The effect of hydrophilic chain length and iRGD on drug delivery from poly(ε-caprolactone)-poly(N-vinylpyrrolidone) nanoparticles

Poly(ε-caprolactone)-b-Poly(N-vinylpyrrolidone) (PCL-b-PVP) copolymers with different PVP block length were synthesized by xanthate-mediated reverse addition fragment transfer polymerization (RAFT) and the xanthate chain transfer agent on chain end was readily translated to hydroxy or aldehyde for conjugating various functional moieties, such as fluorescent dye, biotin hydrazine and tumor homing peptide iRGD. Thus, PCL-PVP nanoparticles were prepared by these functionalized PCL-b-PVP copolymers. Furthermore, paclitaxel-loaded PCL-PVP nanoparticles with satisfactory drug loading content (15%) and encapsulation efficiency (>90%) were obtained and used in?vitro and in?vivo antitumor examination. It was demonstrated that the length of PVP block had a significant influence on cytotoxicity, anti-BSA adsorption, circulation time, stealth behavior, biodistribution and antitumor activity for the nanoparticles. iRGD on PCL-PVP nanoparticle surface facilitated the nanoparticles to accumulate in tumor site and enhanced their penetration in tumor tissues, both of which improved the efficacy of paclitaxel-loaded nanoparticles in impeding tumor growth and prolonging the life time of H22 tumor-bearing mice.     

Studies on functionalization of poly(ε-caprolactone) by a cholesteryl moiety

Biodegradable polymers/oligomers based on ε-caprolactone (CL) were end-functionalized by a cholesteryl moiety. The functionalized polymers/oligomers, Chol-(CL) _n , were synthesized through ring-opening polymerization initiated by cholesterol with a hydroxyl group. The chemical structure of end-functionalized polymers/oligomers was confirmed by FT-IR and ¹H-NMR. The molecular weight of the functionalized polymer/oligomer increases with decreasing feed ratio of the initiator cholesterol to the monomer CL. Incorporation of the cholesteryl moiety to the polymer chain results in liquid crystallinity for the resultant oligomers when their molecular chains are not very long. The enzymatic degradation of the functionalized polymers/oligomers was investigated. The microsphere drug-delivery system of a functionalized oligomer was fabricated and its drug release properties were evaluated. The cell-culture experiment indicates the incorporation of cholesteryl moiety to the polymer chain results in improved cell proliferation.     

Adjustable degradation and drug release of a thermosensitive hydrogel based on a pendant cyclic ether modified poly(ε-caprolactone) and poly(ethylene glycol)co-polymer

The convenient and precise fabrication of drug–hydrogel formulations with satisfactory degradability and a well-controlled drug release profile are crucial factors for injectable hydrogel formulations in clinical applications. Here a new injectable thermosensitive hydrogel formed from poly(ε-caprolactone) (PCL)–poly(ethylene glycol)–poly(ε-caprolactone) amphiphilicco-polymers with 1,4,8-trioxa[4.6]spiro-9-undecanone (TOSUO) moieties incorporated in the poly(ε-caprolactone) (PCL)block (PECT) was constructed to provide a route to tailor the degradation and drug release behavior. The effect of hydrophilic cyclic ether moieties on the degradation of and drug release by PECT hydrogels were evaluated in vitro and in vivo. The results indicated that a freeze-dried powder of paclitaxel-loaded PECT nanoparticles rapidly dissolved in water at ambient temperature with slightly shaking and formed a stable injectable in situ drug–hydrogel formulation at body temperature, which is convenient for clinical operations because it avoids the need for pre-quenching or long-term incubation. The paclitaxel distribution was also more quantitative and homogeneous on entrapping paclitaxel in PECT nanoparticles. Further, the small number of pendant cyclic ether groups in PCL could decrease the cystallinity and hydrophobicity and, as a result, the in vitro and in vivo retention time of PECT hydrogels and the release of entrapped paclitaxel could be tuned from a few weeks to months by varying the amount of PTOSUO in the hydrophobic block. Significantly, paclitaxel-loaded PECT nanoparticles and free paclitaxel could be simultaneously released during the in vitro paclitaxel release from PECT hydrogels. A histopathological evaluation indicated that in vivo injected PECT hydrogels produced only a modest inflammatory response. Thus pendant cyclic ether modification of PCL could be an effective way to achieve the desired degradation and drug release profiles of amphiphilicco-polymer thermosensitive hydrogels and PECT hydrogels may be suitable for local drug delivery.     

