination of six and four descriptors for cellular response and protein adsorption, respectively. The generated models were strictly validated using internal and external metrics to determine the predictive ability and robustness of proposed models. Subsequently, the validated individual models for each response endpoints were used for the generation of ‘intelligent’ consensus models (http://teqip.jdvu.ac.in/QSAR_Tools/DTCLab/) to improve the quality of predictions for the external data set. These models may help in prediction of virtual polymer libraries for rational design/optimization for properties relevant to biomedical applications prior to their synthesis.

A facile method for the deposition of volatile natural compound-based nanoparticles on biodegradable polymer surfaces.

In the current work, stable nanoparticles (NPs) of vanillin are formed in situ from an aqueous/ethanol solution and deposited on the surface of chitosan, a natural polymer, using a high-intensity ultrasonic method. The spectroscopic, physical, mechanical and morphological properties of the coated chitosan films are examined by helium-ion microscopy (HIM), atomic-force microscopy (AFM), Fourier-transform infrared spectroscopy (FTIR), UV-vis spectroscopy, X-ray diffractometry (XRD), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC) and texture analysis, and compared with the original film properties. Vanillin NPs were detected on the film surface. It was also found that the sonochemical deposition method does not affect the bulk properties of the chitosan films. All the chitosan films demonstrated antimicrobial activity against Gram-negative and Gram-positive bacteria. The deposition of vanillin NPs on the chitosan film also leads to significant antibiofilm activity, especially against the biofilm formation of Escherichia coli bacteria. The in vivo antimicrobial effect of the modified chitosan films was examined on fresh-cut watermelon, melon and strawberry. Vanillin NP-coated chitosan films led to inhibition of total microbial growth and the substantial inhibition of mold and yeast on the fruit. This research can serve as a platform for the development of a mild and effective method for the activation and modification of natural polymers for their future application in biomedical devices and biodegradable active packaging materials.

Control of the Hydrophilic/Hydrophobic Behavior of Biodegradable Natural Polymers by Decorating Surfaces with Nano‐ and Micro‐Components

AbstractPackaging materials based on natural polymers are becoming popular because these polymers are derived from renewable resources and can display biodegradability. However, natural polymers are typically highly hydrophilic, and packaging films produced with them can absorb water, leading to dimensional changes and reductions in mechanical properties. In this work, films of thermoplastic starch (TPS) and blends of TPS/low‐density polyethylene (LDPE) were prepared, and their surfaces were decorated to alter their hydrophilic characteristics. Micro‐ (polymer microspheres) and nano‐components (polycaprolactone electrospun nanofibers) were deposited on the surface of starch and its blends with LDPE. Nanofibers containing silver sulfadiazine were also used to decorate the starch and its blends to change the topography (evaluated by SEM and atomic force microscopy) and to provide anti‐bacterial properties. High values of contact angle (CA) and low values of CA hysteresis were measured for the modified surfaces, including a CA higher than 150° and a hysteresis lower than 10°. Therefore, it was demonstrated that the intrinsically hydrophilic surfaces of biodegradable natural polymers could be altered by creating topographical patterns through decoration with nano‐/micro‐components to generate hydrophobic and even superhydrophobic features that can be useful in minimizing the water absorption of these materials.

A hybrid microfluidic system for regulation of neural differentiation in induced pluripotent stem cells.

Controlling cellular orientation, proliferation, and differentiation is valuable in designing organ replacements and directing tissue regeneration. In the present study, we developed a hybrid microfluidic system to produce a dynamic microenvironment by placing aligned PDMS microgrooves on surface of biodegradable polymers as physical guidance cues for controlling the neural differentiation of human induced pluripotent stem cells (hiPSCs). The neuronal differentiation capacity of cultured hiPSCs in the microfluidic system and other control groups was investigated using quantitative real time PCR (qPCR) and immunocytochemistry. The functionally of differentiated hiPSCs inside hybrid system's scaffolds was also evaluated on the rat hemisected spinal cord in acute phase. Implanted cell's fate was examined using tissue freeze section and the functional recovery was evaluated according to the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Our results confirmed the differentiation of hiPSCs to neuronal cells on the microfluidic device where the expression of neuronal-specific genes was significantly higher compared to those cultured on the other systems such as plain tissue culture dishes and scaffolds without fluidic channels. Although survival and integration of implanted hiPSCs did not lead to a significant functional recovery, we believe that combination of fluidic channels with nanofiber scaffolds provides a great microenvironment for neural tissue engineering, and can be used as a powerful tool for in situ monitoring of differentiation potential of various kinds of stem cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1534-1543, 2016.

