Publications (18)101.09 Total impact
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Article: Using extracellular matrix for regenerative medicine in the spinal cord.
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ABSTRACT: Regeneration within the mammalian central nervous system (CNS) is limited, and traumatic injury often leads to permanent functional motor and sensory loss. The lack of regeneration following spinal cord injury (SCI) is mainly caused by the presence of glial scarring, cystic cavitation and a hostile environment to axonal growth at the lesion site. The more prominent experimental treatment strategies focus mainly on drug and cell therapies, however recent interest in biomaterial-based strategies are increasing in number and breadth. Outside the spinal cord, approaches that utilize the extracellular matrix (ECM) to promote tissue repair show tremendous potential for various application including vascular, skin, bone, cartilage, liver, lung, heart and peripheral nerve tissue engineering (TE). Experimentally, it is unknown if these approaches can be successfully translated to the CNS, either alone or in combination with synthetic biomaterial scaffolds. In this review we outline the first attempts to apply the potential of ECM-based biomaterials and combining cell-derived ECM with synthetic scaffolds.Biomaterials 04/2013; · 7.40 Impact Factor -
Article: Dermal fibroblast infiltration of poly(ε-caprolactone) scaffolds fabricated by melt electrospinning in a direct writing mode.
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ABSTRACT: Melt electrospinning in a direct writing mode is a recent additive manufacturing approach to fabricate porous scaffolds for tissue engineering applications. In this study, we describe porous and cell-invasive poly (ε-caprolactone) scaffolds fabricated by combining melt electrospinning and a programmable x-y stage. Fibers were 7.5 ± 1.6 µm in diameter and separated by interfiber distances ranging from 8 to 133 µm, with an average of 46 ± 22 µm. Micro-computed tomography revealed that the resulting scaffolds had a highly porous (87%), three-dimensional structure. Due to the high porosity and interconnectivity of the scaffolds, a top-seeding method was adequate to achieve fibroblast penetration, with cells present throughout and underneath the scaffold. This was confirmed histologically, whereby a 3D fibroblast-scaffold construct with full cellular penetration was produced after 14 days in vitro. Immunohistochemistry was used to confirm the presence and even distribution of the key dermal extracellular matrix proteins, collagen type I and fibronectin. These results show that melt electrospinning in a direct writing mode can produce cell invasive scaffolds, using simple top-seeding approaches.Biofabrication 02/2013; 5(2):025001. · 3.48 Impact Factor -
Article: Design and fabrication of tubular scaffolds via direct writing in a melt electrospinning mode.
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ABSTRACT: Flexible tubular structures fabricated from solution electrospun fibers are finding increasing use in tissue engineering applications. However it is difficult to control the deposition of fibers due to the chaotic nature of the solution electrospinning jet. By using non-conductive polymer melts instead of polymer solutions the path and collection of the fiber becomes predictable. In this work we demonstrate the melt electrospinning of polycaprolactone in a direct writing mode onto a rotating cylinder. This allows the design and fabrication of tubes using 20 μm diameter fibers with controllable micropatterns and mechanical properties. A key design parameter is the fiber winding angle, where it allows control over scaffold pore morphology (e.g. size, shape, number and porosity). Furthermore, the establishment of a finite element model as a predictive design tool is validated against mechanical testing results of melt electrospun tubes to show that a lesser winding angle provides improved mechanical response to uniaxial tension and compression. In addition, we show that melt electrospun tubes support the growth of three different cell types in vitro and are therefore promising scaffolds for tissue engineering applications.Biointerphases 12/2012; 7(1-4):13. · 2.21 Impact Factor -
Article: Direct writing by way of melt electrospinning.
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ABSTRACT: Melt electrospun fibers of poly(ϵ-caprolactone) are accurately deposited using an automated stage as the collector. Matching the translation speed of the collector to the speed of the melt electrospinning jet establishes control over the location of fiber deposition. In this sense, melt electrospinning writing can be seen to bridge the gap between solution electrospinning and direct writing additive manufacturing processes.Advanced Materials 11/2011; 23(47):5651-7. · 13.88 Impact Factor -
Article: Degradable polyester scaffolds with controlled surface chemistry combining minimal protein adsorption with specific bioactivation.
