Among other biomedical applications, magnetic nanoparticles and liposomes have a vast field of applications in tissue engineering and regenerative medicine. Magnetic nanoparticles and liposomes, when introduced into cells to be cultured, maneuver the cell's positioning by the appropriate use of magnets to create more complex tissue structures than those that are achieved by conventional culture methods. ; This work was supported by the Portuguese Foundation for Science and Technology (FCT) and the Andalusian Initiative for Advanced Therapies (Ministry of Health of the Andalusian Regional Government). Special thanks to Dr. Vega Asensio (www.NorArte.es) and her beautiful scientific illustrations for the review. Emilio Castro thanks his postdoctoral fellowship from Health and Progress Foundation (Mobility Program for ...
Many proteins in the inorganic=organic matrix of bone induce or modulate or inhibit mineralization of apatite in vivo. Many attempts have been made to mimic and understand this mechanism as part of bone formation, and ectopic mineralization and control thereof. Many attempts have also been made to use such proteins or protein fragments to harness their potential for improved mineralization. Such proteins and peptide motifs have also been the inspiration for attempts of making mimics of their structures and motifs using chemical or biological synthesis. The aim of this review is to highlight how proteins and (poly)peptides themselves impact mineralization in the human body, and how those could be used and have been used for improving apatite mineralization, for example, on or in materials that by themselves do not induce apatite mineralization but otherwise have interesting properties for use as bone tissue engineering scaffolds. ; J. Benesch wishes to acknowledge the financial support from FCT, postdoctoral fellowship scholarship SFRH/BPD/17584/2004. This work was carried out under the scope of the European Union NoE EXPERTISSUES (NMP3-CT-2004500283) and partially funded by the European Union FP6 STREP Project HIPPOCRATES (NMP3-CT-2003-505758) and FCT project ProteoLight ...
Chitin and chitosan are natural based non-toxic, biodegradable and biocompatible polymers and have been used in biomedical areas in the form of sutures, wound healing materials and artificial skin, and for the sustained release of drugs as well as in various industrial applications. However, practical use of these polymers has been mainly confined to the unmodified forms. Recently, there has been a growing interest in chemical modification of chitin and chitosan to improve their solubility and widen their applications. Among them, phosphorylated chitin and chitosan have attracted considerable interest because of their various advantages: anti-inflammatory property, ability to form metal complexes, blood compatibility and formation of anionic polyelectrolyte hydrogels. The purpose of this review is to take a closer look of different synthetic methods of phosphorylated chitin and chitosan and their potential applications in environmental, food, fuel cell, and biomedical fields. Based on current research and existing products, some new and futuristic approaches in this context area are discussed. ; R. Jayakumar acknowledges the Portuguese Foundation for Science and Technology for providing him a Post-Doc scholarship (SFRH/BPD/14670/2003). This work was partially supported by FCT Foundation for Science and Technology, through funds from the POCTI and/or FEDER program. This work was partially supported by the European Union funded STREP Project HIPPOCRATES ...
Engineered cell instructive microenvironments with the ability to stimulate specific cellular responses is a topic of high interest in the fabrication and development of biomaterials for application in tissue engineering. Cells are inherently sensitive to the in vivo microenvironment that is often designed as the cell "niche". The cell "niche" comprising the extracellular matrix and adjacent cells, influences not only cell architecture and mechanics, but also cell polarity and function. Extensive research has been performed to establish new tools to fabricate biomimetic advanced materials for tissue engineering that incorporate structural, mechanical and biochemical signals that interact with cells in a controlled manner and to recapitulate the in vivo dynamic microenvironment. Bioactive tunable microenvironments using micro and nanofabrication have been successfully developed and proven to be extremely powerful to control intracellular signaling and cell function. This review is focused in the assortment of biochemical signals that have been explored to fabricate bioactive cell microenvironments and the main technologies and chemical strategies to encode them in engineered biomaterials with biological information. ; The authors thank Fundacao para a Ciencia e Tecnologia for C.A.C.'s PhD grant (SFRH/BD/61390/2009). This work was carried out under the scope of the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no ...
