First Clinical Case of Ilizarov Femur Lengthening over a Bioactive and Degradable Intramedullary Implant.

Introduction: The Ilizarov distraction osteogenesis is a recognized method of limb lengthening in orthopaedic practice. Its most challenging problems are long duration of external fixation and related pin-tract infection and joint contractures. The solution might be the use of a bioactive degradable intramedullary implant stimulating bone healing. Case Presentation. We present a case of a 14-year-old boy with 6 cm posttraumatic shortening of the femur and associated varus deformity of 20 degrees. He was treated with the Ilizarov technique of femur lengthening over an intramedullary degradable polycaprolactone (PCL) implant with hydroxyapatite (HA) filling. We faced no complications within the lengthening process. Shortening and deformity of the femur were corrected in 90 days. The index of external fixation was 15 days/cm. External fixation time was reduced almost twice comparing to the conventional method. Degradable intramedullary nails ensured the advantage of avoidance of the removal procedure. Radiography and CT confirmed faster new bone healing and remodeling. Conclusion: The combined lengthening technique over a PCL/HA implant might be used to shorten external fixation time and to stimulate bone healing especially in patients with compromised bone. Using a bioabsorbable material presents the benefit of eliminating the need for a second surgery to remove the nail, thereby reducing soft tissue damage.

Prolonged and Controllable Release of Doxorubicin Hydrochloride from the Composite Electrospun Poly(ε-Caprolactone)/Polyvinylpyrrolidone Scaffolds.

Burst release, typical for the drug-loaded electrospun poly(ε-caprolactone) (PCL) scaffolds is unfavorable in case of cytostatics due to the toxic levels reached during the initial implantation period. In the present short communication, we report an unexpected ability of the composite scaffolds made of PCL and water-soluble polyvinylpyrrolidone (PVP) to provide long-term release of widely used anti-cancer drug doxorubicin hydrochloride (DOX-HCl). That effect was observed for electrospun DOX-HCl-loaded composite scaffolds based on PCL and PVP with various mass ratios (100/0, 95/5, 90/10, 75/25 and 50/50). After the morphology and water contact angle studies, it was concluded that PVP content has no effect on the average fiber diameter, while PVP content higher 10 wt. % changes the hydrophobic character of the scaffolds surface (water contact angle of 123.9 ± 3.5°) to superhydrophilic (water contact angle of 0°). Despite the dramatic change in water wettability, by high performance liquid chromatography (HPLC), it was revealed that the PVP content in the scaffolds reduces the DOX-HCl release rate under short (first hours) and long-term (during 1 month) exposure to phosphate buffer saline (PBS). These results are in good agreement with in vitro studies, in which the viability of HeLa cervical cancer cells was higher after 24 h of culture with scaffolds with high PVP content.

Antibacterial Calcium Phosphate Coatings for Biomedical Applications Fabricated via Micro-Arc Oxidation.

A promising method for improving the functional properties of calcium-phosphate coatings is the incorporation of various antibacterial additives into their structure. The microbial contamination of a superficial wound is inevitable, even if the rules of asepsis and antisepsis are optimally applied. One of the main problems is that bacteria often become resistant to antibiotics over time. However, this does not apply to certain elements, chemical compounds and drugs with antimicrobial properties. In this study, the fabrication and properties of zinc-containing calcium-phosphate coatings that were formed via micro-arc oxidation from three different electrolyte solutions are investigated. The first electrolyte is based on calcium oxide, the second on hydroxyapatite and the third on calcium acetate. By adding zinc oxide to the three electrolyte solutions, antibacterial properties of the coatings are achieved. Although the same amount of zinc oxide has been added to each electrolyte solution, the zinc concentration in the coatings obtained vary greatly. Furthermore, this study investigates the morphology, structure and chemical composition of the coatings. The antibacterial properties of the zinc-containing coatings were tested toward three strains of bacteria-Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Coatings of calcium acetate and zinc oxide contained the highest amount of zinc and displayed the highest zinc release. Moreover, coatings containing hydroxyapatite and zinc oxide show the highest antibacterial activity toward Pseudomonas aeruginosa, and coatings containing calcium acetate and zinc oxide show the highest antibacterial activities toward Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.

