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Bradshaw M.,University of Western Australia | Ho D.,University of Western Australia | Fear M.W.,University of Western Australia | Gelain F.,Center for Nanomedicine and Tissue Engineering | And 2 more authors.
Scientific Reports | Year: 2014

There is a need to develop economical, efficient and widely available therapeutic approaches to enhance the rate of skin wound healing. The optimal outcome of wound healing is restoration to the pre-wound quality of health. In this study we investigate the cellular response to biological stimuli using functionalized nanofibers from the self-assembling peptide, RADA16. We demonstrate that adding different functional motifs to the RADA16 base peptide can influence the rate of proliferation and migration of keratinocytes and dermal fibroblasts. Relative to unmodified RADA16; the Collagen I motif significantly promotes cell migration, and reduces proliferation.

Cunha C.,University of Milan Bicocca | Cunha C.,Center for Nanomedicine and Tissue Engineering | Brambilla R.,San Raffaele Scientific Institute | Thomas K.L.,University of Cardiff
Frontiers in Molecular Neuroscience | Year: 2010

Since its discovery almost three decades ago, the secreted neurotrophin brain-derived neurotrophic factor (BDNF) has been firmly implicated in the differentiation and survival of neurons of the CNS. More recently, BDNF has also emerged as an important regulator of synaptogenesis and synaptic plasticity mechanisms underlying learning and memory in the adult CNS. In this review we will discuss our knowledge about the multiple intracellular signaling pathways activated by BDNF, and the role of this neurotrophin in long-term synaptic plasticity and memory formation as well as in synaptogenesis. We will show that maturation of BDNF, its cellular localization and its ability to regulate both excitatory and inhibitory synapses in the CNS may result in confl icting alterations in synaptic plasticity and memory formation. Lack of a precise knowledge about the mechanisms by which BDNF infl uences higher cognitive functions and complex behaviours may constitute a severe limitation in the possibility to devise BDNF-based therapeutics for human disorders of the CNS. © 2010 Cunha, Brambilla and Thomas.

Gelain F.,Center for Nanomedicine and Tissue Engineering | Gelain F.,Massachusetts Institute of Technology | Unsworth L.D.,University of Alberta | Unsworth L.D.,Canadian National Institute For Nanotechnology | Zhang S.,Massachusetts Institute of Technology
Journal of Controlled Release | Year: 2010

Controlling the cellular microenvironment is thought to be critical for the successful application of biomaterials for regenerative medicine strategies. Self-assembling peptides are proving to be a promising platform for a variety of regenerative medicine applications. Specifically, RADA16-I self-assembling peptides have been successfully used for 3D cell culture, accelerated wound healing, and nerve-repair. Understanding the fundamental mechanisms for protein mobility within, and ultimately release from, this nanostructured system is a critical aspect for controlling cellular activity; studies which are largely lacking within the literature. Herein, we report that designer self-assembling peptide scaffolds facilitate slow and sustained release of active cytokines that are extremely relevant to many areas of regenerative medicine. In addition, multiple diffusive mechanisms are observed to exist for human βFGF, VEGF and BDNF within RADA16-I and two different RADA16-I nanofiber forming peptides with net positive or negative charges located at the C-terminus. In some cases, two populations of diffusing molecules are observed at the molecular level: one diffusing fully within the solvent, and another that exhibits hindered mobility. Results suggest that protein mobility is inhibited by both physical hinderances and charge induced interactions between the protein and peptide nanofibers. Moreover, assays using adult neural stem cells (NSCs) are employed to assess the functional release of active cytokine (βFGF) up to three weeks. Our results not only provide evidence for long-term molecular release from self-assembling peptide scaffolds but also inspiration for a plethora of slow molecular release strategies for clinical applications. © 2010 Elsevier B.V.

Campagnolo L.,Rizzoli Orthopaedic Institute | Fenoglio I.,IRCCS Casa Sollievo della Sofferenza Opera di San Pio da Pietrelcina | Massimiani M.,Center for Nanomedicine and Tissue Engineering | Magrini A.,Center for Nanomedicine and Tissue Engineering | Pietroiusti A.,Center for Nanomedicine and Tissue Engineering
Methods in Molecular Biology | Year: 2013

Due to the increasing use of engineered nanoparticles in many consumer products, rapid and economic tests for evaluating possible adverse effects on human health are urgently needed. In the present chapter the use of mouse embryonic stem cells as a valuable tool to in vitro screen nanoparticle toxicity on embryonic tissues is described. This in vitro method is a modification of the embryonic stem cell test, which has been widely used to screen soluble chemical compounds for their embryotoxic potential. The test offers an alternative to animal experimentation, reducing experimental costs and ethical issues. © Springer Science+Business Media New York 2013.

Raspa A.,Center for Nanomedicine and Tissue Engineering | Saracino G.A.A.,Center for Nanomedicine and Tissue Engineering | Saracino G.A.A.,University of Milan Bicocca | Pugliese R.,University of Milan Bicocca | And 6 more authors.
Advanced Functional Materials | Year: 2014

Self-assembling biomaterials offer an unprecedented chance of successfully facing most of the challenges of various biomedical fields, and, in particular, of tissue engineering. Nonetheless co-assembling peptides (CAPs), taking advantage of the theory and empirical findings developed for self-assembling peptides, could provide an even better control over cell cultures, drug delivery, and transplantation therapies. This study follows a "full" bottom-up approach to develop new CAPs for neural tissue engineering applications. After molecular aggregation analysis via coarse-grained simulations, LKLK12, LDLD12, and the functionalized KLPGWSG-LDLD12 CAPs are synthesized and characterized assessing their co-assembled secondary structures, the biomechanical properties of the obtained hydrogels, and the morphological features of the assembled nanofibers. The biological influence on viability and differentiation of human and murine neural stem cells are tested in vitro and neuroregenerative potentials in complete spinal cord transections are verified in vivo. Upon mixing of CAPs, the spontaneous formation of double layers of β-sheets with a high degree of integration of the two CAP species is demonstrated. The formation of entangled nanofibrous structures give rise to shear-thinning hydrogels. The in vitro results are comparable to a standard state-of-the-art cell culture substrate and nervous regeneration in vivo is enhanced. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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