From the use of botanical plants in early human civilizations through synthetic chemistry and biotechnology, drug research has always passionate scientists creating exciting challenges to a large number of researchers from different fields, thus, promoting a collaborative effort between polymer scientists, pharmacologists, engineers, chemists and medical researchers. Worldwide, there is an increasing concern on health care that creates a major opportunity for development of new pharmaceutical formulations. Ageing populations worried about the quality of life in the older years are actively seeking for new, more effective and patient compliant drug delivery devices. This has been the driving force for the continuous growth of the research made on delivery devices, which has become a powerful technique in health care. It has been recognized for long that simple pills or injections may not be the suitable methods of administration of a certain active compound. These medications present several problems and/or limitations, like poor drug bioavailability and systemic toxicity, derived essentially from pharmacokinetic and other carrier limitations and low solubility of the drugs in water. Therefore and to overcome these drawbacks, clinicians recommend frequent drug dosing, at high concentrations, in order to overcome poor drug bioavailability but causing a potential risk of systemic toxicity. Polymer science has open new strategies for drug delivery systems. This Chapter overviews of possible strategies involving polymer modification and processing for controlled drug delivery and drug delivery in tissue engineering. ; European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number REGPOT-CT2012-316331-POLARIS and from the project "Novel smart and biomimetic materials for innovative regenerative medicine approaches" RL1 -ABMR-NORTE-01-0124-FEDER-000016 cofinanced by North Portugal Regional Operational Programme (ON.2 –O Novo Norte), under the National Strategic Reference Framework (NSRF), ...
The objective of this study was to investigate the influence of silk fibroin and oxidized starch conjugation on the enzymatic degradation behavior and the cytocompatability of chitosan based biomaterials. The tensile stress of conjugate membranes, which was at 50 Megapascal (MPa) for the lowest fibroin and starch composition (10 weight percent (wt.%)), was decreased significantly with the increased content of fibroin and starch. The weight loss of conjugates in α-amylase was more notable when the starch concentration was the highest at 30 wt.%. The conjugates were resistant to the degradation by protease and lysozyme except for the conjugates with the lowest starch concentration. After 10 days of cell culture, the proliferation of osteoblast-like cells (SaOS-2) was stimulated significantly by higher fibroin compositions and the DNA synthesis on the conjugate with the highest fibroin (30 wt.%) was about two times more compared to the native chitosan. The light microscopy and the image analysis results showed that the cell area and the lengths were decreased significantly with higher fibroin/chitosan ratio. The study proved that the conjugation of fibroin and starch with the chitosan based biomaterials by the use of non-toxic reductive alkylation crosslinking significantly improved the cytocompatibility and modulated the biodegradation, respectively. ; E.T. Baran thanks the Portuguese Foundation for Science and Technology for providing him a PostDoc scholarship (SFRH/BPD/30768/2006). This work was partially supported by the European Union funded STREP Project HIPPOCRATES ...
Polymers have gained a remarkable place in the biomedical fi eld as materials for the fabrication of various devices and for tissue engineering applications. The initial acceptance or rejection of an implantable device is dictated by the crosstalk of the material surface with the bioentities present in the physiological environment. Advances in microfabrication and nanotechnology offer new tools to investigate the complex signaling cascade induced by the components of the extracellular matrix and consequently allow cellular responses to be tailored through the mimicking of some elements of the signaling paths. Patterning methods and selective chemical modifi cation schemes at different length scales can provide biocompatible surfaces that control cellular interactions on the micrometer and sub-micrometer scales on which cells are organized. In this review, the potential of chemically and topographically structured micro- and nanopolymer surfaces are discussed in hopes of a better understanding of cell–biomaterial interactions, including the recent use of biomimetic approaches or stimuli-responsive macromolecules. Additionally, the focus will be on how the knowledge obtained using these surfaces can be incorporated to design biocompatible materials for various biomedical applications, such as tissue engineering, implants, cell-based biosensors, diagnostic systems, and basic cell biology. The review focusses on the research carried out during the last decade. ; The research leading to these results has received partial funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. NMP4-SL-2009-229292 and by the FCT projects PTDC/FIS/68517/2006, PTDC/QUI/69263/2006, PTDC/FIS/68209/2006, and ...
The use of superhydrophobic surfaces to produce polymeric particles proves to be biologically friendly since it entails the pipetting and subsequent cross-linking of polymeric solutions under mild experimental conditions. Moreover, it renders encapsulation efficiencies of ∼100%. However, the obtained particles are 1 to 2 mm in size, hindering to a large extent their application in clinical trials. Improving on this technique, we propose the fabrication of polymeric microparticles by spraying a hydrogel precursor over superhydrophobic surfaces followed by photo-cross-linking. The particles were produced from methacrylamide chitosan (MA-CH) and characterized in terms of their size and morphology. As demonstrated by optical and fluorescence microscopy, spraying followed by photo-cross-linking led, for the first time, to the production of spherical particles with diameters on the order of micrometers, nominal sizes not attainable by pipetting. Particles such as these are suitable for medical applications such as drug delivery and tissue engineering. ; We thank Ivo Aroso and Ana Isabel Neto for their valuable support with FTIR and compression experiments, respectively. A.M.S.C. thanks FCT for financial support through grant BIM/PTDC/CTM-BPC/112774/2009_02. M.A.-M. thanks CONACyT (Mexico) for financial support through post-doc grant no. 203732. N.M.O. thanks FCT for financial support through Ph.D. scholarship no. SFRH/BD/73172/2010. This work was funded by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. REGPOT-CT2012-316331-POLARIS, by FEDER through the Competitive Factors Operation Program-COMPETE, and by national funds through FCT - Fundacao para a Ciencia e a Tecnologia in the scope of project ...