Effect of Nitrogen Arc Discharge Plasma Treatment on Physicochemical Properties and Biocompatibility of PLA-Based Scaffolds.

The effect of low-temperature arc discharge plasma treatment in a nitrogen atmosphere on the modification of the physicochemical properties of PLA-based scaffolds was studied. In addition, the cellular-mediated immune response when macrophages of three donors interact with the modified surfaces of PLA-based scaffolds was investigated. PLA surface carbonization, accompanied by a carbon atomic concentration increase, was revealed to occur because of plasma treatment. Nitrogen plasma significantly influenced the PLA wettability characteristics, namely, the hydrophilicity and lipophilicity were improved, as well as the surface energy being raised. The viability of cells in the presence of the plasma-modified PLA scaffolds was evaluated to be higher than that of the initial cells.

Electrospun Poly-L-Lactic Acid Scaffolds Surface-Modified via Reactive Magnetron Sputtering Using Different Mixing Ratios of Nitrogen and Xenon.

Controlled regeneration processes involving tissue growth using the surface and structure of scaffolds, are actively used in tissue engineering. Reactive magnetron sputtering is a versatile surface modification method of both metal and polymer substrates, as the properties of the formed coatings can be modified in a wide range by changing the process parameters. In magnetron sputtering, the working gas and its composition have an influence on the chemical composition and physical characteristics of the obtained coatings. However, there are no studies addressing the influence of the nitrogen/xenon gas mixture ratio in direct current magnetron sputtering on the deposition rate, physicochemical and in vitro properties of surface-modified biocompatible poly-L-lactic acid scaffolds. In this study, the application of mixtures of nitrogen and xenon in various ratios is demonstrated to modify the surface of non-woven poly-L-lactic acid scaffolds by direct current magnetron sputtering of a titanium target. It has been found that the magnetron sputtering parameters chosen do not negatively influence the morphology of the prepared scaffolds, but increase the hydrophilicity. Moreover, quantitative spectroscopic analysis results indicate that the formed coatings are primarily composed of titanium oxide and titanium oxynitride compounds and is dependent on the gas mixture ratio only to a certain extent. Atomic force microscopy investigations of the roughness of the fibers of the electrospun scaffolds and the thickness of the coatings formed on them show that the considerable variations observed in the intrinsic fiber reliefs are due to the formation of a fine layer on the fiber surfaces. The observed decrease in roughness after plasma modification is due to temperature and radiation effects of the plasma. In vitro experiments with human osteosarcoma cells show that the scaffolds investigated here have no cytotoxic effect on these cells. The cells adhere and proliferate well on each of the surface-modified electrospun scaffolds, with stimulation of cell differentiation in the osteogenic direction.

Long Bone Defect Filling with Bioactive Degradable 3D-Implant: Experimental Study.

Previously, 3D-printed bone grafts made of titanium alloy with bioactive coating has shown great potential for the restoration of bone defects. Implanted into a medullary canal titanium graft with cellular structure demonstrated stimulation of the reparative osteogenesis and successful osseointegration of the graft into a single bone-implant block. The purpose of this study was to investigate osseointegration of a 3D-printed degradable polymeric implant with cellular structure as preclinical testing of a new technique for bone defect restoration. During an experimental study in sheep, a 20 mm-long segmental tibial defect was filled with an original cylindrical implant with cellular structure made of polycaprolactone coated with hydroxyapatite. X-ray radiographs demonstrated reparative bone regeneration from the periosteum lying on the periphery of cylindrical implant to its center in a week after the surgery. Cellular structure of the implant was fully filled with newly-formed bone tissue on the 4th week after the surgery. The bone tissue regeneration from the proximal and distal bone fragments was evident on 3rd week. This provides insight into the use of bioactive degradable implants for the restoration of segmental bone defects. Degradable implant with bioactive coating implanted into a long bone segmental defect provides stimulation of reparative osteogenesis and osseointegration into the single implant-bone block.

Improvement of the Surface Properties of Polyether Ether Ketone via Arc Evaporation for Biomedical Applications.

