Tissue engineering scaffolds of mesoporous magnesium silicate and poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) composite

Mesoporous magnesium silicate (m-MS) and poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) composite scaffolds were fabricated by solvent-casting and particulate leaching method. The results suggested that the incorporation of m-MS into PCL–PEG–PCL could significantly improve the water adsorption of the m-MS/PCL–PEG–PCL composite (m-MPC) scaffolds. The in vitro degradation behavior of m-MPC scaffolds were determined by testing weight loss of the scaffolds after soaking into phosphate buffered saline (PBS), and the result showed that the degradation of m-MPC scaffolds was obviously enhanced by addition of m-MS into PCL–PEG–PCL after soaking for 10 weeks. Proliferation of MG63 cells on m-MPC was significantly higher than MPC scaffolds at 4 and 7 days. ALP activity on the m-MPC was obviously higher than MPC scaffolds at 7 days, revealing that m-MPC could promote cell differentiation. Histological evaluation showed that the introduction of m-MS into PCL–PEG–PCL enhanced the efficiency of new bone formation when the m-MPC scaffolds implanted into bone defect of rabbits. The results suggested that the inorganic/organic composite of m-MS and PCL–PEG–PCL scaffolds exhibited good biocompatibility, degradability and osteogenesis.     

Fabrication and characterization of injection molded poly (ε-caprolactone) and poly (ε-caprolactone)/hydroxyapatite scaffolds for tissue engineering

In this study, poly(ε-caprolactone) (PCL)/sodium chloride (NaCl), PCL/poly(ethylene oxide) (PEO)/NaCl and PCL/PEO/NaCl/hydroxyapatite (HA) composites were injection molded and characterized. The water soluble and sacrificial polymer, PEO, and NaCl particulates in the composites were leached by deionized water to produce porous and interconnected microstructures. The effect of leaching time on porosity, and residual contents of NaCl and NaCl/HA, as well as the effect of HA addition on mechanical properties was investigated. In addition, the biocompatibility was observed via seeding human mesenchymal stem cells (hMSCs) on PCL and PCL/HA scaffolds.The results showed that the leaching time depends on the spatial distribution of sacrificial PEO phase and NaCl particulates. The addition of HA has significantly improved the elastic (E′) and loss moduli (E″) of PCL/HA scaffolds. Human MSCs were observed to have attached and proliferated on both PCL and PCL/HA scaffolds. Taken together, the molded PCL and PCL/HA scaffolds could be good candidates as tissue engineering scaffolds. Additionally, injection molding would be a potential and high throughput technology to fabricate tissue scaffolds.     

Preparation and characterization of magnetic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) microspheres

In this article, nano-magnetite particles (ferrofluid, Fe₃O₄) were prepared by chemical co-deposition method. A series of biodegradable triblock poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymers were synthesized by ring-opening polymerization method from ε-caprolactone (ε-CL) initiated by poly(ethylene glycol) diol (PEG) using stannous octoate as catalyst. And the magnetic PCEC composite microspheres were prepared by solvent diffusion method. The properties of the ferrofluid, PCEC copolymer, and magnetic PCEC microspheres were studied in detail by SEM, VSM, XRD, Malvern Laser Particle Sizer, ¹H-NMR, GPC, and TG/DTG. Effects of macromolecular weight and concentration of polymer, and the time for ultrasound dispersion on properties of magnetic microspheres were also investigated. The obtained magnetic PCEC microspheres might have great potential application in targeted drug delivery system or cell separation. This work was financially supported by Chinese Key Basic Research Program (2004CB518800 and 2004CB518807), and Sichuan Key Project of Science and Technology (06(05SG022-021-02)). Qian ZY and Wang H did the even work with Gou ML, and are the co-first authors for this paper.     

Alkaline degradation study of linear and network poly(ε-caprolactone)

Alkaline hydrolysis of a polycaprolactone (PCL) network obtained by photopolymerization of a PCL macromer was investigated. The PCL macromer was obtained by the reaction of PCL diol with methacrylic anhydride. Degradation of PCL network is much faster than linear PCL; the weight loss rate is approximately constant until it reaches around 70%, which happens after approximately 60 h in PCL network and 600 h in linear PCL. Calorimetric results show no changes in crystallinity throughout degradation, suggesting that it takes place in the crystalline and amorphous phases simultaneously. Scanning electron microscopy microphotographs indicate that degradation is produced by a different erosion mechanism in both kinds of samples. The more hydrophilic network PCL would follow a bulk-erosion mechanism, whereas linear PCL would follow a surface-erosion mechanism. Mechanical testing of degraded samples shows a decline in mechanical properties due to changes in sample porosity as a consequence of the degradation process.     