Cells microencapsulated in biocompatible semi-permeable polymeric membranes are effective as cell delivery systems while protecting the host against immune responses. In this study, cell encapsulation membranes were prepared based on carrageenan and alginate, two natural cationic polymers. Different formulations/conditions were explored to optimize the microcapsules which were characterized with respect to their morphology, mechanical stability, and cytotoxicity. Spherical-shaped microcapsules were obtained from all the polymeric systems. The iota-carrageenan/sodium alginate microcapsules exhibited the best stability and permeability, and therefore, these were selected for the cell encapsulation. These capsules provided an environment that supported cell proliferation and have the potential for tissue engineering as well as other cell-based therapy applications. ; One of the authors (SML) acknowledges the support of the Programme Alssan-the European Union Programme of High Level Scholarships for Latin America (scholarship no. E04M041362CO). This work was partially supported by the European STREP HIPPOCRATES (NMP3-CT-2003-505758) and by the Fundacao para a Ciencia e Tecnologia (project PTDC/QUI/68804/2006) and carried out under the scope of European NoE EXPERTISSUES ...
Purpose: To implement a bioinspired methodology using superhydrophobic surfaces suitable for producing smart hydro- gel beads in which the bioactive substance is introduced in the particles during their formation. Methods: Several superhydrophobic surfaces, including polystyrene, aluminum and copper, were prepared. Polymeric solutions composed by photo-crosslinked dextran-methacrylated and thermal responsive poly(N-isopropylacrylamide) mixed with a protein (insulin or albumin) were dropped on the superhydrophobic surfaces, and the obtained millimetric spheres were hardened in a dry environment under UV light. Results: Spherical and non-sticky hydrogels particles were formed in few minutes on the superhydrophobic surfaces. The proteins included in the liquid formulation were homogeneously distributed in the particle network. The particles exhibited temperature-sensitive swelling, porosity and protein release rate, with the responsiveness tunable by the dextran-MA/PNIPAAm weight ratio.Conclusions: The proposed method permitted the preparation of smart hydrogel particles in one step with almost 100% encapsulation yield. The temperature-sensitive release profiles suggest that the obtained spherical-shaped biomaterials are suitable as protein carriers. These stimuli-responsive beads could have potential to be used in pharmaceutical or other biomedical applications, including tissue engineering and regenerative medicine. ; The authors acknowledge funding from the project: PTDC/QUI/68804/2006 (FCT), IBEROMARE-Procept, FEDER and MICINN (SAF2008-01679). The research leading to these results has also received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement #NMP4-SL-2009-229292. The authors are grateful to project DISC REGENERATION, Collaborative Project-Large-scale integrating project, NMP3-LA-2008-213904 for the use of the UV ...
Since the pioneering work dealing with the synthesis and physicochemical aspects of dendrimers, a predictable and tunable set of compositions for therapeutic, scaffolding and imaging systems has been reported. These are well documented, butmanyhot issues should be examined and reviewed. Herein, a review is given on dendritic nanopolymers and their applications that show promise in the field of regenerative medicine. This review begins with a brief overview on research merging nanotechnology and regenerative medicine. Fundamentals of the synthesis and macromolecular structure of dendritic polymers are provided. Dendrimers fulfill the requirements as carriers for gene, nucleic acids, bioactive molecules and peptide/protein delivery aimed at modulate the cells functions, in vitro and in vivo. However, to make use of this potential, toxicological, drug-loading capacity, surface engineering and host–guest chemistries in dendrimers must be addressed and thus are also discussed. We focus on recent work involving dendrimers with applications in tissue engineering and the central nervous system. Due to their innovative character, applications beyond drug delivery systems became possible, namely as scaffolding and chemoattractants for tissue regeneration, and implantable biodegradable nanomaterialbased medical devices integrated with drug delivery functions (theranostics). Finally, we highlight promising areas for further research and comment on how and why dendrimer and dendron technology should be viewed as the next generation of biomaterials for the 21st century. ; The authors wish to acknowledge the funding provided by the Portuguese Foundation for Science and Technology (FCT) through the POCTI and FEDER programs, and FCT project (SMARTCARBO). This work was carried out under the scope of the European NoE EXPERTISSUES (NMP3-CT-2004-500283) and European Union HIPPOCRATES STREP Project (NMP3-CT-2003-505758). Canon Foundation in Europe is also gratefully ...