Polyether ether ketone is a bioinert polymer, that is of high interest in research and medicine as an alternative material for the replacement of bone implants made of metal. The biggest deficit of this polymer is its hydrophobic surface, which is rather unfavorable for cell adhesion and thus leads to slow osseointegration. In order to address this drawback, 3D-printed and polymer extruded polyether ether ketone disc samples that were surface-modified with titanium thin films of four different thicknesses via arc evaporation were investigated and compared with non-modified disc samples. Depending on the modification time, the thickness of the coatings ranged from 40 nm to 450 nm. The 3D-printing process does not affect the surface or bulk properties of polyether ether ketone. It turned out that the chemical composition of the coatings obtained did not depend on the type of substrate. Titanium coatings contain titanium oxide and have an amorphous structure. Microdroplets formed on the sample surfaces during treatment with an arc evaporator contain a rutile phase in their composition. Surface modification of the samples via arc evaporation resulted in an increase in the arithmetic mean roughness from 20 nm to 40 nm for the extruded samples and from 40 nm to 100 nm for the 3D-printed samples, with the mean height difference increasing from 100 nm to 250 nm and from 140 nm to 450 nm. Despite the fact that the hardness and reduced elastic modulus of the unmodified 3D-printed samples (0.33 GPa and 5.80 GPa) are higher than those of the unmodified extruded samples (0.22 GPa and 3.40 GPa), the surface properties of the samples after modification are approximately the same. The water contact angles of the polyether ether ketone sample surfaces decrease from 70° to 10° for the extruded samples and from 80° to 6° for the 3D-printed samples as the thickness of the titanium coating increases, making this type of coating promising for biomedical applications.

Antibacterial Activity and Cytocompatibility of Electrospun PLGA Scaffolds Surface-Modified by Pulsed DC Magnetron Co-Sputtering of Copper and Titanium.

Biocompatible poly(lactide-co-glycolide) scaffolds fabricated via electrospinning are having promising properties as implants for the regeneration of fast-growing tissues, which are able to degrade in the body. The hereby-presented research work investigates the surface modification of these scaffolds in order to improve antibacterial properties of this type of scaffolds, as it can increase their application possibilities in medicine. Therefore, the scaffolds were surface-modified by means of pulsed direct current magnetron co-sputtering of copper and titanium targets in an inert atmosphere of argon. In order to obtain different amounts of copper and titanium in the resulting coatings, three different surface-modified scaffold samples were produced by changing the magnetron sputtering process parameters. The success of the antibacterial properties' improvement was tested with the methicillin-resistant bacterium Staphylococcus aureus. In addition, the resulting cell toxicity of the surface modification by copper and titanium was examined using mouse embryonic and human gingival fibroblasts. As a result, the scaffold samples surface-modified with the highest copper to titanium ratio show the best antibacterial properties and no toxicity against mouse fibroblasts, but have a toxic effect to human gingival fibroblasts. The scaffold samples with the lowest copper to titanium ratio display no antibacterial effect and toxicity. The optimal poly(lactide-co-glycolide) scaffold sample is surface-modified with a medium ratio of copper and titanium that has antibacterial properties and is non-toxic to both cell cultures.

Electrospinning vs. Electro-Assisted Solution Blow Spinning for Fabrication of Fibrous Scaffolds for Tissue Engineering.

Biodegradable polymeric fibrous non-woven materials are widely used type of scaffolds for tissue engineering. Their morphology and properties could be controlled by composition and fabrication technology. This work is aimed at development of fibrous scaffolds from a multicomponent polymeric system containing biodegradable synthetic (polylactide, polycaprolactone) and natural (gelatin, chitosan) components using different methods of non-woven mats fabrication: electrospinning and electro-assisted solution blow spinning. The effect of the fabrication technique of the fibrous materials onto their morphology and properties, including the ability to support adhesion and growth of cells, was evaluated. The mats fabricated using electrospinning technology consist of randomly oriented monofilament fibers, while application of solution blow spinning gave a rise to chaotically arranged multifilament fibers. Cytocompatibility of all fabricated fibrous mats was confirmed using in vitro analysis of metabolic activity, proliferative capacity and morphology of NIH 3T3 cell line. Live/Dead assay revealed the formation of the highest number of cell-cell contacts in the case of multifilament sample formed by electro-assisted solution blow spinning technology.

Surface Modification of Additively Fabricated Titanium-Based Implants by Means of Bioactive Micro-Arc Oxidation Coatings for Bone Replacement.

