[Show abstract][Hide abstract] ABSTRACT: Restenosis caused by thrombopoiesis is one of the biggest hinders of endovascular stent-graft used in small-diameter vessels. Rapid endothelialization of the lumen of stent is a promising approach to prevent thrombosis. In this study, we aimed at loading heparin, a potent anticoagulants,
and vascular endothelial growth factor (VEGF) into the core of poly(L-lactide-co-caprolactone) nanofiber via emulsion electrospinning. The nanofiber was covered on the stent and applied in the treatment of vascular diseases such as aneurysm. The morphologies of the emulsion electrospun nanofibers
and core–shell structure were observed by scanning electron microscope and laser scanning confocal microscope. The release profiles of heparin and VEGF, degradation rate of nanofiber mats and cell proliferation in vitro were investigated. It was found that the release of both
heparin and VEGF from the nanofiber lasted for more than 30 days without serious initial burst release. The degradation rate of nanofiber mats containing heparin and VEGF was faster than that of pure PLCL nanofiber mats. Moreover, the released VEGF could promote the proliferation of Pig iliac
endothelial cells (PIECs) cultured on the nanofiber mat, which was of great benefit to stent endothelialization. The results of digital subtraction angiography (DSA) follow-up indicated the aneurysm was obliterated by separating the aneurysm dome from the blood circulation and the parent artery
kept long-term patency. Results of the study demonstrated that the heparin and VEGF loaded nanofiber could provide an approach to fabricate covered stent-graft with properties of anticoagulation and induction of rapid endothelialization.
[Show abstract][Hide abstract] ABSTRACT: Bone morphogenetic protein-2 (BMP-2), a growth factor that induces osteoblast differentiation and promotes bone regeneration, has been extensively investigated in bone tissue engineering. The peptides of bioactive domains, corresponding to residues 73-92 of BMP-2 become an alternative to reduce adverse side effects caused by the use of high doses of BMP-2 protein. In this study, BMP-2 peptide functionalized mesoporous silica nanoparticles (MSNs-pep) were synthesized by covalently grafting BMP-2 peptide on the surface of nanoparticles via an aminosilane linker, and dexamethasone (DEX) was then loaded into the channel of MSNs to construct nanoparticulate osteogenic delivery systems (DEX@MSNs-pep). The in vitro cell viability of MSNs-pep was tested with bone mesenchymal stem cells (BMSCs) exposure to different particle concentrations, revealing that the functionalized MSNs had better cytocompatibility than their bare counterparts, and the cellular uptake efficiency of MSNs-pep was remarkably larger than that of bare MSNs. The in vitro results also show that the MSNs-pep promoted osteogenic differentiation of BMSCs in terms of the levels of alkaline phosphatase (ALP) activity, calcium deposition, and expression of bone-related protein. Moreover, the osteogenic differentiation of BMSCs can be further enhanced by incorporating of DEX into MSNs-pep. After intramuscular implantation in rats for three weeks, the computed tomography (CT) images and histological examination indicate that this nanoparticulate osteogenic delivery system induces effective osteoblast differentiation and bone regeneration in vivo. Collectively, the BMP-2 peptide and DEX incorporated MSNs can act synergistically to enhance osteogenic differentiation of BMSCs, which have potential applications in bone tissue engineering.
[Show abstract][Hide abstract] ABSTRACT: Although the thiol click reaction is an attractive tool for post-polymerization modiﬁcation of thiolmers, thiol groups are easily oxidized, limiting the potential for covalent immobilization of bioactive molecules. In this study, a series of biodegradable polyurethane elastomers incorporating stable cyclic disulfide groups was developed and characterized. These poly(ester urethane)urea (PEUU-SS) polymers were based on polycaprolactone diol (PCL), oxidized DL-dithiothreitol (O-DTT), lysine diisocyanate (LDI) or butyl diisocyanate (BDI), with chain extension by putrescine. The ratio of O-DTT:PCL was altered to investigate different levels of potential functionalization. PEG acrylate was employed to study the mechanism and availability of both bulk and surface click modification of PEUU-SS polymers. All synthesized PEUU-SS polymers were elastic with breaking strengths of 38-45 MPa, while the PEUU-SS(LDI) polymers were more amorphous, possessing lower moduli and relatively small permanent deformations versus PEUU-SS(BDI) polymers. Variable bulk click modification of PEUU-SS(LDI) polymers was achieved by controlling the amount of reduction reagent, and rapid reaction rates occurred using a one-pot, two-step process. Likewise, surface click reaction could be carried out quickly under mild, aqueous conditions. Furthermore, a maleimide-modified affinity peptide (TPS) was successfully clicked on the surface of an electrospun PEUU-SS(BDI) fibrous sheet, which improved endothelial progenitor cell adhesion versus corresponding unmodified films. The cyclic disulfide containing biodegradable polyurethanes described provide an option for soft tissue regenerative medicine applications where a temporary, elastic scaffold with designed biofunctionality from a relatively simple click chemistry approach is desired.