Scaffolds of poly (ε-caprolactone) with whiskers of hydroxyapatite

Scaffolds of Poly (ε-caprolactone)/hydroxyapatite were produced and studied for tissue engineering applications. The materials were selected due to its biodegradability (PCL) and bioactivity (HA), and above all their biocompatibility toward the human tissue. The composites produced were characterized by SEM, XRD, and EDS. By analyzing these characterizations it was possible to obtain further information about the composition and morphology aspects of all portions of the composite scaffold.     

Non-conventional injection molding of poly(lactide) and poly(ε-caprolactone) intended for orthopedic applications

Biodegradable polymers such as poly(lactide) (PLA) and poly(epsilon-caprolactone) (PCL) are increasingly used in biomedical applications as temporary implants. However, melt processing of these materials in particular of PLA is difficult due to the temperature sensitivity. Within this study, PLA and PCL were injection molded conventionally and by using the process shear controled orientation in injection molding (SCORIM) in order to investigate the effect of processing parameters on the physical properties of the moldings. Therefore, flexural testing, differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), molecular weight (MW) and orientation measurements were performed. PLA showed high sensitivity to melt temperature. In the case of amorphous poly(DL-lactide), the molecular weight and subsequently the ductility is substantially reduced by processing at higher melt temperatures. In the case of crystallizable poly(L-lactide), higher melt temperatures and shear induced by the SCORIM process resulted in enhanced crystallinity, which compromised the mechanical properties. Generally, SCORIM processing improved the mechanical properties, in particular the ductility, by orientating the molecular structure. PCL was shown to be less sensitive to shear and temperature than PLA. Stress at yield and stiffness are more improved by SCORIM processing. However, the processing temperature in combination with the grade used proved to be influential for the mechanical properties of resulting moldings.     

Thermal behaviour of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) tri-block copolymers

Thermal behavior of poly(-caprolactone)-poly(ethylene glycol)-poly(-caprolactone) tri-block copolymers with different block lengths is examined. Thermal behavior of specimens crystallized under the isothermal and dynamic condition are characterized by DSC. Also WAXD and SAXS are employed to investigate the structure. Depending on the relative length of each block, tri-block copolymers can be classified into three groups: PCL dominant crystallization; PEG dominant crystallization; and the competing case. When the crystallization of PEG and PCL are competing, the crystallization of each block shows strong dependency on the thermal hystory of crystallization, leading to multiple melting and crystallization peaks. Also, the typical micro-phase separation of block copolymers seems to play an important role, competing with crystallization, especially under the dynamic crystallization condition.     

Nanocomposites of poly(ε-caprolactone) doped with titanium species

Organic–inorganic hybrid nanocomposites were prepared via in situ sol–gel process. The organic phase is a biodegradable polymer, poly(ε-caprolactone) (PCL), while the tetrabutyl titanate (TBT, Ti(OBu)₄) was used as inorganic precursor. Synthesis parameters like acidity medium and precursor amount were investigated in order to assess their influence on hybrid properties. The obtained nanocomposites were characterised by thermal analysis, spectroscopic techniques, transmission electronic microscopy (TEM) and X-ray diffraction to gather information on the structure of the nanocomposites. Mechanical properties and biodegradability were also evaluated. A reaction mechanism based on Fourier transform infrared spectroscopy and NMR results was proposed using methyl acetate as model compound. TEM micrographs of the nanocomposites show a fine good nanoparticles dispersion. Acidic conditions and 10 wt% of precursor lead to a nanocomposite with higher mechanical properties and biodegradability than PCL.     

Preparation and characterization of electrospun poly(ε-caprolactone)-poly(l-lactic acid) nanofiber tubes