In this work, the micro-arc oxidation method is used to fabricate surface-modified complex-structured titanium implant coatings to improve biocompatibility. Depending on the utilized electrolyte solution and micro-arc oxidation process parameters, three different types of coatings (one of them-oxide, another two-calcium phosphates) were obtained, differing in their coating thickness, crystallite phase composition and, thus, with a significantly different biocompatibility. An analytical approach based on X-ray computed tomography utilizing software-aided coating recognition is employed in this work to reveal their structural uniformity. Electrochemical studies prove that the coatings exhibit varying levels of corrosion protection. In vitro and in vivo experiments of the three different micro-arc oxidation coatings prove high biocompatibility towards adult stem cells (investigation of cell adhesion, proliferation and osteogenic differentiation), as well as in vivo biocompatibility (including histological analysis). These results demonstrate superior biological properties compared to unmodified titanium surfaces. The ratio of calcium and phosphorus in coatings, as well as their phase composition, have a great influence on the biological response of the coatings.

Surface Modification of Electrospun Bioresorbable and Biostable Scaffolds by Pulsed DC Magnetron Sputtering of Titanium for Gingival Tissue Regeneration.

In this study, polymer scaffolds were fabricated from biodegradable poly(lactide-co-glycolide) (PLGA) and from non-biodegradable vinylidene fluoride-tetrafluoroethylene (VDF-TeFE) by electrospinning. These polymer scaffolds were subsequently surface-modified by sputtering titanium targets in an argon atmosphere. Direct current pulsed magnetron sputtering was applied to prevent a significant influence of discharge plasma on the morphology and mechanical properties of the nonwoven polymer scaffolds. The scaffolds with initially hydrophobic properties show higher hydrophilicity and absorbing properties after surface modification with titanium. The surface modification by titanium significantly increases the cell adhesion of both the biodegradable and the non-biodegradable scaffolds. Immunocytochemistry investigations of human gingival fibroblast cells on the surface-modified scaffolds indicate that a PLGA scaffold exhibits higher cell adhesion than a VDF-TeFE scaffold.

Polyether Ether Ketone Coated with Ultra-Thin Films of Titanium Oxide and Zirconium Oxide Fabricated by DC Magnetron Sputtering for Biomedical Application.

Recently, polyether ether ketone has raised increasing interest in research and industry as an alternative material for bone implants. This polymer also has some shortcomings, as it is bioinert and its surface is relatively hydrophobic, causing poor cell adhesion and therefore slow integration with bone tissue. In order to improve biocompatibility, the surface of polyether ether ketone-based implants should be modified. Therefore, polished disc-shaped polyether ether ketone samples were surface-modified by direct current magnetron sputtering with ultrathin titanium and zirconium coatings (thickness < 100 nm). The investigation results show a uniform distribution of both types of coatings on the sample surfaces, where the coatings mostly consist of titanium dioxide and zirconium dioxide. Differential scanning calorimetry revealed that the crystalline structure of the polyether ether ketone substrates was not changed by the coating deposition. Both coatings are amorphous, as shown by X-ray diffraction investigations. The roughness of both coating types increases with increasing coating thickness, which is beneficial for cell colonization. The coatings presented and investigated in this study improve wettability, increasing surface energies, in particular the polar component of the surface energies, which, in turn, are important for cell adhesion.

Biodegradable magnesium fuel-based Janus micromotors with surfactant induced motion direction reversal.

The speed and motion directionality of bubble-propelled micromotors is dependent on bubble lifetime, bubble formation frequency and bubble stabilization. Absence and presence of bubble stabilizing agents should significantly influence speed and propulsion pattern of a micromotor, especially for fast-diffusing molecules like hydrogen. This study demonstrates a fully biodegradable Janus structured micromotor, propelled by hydrogen bubbles generated by the chemical reaction between hydrochloric acid and magnesium. Six different concentrations of hydrochloric acid and five different concentrations of the surfactant Triton X-100 were tested, which also cover the critical micelle concentration at a pH corresponding to an empty stomach. The Janus micromotor reverses its propulsion direction depending on the availability and concentration of a surfactant. Upon surfactant-free condition, the Janus micromotor is propelled by bubble cavitation, causing the micromotor to be pulled at high speed for short time intervals into the direction of the imploding bubble and thus backwards. In case of available surfactant above the critical micelle concentration, the Janus micromotor is pushed forward by the generated bubbles, which emerge at high frequency and form a bubble trail. The finding of the propulsion direction reversal effect demonstrates the importance to investigate the motion properties of artificial micromotors in a variety of different environments prior to application, especially with surfactants, since biological media often contain large amounts of surface-active components.

