PCL Matrices Research Articles

Экспериментальное исследование биодеградации синтетических полимерных матриц как перспективных подложек для лимбальных стволовых клеток

Aim. To study in experimental conditions and conduct a comparative assessment of the terms of biodegradation of three different types of synthetic polyester matrices as promising carriers of limbal stem cells. Material and methods. We performed matrices from poly(lactide-glycolide) (PLG), poly(lactide-caprolactone) (PLC) and poly(ε-caprolactone) (PCL). On the basis of the S.M. Kirov Military Medical Academy (St. Petersburg) estimated the timing of the biodegradation of matrices from the PLG, PLC and PCL with a thickness of 5; 10 and 15 microns by binding in vitro to the ocular surface of laboratory animals. Results. During the study, the terms of biodegradation of matrices from PLG, PLC and PCL of various thickness were studied. The time of complete biodegradation of PCL matrices with a thickness of 5 μm was about 30 days, which is the most acceptable for the purpose of their transplantation to the eye surface. Conclusion. The obtained results indicate the possibility of using PLC as a material for the manufacture of matrix carriers with a thickness of 5 μm for the cultivation and transplantation of limbal stem cells. Keywords: poly (lactide-glycolide), poly (lactide-caprolactone), poly (ε-caprolactone), biodegradation, limbal stem cells.

Control of drug release kinetics from hot-melt extruded drug-loaded polycaprolactone matrices.

Sustained local delivery of meloxicam by polymeric structures is desirable for preventing subacute inflammation and biofilm formation following tissue incision or injury. Our previous study demonstrated that meloxicam release from hot-melt extruded (HME) poly(ε-caprolactone) (PCL) matrices could be controlled by adjusting the drug content. Increasing drug content accelerated the drug release as the initial drug release generated a pore network to facilitate subsequent drug dissolution and diffusion. In this study, high-resolution micro-computed tomography (HR μCT) and artificial intelligence (AI) image analysis were used to visualize the microstructure of matrices and simulate the drug release process. The image analysis indicated that meloxicam release from the PCL matrix was primarily driven by diffusion but limited by the amount of infiltrating fluid when drug content was low (i.e., the connectivity of the drug/pore network was poor). Since the drug content is not easy to change when a product has a fixed dose and dimension/geometry, we sought an alternative approach to control the meloxicam release from the PCL matrices. Here, magnesium hydroxide (Mg(OH)2) was employed as a solid porogen in the drug-PCL matrix so that Mg(OH)2 dissolved with time in the aqueous environment creating additional pore networks to facilitate local dissolution and diffusion of meloxicam. PCL matrices were produced with a fixed 30wt% meloxicam loading and variable Mg(OH)2 loadings from 20wt% to 50wt%. The meloxicam release increased in proportion to the Mg(OH)2 content, resulting in almost complete drug release in 14 d from the matrix with 50wt%Mg(OH)2. The porogen addition is a simple strategy to tune drug release kinetics, applicable to other drug-eluting matrices with similar constraints.

Hypoxia Promotes Cartilage Regeneration in Cell-Seeded 3D-Printed Bioscaffolds Cultured with a Bespoke 3D Culture Device

In this study, we investigated the effect of oxygen tension on the expansion of ADMSCs and on their differentiation toward their chondrocytic phenotype, regenerating a lab-based cartilaginous tissue with superior characteristics. Controversial results with reference to MSCs that were cultured under different hypoxic levels, mainly in 2D culturing settings combined with or without other biochemical stimulus factors, prompted our team to study the role of hypoxia on MSCs chondrogenic differentiation within an absolute 3D environment. Specifically, we used 3D-printed honeycomb-like PCL matrices seeded with ADMSCs in the presence or absence of TGF and cultured with a prototype 3D cell culture device, which was previously shown to favor nutrient/oxygen supply, cell adhesion, and infiltration within scaffolds. These conditions resulted in high-quality hyaline cartilage that was distributed uniformly within scaffolds. The presence of the TGF medium was necessary to successfully produce cartilaginous tissues with superior molecular and increased biomechanical properties. Despite hypoxia's beneficial effect, it was overall not enough to fully differentiate ADMSCs or even promote cell expansion within 3D scaffolds alone.