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ABSTRACT: Advanced biomaterials and scaffolds for tissue engineering place high demands on materials and exceed the passive biocompatibility requirements previously considered acceptable for biomedical implants. Together with degradability, the activation of specific cell–material interactions and a three-dimensional environment that mimics the extracellular matrix are core challenges and prerequisites for the organization of living cells to functional tissue. Moreover, although bioactive signalling combined with minimization of non-specific protein adsorption is an advanced modification technique for flat surfaces, it is usually not accomplished for three-dimensional fibrous scaffolds used in tissue engineering. Here, we present a one-step preparation of fully synthetic, bioactive and degradable extracellular matrix-mimetic scaffolds by electrospinning, using poly(D,L-lactide-co-glycolide) as the matrix polymer. Addition of a functional, amphiphilic macromolecule based on star-shaped poly(ethylene oxide) transforms current biomedically used degradable polyesters into hydrophilic fibres, which causes the suppression of non-specific protein adsorption on the fibres’ surface. The subsequent covalent attachment of cell-adhesion-mediating peptides to the hydrophilic fibres promotes specific bioactivation and enables adhesion of cells through exclusive recognition of the immobilized binding motifs. This approach permits synthetic materials to directly control cell behaviour, for example, resembling the binding of cells to fibronectin immobilized on collagen fibres in the extracellular matrix of connective tissue.Nature Material 01/2011; 10(1):67-73. · 32.84 Impact Factor -
Article: Melt electrospinning.
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ABSTRACT: Melt electrospinning is relatively under-investigated compared to solution electrospinning but provides opportunities in numerous areas, in which solvent accumulation or toxicity are a concern. These applications are diverse, and provide a broad set of challenges to researchers involved in electrospinning. In this context, melt electrospinning provides an alternative approach that bypasses some challenges to solution electrospinning, while bringing new issues to the forefront, such as the thermal stability of polymers. This Focus Review describes the literature on melt electrospinning, as well as highlighting areas where both melt and solution are combined, and potentially merge together in the future.Chemistry - An Asian Journal 11/2010; 6(1):44-56. · 4.50 Impact Factor -
Article: Melt electrospinning of polycaprolactone and its blends with poly(ethylene glycol)
Polymer International 10/2010; 59(11):1558 - 1562. · 1.90 Impact Factor -
Article: Snapshot: Polymer scaffolds for tissue engineering.
Biomaterials 03/2009; 30(4):701-2. · 7.40 Impact Factor -
Article: Human neural cell interactions with orientated electrospun nanofibers in vitro.
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ABSTRACT: Electrospun nanofibers represent potent guidance substrates for nervous tissue repair. Development of nanofiber-based scaffolds for CNS repair requires, as a first step, an understanding of appropriate neural cell type-substrate interactions. Astrocyte-nanofiber interactions (e.g., adhesion, proliferation, process extension and migration) were studied by comparing human neural progenitor-derived astrocytes (hNP-ACs) and a human astrocytoma cell line (U373) with aligned polycaprolactone (PCL) nanofibers or blended (25% type I collagen/75% PCL) nanofibers. Neuron-nanofiber interactions were assessed using a differentiated human neuroblastoma cell line (SH-SY5Y). U373 cells and hNP-AC showed similar process alignment and length when associated with PCL or Type I collagen/PCL nanofibers. Cell adhesion and migration by hNP-AC were clearly improved by functionalization of nanofiber surfaces with type I collagen. Functionalized nanofibers had no such effect on U373 cells. Another clear difference between the U373 cells and hNP-AC interactions with the nanofiber substrate was proliferation; the cell line demonstrating strong proliferation, whereas the hNP-AC line showed no proliferation on either type of nanofiber. Long axonal growth (up to 600 microm in length) of SH-SY5Y neurons followed the orientation of both types of nanofibers even though adhesion of the processes to the fibers was poor. The use of cell lines is of only limited predictive value when studying cell-substrate interactions but both morphology and alignment of human astrocytes were affected profoundly by nanofibers. Nanofiber surface functionalization with collagen significantly improved hNP-AC adhesion and migration. Alternative forms of functionalization may be required for optimal axon-nanofiber interactions.Nanomedicine 01/2009; 4(1):11-30. · 5.05 Impact Factor -
Article: Deposition of electrospun fibers on reactive substrates for in vitro investigations.