Surface wettability and energy effects on the biological performance of poly-3-hydroxybutyrate films treated with RF plasma

The surface properties of poly-3-hydroxybutyrate (P3HB) membranes were modified using oxygen and an ammonia radio-frequency (RF, 13.56MHz) plasma. The plasma treatment procedures used in the study only affected the surface properties, including surface topography, without inducing any significant changes in the crystalline structure of the polymer, with the exception being a power level of 250W. The wettability of the modified P3HB surfaces was significantly increased after the plasma treatment, irrespective of the treatment procedure used. It was revealed that both surface chemistry and surface roughness changes caused by the plasma treatment affected surface wettability. A treatment-induced surface aging effect was observed and resulted in an increase in the water contact angle and a decrease in the surface free energy. However, the difference in the water contact angle between the polymers that had been treated for 4weeks and the untreated polymer surfaces was still significant. A dependence between cell adhesion and proliferation and the polar component of the surface energy was revealed. The increase in the polar component after the ammonia plasma modification significantly increased cell adhesion and proliferation on biodegradable polymer surfaces compared to the untreated P3HB and the P3HB modified using an oxygen plasma.

Nanoscale patterning of biopolymers for functional biosurfaces and controlled drug release.

We compare the rates of drug release from nanopatterned and flat biodegradable polymer surfaces, and observe significantly lower release rates from the nanopatterned surfaces. Specifically, we nanopattern poly(l-lactic acid) (PLLA), a biodegradable polymer frequently used for fabricating drug-eluting coronary stents, through microtransfer molding and solvent casting and investigate the nanopattern's impact on the release of sirolimus, an immunosuppressant agent, coated on the PLLA surface using high performance liquid chromatography/mass spectrometry. We find that PLLA surfaces nanopatterned with 750 nm-pitch nanocup or nanocone arrays exhibit drug release rates significantly lower (25-30%) than that of the flat surface, which is counter-intuitive given the nanopattern-induced increase in their surface areas. Based on diffusion and meniscus curvature minimization analyses, we attribute the decreased drug release rate to the incomplete wetting of the nanopatterned surface. These results provide new insights on how the surface nanopatterning of biomaterials can functionalize the surface and tailor the release kinetics of therapeutic agents coated on it for controlled drug elution.

Zeta potential study of biodegradable antimicrobial polymers

Abstract Biodegradable polymers have gained increasing interest in recent years, especially in food packaging industry. The biodegradation process is intrinsically related to adhesion of degradation-promoting bacteria on the surface of a biodegradable packaging. On the other hand, because of a direct contact with food, these materials should be resistant to colonisation by pathogenic bacteria. Thus, successful design of a biodegradable antimicrobial material critically depends on the interplay between the ability to control the strength of bacteria–polymer interactions. The aim of this work was to measure and analyse the effect of three positively charged antibacterial polyhexamethylene guanidine hydrochloride (PHMG) derivatives (sulfanilic acid salt, stearic acid salt, and polyethylene (PE) wax blend) on electrokinetic potential ( ζ ) of three biodegradable polymers: poly(hydroxybutyric acid) (PHB), polycaprolactone (PCL) and poly(lactic acid) (PLA). For this purpose, the streaming current vs pressure curves were recorded and analysed using the Helmholtz–Smoluchowski theory. The ζ vs pH dependency provides a simple and useful characterisation of an electrical double layer forming on the surface of biodegradable polymers in contact with an aqueous electrolyte. The undoped polymers displayed the ζ vs pH curves typical for electrically neutral polymers, with the isoelectric point, IEP = 3.5–4.0. The effect of PHMG on ζ vs pH curves depends on both the nature of the matrix polymer and the chemical form of PHMG. The stearate salt is shown to affect the curves to the smallest extent, while the most pronounced shifts towards higher pH were observed for PHMG in the form of PE wax (for PCL and PHB), or sulfanilic acid salt (for PLA). The surface of almost all PHMG-doped polymers used in this study (with exception of PLA doped with PHMG stearate) was more positive than the bare biodegradable polymers. From the point of view of electrostatic interactions, the addition of PHMG (especially in the form of PE wax, and especially for PHB) would thus probably enhance electrostatic polymer–bacteria interactions, possibly altering the antimicrobial activity of such polymers.