Antibacterial effect and tetracycline release of poly(Ɛ-caprolactone) matrices obtained by iodine polymerization

The development of devices to controlled the release of drugs are in constant technological innovation. The aim is to improve the release of drugs on target areas. Poly (ε-caprolactone) (PCL) has been widely investigated because of degradation rate, biocompatibility, availability, no toxicity, cost and good adhesion to a large number of drugs. Thus, in the present study was associated polymer PCL with antibiotics tetracycline as local delivery system. PCL was obtained by ring-opening polymerization of monomer Ɛ-caprolactone (Ɛ-CL). The samples were characterized by fourier transformed infrared (FTIR), differential scanning calorimetric (DSC), thermogravimetric analyses (TGA) and X-ray diffraction analysis (X-rays). Likewise, was investigated antimicrobial activity against gram-positive bacteria (S. aureus) and gram-negative bacteria (E. coli, P. mirabilis, P. aeruginosa and K. pneumoniae). According to the results, the antibiotics tetracycline has been successfully incorporated to PCL matrices. They release tetracycline in the ideal rates and shows antibacterial activity. So, this material has a potential to been used in implants for drug release.

Development of hot-melt extruded drug/polymer matrices for sustained delivery of meloxicam

For effective resolution of regional subacute inflammation and prevention of biofouling formation, we have developed a polymeric implant that can release meloxicam, a selective cyclooxygenase (COX)-2 inhibitor, in a sustained manner. Meloxicam-loaded polymer matrices were produced by hot-melt extrusion, with commercially available biocompatible polymers, poly(ε-caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), and poly(ethylene vinyl acetate) (EVA). PLGA and EVA had a limited control over the drug release rate partly due to the acidic microenvironment and hydrophobicity, respectively. PCL allowed for sustained release of meloxicam over two weeks and was used as a carrier of meloxicam. Solid-state and image analyses indicated that the PCL matrices encapsulated meloxicam in crystalline clusters, which dissolved in aqueous medium and generated pores for subsequent drug release. The subcutaneously implanted meloxicam-loaded PCL matrices in rats showed pharmacokinetic profiles consistent with their in vitro release kinetics, where higher drug loading led to faster drug release. This study finds that the choice of polymer platform is crucial to continuous release of meloxicam and the drug release rate can be controlled by the amount of drug loaded in the polymer matrices.

Breathable Materials and Hybrid Nanocomposites with Antimicrobial Activity Based on Porous Poly(ε‐Caprolactone) Obtained via Environmental Crazing

AbstractStructural modification of poly(ε‐caprolactone) (PCL) allows the fabrication of new functional materials obtained via the PCL films/fibers stretching in ethanol by the crazing mechanism. Atomic force microscopy, X‐ray scattering, and differential scanning calorimetry are employed to study the evolution of PCL structure. It is shown that ethanol plasticizes the polymer being deformed, and the stretching of PCL films/fibers occurs with formation of a fibrillar‐porous structure in the interlamellar space. The obtained porous matrices have pore size below 50 nm and bulk porosities of 28% and 48% for fibers and films, respectively. Thermal stabilization of the PCL films’ porous structure made it possible to obtain breathable materials with a vapor permeability of 625–652 g m−2 per day. The resulting porous PCL fibers and films can be used as matrices for the incorporation of useful additives and preparation of functional nanocomposites (NCs), biodegradable surgical suture, packaging, covering, and textile vapor‐permeable materials. Hybrid NCs with antibacterial and fungicidal activities are obtained on the basis of the porous PCL matrices and functional components (5% silver, 1% brilliant green, 28% Betadine, etc.) incorporated into them.

Photochemical transformation of diketone dopants in polyester matrices: Effect of dopants concentration and polyester structure on changes in molecular characteristics and hydrolysis of the matrices

Photochemical transformations of photoactive diketone derivatives, 1,2-diphenylethane-1,2-dione (benzil, BZ) and 1,4-bis(benzoylcarbonyl)benzene (bisbenzil, BIS), and the effects of their transformations on changes in the molecular characteristics and hydrolytic properties of poly(ε-caprolactone) (PCL) and polylactide (PLA) matrices are reported. Studies were performed in a broad dopant concentration range of 0.2–7.5 wt%. Structural changes were observed by FTIR spectroscopy. FTIR spectroscopy proved the progressive transformation of BZ to benzoyl peroxides and, in the case of PCL, the formation of polar groups. Changes in molecular characteristics were observed in GPC traces. Irradiation of the doped polymer films at λ > 400 nm under an air atmosphere resulted mainly in the degradation of the polymer matrices. Additionally, high dopant concentrations in PCL led to partially crosslinked structures with gel contents up to 15%. The photochemical transformation of dopants had a large impact on the PCL matrices compared to that of the PLA matrices. A subsequent hydrolysis process was investigated by determining the extractable products as well as using GPC. Hydrolysis of irradiated PCL samples showed a significant acceleration of hydrolysis compared to that of nonirradiated samples. Furthermore, the hydrolysis rate gradually increased with increasing dopant concentration. The PCL crosslinking and degradation is adjustable by the type of dopant, concentration of dopant and intensity of light during irradiation of PCL. In contrast, a photochemical pretreatment had no observable effect on the hydrolysis of PLA under the investigated conditions.

