Embracing complexity in biomaterials design

Animate materials, man-made materials behaving like living systems, are attracting enormous interest across a range of sectors, from construction and transport industry to medicine. In this leading opinion article, we propose that embracing complexity in biomaterials design offers untapped opportunities to create biomaterials with innovative life-like properties that extend their capabilities and unleash new paradigms in medical treatmen

Unravelling the Enzymatic Degradation Mechanism of Supramolecular Peptide Nanofibers and Its Correlation with Their Internal Viscosity.

Enzyme-responsive supramolecular peptide biomaterials have attracted growing interest for disease diagnostics and treatments. However, it remains unclear whether enzymes target the peptide assemblies or dissociated peptide monomers. To gain further insight into the degradation mechanism of supramolecular peptide amphiphile (PA) nanofibers, cathepsin B with both exopeptidase and endopeptidase activities was exploited here for degradation studies. Hydrolysis was found to occur directly on the PA nanofibers as only surface amino acid residues were cleaved. The number of cleaved residues and the degradation efficiency was observed to be negatively correlated with the internal viscosity of the PA nanofibers, quantified to be between 200-800 cP (liquid phase) using fluorescence lifetime imaging microscopy combined with an environmentally sensitive molecular rotor, BODIPY-C10. These findings enhance our understanding on the enzymatic degradation of supramolecular PA nanofibers and have important implications for the development of PA probes for the real-time monitoring of disease-related enzymes

Surface modification of stainless steel for biomedical applications: Revisiting a century-old material

Stainless steel (SS) has been widely used as a material for fabricating cardiovascular stents/valves, orthopedic prosthesis, and other devices and implants used in biomedicine due to its malleability and resistance to corrosion and fatigue. Despite its good mechanical properties, SS (as other metals) lacks biofunctionality. To be successfully used as a biomaterial, SS must be made resistant to the biological environment by increasing its anti-fouling properties, preventing biofilm formation (passive surface modification), and imparting functionality for eluting a specific drug or capturing selected cells (active surface modification); these features depend on the final application. Various physico-chemical techniques, including plasma vapor deposition, electrochemical treatment, and attachment of different linkers that add functional groups, are used to obtain SS with increased corrosion resistance, improved osseointegration capabilities, added hemocompatibility, and enhanced antibacterial properties. Existing literature on this topic is extensive and has not been covered in an integrated way in previous reviews. This review aims to fill this gap, by surveying the literature on SS surface modification methods, as well as modification routes tailored for specific biomedical applications. STATEMENT OF SIGNIFICANCE: Stainless steel (SS) is widely used in many biomedical applications including bone implants and cardiovascular stents due to its good mechanical properties, biocompatibility and low price. Surface modification allows improving its characteristics without compromising its important bulk properties. SS with improved blood compatibility (blood contacting implants), enhanced ability to resist bacterial infection (long-term devices), better integration with a tissue (bone implants) are examples of successful SS surface modifications. Existing literature on this topic is extensive and has not been covered in an integrated way in previous reviews. This review paper aims to fill this gap, by surveying the literature on SS surface modification methods, as well as to provide guidance for selecting appropriate modification routes tailored for specific biomedical applications.Accepted manuscrip

Photoconfigurable, Cell-Remodelable Disulfide Cross-linked Hyaluronic Acid Hydrogels.

Dynamic photoresponsive synthetic hydrogels offer important advantages for biomaterials design, from the ability to cure hydrogels and encapsulate cells in situ to the light-mediated control of cell-spreading and tissue formation. We report the facile and effective photocuring and photoremodeling of disulfide-cross-linked hyaluronic acid hydrogels, based on photo-oxidation of corresponding thiol residues and their radical-mediated photodegradation. We find that the mechanical properties of disulfide hydrogels and the extent of their photoremodeling can be tuned by controlling the photo-oxidation and photodegradation reactions, respectively. This enables not only the photopatterning of the mechanical properties of hydrogels but also their self-healing and photomediated healing. Finally, we demonstrate the ability to encapsulate mesenchymal stromal cells within these materials and to regulate their protrusion and spreading in 3D matrices by controlling the mechanical properties of the disulfide networks. Therefore, synthetically accessible photoconfigurable disulfide hydrogels offer interesting opportunities for the design of soft biomaterials and the regulation of cell encapsulation and matrix remodeling for tissue engineering

Host-Guest-Mediated Epitope Presentation on Self-Assembled Peptide Amphiphile Hydrogels

A key feature in biomaterial design is the incorporation of bioactive signals into artificial constructs to stimulate tissue regeneration. Most currently used hydrogel cell culture systems depend on the covalent attachment of extracellular matrix (ECM)-derived peptides to either macromolecular units or smaller self-assembling building blocks, thereby restricting biosignal presentation and adaptability. However, new ways to rationally incorporate adhesion epitopes through noncovalent interactions would offer opportunities to better recreate the dynamic and reversible nature of the native ECM. Here, we report on a noncovalent epitope presentation approach mediated by host–guest interactions. Using peptide amphiphile hydrogels, we demonstrate that the adamantane/β-cyclodextrin pair can be used to anchor RGDS cell adhesion signals onto self-assembled hydrogels via host–guest interactions. We evaluate hydrogel morphological and rheological properties as well as fibroblast attachment, organization, and spreading when cultured atop these scaffolds. This host–guest-mediated epitope display might lead to new self-assembling hydrogels for improved cell culture applications in fields such as tissue engineering and regenerative medicine

Phage Display Technology in Biomaterials Engineering: Progress and Opportunities for Applications in Regenerative Medicine

This work was supported by national funds through the Portuguese Foundation for Science and Technology under the scope of the project PTDC/EBB-BIO/114523/2009 and by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme “COMPETE” (FCOMP-01-0124-FEDER-014758). The authors are also thankful for the financial support of the Portuguese Foundation for Science and Technology under the strategic funding of UID/ BIO/04469/2013 unit and RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the European Union under the Marie Curie Career Integration Grant SuprHApolymers (PCIG14-GA-2013-631871)

In vitro blood-brain barrier models for drug research: state-of-the-art and new perspectives on reconstituting these models on artificial basement membrane platforms

HS Azevedo acknowledges the financial support of the European Union under the Marie Curie Career Integration Grant SuprHApolymers (PCIG14-GA-2013-631871). J Banerjee is supported by Marie Sklodowska-Curie Individual Fellowship granted by the European Commission (MSCA-IF-2014-658351) and Y Shi acknowledges China Scholarship Council for her PhD Scholarshi