Luciano F. Boesel

Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends

The fields of tissue engineering and regenerative medicine aim at promoting the regeneration of tissues or replacing failing or malfunctioning organs, by means of combining a scaffold/support material, adequate cells and bioactive molecules. Different materials have been proposed to be used as both three-dimensional porous scaffolds and hydrogel matrices for distinct tissue engineering strategies. Among them, polymers of natural origin are one of the most attractive options, mainly due to their similarities with the extracellular matrix (ECM), chemical versatility as well as typically good biological performance. In this review, the most studied and promising and recently proposed naturally derived polymers that have been suggested for tissue engineering applications are described. Different classes of such type of polymers and their blends with synthetic polymers are analysed, with special focus on polysaccharides and proteins, the systems that are more inspired by the ECM. The adaptation of conventional methods or non-conventional processing techniques for processing scaffolds from natural origin based polymers is reviewed. The use of particles, membranes and injectable systems from such kind of materials is also overviewed, especially what concerns the present status of the research that should lead towards their final application. Finally, the biological performance of tissue engineering constructs based on natural-based polymers is discussed, using several examples for different clinically relevant applications.

Cork: properties, capabilities and applications

Abstract Cork is a natural, renewable, sustainable raw material that has been used for many centuries. As a result of this very long term interest, the scientific literature on cork is extensive. The present review focuses on the chemical composition, physical and mechanical properties of cork and on its products and sub-products. The substantial efforts to fully characterise cork, as well as new developments and evolving research, are reviewed, beginning with its histology, growth and morphology (at macro- and microscales). The chemical structure is analysed in detail, covering both the materials that form the wall structure and the low molecular weight, extractable components. The unique properties of cork are discussed and correlated with current knowledge on morphology and chemical structure. Finally, the important industrial applications of cork are reviewed, in the context of research to provide cork with novel, high added-value applications.

Gecko‐Inspired Surfaces: A Path to Strong and Reversible Dry Adhesives

The amazing adhesion of gecko pads to almost any kind of surfaces has inspired a very active research direction over the last decade: the investigation of how geckos achieve this feat and how this knowledge can be turned into new strategies to reversibly join surfaces. This article reviews the fabrication approaches used so far for the creation of micro- and nanostructured fibrillar surfaces with adhesive properties. In the light of the pertinent contact mechanics, the adhesive properties are presented and discussed. The decisive design parameters are fiber radius and aspect ratio, tilt angle, hierarchical arrangement and the effect of the backing layer. Also first responsive systems that allow thermal switching between nonadhesive and adhesive states are described. These structures show a high potential of application, providing the remaining issues of robustness, reliability, and large-area manufacture can be solved.

Melt-based compression-molded scaffolds from chitosan-polyester blends and composites: Morphology and mechanical properties

Blends of chitosan and synthetic aliphatic polyesters (polybutylene succinate, polybutylene succinate adipate, polycaprolactone, and polybutylene terepthalate adipate) were compounded with and without hydroxyapatite, a bioactive mineral filler known to enhance osteoconduction. The blends and composites were compression molded with two different granulometric salt sizes (63-125 microm and 250-500 microm) having different levels of salt content (60, 70, and 80%) by weight. By leaching the salt particles, it was possible to produce porous scaffolds with distinct morphologies. The relationship between scaffold morphology and mechanical properties was evaluated using scanning electron microscopy, microcomputed tomography, compression testing, differential scanning calorimetry, small-angle X-ray scattering (SAXS), and wide-angle X-ray scattering. The produced scaffolds are characterized by having different morphologies depending on the average particle size and the amount of NaCl used. Specimens with higher porosity level have a less organized pore structure but increased interconnectivity of the pores. The stress-strain curve under compression displayed a linear elasticity followed by a plateau whose characteristics depend on the scaffold polymer composition. A decrease in the salt particle size used to create the porosity caused in general a decrease in the mechanical properties of the foams. Composites with hydroxyapatite had a sharp reduction in yield stress, modulus, and strain at break. The melting temperature decreased with increased chitosan content. SAXS results indicate no preferential crystalline orientation in the scaffolds. Cytotoxicity evaluation were carried out using standard tests (accordingly to ISO/EN 10993 part 5 guidelines), namely MTS test with a 24-h extraction period, revealing that L929 cells had comparable metabolic activities to that obtained for the negative control.

Bioinspired Actuated Adhesive Patterns of Liquid Crystalline Elastomers

Gecko-inspired arrays of micropillars made of a liquid crystalline elastomer display thermoswitchable adhesive behavior as a consequence of elongation changes caused by reorientation of the mesogens at the nematic-isotropic (N-I) phase transition.