Development and characterization of a new cork-based material

The use of cork in polymers is an effective approach to develop new sustainable materials, with the current challenges facing the world regarding on the environmental impact of synthetic polymers. Cork granules are delivered as waste by the industry preparing coating plate and cork ventures. These granules can be used in the preparation of composites, to the reason of their low density. This work presents the preparation of biocomposites resulting from the combination of the poly (ε-caprolactone) with cork (10–30 wt and maleic anhydride-grafted polyethylene (MAPE) as compatibiliezr agent. A twin-screw extruder and injection molding are used in order to obtain the tensile samples. The obtained composites were characterized for mechanical and thermal properties, morphology, and water absorption behavior. All composites demonstrated a better dispersion of cork and a solid interfacial bond between the cork particles and the PCL matrices as confirm by SEM. The Young's modulus values of the composites were little affected by a rate of 10% of fillers; but for higher loads, a significant decrease in this parameter was observed, resulting in more flexible materials. The treatment delayed thermal degradation. These attractive performances reveal that sustainable cork based materials proposed in this work could be a good alternative to traditional and could find applications in a number of domains.

Laser-triggered shape memory based on thermoplastic and thermoset matrices with silver nanoparticles

Stimuli responsive shape memory polymers (SMPs) are challenging theme as the materials not only shows the shape changing under the traditional thermal treatment but also under other external stimuli. The present work proposes an in-situ ring opening polymerization (ROP) to combine the thermoset hard segment, i.e. polybenzoxazine, and thermoplastic soft segment, i.e. polycaprolactone and silver nanoparticles (AgNPs) as the laser-trigger. The melamine-based benzoxazine (mBz) plays its important role in allowing the ROP to create the thermoset polybenzoxazine network (PmBz) as well as providing many hydroxyl groups to further conjugation with thermoplastic polycaprolactone matrices (PCL). The AgNPs are the good alternative to select based on their function to be expressed by the very low energy (violet laser at 408 nm, 780 mW) and the surface modifiable with disulfide polycaprolactone (SS-PCL) hybridization for the highly miscible and readily dispersible in PCL matrices. The present work, for the first time, proposes light-triggered SMPs via simple molecular design and synthesis based on an in-situ ROP to combine PmBz thermoset networks and PCL thermoplastic matrices with the AgNPs-PCL to provide the light-thermal responsive function.

Poly (Butylene Adipate-Co-Terephthalate) and Poly (Ɛ-Caprolactone) and Their Bionanocomposites with Cellulose Nanocrystals: Thermo-Mechanical Properties and Cell Viability Study

Although nanocomposites have recently attracted special interest in the tissue engineering area, due to their potential to reinforce scaffolds for hard tissues applications, a number of variables must be set prior to any clinical application. This manuscript addresses the evaluation of thermo-mechanical properties and of cell proliferation of cellulose nanocrystals (CNC), poly(butylene adipate-co-terephthalate) (PBAT), poly(ε-caprolactone) (PCL) films and their bionanocomposites with 2 wt% of CNC obtained by casting technique. Cellulose nanocrystals extracted from Balsa wood by acid hydrolysis were used as a reinforcing phase in PBAT and PCL matrix films. The films and pure CNC at different concentrations were cultured with osteoblasts MG-63 and the cell proliferation was assessed by AlamarBlue® assay. The thermal-mechanical properties of the films were evaluated by dynamic-mechanical thermal analysis (DMTA). It was found by DMTA that the CNC acted as reinforcing agent. The addition of CNCs in the PBAT and PCL matrices induced higher storage moduli due to the reinforcement effects of CNCs. The cell viability results showed that neat CNC favored osteoblast proliferation and both PBAT and PCL films incorporated with CNC were biocompatible and supported cell proliferation along time. The nature of the polymeric matrix or the presence of CNC practically did not affect the cell proliferation, confirming they have no in vitro toxicity. Such features make cellulose nanocrystals a suitable candidate for the reinforcement of biodegradable scaffolds for tissue engineering and biomedical applications.

