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.     

Differentiation of human adipose-derived stem cells seeded on mineralized electrospun co-axial poly(ε-caprolactone) (PCL)/gelatin nanofibers

Mineralized poly(ε-caprolactone)/gelatin core–shell nanofibers were prepared via co-axial electrospinning and subsequent incubation in biomimetic simulated body fluid containing ten times the calcium and phosphate ion concentrations found in human blood plasma. The deposition of calcium phosphate on the nanofiber surfaces was investigated through scanning electronic microscopy and X-ray diffraction. Energy dispersive spectroscopy results indicated that calcium-deficient hydroxyapatite had grown on the fibers. Fourier transform infrared spectroscopy analysis suggested the presence of hydroxyl-carbonate-apatite. The results of a viability assay (MTT) and alkaline phosphatase activity analysis suggested that these mineralized matrices promote osteogenic differentiation of human adipose-derived stem cells (hASCs) when cultured in an osteogenic medium and have the potential to be used as a scaffold in bone tissue engineering. hASCs cultured in the presence of nanofibers in endothelial differentiation medium showed lower rates of proliferation than cells cultured without the nanofibers. However, endothelial cell markers were detected in cells cultured in the presence of nanofibers in endothelial differentiation medium.     

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.     

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.     

Fabrication of three-dimensional poly(ε-caprolactone) scaffolds with hierarchical pore structures for tissue engineering

The physical properties of tissue engineering scaffolds such as microstructures play important roles in controlling cellular behaviors and neotissue formation. Among them, the pore size stands out as a key determinant factor. In the present study, we aimed to fabricate porous scaffolds with pre-defined hierarchical pore sizes, followed by examining cell growth in these scaffolds. This hierarchical porous microstructure was implemented via integrating different pore-generating methodologies, including salt leaching and thermal induced phase separation (TIPS). Specifically, large (L, 200–300 μm), medium (M, 40–50 μm) and small (S, < 10 μm) pores were able to be generated. As such, three kinds of porous scaffolds with a similar porosity of ~ 90% creating pores of either two (LS or MS) or three (LMS) different sizes were successfully prepared. The number fractions of different pores in these scaffolds were determined to confirm the hierarchical organization of pores. It was found that the interconnectivity varied due to the different pore structures. Besides, these scaffolds demonstrated similar compressive moduli under dry and hydrated states. The adhesion, proliferation, and spatial distribution of human fibroblasts within the scaffolds during a 14-day culture were evaluated with MTT assay and fluorescence microscopy. While all three scaffolds well supported the cell attachment and proliferation, the best cell spatial distribution inside scaffolds was achieved with LMS, implicating that such a controlled hierarchical microstructure would be advantageous in tissue engineering applications.     

Biodegradation trend of poly(ε-caprolactone) and nanocomposites

PCL nanocomposites based on two organically modified montmorillonites at 5% clay loading were biodegraded in a mature compost. All samples showed an effective degradation in compost but nanoclays were found to partially delay the process. Biodegradation carried out by microorganisms isolated from the compost showed that the bacterium Bacillus licheniformis was able to degrade the studied systems without considerable differences in the polymer degradation trend due to the presence of nanoclays.     

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.     

Assessment of bone regeneration of a tissue-engineered bone complex using human dental pulp stem cells/poly(ε-caprolactone)-biphasic calcium phosphate scaffold constructs in rabbit calvarial defects

The objective of the present study was to investigate the effect of a fabricated combination of poly-?-caprolactone (PCL)–biphasic calcium phosphate (BCP) with the modified melt stretching and multilayer deposition (mMSMD) technique on human dental pulp stem cell (hDPSC) differentiation to be osteogenic like cells for bone regeneration of calvarial defects in rabbit models. hDPSCs extracted from human third molars were seeded onto mMSMD PCL-BCP scaffolds and the osteogenic gene expression was tested prior to implantation in vivo. Two standardized 11?mm in diameter circular calvarial defects were created in 18 adult male New Zealand white rabbits. The rabbits were divided into 4 groups: (1) hDPSCs seeded in mMSMD PCL-BCP scaffolds; (2) mMSMD PCL-BCP scaffolds alone, (3) empty defects and (4) autogenous bone (n?=?3 site/time point/groups). After two, four and eight weeks after the operation, the specimens were harvested for micro-CT including histological and histomorphometric analysis. The explicit results presented an interesting view of the bioengineered constructs of hDPSCs in PCL-BCP scaffolds that increased the newly formed bone compared to the empty defect and scaffold alone groups. The results demonstrated that hDPSCs combined with mMSMD PCL-BCP scaffolds may be an augmentation material for bony defect.     