Surface modification of poly(ε-caprolactone) using a dielectric barrier discharge in atmospheric pressure glow discharge mode

The role of roughening and functionalization processes involved in modifying the wettability of poly(ε-caprolactone) (PCL) after treatment by an atmospheric pressure glow discharge plasma is discussed. The change in the ratio of CO/C–O bonds is a significant factor influencing the wettability of PCL. As the contact angle decreases, the level of CO bonds tends to rise. Surface roughness alterations are the driving force for lasting increases in wettability, while the surface functional species are shorter lived. We can approximate from ageing that the increase in wettability for PCL after plasma treatment is 55–60% due to roughening and 40–45% due to surface functionalization for the plasma device investigated.     

Lamellar stack formation and degradative behaviors of hydrolytically degraded poly(ε-caprolactone) and poly(glycolide-ε-caprolactone) blended fibers

Electrospun fibrous mats have gained popularity in bioengineering over the past decade, but few papers detail their degradative mechanisms. To address this, blends of hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic PGA-PCL-PGA triblock copolymer were electrospun into aligned fibrous mats to assess the copolymers' mechanical and degradative properties. Increased hydrophilic triblock content led to enhanced morphological uniformity of fiber, tightening of fiber diameters, increased storage and Young's modulus, and decreased elongation. The corresponding decrease in hydrophobic PCL content led to faster hydrolytic degradation rate, as reflected by enhanced decrease in mass, molecular weight, and modulus loss at 25, 37, and 45°C. The activation energy for hydrolytic degradation for 15:85 PCL: triblock copolymer was approximately half that of 85:15 PCL: triblock copolymer. Detailed examination of fiber morphology and crystallinity revealed initial surface erosion followed by the evolution of crystalline lamellar stacks and bulk degradation at 37°C. Because of the high surface to volume and short diffusion length scale of the small diameter fibers, surface and bulk degradation may both contribute to the hydrolytic degradative behavior of these electrospun fibrous mats. Electrospun mats' distinct architecture that embodies high specific surface to volume and interfiber porous ultrastructures that lead to their unique degradative behaviors hold much potential for significant impact in the field of tissue engineering and controlled drug delivery.     

Synthesis and characterization of phosphoryl-choline-capped poly(ε-caprolactone)-poly(ethylene oxide) di-block co-polymers and its surface modification on polyurethanes

By sequential ring-opening polymerization of ethylene oxide and ε-caprolactone, poly(ethylene oxide) (PEO)-poly(ε-caprolactone) (PCL) di-block co-polymers with a phosphoryl choline (PC)-terminated group were synthesized. Using FT-IR, NMR, DSC and SEC, the products were characterized and the results proved the successful synthesis of functionalized di-block co-polymer. After blending the products with polyurethane (PU) and casting the result as film, the PEO segments migrated to the surface of the blend and the PCL segments acted as an anchor to fix the co-polymer on PU matrix, while the PEO segments provided PU the hydrophibility to prevent the fibrinogen adsorption on PU. This specific di-block co-polymer and the method of processing are hoped to be applied in the biomedical field to improve the biocompatibility of polymer materials.     

Phase transfer and characterization of poly(ε-caprolactone) and poly(L-lactide) microspheres

A method suitable for transfer of poly(ε-caprolactone) and poly(L-lactide) microspheres (synthesized by pseudoanionic dispersion polymerization of ε-caprolactone and L-lactide in heptane1,4-dioxane mixed solvent) from heptane to water was developed. This method consists of treating the microspheres with KOH-ethanol in the presence of surfactants (nonionic Triton X-405, anionic sodium dodecyl sulfate (SDS), and zwitterionic ammonium sulfobetaine-2 (ASB)). Partial hydrolysis of polyesters results in the formation of hydroxyl and carboxyl groups in the surface layer of microspheres and enhances their stability in water-based media. Minimal concentrations of surfactants, needed to obtain stable suspensions of particles, were equal to 3 × 10^-2, and 6 × 10^-2, and 3 × 10^-2 mol l^-1 for Triton X-405, SDS, and ASB, respectively. In the case of poly(ε-caprolactone) microspheres, suspensions in water were stable for all three surfactants for pH values ranging from 3 to 11. Suspensions of poly(L-lactide) were stable in the same range of pH values only for ASB. Surface charge density determined by electrophoretic mobility varied for poly(ε-caprolactone) microspheres from 2.6 × 10^-7 to 8.9 × 10^-7 mol m^-2, for particles stabilized with Triton X-405 and ASB, respectively. In the case of poly(L-lactide) microspheres, surface charge density varied from 3.9 × 10-7 (stabilizer: Triton X-405) to 7.4 × 10^-7 mol m^-2 (stabilizer: ASB). Carboxyl groups located in the surface layer of poly(L-lactide) microspheres were used for covalent immobilization of 6-aminoquinoline, a fluorophore with an amino group. Maximum surface concentration of immobilized 6-aminoquinoline was equal to 1.9 × 10^-6 mol m^-2. Poly(ε-caprolactone) microspheres transferred into water were loaded with ethyl salicylate. Loading up to 38% (w/w) was obtained.     