Controlled delivery of the antiprotozoal agent (tinidazole) from intravaginal polymer matrices for treatment of the sexually transmitted infection, trichomoniasis

Microporous polymeric matrices prepared from poly(ɛ-caprolactone) [PCL] were evaluated for controlled vaginal delivery of the antiprotozoal agent (tinidazole) in the treatment of the sexually transmitted infection, trichomoniasis. The matrices were produced by rapidly cooling co-solutions of PCL and tinidazole in acetone to −80 °C to induce crystallisation and hardening of the polymer. Tinidazole incorporation in the matrices increased from 1.4 to 3.9% (w/w), when the drug concentration in the starting PCL solution was raised from 10 to 20% (w/w), giving rise to drug loading efficiencies up to 20%. Rapid ‘burst release’ of 30% of the tinidazole content was recorded over 24 h when the PCL matrices were immersed in simulated vaginal fluid. Gradual drug release occurred over the next 6 days resulting in delivery of around 50% of the tinidazole load by day 7 with the released drug retaining antiprotozoal activity at levels almost 50% that of the ‘non-formulated’ drug in solution form. Basic modelling predicted that the concentration of tinidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration against Trichomonas vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of antiprotozoal agents in the treatment and prevention of sexually transmitted infections.

Electrospun poly(ε-caprolactone) matrices containing silver sulfadiazine complexed with β-cyclodextrin as a new pharmaceutical dosage form to wound healing: preliminary physicochemical and biological evaluation.

Cooperation between researchers in the areas of medical, pharmaceutical and materials science has facilitated the development of pharmaceutical dosage forms that elicit therapeutic effects and protective action with a single product. In addition to optimizing pharmacologic action, such dosage forms provide greater patient comfort and increase success and treatment compliance. In the present work, we prepared semipermeable bioactive electrospun fibers for use as wound dressings containing silver sulfadiazine complexed with β-cyclodextrin in a poly(Ɛ-caprolactone) nanofiber matrix aiming to reduce the direct contact between silver and skin and to modulate the drug release. Wound dressings were prepared by electrospinning, and were subjected to ATR-FT-IR and TG/DTG assays to evaluate drug stability. The hydrophilicity of the fibrous nanostructure in water and PBS buffer was studied by goniometry. Electrospun fibers permeability and swelling capacity were assessed, and a dissolution test was performed. In vitro biological tests were realized to investigate the biological compatibility and antimicrobial activity. We obtained flexible matrices that were each approximately 1.0 g in weight. The electrospun fibers were shown to be semipermeable, with water vapor transmission and swelling indexes compatible with the proposed objective. The hydrophilicity was moderate. Matrices containing pure drug modulated drug release adequately during 24 h but presented a high hemolytic index. Complexation promoted a decrease in the hemolytic index and in the drug release but did not negatively impact antimicrobial activity. The drug was released predominantly by diffusion. These results indicate that electrospun PCL matrices containing β-cyclodextrin/silver sulfadiazine inclusion complexes are a promising pharmaceutical dosage form for wound healing.

Sustained Simultaneous Delivery of Metronidazole and Doxycycline From Polycaprolactone Matrices Designed for Intravaginal Treatment of Pelvic Inflammatory Disease

Poly(ɛ-caprolactone) (PCL) intravaginal matrices were produced for local delivery of a combination of antibacterials, by rapidly cooling a mixture of drug powders dispersed in PCL solution. Matrices loaded with different combinations of metronidazole (10%, 15%, and 20% w/w) and doxycycline (10% w/w) were evaluated in vitro for release behavior and antibacterial activity. Rapid “burst release” of 8%-15% of the doxycycline content and 31%-37% of the metronidazole content occurred within 24 h when matrices were immersed in simulated vaginal fluid at 37°C. The remaining drug was extracted gradually over 14 days to a maximum of 65%-73% for doxycycline and 62%-71% for metronidazole. High levels of antibacterial activity up to 89%-91% against Gardnerella vaginalis and 84%-92% against Neisseria gonorrhoeae were recorded in vitro for release media collected on day 14, compared to “nonformulated” metronidazole and doxycycline solutions. Based on the in vitro data, the minimum levels of doxycycline and metronidazole released from PCL matrices in the form of intravaginal rings into vaginal fluid in vivo were predicted to exceed the minimum inhibitory concentrations for N. gonorrhea (reported range 0.5-4.0 μg/mL) and G. vaginalis (reported range 2-12.8 μg/mL) respectively, which are 2 of the major causative agents for pelvic inflammatory disease.