[Show abstract][Hide abstract] ABSTRACT: Particular attention has been given to
three-dimensional scaffolds for bone tissue regeneration. In this study, poly(l-lactic acid-co-ε-caprolactone) (P(LLA-CL) nanoyarn scaffold and poly(l-lactic acid-co-caprolactone)/silk fibroin (P(LLA-CL)/SF) nanoyarn scaffold were fabricated by a dynamic liquid support electrospinning system; and then the three-dimensional (3D) nanoyarn scaffolds were prepared by freeze-drying processes. The results indicated the average diameter of P(LLA-CL) and P(LLA-CL)/SF nanoyarns were 29.44 ± 3.47 μm and 11.59 ± 0.46 μm, respectively. The yarn in the nanoyarn scaffold was twisted by many nanofibers as evidenced by scanning electron microscope (SEM) result. These nanoyarn scaffolds were biomineralized by alternatively immersing the nanoyarn scaffolds into phosphoric acid and calcium ion solutions. After biomineralization, the existence of hydroxyapatite (HA) particles on the scaffolds was confirmed using fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis. In vitro study of cell proliferation was found to be higher on P(LLA-CL)/SF scaffold as compared to P(LLA-CL) scaffold after culturing for 14 days. H&E staining results showed that cells not only attached to the surface of 3D scaffold but also infiltrated into the scaffold. This study indicated that the electrospun P(LLA-CL)/SF scaffold with nanostructure morphology could improve cell adhesion and proliferation and electrospun P(LLA-CL)/SF scaffold with biomineralization has a potential application for bone tissue engineering.
[Show abstract][Hide abstract] ABSTRACT: While surface modification is well suited for imparting biomaterials with specific functionality for favorable cell interactions, the modification of degradable polymers would be expected to provide only temporary benefit. Bulk modification by incorporating pendant reactive groups for subsequent functionalization of biodegradable polymers would provide a more enduring approach. Towards this end, a series of biodegradable poly(ester urethane)urea elastomers with variable amino content (PEUU-NH2 polymers) were developed. Carboxylated phosphorycholine was synthesized and conjugated to the PEUU-NH2 polymers for subsequent bulk functionalization to generate PEUU-PC polymers. Synthesis was verified by proton nuclear magnetic resonance, X-ray photoelectron spectroscopy and attenuated total reflection Fourier transform infrared spectroscopy. The impact of amine incorporation and phosphorylcholine conjugation was shown on mechanical, thermal and degradation properties. Water absorption increased with increasing amine content, and further with PC conjugation. In wet conditions, tensile strength and initial modulus generally decreased with increasing hydrophilicity, but remained in the range of 5-30 MPa and 10-20 MPa, respectively. PC conjugation was associated with significantly reduced platelet adhesion in blood contact testing and the inhibition of rat vascular smooth muscle cell proliferation. These biodegradable PEUU-PC elastomers offer attractive properties for applications as non-thrombogenic, biodegradable coatings and for blood-contacting scaffold applications. Further, the PEUU-NH2 base polymers offer the potential to have multiple types of biofunctional groups conjugated onto the backbone to address a variety of design objectives.
