Annual Report of Activities CNC 2008 - Center for Neuroscience and ...

Biomaterials and Stem Cell‐Based Therapeutics | Head: Lino FerreiraObjectivesThe group of biomaterials and stem cell‐basedtherapeutics created in September 2006 is anemerging group at CNC. The group has two majoravenues of research: i) to develop new biomaterialsfor stem cell differentiation, tracking andtransplantation, and ii) to develop biomaterialswith antimicrobial properties. We are designingbiomaterials which provide different types ofinformation to stem cells, with the purpose ofcontrolling their differentiation and enhancingtheir grafting after in vivo transplantation. In thiscontext we are developing or modifying natural orsynthetic polymers and to characterize theirphysico‐chemical and biological properties. One ofthe major interests in our group is to identifybiomaterials that will improve the differentiation ofstem cells in vascular or cardiomyocyte lineagesand to obtain fundamental knowledge regardingthe effect of chemistry, mechanics and threedimensionalorganization of the scaffold in termsof stem cell differentiation.Another focus of our group is the design ofbiomaterials with antimicrobial properties. A majorproblem associated with the implantation ofbiomedical devices in the human body is theinherent risk of microbial infections. We aredeveloping effective strategies to controlantimicrobial infections by developing coatingtechnologies to immobilize antimicrobial agents.Confocal microscopy of cellular uptake of nanoparticles. BlueTopro‐3 stains the nucleus, green lysosensor indicatesendosomes, green phalloidin indicates cytoplasm, and TRITClabellednanoparticles are displayed in red. Nanoparticles can beseen co‐localized with endosomes as a yellow colour anddistributed mainly in the perinuclear region. For all pictures,bar corresponds to 20 μm. Taken from Ferreira et al. AdvancedMaterials 2008.Main AchievementsRecently we reported a new approach for thedelivery of vascular growth factors into humanembryonic stem cells (hESCs), by incorporatinggrowth factor‐release particles into embryoidbodies (EBs) (Ferreira et al., Advanced Materials2008). We demonstrated that the incorporation ofthese polymeric biodegradable particles had aminimal effect on cell viability and proliferationbut a great impact on differentiation. In some cases,the effect on vascular differentiation ofincorporation of particles containing growth factorswas superior to that produced by exposing EBs tolarge extrinsic doses of the same growth factors.Recently we have also contributed for thedevelopment of new nanomaterials for drugrelease and cell tracking (Fuller et al., Biomaterials2008). Highly fluorescent core‐shell silicananoparticles made by the modified Stober process(C dots) are promising as tools for sensing andimaging subcellular agents and structures. Wereported that C dots can be electrostatically coatedwith cationic polymers, changing their surfacecharge and enabling them to escape fromendosomes and enter the cytoplasm and nucleus.As an example of cellular delivery, wedemonstrated that these particles can also becomplexed with DNA and mediate and trace DNAdelivery and gene expression. During 2008, ourresearch group was also involved in thedevelopment of new bio‐adhesives (Mahdavi et al.,PNAS 2008). We approached this objective byutilizing a novel polymer poly(glycerol sebacic acidacrylate) (PGSA) and modifying the surface tomimic the nanotopography of gecko feet thatallows attachment to vertical surfaces. Coatingthese nano‐molded pillars of biodegradableelastomers with a thin layer of oxidized dextransignificantly increased the interfacial adhesionstrength on tissue either in vitro or in vivoenvironments. This gecko‐inspired medicaladhesive has potential applications for sealingwounds and for replacement or augmentation ofsutures or staples.39