Biodegradable Scaffolds for Vascular Regeneration Based on Electrospun Poly(L-Lactide-co-Glycolide)/Poly(Isosorbide Sebacate) Fibers.

Vascular regeneration is a complex process, additionally limited by the low regeneration potential of blood vessels. Hence, current research is focused on the design of artificial materials that combine biocompatibility with a certain rate of biodegradability and mechanical robustness. In this paper, we have introduced a scaffold material made of poly(L-lactide-co-glycolide)/poly(isosorbide sebacate) (PLGA/PISEB) fibers fabricated in the course of an electrospinning process, and confirmed its biocompatibility towards human umbilical vein endothelial cells (HUVEC). The resulting material was characterized by a bimodal distribution of fiber diameters, with the median of 1.25 µm and 4.75 µm. Genotyping of HUVEC cells collected after 48 h of incubations on the surface of PLGA/PISEB scaffolds showed a potentially pro-angiogenic expression profile, as well as anti-inflammatory effects of this material. Over the course of a 12-week-long hydrolytic degradation process, PLGA/PISEB fibers were found to swell and disintegrate, resulting in the formation of highly developed structures resembling seaweeds. It is expected that the change in the scaffold structure should have a positive effect on blood vessel regeneration, by allowing cells to penetrate the scaffold and grow within a 3D structure of PLGA/PISEB, as well as stabilizing newly-formed endothelium during hydrolytic expansion.

Antibacterial and cytocompatible coatings based on poly(adipic anhydride) for a Ti alloy surface.

This paper describes a formation of hybrid coatings on a Ti-2Ta-3Zr-36Nb surface. This is accomplished by plasma electrolytic oxidation and a dip-coating technique with poly(adipic anhydride) ((C6H8O3)n) that is loaded with drugs: amoxicillin (C16H19N3O5S), cefazolin (C14H14N8O4S3) or vancomycin (C66H75Cl2N9O24 · xHCl). The characteristic microstructure of the polymer was evaluated using scanning electron microscopy and confocal microscopy. Depending on the surface treatment, the surface roughness varied (between 1.53 µm and 2.06 µm), and the wettability was change with the over of time. X-ray photoelectron spectroscopy analysis showed that the oxide layer did not affect the polymer layer or loaded drugs. However, the drugs lose their stability in a phosphate-buffered saline solution after 6.5 h of exposure, and its decrease was greater than 7% (HPLC analysis). The stability, drug release and concentration of the drug loaded into the material were precisely analyzed by high-performance liquid chromatography. The results correlated with the degradation of the polymer in which the addition of drugs caused the percent of degraded polymer to be between 35.5% and 49.4% after 1 h of material immersion, depending on the mass of the loaded drug and various biological responses that were obtained. However, all of the coatings were cytocompatible with MG-63 osteoblast-like cells. The drug concentrations released from the coatings were sufficient to inhibit adhesion of reference and clinical bacterial strains (S. aureus). The coatings with amoxicillin showed the best results in the bacterial inhibition zone, whereas coatings with cefazolin inhibited adhesion of the above bacteria on the surface.

Physico-chemical and biological evaluation of doxycycline loaded into hybrid oxide-polymer layer on Ti-Mo alloy.

Oxide-polymer coatings were formed on the surface of the vanadium-free Ti-15Mo titanium alloy. The Ti alloy surface was modified by the plasma electrolytic oxidation process, and then, the polymer layer of a poly (D, l-lactide-co-glycolide) with doxycycline was formed. The polymer evenly covered the porous oxide layer and filled some of the pores. However, the microstructure of the polymer surface was completely different from that of the PEO layer. The surface morphology, roughness and microstructure of the polymer layer were examined by scanning electron microscopy (SEM) and a confocal microscope. The results confirmed the effectiveness of polymer and doxycycline deposition in their stable chemical forms. The drug analysis was performed by high-performance liquid chromatography. The 1H NMR technique was used to monitor the course of hydrolytic degradation of PLGA. It was shown that the PLGA layer is hydrolysed within a few weeks, and the polyglycolidyl part of the copolymer is hydrolysed to glycolic acid as first and much faster than the polylactide one to lactic acid. This paper presents influence of different microstructures on the biological properties of modified titanium alloys. Cytocompatibility and bacterial adhesion tests were evaluated using osteoblast-like MG-63 cells and using the reference S. aureus and S. epidermidis strains. The results showed that the optimum concentration of doxycycline was found to inhibit the growth of the bacteria and that the layer is still cytocompatible.