Effect of Chemically Modified Carbon-Coated Iron Nanoparticles on the Structure of Human Atherosclerotic Plaques Ex Vivo and on Adipose Tissue in Chronic Experiment In Vivo.

The high mortality rate caused by atherosclerosis makes it necessary to constantly search for new and better treatments. In previous reports, chemically modified carbon-coated iron nanoparticles (Fe@C NPs) have been demonstrated a high biocompatibility and promising anti-plaque properties. To further investigate these effects, the interaction of these nanoparticles with the adipose tissue of Wistar rats (in vivo) and human atherosclerotic plaques (ex vivo) was studied. For the in vivo study, cobalt-chromium (CoCr) alloy tubes, which are used for coronary stent manufacturing, were prepared with a coating of polylactic acid (PLA) which contained either modified or non-modified Fe@C NPs in a 5% by weight concentration. The tubes were implanted into an area of subcutaneous fat in Wistar rats, where changes in the histological structure and functional properties of the surrounding tissue were observed in the case of coatings modified with Fe@C NPs. For the ex vivo study, freshly explanted human atherosclerotic plaques were treated in the physiological solution with doses of modified Fe@C NPs, with mass equal to 5% or 25% relative to the plaques. This treatment resulted in the release of cholesterol-like compounds from the surface of the plaques into the solution, thus proving a pronounced destructive effect on the plaque structure. Chemically modified Fe@C NPs, when used as an anti-atherosclerosis agent, were able to activate the activity of macrophages, which could lead to the destruction of atherosclerotic plaques structures. These findings could prove the fabrication of next-generation vascular stents with built-in anti-atherosclerotic agents.

Nitrogen-doped titanium dioxide films fabricated via magnetron sputtering for vascular stent biocompatibility improvement.

Nowadays, vascular stents are commonly used to treat cardiovascular diseases. This article focuses on the influence of nitrogen doping of titanium dioxide thin films, utilized for coating metallic stents to improve their biological properties and biocompatibility. The hereby-investigated titanium oxide thin films are fabricated by magnetron sputtering in a reactive gas atmosphere consisting of argon and oxygen in the first case and argon, nitrogen and oxygen in the second case. Control of the nitrogen and oxygen gas flow rates, and hence their mixing ratios, allows adjustment of the nitrogen-doping level within the titanium dioxide thin films. A correlation of the thin film internal structure on the in vitro behavior of human mesenchymal stem cells derived from adipose tissue is hereby demonstrated. Different nitrogen doping levels affect the surface energy, the wettability, the cell adhesion and thus the cellular proliferation on top of the thin films. The surface colonization of cells on titanium dioxide thin films decreases up to a nitrogen-doping level of âˆ¼ 3.75 at.%, which is associated with a decreasing polar component of the surface energy. For non-doped titanium dioxide thin films, a weak chondrogenesis of adult human adipose-derived mesenchymal stem cells with lower chondrogenic differentiation compared to glass is observed. An increasing nitrogen-doping level leads to linear increase in the chondrogenic differentiation rate, which is comparable to the control value of uncoated glass. Other investigated differentiated cell types do not display this behavior.

Reactive Magnetron Plasma Modification of Electrospun PLLA Scaffolds with Incorporated Chloramphenicol for Controlled Drug Release.

Surface modification with the plasma of the direct current reactive magnetron sputtering has demonstrated its efficacy as a tool for enhancing the biocompatibility of polymeric electrospun scaffolds. Improvement of the surface wettability of materials with water, as well as the formation of active chemical bonds in the near-surface layers, are the main reasons for the described effect. These surface effects are also known to increase the release rate of drugs incorporated in fibers. Herein, we investigated the effect of plasma modification on the chloramphenicol release from electrospun poly (lactic acid) fibrous scaffolds. Scaffolds with high-50 wt./wt.%-drug content were obtained. It was shown that plasma modification leads to an increase in the drug release rate and drug diffusion coefficient, while not deteriorating surface morphology and mechanical properties of scaffolds. The materials' antibacterial activity was observed to increase in the first day of the experiment, while remaining on the same level as the unmodified group during the next six days. The proposed technique for modifying the surface of scaffolds will be useful for obtaining drug delivery systems with controlled accelerated release, which can expand the possibilities of local applications of antibiotics and other drugs.