Osteogenic differentiation of bone marrow stromal cells on poly(ε-caprolactone) nanofiber scaffolds

Nanofiber poly(ε-caprolactone) (PCL) scaffolds were fabricated by electrospinning, and their ability to enhance the osteoblastic behavior of marrow stromal cells (MSCs) in osteogenic media was investigated. MSCs were isolated from Wistar rats and cultured on nanofiber scaffolds to assess short-term cytocompatibility and long-term phenotypic behavior. Smooth PCL substrates were used as control surfaces. The short-term cytocompatibility results indicated that nanofiber scaffolds supported greater cell adhesion and viability compared with control surfaces. In osteogenic conditions, MSCs cultured on nanofiber scaffolds also displayed increased levels of alkaline phosphatase activity for 3 weeks of culture. Calcium phosphate mineralization was substantially accelerated on nanofiber scaffolds compared to control surfaces as indicated through von Kossa and calcium staining, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Increased levels of intra- and extracellular levels of osteocalcin and osteopontin were observed on nanofiber scaffolds using immunofluorescence techniques after 3 weeks of culture. These results demonstrate the enhanced tissue regeneration property of nanofiber scaffolds, which may be of potential use for engineering osteogenic scaffolds for orthopedic applications.     

Itraconazole-loaded micelles based on linear-dendritic poly (ethylene glycol)-b-poly (ε-caprolactone)

Abstract

A copolymeric micelle formulation of itraconazole (ITR-M) was prepared using linear-dendritic monoallyloxy poly (ethylene glycol)-b-poly (ε-caprolactone) (APEG-PCL) as drug carrier materials. DL and EE values of ITR-M were 5.70?±?0.12% and 91.30?±?1.90%, respectively. The micelle formulation enhanced the ITR solubility up to 30.42?μg/mL. In vitro release of ITR from the ITR-M was mainly drug diffusion process followed by the copolymer’s degradation. ITR-M showed similar anti-Candida albicans activity to that of crude ITR although its release of ITR was slow and continuous. The in vivo pharmacokinetic study demonstrated that the ITR-M could improve tissue distribution of ITR. In conclusion, APEG-PCL could be a potential carrier in the development of antifungal drug delivery system.     

BHK cell attachment and growth on EDA-plasma-modified poly(L-lactide/ε-caprolactone) biodegradable films

In this study, attachment and growth of Baby Hamster Kidney (BHK) cells on ethylene diamine (EDA)-plasma-treated poly(L-lactide/ε-caprolactone) biodegradable copolymer films were investigated. The co-polymer (M_w: 58 000; M_n: 35 000 and PI 1.60) was synthesised by ring-opening polymerization of the respective dimers with using stannous octoate as the catalyst. The final ratio of L-lactide to ε-caprolactone obtained by ¹H-NMR was 87 :13. The co-polymer films were treated with the EDA-plasma in a glow-discharge apparatus. The BHK-30 cell line was cultured on plain and EDA-plasma-treated films and their pre-wetted forms (with ethanol and/or cell culture medium before use). Cell attachment and growth were followed. Alkaline phosphatase (ALP) activity and glucose uptake in cell culture medium were also investigated. There was no attachment in the first 12 h. Glow-discharge treatment increased significantly the attachment and growth. Pre-wetting with ethanol and cell culture medium was also increase significantly both the attachment and growth.     