Functionalization of PEO layer formed on Ti-15Mo for biomedical application.

In the present work, deposition of poly(sebacic anhydride) PSBA loaded by amoxicillin, cefazolin, or vancomycin on a previously anodized Ti-15Mo surface is presented. PSBA loaded by the drug was deposited so as not to lose the functionality of the porous oxide layer microstructure. The morphology was evaluated using scanning electron microscopy, surface roughness, and wettability. The drug concentration was evaluated using high-performance liquid chromatography. It was determined that the drugs were loaded into coatings in the range of 35.2-122.87 µg/cm2 of Ti sample. The drugs released more than 16% after 0.5 hr of the hybrid coating immersion in artificial saliva. After 3 days, the PSBA coatings were degraded by 51.3 mol %, and after 7 days by 77.8 mol %, which makes it possible to load the material by different, biologically active substances. An antimicrobial investigation of Staphylococcus aureus (DSM 24167) and Staphylococcus epidermidis (ATCC 700296) confirmed the activity of the hybrid layers against the pathogens. Hybrid layer with vancomycin best inhibits the adhesion of the bacteria, whereas coatings with amoxicillin and cefazolin showed a much better bactericidal activity. In this article, the difference in the obtained results is discussed, as well as the possibility of the application of this functional material in biomedicine.

PLGA-amoxicillin-loaded layer formed on anodized Ti alloy as a hybrid material for dental implant applications.

In this paper, the preparation of a functional hybrid coating loaded with a drug (amoxicillin) on a promising titanium alloy - Ti-15Mo alloy is presented. The titanium alloy surface was anodized in solution with bioactive compounds to obtain a porous oxide layer favorable for MG-63 osteoblast-like cell adhesion. Then, a poly(lactide-co-glycolide) (PLGA) loaded with amoxicillin layer was formed using a dip-coating technique to cover the oxide layer, without filling in all of the pores. The morphology of the surface was evaluated using scanning electron microscopy supported by 3D Roughness Reconstruction software. The surface treatment of the Ti-15Mo alloy surface caused the surface roughness to increase up to 1.71 µm. The anodization process caused the Ti-15Mo alloy surface to become slightly more hydrophilic; however, the formation of the PLGA layer loaded with drug increased the contact angle to 96.5°â€¯±â€¯2.2°, respectively. After 4 weeks of polymer layer degradation, the registered signals on the 1H NMR spectrum were identical to the signals registered for lactic acid (LAc), which confirms that the polymer layer was degraded within a short period of time. The concentration of drug released into the artificial saliva was investigated using high-performance liquid chromatography (HPLC) up to 12 h of coatings immersion. During the first hour of coating degradation in artificial saliva, and the concentration of the drug (13 µg/ml) was enough to inhibit bacterial growth of S. aureus and S. epidermidis. These results were confirmed by agar plate diffusion method and evaluation of the minimal inhibitory concentration (MIC). The cytocompatibility of the materials was determined using the osteoblast-like cells MG-63, and the viability and cell morphology (live/dead staining) were also evaluated. The results showed that amoxicillin influences the osteoblast-like MG-63 cells' behavior during cell culture, especially for the first few hours. The influence on the type of surface treatment on MG-63 cell behavior during 7 days of culture is discussed in this paper. To the best of our knowledge, this is the first time that a fast-degrading layer with amoxicillin has been deposited on previously anodized Ti surface. The formation of functional coating may find application as a cytocompatible coating to prevent bacterial adhesion on long-term implant surfaces.

Poly(isosorbide succinate)-based in situ forming implants as potential systems for local drug delivery: Preliminary studies.

In situ forming implants (ISFI) are proved to be effective drug delivery systems in various local therapies. This research focuses on preliminary characteristics of a new biodegradable ISFI formulation based on poly(isosorbide succinate) (PISU) for modulated, over 3-week, release of doxycycline hyclate (DOXY). The Alamar Blue cytotoxicity assay was carried out for PISU using FK-1 and AoSMC cell lines. PISU resin was found to be non-toxic in wide range of concentrations. The formulation viscosity, dependent on shear rate, facilitates its easy injection into required site where solid depot is formed immediately after injection. DOXY, incorporated into this formulation, was released in vitro within 21 days, during which collected solutions exhibited antibacterial activity against gram-positive and gram-negative bacteria Staphylococcus aureus and Escherichia coli, respectively. The morphology of the precipitated depots was characterized by scanning electron microscopy (SEM). The obtained results suggest potential applicability of this new PISU-based formulation as injectable drug delivery system forming implant at an injection site by phase separation and precipitation of the polymer.