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ABSTRACT: Recent in vitro studies with electrospun nanofibers have used a range of techniques. The in vitro system presented in this article describes electrospun fibers deposited onto chemically reactive substrates to provide fiber adherence and surface chemistry control of the substrate. Fibers of poly(epsilon-caprolactone) (PCL) or of a blend of PCL and collagen type I (C/PCL) were electrospun directly onto collectors coated with isocyanate-terminated star (polyethylene glycol) (sPEG). Alternatively, parallel electrospun fibers were collected on dual collectors in "dilute" quantities and transferred onto sPEG-coated substrates. The initial reactive nature of the substrates allows the collection of very few fibers, which adhere well during frequent washes. Furthermore, the sPEG layer transforms into protein-repellent substrates with the additional potential to include specific cellular mediators such as glycine-arginine-glycine-aspartate-serine (GRGDS) peptides to promote cell adhesion. Therefore, the fiber and substrate chemistry can be modified independently, which is particularly useful for in vitro studies of guided migrating cells. In the present work, dissociated cells of dorsal root ganglia seeded onto the substrates were investigated to assess the influence of different combinations of fiber material, fiber orientation, and surface functionalization. Cell adhesion was observed predominantly on the nanofibers, except when the sPEG layer on the substrate contained GRGDS. On the cell-repellent sPEG substrates, neurites were aligned in direct contact with parallel C/PCL fibers and less so with PCL fibers. In contrast, neurite alignment showed less guidance effect with C/PCL electrospun fibers on the GRGDS/sPEG-coated substrates. Therefore, the combination of oriented biologically active fibers on cell-repellent surfaces enhanced the guidance of such cells. These reactive substrate systems provide a multitude of in vitro combinations for providing cells with specific mediators and, in turn, defining the optimum environment of regenerating devices for in vivo studies.Tissue Engineering Part C Methods 01/2009; 15(1):77-85. · 4.64 Impact Factor -
Article: Structure and properties of urea-crosslinked star poly[(ethylene oxide)-ran-(propylene oxide)] hydrogels.
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ABSTRACT: Isocyanate-terminated six armed star shaped macromers with a statistical copolymer backbone consisting of 80% EO and 20% PO have previously demonstrated excellent protein and cell repellence as nano-layered surfaces. In this study, various macromers are mixed with water and provide a spectrum of materials that range from particles to uniform hydrogels. Due to hydrophobic end groups, 3 kDa molecular weight macromers result in micro and nano-particles, while 18 kDa macromers completely dissolve and consequently uniform, transparent, high water content hydrogels are formed. Oriented channels may be induced into these hydrogels through the controlled freezing of water in the preformed hydrogel.Macromolecular Bioscience 10/2008; 8(10):923-31. · 3.89 Impact Factor -
Article: Patterned melt electrospun substrates for tissue engineering.
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ABSTRACT: Tissue engineering scaffolds can be built with patterning techniques that allow discrete placement of structures. In this study, electrospun fibres are collected in focused spots; the patterning and drawing of a cell adhesive scaffold is shown. Blends of biodegradable poly(ethylene glycol)-block-poly(epsilon-caprolactone) (PEG-b-PCL) and PCL were melt electrospun onto glass collectors, and the optimal electrospinning parameters determined. The quality of the fibre was largely influenced by the flow rate of the melt to the spinneret; however, this can be adjusted with the voltage. A collection distance between 3 cm and 5 cm was optimal, and at 10 cm the fibres became unfocused in their deposition although the diameter remained similar (0.96 +/- 0.19 microm). Aligned lines of electrospun fibres 200-400 microm in width could be applied onto the slide with an x-y stage, continuously and discretely. Lines of electrospun fibres could be applied on top of one another and were very uniform in diameter. Fibroblasts adhered primarily in the fibre region, due to the poor cell adhesion to the PEG substrate. Improvements in depositing hydrophilic electrospun fibres that wet and adhere to in vitro substrates and the use of stage automation for the writing interface could provide scaffold-building devices suitable for tissue engineering applications.Biomedical Materials 10/2008; 3(3):034109. · 2.16 Impact Factor -
Article: Biofunctionalized poly(ethylene glycol)-block-poly(epsilon-caprolactone) nanofibers for tissue engineering.
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ABSTRACT: Electrospun fibers with contrasting cell adhesion properties provided non-woven substrates with enhanced in vitro acceptance and controllable cell interactions. Poly(ethylene glycol)-block-poly(epsilon-caprolactone) (PEG-b-PCL) block copolymers with varying segment lengths were synthesized in two steps and characterized by NMR and GPC. A cell adhesive peptide sequence, GRGDS, was covalently coupled to the PEG segment of the copolymer in an additional step. The suitability of polymers with molecular weights ranging from 10 to 30 kDa for electrospinning and the influences of molecular weight, solvent, and concentration on the resulting morphologies were investigated. Generally, electrospun fibers were obtained by electrospinning polymers with molecular weight larger than 25 kDa and concentrations of 10 wt%. Methanol/chloroform (25/75, v/v) mixtures proved to be good solvent systems for electrospinning the PEG-b-PCL and resulted in hydrophilic, non-woven fiber meshes (contact angle 30 degrees ). The mesh without cell adhesive GRGDS ligands showed no attachment of human dermal fibroblasts after 24 h cell culture demonstrating that the particular combination of the material and electrospinnig conditions yielded protein and cell repellent properties. The GRGDS immobilized mesh showed excellent cellular attachment with fibroblasts viable after 24 h with spread morphology. Electrospun nanofibers based on block copolymers have been produced which are capable of specifically targeting cell receptor binding and are a promising material for tissue engineering and controlling cell material interactions.Journal of Materials Science Materials in Medicine 05/2008; 19(4):1479-84. · 2.32 Impact Factor -
Article: Control of protein adsorption on functionalized electrospun fibers.