生分解性ポリマーのレーザプロセシングとそのバイオ・メディカル応用

During the last decades, biodegradable polymers have been attracting increasing attention in tissue engineering and drug delivery due to its high biocompatibility and biodegradability. Chemical structure and surface properties of biodegradable polymers are known to be a key factor to decide its functionality as biomaterials. Among various methods to process or modify biodegradable polymer surfaces, laser processing has advantages in a dry processing which is able to process complex-shaped surfaces without using a toxic chemical component. This review gives an overview of laser processing of biodegradable polymer surfaces for biomedical applications. The formation of laser induced periodic surface structure (LIPSS) on a biodegradable polymer is also discussed.

The Influence of Radio Frequency Magnetron Sputtering on Biodegradable Polymers Surface Properties

The paper investigated the modifying possibility of the biodegradable polymer materials surface (polylactic acid and polycaprolactone) in radio frequency discharge plasma, initiating hydroxyapatite solid target sputtering. It was demonstrated that discharge plasma treatment adjusts the surface properties of biodegradable polymers – surface free energy and the wetting angle. The disadvantage of biodegradable polymers, limiting their use in reconstructive medicine, is their hydrophobicity. The surface of biodegradable polymers becomes hydrophilic after modification.

Mechanical properties of nanostructured nitinol/chitosan composite material

The mechanical properties and degradation behavior of a composite material based on nanostructured nitinol and a biodegradable polymer surface coating of chitosan of various molecular weights are studied. The formation of a biodegradable surface layer of any composition does not change the properties of the base material. The created biodegradable polymer surface coating disintegrates upon applying the yield stress, i.e., within the operating range of loadings on medical items. The base disintegrates with the formation of a neck. Surface layer cracking is observed only near the fracture.

Grafting of a model protein on lactide and caprolactone based biodegradable films for biomedical applications

Thermoplastic biodegradable polymers displaying elastomeric behavior and mechanical consistency are greatly appreciated for the regeneration of soft tissues and for various medical devices. However, while the selection of a suitable base material is determined by mechanical and biodegradation considerations, it is the surface properties of the biomaterial that are responsible for the biological response. In order to improve the interaction with cells and modulate their behavior, biologically active molecules can be incorporated onto the surface of the material. With this aim, the surface of a lactide and caprolactone based biodegradable elastomeric terpolymer was modified in two stages. First, the biodegradable polymer surface was aminated by atmospheric pressure plasma treatment and second a crosslinker was grafted in order to covalently bind the biomolecule. In this study, albumin was used as a model protein. According to X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM), albumin was efficiently immobilized on the surface of the terpolymer, the degree of albumin surface coverage (ΓBSA) reached ~35%. Moreover, gel permeation chromatography (GPC) studies showed that the hydrolytic degradation kinetic of the synthesized polymer was slightly delayed when albumin was grafted. However, the degradation process in the bulk of the material was unaffected, as demonstrated by Fourier transform infrared (FTIR) analyses. Furthermore, XPS analyses showed that the protein was still present on the surface after 28 days of degradation, meaning that the surface modification was stable, and that there had been enough time for the biological environment to interact with the modified material.

Comparison of biolimus-eluting stent with a biodegradable polymer with newest-generation drug-eluting stents with durable polymers in patients with acute myocardial infarction

Purpose: Durable polymer coating has been identified as a potential trigger for late adverse events and led to the development of newer generation drug-eluting stents (DES) with durable polymers and biodegradable polymer surface coating with improved biocompatibility. In the COMFORTABLE AMI trial, biolimus-eluting stent with a biodegradable polymer showed a lower rate of the composite of major adverse cardiac events (MACE) at 1 year when compared with bare-metal stent. We aimed to determine the effectiveness and safety of biolimus-eluting stent with a biodegradable polymer compared with newest-generation DES with durable polymers in acute myocardial infarction (MI). Methods: A total of 860 patients, who underwent percutaneous coronary intervention (PCI) with biolimus-eluting stents with a biodegradable polymer (n=303) or newest-generation DES with durable polymers (n=557), were selected from 13,472 patients in the Korea Working Group on Myocardial Infarction Registry. The composite of MACE (defined as death, MI, or revascularization) and stent thrombosis at one-year were compared. Results: The composite of MACE at one-year occurred in 11 patients (3.9%) receiving biolimus-eluting stents with a biodegradable polymer and 16 patients (3.9%) receiving newest-generation DES with durable polymers (p=0.541). Stent thrombosis at one-year occurred in 1 patient (0.9%) treated with biolimus-eluting stent and 2 patients treated with newest-generation DES (p=1.0). In Kaplan-Meier curve, MACE-free survival was not different (log rank p=0.512). ![Figure][1] Conclusions: Compared with newest-generation DES with durable polymers, the use of biolimus-eluting stent with a biodegradable polymer resulted in similar rates of the composite of MACE and stent thrombosis at one-year in patients with acute MI who underwent PCI. [1]: pending:yes