Novel bioactive polyester scaffolds prepared from unsaturated resins based on isosorbide and succinic acid.

In this study new biodegradable materials obtained by crosslinking poly(3-allyloxy-1,2-propylene succinate) (PSAGE) with oligo(isosorbide maleate) (OMIS) and small amount of methyl methacrylate were investigated. The porous scaffolds were obtained in the presence of a foaming system consisted of calcium carbonate/carboxylic acid mixture, creating in situ porous structure during crosslinking of liquid formulations. The maximum crosslinking temperature and setting time, the cured porous materials morphology as well as the effect of their porosity on mechanical properties and hydrolytic degradation process were evaluated. It was found that the kind of carboxylic acid used in the foaming system influenced compressive strength and compressive modulus of porous scaffolds. The MTS cytotoxicity assay was carried out for OMIS using hFOB1.19 cell line. OMIS resin was found to be non-toxic in wide range of concentrations. On the ground of scanning electron microscopy (SEM) observations and energy X-ray dispersive analysis (EDX) it was found that hydroxyapatite (HA) formation at the scaffolds surfaces within short period of soaking in phosphate buffer solution occurs. After 3h immersion a compact layer of HA was observed at the surface of the samples. The obtained results suggest potential applicability of resulted new porous crosslinked polymeric materials as temporary bone void fillers.

Novel injectable biomaterials for bone augmentation based on isosorbide dimethacrylic monomers.

Drawbacks with the commonly used PMMA-based bone cements, such as an excessive elastic modulus and potentially toxic residual monomer content, motivate the development of alternative cements. In this work an attempt to prepare an injectable biomaterial based on isosorbide-alicyclic diol derived from renewable resources was presented. Two novel dimethacrylic monomers ISDGMA - 2,5-bis(2-hydroxy-3-methacryloyloxypropoxy)-1,4:3,6-dianhydro-sorbitol and ISETDMA - dimethacrylate of ethoxylated isosorbide were synthesized and used to prepare a series of low-viscosity compositions comprising bioactive nano-sized hydroxyapatite in the form of a two-paste system. Formulations exhibited a non-Newtonian shear-thinning behavior, setting times between 2.6 min and 5.3 min at 37°C and maximum curing temperatures of 65°C. Due to the hydrophilic nature of ISDGMA, cured compositions could absorb up to 13.6% water and as a result the Young's modulus decreased from 1,429 MPa down to 470 MPa. Both, poly(ISDGMA) and poly(ISETDMA) were subjected to a MTT study on mice fibroblasts (BALB/3T3) and gave relative cell viabilities above 70% of control. A selected model bone cement was additionally investigated using human osteosarcoma cells (SaOS-2) in an MTS test, which exhibited concentration-dependent cell viability. The preliminary results, presented in this work reveal the potential of two novel dimethacrylic monomers in the preparation of an injectable biomaterial for bone augmentation, which could overcome some of the drawbacks typical for conventional acrylic bone cement.

Characterization of new biodegradable bone cement compositions based on functional polysuccinates and methacrylic anhydride.

New biodegradable poly(3-allyloxy-1,2-propylene)succinate-based materials were obtained by cross-linking poly(3-allyloxy-1,2-propylene)succinate (PSAGE) with methyl methacrylate (MMA) and methacrylic anhydride (MAAH). The aim of this study was to examine the influence of MAAH/MMA ratio and incorporation of biphasic calcium phosphate (BCP) filler on the maximum curing temperature, setting time, compressive strength and modulus of the cured materials, as well as on their hydrolytic degradation. The latter was characterized by determination of the weight loss and observation of changes in samples morphology by SEM. The maximum temperature during cross-linking was found to decrease with increasing MAAH content. The setting time was affected strongly by the concentration of double bonds and was rapidly shortened with its increase. The compressive strength and compressive modulus values increased with increasing MAAH/MMA ratio. Moreover, addition of bioactive mineral filler (BCP) improves significantly mechanical properties of these materials. On the other hand, it slows down their hydrolytic degradation.