Recently, attempts have been made to develop nanofiber tubes suitable for nerve regeneration made of biodegradable nanofibers. Among all polymeric nanofibers, poly(ε-caprolactone) (PCL) is distinctively known for better mechanical stability and poly(l-lactic acid) (PLLA) for relatively faster biodegradability. Our purpose of study is to investigate their blending compatibility and the ability to form nanofiber tubes via electrospinning. We electrospun the PCL–PLLA nanofiber tubular using different blend ratios of PCL–PLLA. The electrospun nanofibers were continuously deposited over high speed rotating mandrel to fabricate nanofiber tubes having inner diameter of 2 mm and the wall thickness of 55–65 μm. The diameters of nanofibers were between 715 and 860 nm. The morphologies of PCL–PLLA nanofiber tubes were examined under scanning electron microscope, and showed better structural stability and formability than the neat PLLA nanofibers. Fourier transform infrared spectroscopy study revealed that the PCL–PLLA blend nanofiber exhibited characteristic peaks of both PCL and PLLA and was composition-dependent. Raman and X-ray diffraction studies showed that the increasing PCL ratio in the PCL–PLLA blend increased crystallinity of PCL–PLLA blends. Differential scanning calorimetry revealed recrystallization peaks in PCL–PLLA blends ratios of 1:2 and 1:1. Based on characterization, the electrospun PCL–PLLA nanofiber tubes is considered to be a better candidate for further in vivo or in vitro investigation, and resolve biocompatibility issues in tissue engineering.     

Non-isothermal crystallization of poly(ε-caprolactone)-grafted multi-walled carbon nanotubes

Non-isothermal crystallization behavior of poly(ε-caprolactone) (PCL)-grafted multi-walled carbon nanotubes (MWNTs) was studied in order to determine the effects of functionalized MWNTs (f-MWNTs) on its crystallization behavior. Differential scanning calorimeter measurements showed that an introduction of f-MWNTs into the PCL molecules induced heterogeneous nucleation and the crystal growth process was significantly affected. X-ray diffraction showed a decrease in the crystallinity of composites with the addition of f-MWNTs in PCL, likely due to the occurrence of more heterogeneous nucleation induced by f-MWNTs in the samples. The activation energy for crystallization of PCL drastically reduced with the presence of 2 wt.% f-MWNTs in the samples and increased slightly with increasing content of f-MWNTs. A spherulite structure of PCL-grafted MWNTs with MWNTs at the center was developed, clearly indicating the nucleating action of MWNTs in the crystallization process. The experimental data were also analyzed using various kinetic models e.g., Avrami, Tobin, Ozawa, etc.     

Electrospun nanofibers composed of poly(ε-caprolactone) and polyethylenimine for tissue engineering applications

Poly(ε-caprolactone) (PCL) electrospun nanofibers have been reported as a scaffold for tissue engineering application. However, high hydrophobicity of PCL limits use of functional scaffold. In this study, PCL/polyethylenimine (PEI) blend electrospun nanofibers were prepared to overcome the limitation of PCL ones because the PEI as a cationic polymer can increase cell adhesion and can improve the electrospinnability of PCL. The structure, mechanical properties and biological activity of the PCL/PEI electrospun nanofibers were studied. The diameters of the PCL/PEI nanofibers ranged from 150.4 ± 33 to 220.4 ± 32 nm. The PCL/PEI nanofibers showed suitable mechanical properties with adequate porosity and increased hydrophilic behavior. The cell adhesion and cell proliferation of PCL nanofibers were increased by blending with PEI due to the hydrophilic properties of PEI.     

Fabrication and characterization of interconnected porous biodegradable poly(ε-caprolactone) load bearing scaffolds

In this study, poly(ε-caprolactone) (PCL)/poly(ethylene oxide) (PEO) (50:50 wt%) immiscible blend was used as a model system to investigate the feasibility of a novel solventless fabrication approach that combines cryomilling, compression molding and porogen leaching techniques to prepare interconnected porous scaffolds for tissue engineering. PCL was cryomilled with PEO to form blend powders. Compression molding was used to consolidate and anneal the cryomilled powders. Selective dissolution of the PEO with water resulted in interconnected porous scaffolds. Sodium chloride salt (NaCl) was subsequently added to cryomilled powder to increase the porosity of scaffolds. The prepared scaffolds had homogeneous pore structures, a porosity of ~50% which was increased by mixing salt with the blend (~70% for 60% wt% NaCl), and a compressive modulus and strength (ε = 10%) of 60 and 2.8 MPa, respectively. The results of the study confirm that this novel approach offers a viable alternative to fabricate scaffolds.     

Electrophoretic deposition of silicon-substituted hydroxyapatite/poly(ε-caprolactone) composite coatings

Silicon-substituted hydroxyapatite/poly(ε-caprolactone) composite coatings were prepared on titanium substrate by electrophoretic deposition in n-butanol and chloroform mixture. The effect of the concentration of poly(ε-caprolactone) in suspension on the morphology and the microstructure of coatings were investigated, furthermore, the thermal behavior and in vitro bioactivity were also investigated. The results show that the coarse and accidented silicon-substituted hydroxyapatite/poly(ε-caprolactone) composite coatings were obtained by electrophoretic deposition when the concentration of poly(ε-caprolactone) in suspension was 6–16 g/l. The adsorption of poly(ε-caprolactone) on the surface of Si–HA particles hinders the electrophoretic deposition of Si–HA. The shear-testing experiments indicated that the addition of poly(ε-caprolactone) in suspension is in favor of improving the bonding strength of the coatings. After immersion in simulated body fluid for 8 days, silicon-substituted hydroxyapatite/poly(ε-caprolactone) composite coatings have the ability to induce the bone-like apatite formation.     