[Show abstract][Hide abstract] ABSTRACT: In the vascular prosthetic field, the prevailing thought is that for clinical, long-term success, especially
bioresorbable grafts, cellular migration and penetration into the prosthetic structure is required to promote
neointima formation and vascular wall development. In this study, we fabricated poly (l-lactic
acid-co-�-caprolactone) P(LLA-CL)/silk fibroin (SF) vascular scaffolds through electrospinning using both
perforated mandrel subjected to various intraluminal air pressures (0–300 kPa), and solid mandrel. The
scaffolds were evaluated the cellular infiltration in vitro and mechanical properties. Vascular scaffolds
were seeded with smooth muscle cells (SMCs) to evaluate cellular infiltration at 1, 7, and 14 days. The
results revealed that air-impedance scaffolds allowed significantly more cell infiltration as compared
to the scaffolds fabricated with solid mandrel. Meanwhile, results showed that both mandrel model and
applied air pressure determined the interfiber distance and the alignment of fibers in the enhanced porosity
regions of the structure which influenced cell infiltration. Uniaxial tensile testing indicated that the
air-impedance scaffolds have sufficient ultimate strength, suture retention strength, and burst pressure
as well as compliance approximating a native artery. In conclusion, the air-impedance scaffolds improved
cellular infiltration without compromising overall biomechanical properties. These results support the
scaffold’s potential for vascular grafting and in situ regeneration.
[Show abstract][Hide abstract] ABSTRACT: Background:
Capping techniques have been used as a treatment modality for the prevention of neuroma formation and the management of neuropathic pain. However, the results are inconsistent and unpredictable. We hypothesize that this situation may be attributable, in part, to the disparities in the type of materials used to manufacturing of the conduits.
In this study, a rat model was used and the sciatic nerve was selected for evaluation. In 1 capping group, a sciatic nerve stump was capped with a nonaligned nanofiber conduit (the nonaligned group), whereas in a second capping group, the conduit was made of aligned nanofibers (the aligned group). In another group, the sciatic nerve stump was not capped as a control (the control group). The results of autotomy behavior, extent of neuroma formation, histological changes in the neuroma, and the expression of c-fos as a pain marker in the fourth lumbar spinal cord were evaluated at 8 weeks postoperatively.
The control group presented more neuroma-like features in all the observed parameters in comparison with the 2 capping groups; of the 2 capping groups, the aligned group achieved even better outcomes than the nonaligned group.
Our findings indicate that the aligned nanofiber conduit is a promising biomaterial for the nerve capping technique, and new treatment strategies using aligned nanofiber conduits may be developed for the management of painful amputated neuromas.
Annals of Plastic Surgery 07/2014; 74(4). DOI:10.1097/SAP.0000000000000266 · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An electrospun-aligned nanoyarn-reinforced nanofibrous scaffold (NRS) was developed for tendon tissue engineering to improve mechanical strength and cell infiltration. The novel scaffold composed of aligned nanoyarns and random nanofibers was fabricated via electrospinning using a two-collector system. The aim of the present study was to investigate three different types of electrospun scaffolds (random nanofibrous scaffold, aligned nanofibrous scaffold and NRS) based on silk fibroin (SF) and poly(l-lactide-co-caprolactone) blends. Morphological analysis demonstrated that the NRS composed of aligned nanoyarns and randomly distributed nanofibers formed a 3D microstructure with relatively large pore sizes and high porosity. Biocompatibility analysis revealed that bone marrow-derived mesenchymal stem cells exhibited a higher proliferation rate when cultured on the NRS compared with the other scaffolds. The mechanical testing results indicated that the tensile properties of the NRS were reinforced in the direction parallel to the nanoyarns and satisfied the mechanical requirements for tendon repair. In addition, cell infiltration was significantly enhanced on the NRS. In conclusion, with its improved porosity and appropriate mechanical properties, the developed NRS shows promise for tendon tissue engineering applications.
[Show abstract][Hide abstract] ABSTRACT: Osteochondral defects affect both the articular cartilage and the underlying subchondral bone, but poor osteochondral regeneration is still a daunting challenge. Although the tissue engineering technology provides a promising approach for osteochondral repair, an ideal biphasic scaffold is in high demand with regards to proper biomechanical strength. In this study, an oriented poly( L -lacticacid)- co -poly( ε -caprolactone) P(LLA-CL)/collagen type I(Col-I) nanofiber yarn mesh, fabricated by dynamic liquid electrospinning served as a skeleton for a freeze-dried Col-I/ Hhyaluronate (HA) chondral phase(SPONGE) to enhance the mechanical strength of the scaffold. In vitro results show that the Yarn Col-I/HA hybrid scaffold (Yarn-CH) can allow the cell infiltration like sponge scaffolds. Using porous beta-tricalcium phosphate (TCP) as the osseous phase, the Yarn-CH/TCP biphasic scaffold was then assembled by freeze drying. After combination of BMSCs, the biphasic complex was successfully used to repair the osteochondral defects in a rabbit model with greatly improved repairing scores and compressive modulus.