Comparison of biolimus eluted from an erodible stent coating with bare metal stents in acute ST-elevation myocardial infarction (COMFORTABLE AMI trial): rationale and design

Compared with bare metal stents (BMS), early generation drug-eluting stents (DES) reduce the risk of revascularisation in patients with ST-elevation myocardial infarction (STEMI) at the expense of an increased risk of very late stent thrombosis (ST). Durable polymer coatings for controlled drug release have been identified as a potential trigger for these late adverse events and this has led to the development of newer generation DES with durable and biodegradable polymer surface coatings with improved biocompatibility. In a recent all-comers trial, biolimus-eluting stents with a biodegradable polymer surface coating were found to reduce the risk of very late ST by 80% compared with sirolimus-eluting stents with durable polymer, which also translated into a lower risk of cardiac death and myocardial infarction (MI) beyond one year. The multicentre COMFORTABLE AMI trial (NCT00962416) randomly assigned 1,161 patients to treatment with biolimus-eluting stents with biodegrable polymer and bare metal stents of otherwise identical design at 11 international sites. The primary endpoint is a composite of cardiac death, target-vessel MI and target lesion revascularisation at one year. Assuming a relative risk reduction of 40% in event rates of the primary endpoint in favour of biolimus-eluting stents with biodegradable polymer, 1,064 patients will provide 80% power to demonstrate superiority. Clinical follow-up will be continued through five years. The COMFORTABLE AMI trial will determine whether biolimus-eluting stents with biodegradable polymer are superior to bare metal stents of otherwise identical design. This is the first randomised controlled trial (RCT) investigating DES with a biodegradable polymer surface coating for drug release in the treatment of patients with STEMI.

Preparation of Roxithromycin-Loaded Poly(l-lactic Acid) Films with Supercritical Solution Impregnation

Supercritical solution impregnation (SSI) was applied to prepare drug-loaded biodegradable films where poly(l-lactic acid) (PLLA) was used as the matrix and roxithromycin as the model drug. The effects of impregnation time, operating temperature, and pressure on drug loading capacity (DLC) of roxithromycin into PLLA matrix were investigated. With the extension of impregnation time, DLC increased gradually to an equilibrium value. DLC was also affected by impregnation temperature and pressure. At the optimal condition, i.e., impregnating at 70 °C and 300 bar for 2 h, the maximal DLC was approximately 10.5%. After SSI process, the PLLA film was still transparent. The SEM images showed that the morphologies of PLLA film did not change with the SSI process. The DSC data and XRD spectra demonstrated that roxithromycin molecules were dispersed into the PLLA film in an amorphous state and the SCCO2 processed PLLA film had a lower crystal degree than raw PLLA film. The residual dichloromethane due to the PLLA film preparation could be removed effectively during the SSI process and meet the Chinese Pharmacopoeia limit. In vitro release of roxithromycin consisted of two stages: initial rapid release and a following slow release. The SSI process is expected to be a promising technique to prepare a drug-loaded biodegradable polymer surface and matrix for antibacterial therapeutic implants.

Novel thin-walled nerve conduit with microgrooved surface patterns for enhanced peripheral nerve repair

Randomly aligned nerve cells in vitro on conventional culture substrata do not represent the complex neuronal network in vivo and neurites growing in uncontrolled manner may form neuroma. It is of great importance to mimic the organised growth pattern of nerve cells in the study of peripheral nerve repair. The aim of this work was to modify and optimize the photolithographic technique in creating a reusable template in the form of a silicon wafer that could be used to produce contact guidance on biodegradable polymer surface for the orientated growth of nerve cells. Micro-grooves (approximately 3 μm in depth) were etched into the silicon template using KOH at increased temperature. The originality of this work lies in the low cost and high efficiency method in producing microgrooves on the surface of biodegradable ultra-thin polymer substrates (50-100 μm), which can be readily rolled up to form clinically implantable nerve conduits. The design of a pattern with small ridge width (i.e., 5 μm) and bigger groove width (i.e., 20 μm) favored the alignment of cells along the grooves rather than on the ridges of the patterns, which minimized the effect of cross growing of neurites between adjacent grooves. Effectively, enhanced nerve regeneration could be anticipated from these patterned conduits.