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.     

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.     

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.     

Osteoblastic cells culture on electrospun poly(ε-caprolacton) scaffolds incorporating amphiphilic PEG–POSS telechelic

In this work, novel poly(ε-caprolactone) (PCL) fibrous membranes incorporating amphiphilic polyhedral oligosilsesquioxane (POSS) telechelic (PEG–POSS telechelic) were prepared via electrospinning. The unique microstructure, morphology, thermal stability of the resulting PCL/PEG–POSS telechelic electrospun nanowebs were investigated by X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis, respectively. The addition of amphiphilic PEG–POSS telechelic strongly influenced the fiber diameters, microstructures of the resultant PCL/PEG–POSS telechelic nanofibers, compared to pure PCL nanofibers. The potential biomedical applications of such PEG–POSS telechelic nanowebs as a scaffolding material were also evaluated in vitro using mouse osteoblast-like MC3T3-E1 cells. The cell adhesion, spreading, and interaction behavior of pure PCL and PCL/PEG–POSS telechelic fibrous membranes were explored. It was found that electrospun PCL fibrous membranes incorporating amphiphilic PEG–POSS telechelic showed higher initial cell attachment than pure PCL due to the higher surface free energy of POSS siloxanes. Moreover, the obtained PCL/PEG–POSS telechelic fibrous scaffolds were found to be nontoxic and to maintain the good adhesion ratio between cells and surface (about ~93 %) after cell culturing for 24 h.     

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.     

The effect of carbon nanofibres on self-healing epoxy/poly(ε-caprolactone) blends

The effects of carbon nanofibres (CNFs) on the mechanical performance and healing efficiency of self-healing epoxy/poly(ε-caprolactone) (PCL) blends were examined. Through a simple polymer blending process, phase-separated epoxy/PCL blends were prepared, which showed self-healing capability upon thermal activation. The introduction of CNFs into a co-continuous phase-structured epoxy/PCL system, at the content of as low as 0.2 wt.%, has been found to yield combinational improvements in the flexural strength, tensile strength, toughness and hardness with no adverse effect on the self-healing performance. Significantly enhanced mechanical performance by low content of CNFs enables the development of epoxies and advanced polymer composites with longer service life and less maintenance.     

Bioactive glass–poly (ε-caprolactone) composite scaffolds with 3 dimensionally hierarchical pore networks

Hierarchically mesoporous–macroporous–giant-porous bioactive glass/poly ε-caprolactone (PCL) composite scaffolds were prepared using a combination of the sol–gel method, evaporation-induced self-assembly process in the presence of nonionic triblock copolymer, EO₁₀₀PO₆₅EO₁₀₀ (F127), as template, salt leaching method, and rapid prototyping techniques. F127 acts as a template, inducing the formation of mesopores, NaCl with sizes between 25 and 33 μm provides macro-pores after leaching, and rapid prototyping produces giant-pores. The structure and morphology of the scaffolds were characterized by the field emission scanning electron microscopy, transmission electron microscopy, and Hg porosimetry. The mechanical properties of the scaffolds were examined by the dynamic mechanical analysis. Their in vitro bioactivities were confirmed by immersing the scaffolds in simulated body fluid. Their biocompatibilities were also evaluated by culturing human bone marrow stromal cells on the scaffolds. The scaffolds show good molding capabilities, mechanical properties, 3 dimensionally well-interconnected pore structures, bioactivities, and biocompatibilities in vitro. Depending on the amount of NaCl, the scaffolds also show unique sponge-like properties, but still retain better mechanical properties than general salt leaching derived PCL scaffolds. All of the data provide good evidence that the obtained scaffolds possess excellent potential for applications in the fields of tissue engineering and drug storage.     

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.