Journal of Biomedical Materials Research Part A 07/2014; 103(2). DOI:10.1002/jbm.a.35206 · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper presents a facile method for the fabrication of uniform hollow mesoporous silica nanoparticles (HMSNs) with tunable shell thickness and pore size. In this method, a series of amphiphilic block copolymers of polystyrene-b-poly (acrylic acid) (PS-b-PAA) with different hydrophobic block (PS) lengths were first synthesized via atom transfer radical polymerization (ATRP). The as-synthesized PS-b-PAA and cetyltrimethylammonium bromide (CTAB) were subsequently used as co-templates to fabricate HMSNs. This approach allows the control of shell thickness and pore size distribution of the synthesized HMSNs simply by changing the amounts of PS-b-PAA and CTAB, respectively. In vitro cytotoxicity and hemolysis assays demonstrated that the synthesized HMSNs had a low and shell thickness-dependent cytotoxicity and hemolytic activity. Therefore, these HMSNs have great potential for biomedical applications due to their good biocompatibility and ease of synthesis.
[Show abstract][Hide abstract] ABSTRACT: Electrospinning has been widely used in fabrication of tissue engineering scaffolds. Currently, most of the electrospun nanofibers performed like a conventional two-dimensional (2D) membrane, which hindered their further applications. Moreover, the low production rate of the traditional needle-electrospinning (NE) also limited the commercialization. In this article, disc-electrospinning (DE) was utilized to fabricate a three-dimensional (3D) scaffold consisting of porous macro/nanoscale fibers. The morphology of the porous structure was investigated by scanning electron microscopy images, which showed irregular pores of nanoscale spreading on the surface of DE polycaprolactone (PCL) fibers. Protein adsorption assessment illustrated the porous structure could significantly enhance proteins pickup, which was 55% higher than that of solid fiber scaffolds. Fibroblasts were cultured on the scaffold. The results demonstrated that DE fiber scaffold could enhance initial cell attachment. In the 7 days of culture, fibroblasts grew faster on DE fiber scaffold in comparison with solid fiber, solvent cast (SC) film and TCP. Fibroblasts on DE fibers showed a stretched shape and integrated with the porous surface tightly. Cells were also found to migrate into the DE scaffold up to 800μm. Results supported the use of DE PCL fibers as a 3D tissue engineering scaffold in soft tissue regeneration.
[Show abstract][Hide abstract] ABSTRACT: Poly(l-lactic acid-co-ε-caprolactone) (P(LLA-CL)) is a kind of copolymer polymerized from lactic acid and ε-caprolactone. Electrospun P(LLA-CL) nanofibers have good biocompatibility, biodegradability, and mechanical property. However, this type of nanofibers will produce acid groups during the degradation, so that, the pH value of the environment will decrease and result in tissue inflammation. On the other hand, Magnesium (Mg) alloy tissue engineering scaffolds will show alkaline during the degradation because of the electrochemical corrosion. Based on the principle of acid-based neutralization, combination of these two kinds of materials through electrospinning could keep the pH of the degradation environment neutral. In this paper, fabrication and characterization of Mg/P(LLA-CL)-blended nanofiber scaffolds with different ratios will be studied by scanning electron microscopy and universal materials testing machines to observe the morphology and mechanical properties of nanofibers, respectively. Furthermore, PIECs were cultured and seeded on the scaffolds for different time to evaluate the proliferation behavior on the scaffolds by MTT assay. The degradation tests of the samples lasted for three months in phosphate-buffered saline to evaluate the pH values of degradation solutions and the weight loss of nanofibers during degradation. The results showed that the mechanical property and biocompatibility of Mg/P(LLA-CL)-blended nanofibers were worse than that of pure P(LLA-CL). Moreover, the addition of Mg in the nanofibers accelerated the weight loss of the Mg/P(LLA-CL) blending fibers and increased the pH values of the environment during degradation of Mg/P(LLA-CL)-blended nanofibers.