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ABSTRACT: Electrospun fibers that are protein resistant and functionalized with bioactive signals were produced by solution electrospinning amphiphilic block copolymers. Poly (ethylene glycol)-block-poly(D,L-lactide) (PEG-b-PDLLA) was synthesized in two steps, with a PEG segment of 10 kDa, while the PDLLA block ranged from 20 to 60 kDa. Depending on the PEG and PDLLA segment ratio, as well as solvent selection, the hydrophilicity and protein adsorption could be altered on the electrospun mesh. Furthermore, an alpha-acetal PEG-b-PDLLA was synthesized that allowed the conjugation of active molecules, resulting in surface functionalization of the electrospun fiber. Electrospun material with varying morphologies and diameter were electrospun from 10, 20, and 30 wt.% solutions. Sessile drop measurements showed a reduction in the contact angle from 120 degrees for pure poly(D,L-lactide) with increasing PEG/PDLLA ratio. All electrospun block PEG-b-PDLLA fibers had hydrophilic properties, with contact angles below 45 degrees . The fibers were collected onto six-arm star-poly(ethylene glycol) (star-PEG) coated silicon wafers and incubated with fluorescently labeled proteins. All PEG-b-PDLLA fibers showed no detectable adsorption of bovine serum albumin (BSA) independent of their composition while a dependence between hydrophobic block length was observed for streptavidin adsorption. Fibers of block copolymers with PDLLA blocks smaller than 39 kDa showed no adsorption of BSA or streptavidin, indicating good non-fouling properties. Fibers were surface functionalized with N(epsilon)-(+)-biotinyl-L-lysine (biocytin) or RGD peptide by attaching the molecule to the PEG block during synthesis. Protein adsorption measurements, and the controlled interaction of biocytin with fluorescently labeled streptavidin, showed that the electrospun fibers were both resistant to protein adsorption and are functionalized. Fibroblast adhesion was contrasting between the unfunctionalized and RGD-coupled electrospun fabrics, confirming that the surface of the fibers was functionalized. The PEG-b-PDLLA surface functionalized electrospun fibers are promising substrates for controlling cell-material interactions, particularly for tissue-engineering applications.Biotechnology and Bioengineering 05/2008; 101(3):609-21. · 3.95 Impact Factor -
Article: Melt electrospinning of poly‐(ethylene glycol‐block‐ϵ‐caprolactone)
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ABSTRACT: Various block copolymers of poly(ethylene glycol) and poly(ϵ-caprolactone) (PEG-b-PCL) with molecular weights between 7000 and 26 900 g/mol were synthesized, and melt electrospun at temperatures between 60°C and 90°C. Two types of fibers were collected, including excellent quality fibers – highly coiled and continuous, with a constant diameter and relatively defect free. Such fibers, termed “solid fibers”, were sufficiently cooled during their path between the spinneret and the collector that the symmetric fiber shape is maintained after landing on the collector. The second type of melt electrospun fiber were poor quality, large diameter fibers, flattened on the collector – termed “molten fibers”. The solid and molten fibers were morphologically distinct from each other as determined from scanning electron microscopy (SEM). Using an SEM imaging method to assess the regional variations of collected electrospun material, we found the spinneret pump rate largely influenced the fiber quality. The polymer flow rate to the spinneret and the molecular weight of PEG-b-PCL had the greatest effect on the electrospun fibers collected, with an optimum rate of 0.05–0.1 mL/h for the highest molecular weight copolymers. The lowest molecular weight PEG-b-PCL tended to electrospray, while the material collected from higher molecular weight copolymers were conducive to fiber formation. The highest quality fibers were PEG-b-PCL block copolymers (22 000 and 26 900 g/mol) melt electrospun at temperatures of 85°C and 90°C, corresponding to shear viscosities of the polymer of between 28.1 and 39.4 Pa.S.Biotechnology Journal 08/2006; 1(9):998 - 1006. -
Article: Direct in vitro electrospinning with polymer melts.