Characterization of the thermo- and pH-responsive assembly of triblock copolymers based on poly(ethylene glycol) and functionalized poly(ε-caprolactone)

A series of novel triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(ε-caprolactone)-bearing benzyl carboxylate on the α-carbon of ε-caprolatone were synthesized through ring opening polymerization of α-benzyl carboxylate-ε-caprolactone by dihydroxylated PEG. The debenzylation of the synthesized copolymer, i.e., poly(α-benzyl carboxylate-ε-caprolactone)-b-PEG-b-poly(α-benzyl-carboxylate-ε-caprolactone) (PBCL-b-PEG-b-PBCL), in the presence of hydrogen gas using different levels of catalyst, was carried out to achieve copolymers with various degrees of free α-carboxyl to α-benzyl-ε-carboxylate groups on the hydrophobic block. Incomplete reduction of PBCL led to the formation of poly(α-carboxyl-co-benzyl caboxylate-ε-caprolactone) PCBCL in the lateral blocks at 27%, 50% and 75% carboxyl group substitution. The molecular weight and polydispersity of the resultant copolymers were estimated by ¹H NMR and MALDI-TOF. Synthesized triblock copolymers formed stable micelles at low concentrations (critical micellar concentrations (CMC) of 0.34–12.5 μg ml⁻¹). Polymers containing carboxyl groups in their structure showed a pH-dependent increase in CMC. As the pH was raised from 4.0 to 9.0, CMC increased from 0.76 to 1.06 μg ml⁻¹, for 27% debenzylated polymer, and from 1.30 to 2.20 μg ml⁻¹, for 50% debenzylated polymers. In contrast, the CMC in polymers without carboxyl group was independent of pH (0.55 μg ml⁻¹). Different changes in micellar size as a function of temperature was observed depending on the degree of debenzylation on the PCBCL block: polymers with 27% degree of debenzylation illustrated a rise in micelle size from ∼38 to 55 nm as the temperature increased above 29 °C, while polymers with 50% debenzylation showed a decrease in micelle size, from ∼52 to 38 nm, with increase in temperature. A similar trend was observed at pH 4.5, 7.0 and 9.0 for polymers containing carboxyl groups on their hydrophobic block. The temperature for the onset of size change and/or the extent of aggregate size change was found to be dependent on the pH of the medium and the polymer concentration. The results point to a potential for the formation of thermo- and pH-responsive micelles from triblock copolymers of PEG and carboxyl substituted caprolactone. The results also imply a potential for the 27% debenzylated PCBCL-b-PEG-b-PCBCL copolymers to form a biodegradable thermoreversible gel with a transition temperature a few degrees below 37 °C.     

Synthesis of biodegradable poly(ε-caprolactone)-organosiloxane hybrid with carboxylate groups

Biodegradable poly(ε-caprolactone)-organosiloxane hybrid with carboxylate groups was newly synthesized by a sol-gel method with the capacity to conjugate cell adhesion ligands for the potential applications as a bone tissue engineering scaffold material. An intermediate hybrid contained positively charged amine groups was synthesized by end-capping α,ω-hydroxyl poly(ε-caprolactone) with (3-isocyanatopropyl)triethoxysilane and a subsequent sol-gel reaction with (3-aminopropyl)triethoxysilane. This resulted in a new hybrid composed of biodegradable organic poly(ε-caprolactone) segments connected by inorganic siloxane linkages containing positively charged amine groups. The successive succinlylation of amine groups created amide bonds and converted the cationic sites of succinic anhydride into negatively charged carboxylate groups. New formations of amine and carboxylate groups could be directly and indirectly confirmed using Fourier transformed infrared spectrometry, zeta potentials, and atomic force microscopy. Biodegradability of hybrid with carboxylate groups was also examined by weight loss in phosphate buffered saline, and it was about 14 wt % after 8 weeks. Conjugating capacity of a cell adhesion ligand was examined by comparing the relative fluorescent intensities of covalently and noncovalently immobilized synthetic GGGGRGDASSK-FITC oligopeptides onto the carboxylated groups of the hybrid using confocal laser scanning microscopy; the relative fluorescent intensity of covalently conjugated RGD peptide was about three times higher than that of noncovalently coated RGD peptide. The hybrid covalently conjugated by GGGGRGDASSK oligopeptides improved proliferation and differentiation activities of preosteoblastic MC3T3-E1 cells. The results suggest that this hybrid possesses an encouraging potential to be used as a bone tissue engineering scaffold material due to its biodegradability and high capacity for conjugating cell adhesion ligands.     