[Show abstract][Hide abstract] ABSTRACT: In the vascular prosthetic field, the prevailing thought is that for clinical, long-term success, especially bioresorbable grafts, cellular migration and penetration into the prosthetic structure is required to promote neointima formation and vascular wall development. In this study, we fabricated poly (l-lactic acid-co-ɛ-caprolactone) P(LLA-CL)/silk fibroin (SF) vascular scaffolds through electrospinning using both perforated mandrel subjected to various intraluminal air pressures (0-300kPa), and solid mandrel. The scaffolds were evaluated the cellular infiltration in vitro and mechanical properties. Vascular scaffolds were seeded with smooth muscle cells (SMCs) to evaluate cellular infiltration at 1, 7, and 14 days. The results revealed that air-impedance scaffolds allowed significantly more cell infiltration as compared to the scaffolds fabricated with solid mandrel. Meanwhile, results showed that both mandrel model and applied air pressure determined the interfiber distance and the alignment of fibers in the enhanced porosity regions of the structure which influenced cell infiltration. Uniaxial tensile testing indicated that the air-impedance scaffolds have sufficient ultimate strength, suture retention strength, and burst pressure as well as compliance approximating a native artery. In conclusion, the air-impedance scaffolds improved cellular infiltration without compromising overall biomechanical properties. These results support the scaffold's potential for vascular grafting and in situ regeneration.
[Show abstract][Hide abstract] ABSTRACT: Silk fibroin (SF) from Bombyx mori has many established excellent properties and has found various applications in the biomedical field. However, some abilities or capacities of SF still need improving to meet the need for using practically. Indeed, diverse SF-based composite biomaterials have been developed. Here we report the feasibility of fabricating pantothenic acid (vitamin B5, VB5)-reinforcing SF nanofibrous matrices for biomedical applications through green electrospinning. Results demonstrated the successful loading of d-pantothenic acid hemicalcium salt (VB5-hs) into resulting composite nanofibers. The introduction of VB5-hs did not alter the smooth ribbon-like morphology and the silk I structure of SF, but significantly decreased the mean width of SF fibers. SF conformation transformed into β-sheet from random coil when composite nanofibrous matrices were exposed to 75% (v/v) ethanol vapor. Furthermore, nanofibers still remained good morphology after being soaked in water environment for five days. Interestingly, as-prepared composite nanofibrous matrices supported a higher level of cell viability, especially in a long culture period and significantly assisted skin cells to survive under oxidative stress compared with pure SF nanofibrous matrices. These findings provide a basis for further extending the application of SF in the biomedical field, especially in the personal skin-care field.
[Show abstract][Hide abstract] ABSTRACT: A novel electrospun nanoyarn scaffold, aimed to improve cell infiltration and vascularization, as well as guide cell behaviors by its biomimetic structure, was fabricated for tissue engineering. Electrospun nanofibers were deposited and twisted into yarns in a water vortex before collecting on a rotating mandrel to form a nanoyarn scaffold. Field emission-scanning electronic microscope (FE-SEM) images revealed that the scaffold, composed of aligned nanoyarns (24 micro m) which were composed of a bundle of nanofibers, created a porous structure which may be conducive to cellular infiltration. Thus, we hypothesized that the biomimetic nanoyarn will have a positive influence on cell proliferation and morphology. Pig iliac endothelial cells (PIECs) and MC3T3-E1 pre-osteoblastic cells cultured on the nanoyarn scaffolds showed significantly higher proliferation rates than that on traditional electrospun nanofiber scaffolds. Histological analysis demonstrated that cells infiltrate throughout the nanoyarn scaffolds over a 10-day period, however, no cell infiltration was observed on the nanofiber scaffolds. Moreover, confocal microscopy images indicated that both PIECs and MC3T3-E1 pre-osteoblastic cells cultured on the nanoyarn scaffolds exhibit an extremely elongated morphology compared to the flattened morphology when cells were cultured on electrospun nanofiber scaffolds or tissue culture plates. Furthermore, complex capillary-like structures were observed when PIECs cultured on the nanoyarn scaffold for 7 days, indicating that the nanoyarns provide templates and topographical cues for the assembly of PIECs and the promotion of a capillary network in vitro. In conclusion, the positive cellular interactions on the nanoyarn scaffold demonstrate potential application for use in tissue engineering.