Biodegradable Defined Shaped Printed Polymer Microcapsules for Drug Delivery.

This work describes the preparation and characterization of printed biodegradable polymer (polylactic acid) capsules made in two different shapes: pyramid and rectangular capsules about 1 and 11 µm in size. Obtained core-shell capsules are described in terms of their morphology, loading efficiency, cargo release profile, cell cytotoxicity, and cell uptake. Both types of capsules showed monodisperse size and shape distribution and were found to provide sufficient stability to encapsulate small water-soluble molecules and to retain them for several days and ability for intracellular delivery. Capsules of 1 µm size can be internalized by HeLa cells without causing any toxicity effect. Printed capsules show unique characteristics compared with other drug delivery systems such as a wide range of possible cargoes, triggered release mechanism, and highly controllable shape and size.

Effect of working gas on physicochemical and biological properties of CaP coatings deposited by RFMS.

Thin calcium phosphate (CaP) coatings were deposited on titanium substrates by radio frequency magnetron sputtering of hydroxyapatite target in neon (Ne), argon (Ar), krypton (Kr) and xenon (Xe). The influence of the working gas (Ne, Ar, Kr and Xe) on the wettability and biodegradation in the RPMI 1640 synthetic culture medium of the CaP coatings was investigated. This paper is the first comprehensive study of working gas effect on properties of the CaP coatings. There was an increase in the polar component of surface free energy (SFE) and a decrease in the dispersion component of SFE with an increase in the atomic mass of the working gas. All CaP coatings had a pronounced protective effect, reducing double the number of dead cells in culture compared to the Ti control. The most soluble CaP coatings formed in the atmosphere of Xe stimulated the hAMMSCs division, which led to an increase in the total number of cells (208% of the initial culture). Samples with CaP coatings formed in an inert gas atmosphere increased the gene expression (ALPL, BMP6, BMP2)in vitro. The most biocompatible coatings were those formed in the atmosphere of Xe and Ar.

Electrosprayed poly(lactic-co-glycolic acid) particles as a promising drug delivery system for the novel JNK inhibitor IQ-1.

Mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), play important role in the regulation of pro-inflammatory cytokine secretion and signaling cascades. Therefore, JNKs are key targets for the treatment of cytokine/JNK-driven diseases. Herein, we developed electrospray poly(lactic-co-glycolic acid) (PLGA) microparticles doped with novel JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1). Optimized electrospray parameters allowed us to produce IQ-1-doped microparticles with round shape, smooth and non-porous surface, and mean diameter of 0.9-1.3 µm. We have shown that IQ-1 was well integrated into the polymer matrix and had a prolonged release in two steps via non-Fickian release. The fabricated particles doped with IQ-1 exhibited anti-inflammatory effects, as indicated by inhibited neutrophil activation and cytokine secretion by human monocytic MonoMac-6 cells. Overall, our study demonstrates that PLGA microparticles doped with a novel JNK inhibitor (IQ-1) could be a promising delivery system for treatment of JNK-mediated diseases.

Modification of PCL Scaffolds by Reactive Magnetron Sputtering: A Possibility for Modulating Macrophage Responses.

Direct current (DC) reactive magnetron sputtering is as an efficient method for enhancing the biocompatibility of poly(ε-caprolactone) (PCL) scaffolds. However, the PCL chemical bonding state, the composition of the deposited coating, and their interaction with immune cells remain unknown. Herein, we demonstrated that the DC reactive magnetron sputtering of the titanium target in a nitrogen atmosphere leads to the formation of nitrogen-containing moieties and the titanium dioxide coating on the scaffold surface. We have provided the possible mechanism of PCL fragmentation and coating formation supported by XPS results and DFT calculations. Our preliminary biological studies suggest that DC reactive magnetron sputtering of the titanium target could be an effective tool to control macrophage functional responses toward PCL scaffolds as it allows to inhibit respiratory burst while retaining cell viability and scavenging activity.