A review on the polymer properties of hydrophilic, partially degradable and bioactive acrylic cements (HDBC)

Acrylic bone cements were developed around 50 years ago for the fixation of hip prostheses during arthroplasty. Over the intervening years, a series of drawbacks have been disclosed that have fostered intensive research on the development of novel or alternative formulations to the standard acrylic cements. Here, we will review the development and characterization of a novel class of cements, the Hydrophilic, partially Degradable and Bioactive Cements (HDBCs), an example of multifunctional cements. They were developed to have improved biocompatibility and initial fixation to the prosthesis and to induce the growth of bone on the surface of the cement and within pores generated by the degradation of the solid component. HDBCs have higher water uptake than typical acrylic cements, leading to press-fitting inside constrained cavities. They are tougher, albeit less stiff and strong than hydrophobic cements, and their mechanical properties may be easily adjusted by small changes in composition. Last, the simultaneous bioactive and degradable character of HDBCs have been shown to allow in vitro growth of calcium phosphates into pores within the bulk of the cement.

Micropatterning of bioactive glass nanoparticles on chitosan membranes for spatial controlled biomineralization

Bioactive glass nanoparticles (BG-NPs) capable of inducing apatite precipitation upon immersion in simulated body fluid (SBF) were patterned on free-standing chitosan membranes by microcontact printing using a poly(dimethylsiloxane) (PDMS) stamp inked in a BG-NPs pad. Formation of the patterns was characterized by scanning electron microscopy (SEM). Mineralization of the bioactive glass patterns was induced in vitro by soaking the samples in SBF over different time points up to 7 days. The confined apatite deposition in the patterned regions with diameters of 50 μm was confirmed by Fourier-transformed infrared spectroscopy (FTIR), energy-dispersive X-ray (EDX) analysis, and SEM. In vitro tests confirmed the preferential attachment and proliferation of L929 cells to the areas printed with BG-NPs of the membranes. This approach permits one to spatially control the properties of biomaterials at the microlevel and could be potentially used in guided tissue regeneration for skin, vascular, articular, and bone tissue engineering and in cellular cocultures or to develop substrates able to confine cells in regions with controlled geometry at the cells length scale.

Hydrogels And Hydrophilic Partially Degradable Bone Cements Based On Biodegradable Blends Incorporating Starch

Bone cements are, traditionally, injectable systems based on acrylic polymers. They are constituted by a solid and a liquid component that harden after mixing due to the polymerization of acrylic monomers in the liquid. Just some minutes after mixing, the paste attains high viscosity and must then be injected into the bone cavity, where the final stages of polymerization will take place. The solid is in most cases constituted by poly(methyl methacrylate) (PMMA) powder (or a copolymer of MMA with others monomers), benzoyl peroxide (BPO, the initiator of the polymerization), and a radio-opacifier, while the liquid is formed by MMA monomer (in some cases with n-butyl methacrylate, BuMA) and dimethyl-p-toluidine (DMT, the activator of the initiator).

Hydrophilic matrices to be used as bioactive and degradable bone cements.

Two different hydrophilic systems were investigated regarding their suitability to be used as enzymatically degradable and highly bioactive bone cements. They contained either acrylic acid (AA) or 2-hydroxyethyl methacrylate (HEMA) as the hydrophilic monomer. Swelling, degradation, mechanical and bioactivity tests were employed to characterise their behaviour. Although both of the systems were very hydrophilic, only the one containing HEMA was able to form an apatite-like layer on its surface. Moreover, this system could be degraded by amylolytic enzymes at a rate easily controlled by the incorporation of different amounts of enzyme to the formulation, as shown by the evolution of the mechanical properties, weight loss and glucose concentration in the solution. These results show these novel systems have a great potential to induce bone ingrowth inside the pores created during the degradation of the material, therefore establishing a strong interface with the tissue.

Innovative Approach for Producing Injectable, Biodegradable Materials Using Chitooligosaccharides and Green Chemistry

Although there are a number of injectable biomaterials currently under development, they present some drawbacks such as being based on synthetic polymers, needing toxic or aggressive synthesis procedures or using raw materials with low availability and/or high production costs. Having this in mind, a novel injectable biomaterial using chitooligosaccharides as starting materials was developed. This system uses a widely available and cheap polymer from marine biomass (chitosan), which can be turned into an injectable material by water-based and ecologically friendly reactions. Chitooligosaccharides were functionalized with methacrylic groups, to allow in situ cross-linking. The degree of substitution, as determined by (1)H NMR, varied between 5 and 50%. The system was characterized in terms of kinetics of gel formation, rheology, degradation behavior and in vitro cytotoxicity. The gelation time could be easily tailored between 1.5 and 60 min by changing the conditions of the methacrylation reaction, and the final gel presented rheological properties typical of strong gels, that is, shear stresses in the kPa range. The cross-linked gel was degradable and nontoxic, presenting indeed an interesting cytokinetic effect. Injectable materials based on chitooligosaccharides are, therefore, an innovative system combining adequate biological performance, ease of preparation, and an ecologically friendly concept of production.