Nano-silver stabilized Pickering emulsions and their antimicrobial electrospun fibrous matrices

Efficacy of nano-silver for its antimicrobial properties is proven and a significant academic and industrial research has been devoted on use of nano-silver in applications including filtration, textiles, biomedical and others. In present work, in situ synthesized nano-silver was used as a Pickering stabilizer for water-in-oil emulsion of poly(ε-caprolactone) (PCL) which upon electrospinning led to formation of nano-silver containing fibrous matrix suitable as wound dressing. Nano-silver was synthetized in high yield using silver nitrate (AgNO3) as precursor and two different reductants viz. sodium borohydride (NaBH4) and poly(ethylene oxide) (PEO) in aqueous media which formed the dispersed phase of the emulsion. PCL solution in toluene comprised the continuous phase. Concentration of AgNO3 and PCL was varied to study the effect on emulsion’s stability. Nano-silver formed using PEO as reducing agent led to formation of highly stable emulsions in comparison to those formed using NaBH4. Emulsions thus produced were reproducibly electrospun to generate uniform fibrous matrices of desired fiber fineness. Nano-silver containing PCL matrices were assessed for their role as wound dressing by examining the antimicrobial properties.

Bioactive PCL matrices with a range of structural & rheological properties

Safer pharmaceutical and medical device excipients are being sought as alternatives to polyvinyl polymers that are commonly plasticised by carcinogenic phthalates. This paper demonstrates a biodegradable and non-toxic bioactive polymer matrix that can be easily modified through plasticiser addition in the presence of low dosage active pharmaceutical ingredient (API). Poly(ε-caprolactone) (PCL) was selected as an alternative polymer to polyvinyls as it is biodegradable and has high amorphous content, which improves drug solubility. Bulk PCL and various blends with 5 and 25% polyethylene glycol (PEG, a plasticiser and pore former) and 5% nalidixic acid (NA, the API) were processed using extrusion and pressed into plaques. The resultant material properties were investigated in terms of microscopic, morphological and topographical modification. No evidence of miscibility was found by IR. The rheology and contact angle of the matrix could be easily manipulated through the addition of PEG. Increased loading of PEG to 25% (w/w) caused a 10-fold increase in the melt flow index, a similar increase in the elongational viscosity, and a contact angle decrease of 10°, indicating that the resultant fluid was becoming more Newtonian. It was concluded that the structural and rheological properties of the blend, while easily modified through the addition of PEG, were unaffected by the monodispersion of the API, nalidixic acid.

Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis

Microporous, poly (ɛ-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis.

Impact Toughness and Ductility Enhancement of Biodegradable Poly(lactic acid)/Poly(ε-caprolactone) Blends via Addition of Glycidyl Methacrylate

Poly(lactic acid) (PLA)/poly(ε-caprolactone) (PCL) blends were prepared via melt blending technique. Glycidyl methacrylate (GMA) was added as reactive compatibilizer to improve the interfacial adhesion between immiscible phases of PLA and PCL matrices. Tensile test revealed that optimum in elongation at break of approximately 327% achieved when GMA loading was up to 3wt%. Slight drop in tensile strength and tensile modulus at optimum ratio suggested that the blends were tuned to be deformable. Flexural studies showed slight drop in flexural strength and modulus when GMA wt% increases as a result of improved flexibility by finer dispersion of PCL in PLA matrix. Besides, incorporation of GMA in the blends remarkably improved the impact strength. Highest impact strength was achieved (160% compared to pure PLA/PCL blend) when GMA loading was up to 3 wt%. SEM analysis revealed improved interfacial adhesion between PLA/PCL blends in the presence of GMA. Finer dispersion and smooth surface of the specimens were noted as GMA loading increases, indicating that addition of GMA eventually improved the interfacial compatibility of the nonmiscible blend.