The thermo-oxidative stability of polypropylene (PP) in composites containing 15 wt.% of cork and the performance of selected cork extracts as stabilizing additives for PP was evaluated by Oxidation Induction Time (OIT) and by Oxidation Onset Temperature (OOT). The results showed that cork increases the OIT of PP in the composite and it was identified that the cork extractives fraction is responsible for such behavior. Selected cork extracts with high antioxidant capacity (determined by dpph radical scavenging and oxygen reactive absorbance capacity assays) were compounded by extrusion with PP in 0.5 and 1.5 wt.%. It was found that the ethanol extract is the most effective as thermo-oxidative stabilizer for PP. At the loading level of 1.5%, the OIT increases from 3.8 (neat PP) to 29.7 min at 200 °C and from 1.2 (neat PP) to 9.0 min at 220 °C. The OOT also increases from 216 °C (neat PP) to 247 °C. Mechanical tests, performed on PP loaded with the cork extracts, showed that the presence of these extracts has no significant effect on the polymer mechanical performance. The results demonstrate the suitability of cork as a source of thermo-oxidative stabilizing additives for the formulation of polyolefins, and enable the exploitation of new routes of cork valorization. ; The authors are grateful to Amorim Cork Composites for providing the cork powder raw material. Ivo Aroso and Emanuel Fernandes are grateful for financial support of FCT through grants SFRH/BD/42273/2007 and SFRH/BPD/96197/2013, respectively. Funding was also granted from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS and from Project "Novel smart and biomimetic materials for innovative regenerative medicine approaches (Ref.: RL1-ABMR-NORTE-01-0124-FEDER-000016)" co-financed by North Portugal Regional Operational Programme (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund ...
Great efforts have been made to introduce growth factors (GFs) onto 2D/3D constructs in order to control cell behavior. Platelet Lysate (PL) presents itself as a cost-effective source of multiple GFs and other proteins. The instruction given by a construct-PL combination will depend on how its instructive cues are presented to the cells. The content, stability and conformation of the GFs affect their instruction. Strategies for a controlled incorporation of PL are needed. Herein, PL was incorporated into nanocoatings by layer-by-layer assembling with polysaccharides presenting different sulfation degrees (SD) and charges. Heparin and several marine polysaccharides were tested to evaluate their PL and GF incorporation capability. The consequent effects of those multilayers on human adipose derived stem cells (hASCs) were assessed in short-term cultures. Both nature of the polysaccharide and SD were important properties that influenced the adsorption of PL, vascular endothelial growth factor (VEGF), fibroblast growth factor b (FGFb) and platelet derived growth factor (PDGF). The sulfated polysaccharides-PL multilayers showed to be efficient in the promotion of morphological changes, serum-free adhesion and proliferation of high passage hASCs (P>5). These biomimetic multilayers promise to be versatile platforms to fabricate instructive devices allowing a tunable incorporation of PL. ; Portuguese Foundation for Science and Technology is gratefully acknowledged for fellowships of Sara M. Oliveira. (SFRH/BD/70107/2010).r The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS and FP7-KBBE-2010-4-266033 - SPECIAL. This work was also supported by the European Research Council grant agreement ERC-2012-ADG 20120216-321266 for the project ComplexiTE. The authors acknowledge Rogerio P. Pirraco for the Flow cytometry ...
Surface properties play a vita role in the functioning of a biomaterial. Cellular adherence and growth onto biomaterials can be enhanced in biomaterial modifications of their surface. In this work, the cell behaviour on chitosan membranes modified by argon and nitron-plasma treatments was investigated. Characterization of the membranes was performed using atomic force microscopy, contact angle measurements, and X-ray photoelectron spectroscopy. Cytotoxicity assessment and direct contact assay were carried out for untreated and treated chitosan membranes using L929 fibroblast-like cells. Cell morphology and cell viability were assessed to evaluate the cell attachment and proliferation. Changes in terms of roughness, surface chemistry, and hydrophilicity/hydrophobic balance of chitosan-modified membranes were observed. Regarding cell studies, the findings revealed that the extracts of all membranes do not induce cytotoxicity effects. Moreover, the in vitro assays evidenced an improvement of the L929 adhesion, and attachment when compared to untreated chitosan membranes. overall, the data obtained clearly demonstrated that plasma treatments constitute an effective way of improving the biocompatibility of chitosan membranes towards to their use in biomedical applications. ; S. M. Luna acknowledges the support of the Programme Alssan - The European Union Programme of High Level Scholarships for Latin America (scholarship No E04M041362CO) and Silva SS acknowledge the support of the Portuguese Foundation for Science and Technology, (SFRH/BPD/45307/2008). This work was also partially supported by the European Union-funded - STREP project HIPPOCRATES (NMP3-CT-2003-505758) and was carried out under the scope of European NoE EXPERTISSUES ...