Engineering of poly(ε-caprolactone) microcarriers to modulate protein encapsulation capability and release kinetic

Drug delivery applications using biodegradable polymeric microspheres are becoming an important means of delivering therapeutic agents. The aim of this work was to modulate the microporosity of poly(ε-caprolactone) (PCL) microcarriers to control protein loading capability and release profile. PCL microparticles loaded with BSA (bovine serum albumin) have been de novo synthesized with double emulsion solvent evaporation technique transferred and adapted for different polymer concentrations (1.7 and 3% w/v) and stabilizer present in the inner aqueous phase (0.05, 0.5 and 1% w/v). SEM (scanning electron microscope) and CLSM (confocal laser scanning microscope) analysis map the drug distribution in homogeneously distributed cavities inside the microspheres with dimensions that can be modulated by varying double emulsion process parameters. The inner structure of BSA-loaded microspheres is greatly affected by the surfactant concentration in the internal aqueous phase, while a slight influence of polymer concentration in the oil phase was observed. The surfactant concentration mainly determines microspheres morphology, as well as drug release kinetics, as confirmed by our in-vitro BSA release study. Moreover, the entrapped protein remained unaltered during the protein encapsulation process, retaining its bio-activity and structure, as shown through a dedicated gel chromatographic analytical method.     

Synthesis and characterization of biodegradable polyurethane based on poly(ε-caprolactone) and L-lysine ethyl ester diisocyanate

A biocompatible diisocyanate, lysine ethyl ester diisocyanate, was prepared. Afterwards, biodegradable polyurethane (PU) was synthesized by the stepgrowth polymerization of this diisocyanate with hydroxyl terminated poly(ε-caprolactone) in the presence of 1,4-butanediol as a chain-extender. The resulting PU was characterized by GPC, IR and DSC measurements. Its mechanical strength was found to increase with increasing the hard segment content. The PU microfiber meshes with high porosity were obtained by solution electrospinning technique. Their degradation behavior in the PBS and enzymatic solution was also investigated.     

Production and characterization of calcium phosphate (CaP) whisker-reinforced poly(ε-caprolactone) composites as bone regenerative

Calcium phosphate (CaP) whisker-reinforced poly(ε-caprolactone) (PCL) composites with various CaP contents (0, 5, 10, and 20 wt.%) were prepared by dispersing CaP whiskers in a PCL solution. To accomplish this, CaP whiskers were synthesized by treating tricalcium phosphate (TCP) powders in a hydrogen peroxide (H₂O₂) solution at 90 °C for 48 h. All the prepared composites showed well dispersed CaP whiskers in the PCL matrix without severe agglomeration. As the CaP content was increased from 0 to 20 wt.%, the ultimate tensile strength decreased from 13.2 ± 0.9 to 8.8 ± 0.4 MPa, while the elastic modulus increased significantly from 173 ± 21 to 334 ± 24 MPa. In addition, the addition of CaP whiskers to the PCL matrix improved the biocompatibility of the composites remarkably.     

Effect of accelerated aging on the viscoelastic properties of Elast-Eon™: A polyurethane with soft poly(dimethylsiloxane) and poly(hexamethylene oxide) segments

The viscoelastic properties of cylinders (diameter 5 mm, height 2.2 ± 0.2 mm) of Elast-Eon? 3, (a polyurethane with poly(dimethylsiloxane) and poly(hexamethylamine oxide) segments) were investigated before and after the specimens had undergone accelerated aging in saline solution at 70 °C for 38, 76 and 114 days (to simulate aging at 37 °C, for 1, 2 and 3 years, respectively). All sets of specimens were immersed in physiological saline solution at 37 °C during testing and the properties were measured using dynamic mechanical analysis (DMA). A sinusoidal cyclic compression of 40 N ± 5 N was applied over a frequency range, f, of 0.02–100 Hz. Values of the storage, E′, and loss, E″, moduli were found to depend on f; the dependence of E′ or E″ on the logarithm (base 10) of f was represented by a second-order polynomial. After accelerated aging, the E′ and E″ increased significantly (p < 0.05) and the specimens became darker and more opaque. SEM images showed that accelerated aging affected the surface morphology but ATR-FTIR spectra did not show any appreciable change in surface chemistry. DSC thermograms showed some slight changes in thermal properties following accelerated aging.     