Preparation of anionic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) copolymeric nanoparticles as basic protein antigen carrier

It is an useful method for polymeric nanoparticles to load protein by electrostatic method to improve the immunogenicity of protein antigen. In this article, anionic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC) nanoparticles were prepared by modified emulsion solvent evaporation method, and human basic fibroblast growth factor (bFGF), as a model protein, was absorbed onto its surface due to electrostatic interaction. The prepared anionic PCEC nanoparticles, with mean diameter of 136.9 nm, had zeta potential of ? 33.14 mV. The surface charge and particle size of bFGF/nanoparticles complex increased with increase of bFGF/nanoparticles mass ratio. The encapsulated bFGF could be released slowly from bFGF/nanoparticle complexes. The animal experiment indicated that the humoral immunity induced by bFGF/PCEC complex was improved greatly than that created by naked bFGF. Otherwise, the cytotoxicity of anionic PCEC nanoparticles was also evaluated by 293 cell viability. The prepared anionic PCEC nanoparticles might have great potential application as basic protein vaccine delivery system.     

Hollow fibers of poly(lactide-co-glycolide) and poly(ε-caprolactone) blends for vascular tissue engineering applications

At present the manufacture of small-diameter blood vessels is one of the main challenges in the field of vascular tissue engineering. Currently available vascular grafts rapidly fail due to development of intimal hyperplasia and thrombus formation. Poly(lactic-co-glycolic acid) (PLGA) hollow fiber (HF) membranes have previously been proposed for this application, but as we show in the present work, they have an inhibiting effect on cell proliferation and rather poor mechanical properties. To overcome this we prepared HF membranes via phase inversion using blends of PLGA with poly(ε-caprolactone) (PCL). The influence of polymer composition on the HF physicochemical properties (topography, water transport and mechanical properties) and cell attachment and proliferation were studied. Our results show that only the ratio PCL/PLGA of 85/15 (PCL/PLGA85/15) yielded a miscible blend after processing. A higher PLGA concentration in the blend led to immiscible PCL/PLGA phase-separated HFs with an inhomogeneous morphology and variation in the cell culture results. In fact, the PCL/PLGA85/15 blend, which had the most homogeneous morphology and suitable pore structure, showed better human adipose stem cell (hASC) attachment and proliferation compared with the homopolymers. This, combined with the good mechanical and transport properties, makes them potentially useful for the development of small-caliber vascular grafts.     

Non-viral gene delivery nanoparticles based on poly(β-amino esters) for treatment of glioblastoma

Glioblastoma (GB) is currently characterized by low survival rates and therapies with insufficient efficacy. Here, we describe biodegradable polymers that can deliver genes to primary GB cells as well as GB tumor stem cells in?vitro with low non-specific toxicity and transfection efficiencies of up to 60.6?±?5% in normal (10%) serum conditions. We developed polymer-DNA nanoparticles that remained more stable in normal serum and could also be stored for at least 3 months in ready-to-use form with no measurable decrease in efficacy, expanding their potential in a practical or clinical setting. A subset of polymers was identified that shows a high degree of specificity to tumor cells compared with healthy astrocytes and human neural stem cells when cultured (separately or in co-culture), yielding higher transfection in GB cells while having little to no apparent effect on healthy cells.     

Characterization of electrospun core/shell poly(vinyl pyrrolidone)/poly(L-lactide-co-ε-caprolactone) fibrous membranes and their cytocompatibility in vitro

Coaxial electrospinning is a new technique to fabricate continuous composite ultrafine fibers with core/shell structure, which has a broad application perspective in the biomedical field. In this study, ultrafine fibrous membranes of core/shell poly(vinyl pyrrolidone)/poly(L-lactide-co-ε-caprolactone) (PVP/PLCL) were produced by coaxial electrospinning and the structural morphology of the obtained ultrafine fibers was observed by scanning electron microscopy and transmission electron microscopy. Electrospun PLCL and chitosan membranes were also prepared by traditional electrospinning as controls. The electrospun PVP/PLCL membranes showed the largest water absorption (501.3%) in phosphate buffer solution due to introduction of the PVP component and the core/shell fiber structure. Results of tensile tests indicated that the electrospun PVP/PLCL membranes possessed higher tensile strength and elongation-at-break, and lower Young's modulus than those of PLCL and chitosan membranes in both dry and wet states. Studies on cell adhesion, viability and morphology on the fibrous membranes showed that PVP/PLCL membranes could mimic the structure of natural extracellular matrices and positively promote cell–cell and cell–matrix interactions because of hydrophilicity/hydrophobicity balance.     

Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma

Dual-targeting nanoparticle drug delivery system was developed by conjugating Angiopep with PEG-PCL nanoparticles (ANG-NP) through bifunctional PEG to overcome the limitations of low transport of chemotherapeutics across the Blood-brain barrier (BBB) and poor penetration into tumor tissue. ANG-NP can target the low-density lipoprotein receptor-related protein (LRP) which is over-expressed on the BBB and glioma cells. Compared with non-targeting nanoparticles, a significantly higher amount of rhodamine isothiocyanate-labeled dual-targeting nanoparticles were endocytosed by U87 MG cells. The antiproliferative and cell apoptosis assay of paclitaxel-loaded ANG-NP (ANG-NP-PTX) demonstrated that ANG-NP-PTX resulted in enhanced inhibitory effects to U87 MG glioma cells. The transport ratios across the BBB model in vitro were significantly increased and the cell viability of U87 MG glioma cells after crossing the BBB was obviously decreased by ANG-NP-PTX. Enhanced accumulation of ANG-NP in the glioma bed and infiltrating margin of intracranial U87 MG glioma tumor-bearing in vivo model were observed by real time fluorescence image. In conclusion, Angiopep-conjugated PEG-PCL nanoparticles were prospective in dual-targeting drug delivery system for targeting therapy of brain glioma.     

Injectable in situ forming drug delivery system based on poly(ε-caprolactone fumarate) for tamoxifen citrate delivery: Gelation characteristics,in vitro drug release and anti-cancer evaluation

The present study deals with the preparation and characterization of an injectable and in situ forming drug delivery system based on photocrosslinked poly(ε-caprolactone fumarate) (PCLF) networks loaded with tamoxifen citrate (TC). Networks were made of PCLF macromers, a photoinitiation system (comprising initiator and accelerator) and the active ingredient N-vinyl-2-pyrrolidone (NVP) as a crosslinker and reactive diluent. Shrinkage behavior, equilibrium swelling and sol fraction ratios of photocrosslinked PCLF gels were determined as functions of NVP content. It was shown that the crosslinking is facilitated up to a certain concentration of NVP and most of NVP remained unreacted above this value. In vitro drug release, biocompatibility evaluation and activity against MCF-7 breast cancer cell line were also investigated. Accurate but simple bipartite expressions were also derived that enable rapid determination of effective diffusion coefficients of TC in photocrosslinked PCLF/NVP disks. Cytotoxicity assay showed that while the photocrosslinked PCLF network with optimum NVP content exhibits no significant cytotoxicity against MCF-7 and L929 cell lines, 40–60% of the MCF-7 cells were killed after incubation with TC-loaded devices.     

Fibroblast culture on surface-modified poly (glycolide-co-ε-caprolactone) scaffold for soft tissue regeneration

Novel porous matrices made of a copolymer of glycolide (G) and ε-caprolactone (CL) (51 : 49, M_w 103 000) was prepared for tissue engineering using a solvent-casting particulate leaching method. Poly(glycolide-co-ε-caprolactone) (PGCL) copolymer showed a rubber-like elastic characteristic, in addition to an amorphous property and fast biodegradability. In order to investigate the effect on the fibroblast culture, PGCL scaffolds of varying porosity and pore size, in addition to surfacehydrolysis or collagen coating, were studied. The large pore-sized scaffold (pore size >150 μm) demonstrated a much greater cell adhesion and proliferation than the small pore-sized one. In addition, the higher porosity, the better the cell adhesion and proliferation. The surface-hydrolyzed PGCL scaffold showed enhanced cell adhesion and proliferation compared with the unmodified one. Type I collagen coating revealed a more pronounced contribution for increased cell interactions than the surface-hydrolyzed one. These results demonstrate that surface-modified PGCL scaffold can provide a suitable substrate for fibroblast culture, especially in the case of soft tissue regenerations.     

In vivo biocompatibility and osteogenesis of electrospun poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone)/nano-hydroxyapatite composite scaffold

A flexible and fibrous composite scaffold composed of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) and 30?wt.% nano-hydroxyapatite (n-HA) was fabricated through electrospinning. In the present study, we investigated its in?vitro and in?vivo performance by means of hydrolytic degradation, muscle pouch implantation, as well as repair the calvarial defects in New Zealand white rabbits. The results demonstrated that the degradable scaffold held good biocompatibility. Qualitative analysis of bone regeneration process was performed by radiological examination and histological analysis. The results indicated that new bone formed originally from the margin of host bone, and then grew toward the center of defects. Moreover, the quantitative determination of newly formed bone was performed using statistical analysis of histological sections at predetermined time points. At 20th week, the defects of treatment group were covered with the new solid cortical bone. In comparison, the control group was filled with a large amount of cancelous bone and bone marrow. It suggested that the composite scaffold had better activity of guided bone regeneration than that of self-healing. So the electrospun PCEC/n-HA fibrous scaffold had the great potential application in bone tissue engineering.