Polyphosphazene functionalized polyester fiber matrices for tendon tissue engineering: in vitro evaluation with human mesenchymal stem cells

Poly[(ethyl alanato)1(p-methyl phenoxy)1] phosphazene (PNEA-mPh) was used to modify the surface of electrospun poly(ε-caprolactone) (PCL) nanofiber matrices having an average fiber diameter of 3000 ± 1700 nm for the purpose of tendon tissue engineering and augmentation. This study reports the effect of polyphosphazene surface functionalization on human mesenchymal stem cell (hMSC) adhesion, cell-construct infiltration, proliferation and tendon differentiation, as well as long term cellular construct mechanical properties. PCL fiber matrices functionalized with PNEA-mPh acquired a rougher surface morphology and led to enhanced cell adhesion as well as superior cell-construct infiltration when compared to smooth PCL fiber matrices. Long-term in vitro hMSC cultures on both fiber matrices were able to produce clinically relevant moduli. Both fibrous constructs expressed scleraxis, an early tendon differentiation marker, and a bimodal peak in expression of the late tendon differentiation marker tenomodulin, a pattern that was not observed in PCL thin film controls. Functionalized matrices achieved a more prominent tenogenic differentiation, possessing greater tenomodulin expression and superior phenotypic maturity according to the ratio of collagen I to collagen III expression. These findings indicate that PNEA-mPh functionalization is an efficient method for improving cell interactions with electrospun PCL matrices for the purpose of tendon repair.

MgCHA particles dispersion in porous PCL scaffolds:in vitromineralization andin vivobone formation

In this work, we focus on the in vitro and in vivo response of composite scaffolds obtained by incorporating Mg,CO3 -doped hydroxyapatite (HA) particles in poly(ε-caprolactone) (PCL) porous matrices. After a complete analysis of chemical and physical properties of synthesized particles (i.e. SEM/EDS, DSC, XRD and FTIR), we demonstrate that the Mg,CO3 doping influences the surface wettability with implications upon cell-material interaction and new bone formation mechanisms. In particular, ion substitution in apatite crystals positively influences the early in vitro cellular response of human mesenchymal stem cells (hMSCs), i.e. adhesion and proliferation, and promotes an extensive mineralization of the scaffold in osteogenic medium, thus conforming to a more faithful reproduction of the native bone environment than undoped HA particles, used as control in PCL matrices. Furthermore, we demonstrate that Mg,CO3 -doped HA in PCL scaffolds support the in vivo cellular response by inducing neo-bone formation as early as 2 months post-implantation, and abundant mature bone tissue at the sixth month, with a lamellar structure and completely formed bone marrow. Together, these results indicate that Mg(2+) and CO3 (2-) ion substitution in HA particles enhances the scaffold properties, providing the right chemical signals to combine with morphological requirements (i.e. pore size, shape and interconnectivity) to drive osteogenic response in scaffold-aided bone regeneration.

Design and Optimization of Polyphosphazene Functionalized Fiber Matrices for Soft Tissue Regeneration

Electrospun polycaprolactone nanofiber matrices surface functionalized with poly[(ethyl alanato), (p-methyl phenoxy),] phosphazene were fabricated for the purpose of soft skeletal tissue regeneration. This preliminary study reports the effect of fiber diameter and polyphosphazene surface functionalization on significant scaffold properties such as morphology, surface hydrophilicity, porosity, tensile properties, human mesenchymal stem cell adhesion and proliferation. Six fiber matrices comprised of average fiber diameters in the range of 400-500, 900-1000, 1400-1500, 1900-2000, 2900-3000 and 3900-4000 nm were considered for primary evaluation. After achieving the greatest proliferation while maintaining moderate tensile modulus, matrices in the diameter range of 2900-3000 nm were selected to examine the effect of coating with 1%, 2% and 3% (weight/volume) polyphosphazene solutions. Polyphosphazene functionalization resulted in rougher surfaces that correlated with coating solution concentration. Analytical techniques such as energy dispersive X-ray analysis, Fourier transform infrared spectroscopy, elemental analysis, differential scanning calorimetry, water contact angle goniometry and confocal microscopy confirmed the presence of polyphosphazene and its distribution on the functionalized fiber matrices. Functionalization achieved through 2% polymer solutions did not affect average pore diameter, tensile modulus, suture retention strength or cell proliferation compared to PCL controls. Surface polyphosphazene functionalization significantly improved the matrix hydrophilicity evidenced through decreased water contact angle of PCL matrices from 130 degrees to 97 degrees. Further, enhanced total protein synthesis by cells during in vitro culture was seen on 2% PPHOS functionalized matrices over controls. Improving PCL matrix hydrophilicity via proposed surface functionalization may be an efficient method to improve cell-PCL matrix interactions.