Chemical and thermomechanical tailoring of the shape memory effect in poly(ε-caprolactone)-based systems

The thermally activated shape memory response of polymeric materials results from a combination of the material molecular architecture with the thermal/deformational history, or ‘programming’. In this work, we investigate the shape memory response of systems based on poly(ε-caprolactone) (PCL) so as to explore the adoption of proper chemical and thermomechanical tailoring routes. Cross-linked semicrystalline PCL-based materials are prepared by different molecular architectures starting from linear, three- and four-arms star PCL functionalized with methacrylate end groups, allowing to tune the melting temperature, T _m, ranging between 36 and 55 °C. The materials’ ability to display the shape memory is investigated by the application of proper thermomechanical cycles on specimens deformed at two different temperatures (23 and 65 °C, i.e. below and above the T _m, respectively). The shape memory response is studied under dynamic thermal conditions in thermally activated recovery tests, to identify the typical transformation temperatures, and under isothermal conditions at given recovery temperatures, to monitor shape recovery as a function of time. All the specimens are capable of full recovery on specific thermal ranges influenced by both melting and deformation temperatures. Specimens deformed above T _m are able to recover the whole deformation in a very narrow temperature region close to T _m, while those deformed at room temperature display broader recovery processes, those onset at about 30 °C. Isothermal tests reveal that when the deformed material is subjected to a constant recovery temperature, the amount of recovered strain and the time required strongly depend on the particular combination of melting temperature, deformation temperature and recovery temperature.     

Microencapsulation of cytarabine using poly(ethylene glycol)–poly(ε-caprolactone) diblock copolymers as surfactant agents

Background: The high water solubility and the low molecular weight of cytarabine (Ara-C) are major obstacles against its particulate formulation as a result of its low affinity to the commonly used hydrophobic polymers. Methods: Biodegradable cytarabine loaded-microparticles (Ara-C MPs) were elaborated using poly(?-caprolactone) (PCL) and monomethoxy polyethylene glycol (mPEG)–PCL diblock copolymer in order to increase the hydrophilicity of the polymeric matrix. For this purpose, a series of mPEG–PCL diblock copolymers with different PCL block lengths were synthesized. Compositions and molecular weights of obtained copolymers were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, size exclusion chromatography, and size exclusion chromatography–multi-angle laser light scattering. Ara-C MPs were prepared by double emulsion-solvent evaporation method. The effects of varying PCL block lengths on microparticle encapsulation efficiency, size, and zeta potential were evaluated. Results: Increasing the PCL block lengths of copolymers substantially increased the Ara-C encapsulation efficiency and the microparticle size but it decreased their zeta potential. Microparticles were spherical in shape, with a smooth surface and composed of homogenously distributed Ara-C-containing aqueous domains in the polymer matrix. The in vitro drug release kinetics of the optimized microparticles showed a hyperbolic profile with an initial burst release. Conclusion: These results showed the important role of the amphiphilic diblock copolymers as stabilizing agent in the encapsulation of Ara-C in PCL microparticles, suggesting their potential use for the microparticulate formulations of other small hydrophilic bioactive molecules.     

Electrospun fibrous scaffold of hydroxyapatite/poly (ε-caprolactone) for bone regeneration

Development of fibrous scaffold of hydroxyapatite/biopolymer nanocomposite offers great potential in the field of bone regeneration and tissue engineering. Hydroxyapatite (HA)/poly (ε-caprolactone) (PCL) fibrous scaffolds were successfully prepared by electrospinning dopes containing HA and PCL in this work. It was found that pre-treating HA with γ-glycioxypropyltrimethoxysilane (A-187) was effective in improving HA dispersion both in solutions and in a PCL matrix. Mechanical properties of the scaffolds were greatly enhanced by the filling of A187-HA. The bioactivity of PCL was remarkably improved by the addition of HA and A187-HA. Fibroblasts and osteoblasts were seeded on scaffolds to evaluate the effect of A-187 on biocompatibility of HA/PCL composites. Based on this study, good dispersion of HA in PCL matrix was granted by pretreatment of HA with A-187 and A187-HA/PCL fibrous scaffolds were obtained by electrospinning. These results demonstrated that the scaffolds may possess improved mechanical performance and good bioactivity due to A187-HA incorporation.