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ABSTRACT: The electrospinning of polymer melts can offer an advantage over solution electrospinning, in the development of layered tissue constructs for tissue engineering. Melt electrospinning does not require a solvent, of which many are cytotoxic in nature, and the use of nonwater soluble polymers allows the collection of fibers on water or onto cells. In this article, melt electrospinning of a blend of PEO-block-PCL with PCL was performed with in vitro cultured fibroblasts as the collection target. The significant parameters governing electrospinning polymer melts were determined before electrospinning directly onto fibroblasts. In general, a high electric field resulted in the most homogeneous and smallest fibers, although it is important that an optimal pump rate to the spinneret needs to be determined for different configurations. Many parameters governing melt electrospinning differ to those reported for solution electrospinning: the pump rate was a magnitude lower and the viscosity a magnitude higher than successful parameters for solution electrospinning. Cell vitality was maintained throughout the electrospinning process. Six days after electrospinning, fibroblasts adhered to the electrospun fibers and appeared to detach from the underlying flat substrate. The morphology of the fibroblasts changed from spread and flat, to long and spindle-shaped as adherence onto the fiber progressed. Therefore, an important step for producing layer-on-layer tissue constructs of cells and polymers in view of scaffold construction for tissue engineering was successfully demonstrated. The process of using cultured cells as the collection target was termed "direct in vitro electrospinning".Biomacromolecules 04/2006; 7(3):686-90. · 5.48 Impact Factor -
Article: Electrospinning of polymer melts: Phenomenological observations
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ABSTRACT: Melt electrospinning is an alternative to solution electrospinning, however, melt electrospinning has typically resulted in fibers with diameters of tens of microns. In this paper we demonstrate that polypropylene fibers can be reduced from 35 ± 8 μm in diameter, to 840 ± 190 nm with a viscosity-reducing additive. Melt electrospun blends of poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG47-b-PCL95) and poly(ɛ-caprolactone) (PCL) produced fibers with micron-scale diameters (2.0 ± 0.3 μm); this was lowered to 270 ± 100 nm by using the gap method of alignment for collection. The collected melt electrospun fibers often fused together where they touched, allowing the stabilization of relatively thick non-woven felts. The melt electrospun collection also included coiled circles and looped patterns of fibers approximately 150–250 μm in diameter. The polymer jet was visible between the collector and spinneret for particularly significant lengths, and underwent coiling and buckling instabilities close to the collector. The focused deposition of melt electrospun fibers was maintained when multiple jets were observed, with the collections from multiple jets separated by 3.8 ± 0.5 mm for a 5 cm collector gap. The frequent fusion points between melt electrospun fibers, and a reduction in diameter for the gap method of alignment, indicated that the melt electrospun fibers are still slightly molten at collection.Polymer. -
Article: Electrospinning with dual collection rings
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ABSTRACT: The formation of electrospun poly(ɛ-caprolactone) (PCL) fibres between two collection rings is described, and the conversion of these fibres into a multi-filament yarn of is demonstrated. During electrospinning, when two grounded rings are placed equidistantly from the spinneret, an array of fibres is formed between the collection rings. These rapidly produced fibres are three-dimensionally suspended in air, and demonstrate low incidence of fibre splitting when lower voltages are applied. Such electrospun fibres, with a diameter of 1.26±0.19 μm and a length between 40 and 100 mm, were oriented and continuous. Furthermore, manufacture of the fibre array was easily achievable, reproducible and not subject to relatively small changes in spinneret-ground distance or applied voltage. Rotation of one of the collection rings results in a wound multi-filament yarn with a diameter below 5 μm, and a length of 50 mm.Polymer.
Top co-authors
Top Journals
Institutions
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2013
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Università degli Studi di Trento
Trento, Trentino-Alto Adige, Italy
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2010–2011
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Queensland University of Technology
- Institute of Health and Biomedical Innovation
Brisbane, Queensland, Australia -
Uppsala University
- Biology Education Centre
Uppsala, Uppsala, Sweden
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2009
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Shanghai Jiao Tong University
Shanghai, Shanghai Shi, China
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2006–2008
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University of Southampton
- Biological Sciences
Southampton, ENG, United Kingdom -
Rheinisch-Westfälische Technische Hochschule Aachen
Aachen, North Rhine-Westphalia, Germany
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