J. Funct. Biomater., Volume 3, Issue 3 (September 2012) – 13 articles , Pages 464-705

The osseointegration rate of implants is related to their composition and surface roughness. Implant roughness favors both bone anchoring and biomechanical stability. Osteoconductive calcium phosphate (Ca-P) coatings promote bone healing and apposition, leading to the rapid biological fixation of implants. It has been clearly shown in many publications that Ca-P coating accelerates bone formation around the implant. This review discusses two main routes for the manufacturing of polymer-based osteoconductive scaffolds for tissue engineering, namely the incorporation of bioceramic particles in the scaffold and the coating of a scaffold with a thin layer of apatite through a biomimetic process. Full article

Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation. Full article

Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. Full article

Biopolymers are easily denatured by heating, a change in pH or chemical substances when they are immobilized on a substrate. To prevent denaturation of biopolymers, we developed a method to trap a polynucleotide on a substrate by hydrogen bonding using silica particles with surfaces modified by aminoalkyl chains ([A-AM silane]/SiO₂). [A-AM silane]/SiO₂ was synthesized by silane coupling reaction of N-2-(aminoethyl)-3-aminopropyltrimethoxysilane (A-AM silane) with SiO₂ particles with a diameter of 5 μm at 100 °C for 20 min. The surface chemical structure of [A-AM silane]/SiO₂ was characterized by Fourier transform infrared spectroscopy and molecular orbital calculations. The surface of the silica particles was modified with A-AM silane and primary amine groups were formed. [A-AM silane]/SiO₂ was trapped with single-stranded nucleic acids [(Poly-X; X = A (adenine), G (guanine) and C (cytosine)] in PBS solution at 37 °C for 1 h. The single-stranded nucleic acids were trapped on the surface of the [A-AM silane]/SiO₂ by hydrogen bonding to form conjugated materials. The resulting complexes were further conjugated by derivatives of acridine orange (AO) as fluorescent labels under the same conditions to form [AO:Poly-X:A-AM silane]/SiO₂ complexes. Changes in the fluorescence intensity of these complexes originating from interactions between the single-stranded nucleic acid and aromatic compounds were also evaluated. The change in intensity displayed the order [AO: Poly-G: A-AM silane]/SiO₂ > [AO:Poly-A:A-AM silane]/SiO₂ >> [AO:Poly-C:A-AM silane]/SiO₂. This suggests that the single-stranded nucleic acids conjugated with aminoalkyl chains on the surfaces of SiO₂ particles and the change in fluorescence intensity reflected the molecular interaction between AO and the nucleic-acid base in a polynucleotide. Full article

Unique functional materials provide a platform as scaffolds for cell/tissue regeneration. Investigation of cell-materials’ chemical and biological interactions will enable the application of more functional materials in the area of bioengineering, which provides a pathway to the novel treatment for patients who suffer from tissue/organ damage and face the limitation of donation sources. Many studies have been made into tissue/organ regeneration. Development of new substrate materials as platforms for cell/tissue regeneration is a key research area. Studies discussed in this paper focus on the investigation of novel ultrananocrystalline diamond (UNCD) films as substrate/scaffold materials for developmental biology. Specially designed quartz dishes have been coated with different types of UNCD films and cells were subsequently seeded on those films. Results showed the cells’ growth on UNCD-coated culture dishes are similar to cell culture dishes with little retardation, indicating that UNCD films have no or little inhibition on cell proliferation and are potentially appealing as substrate/scaffold materials. The mechanisms of cell adhesion on UNCD surfaces are proposed based on the experimental results. The comparisons of cell cultures on diamond-powder-seeded culture dishes and on UNCD-coated dishes with matrix-assisted laser desorption/ionization—time-of-flight mass spectroscopy (MALDI-TOF MS) and X-ray photoelectron spectroscopy (XPS) analyses provided valuable data to support the mechanisms proposed to explain the adhesion and proliferation of cells on the surface of the UNCD platform. Full article

All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and smooth muscle cell proliferation, making these attractive candidates for modulation of vascular device biointegration. However, classically used biomaterial coatings, such as fibronectin and laminin, modulate only one of these components; enhancing endothelial cell attachment, but also activating platelets and triggering thrombosis. This review examines a subset of extracellular matrix molecules that have demonstrated multi-faceted vascular compatibility and accordingly are promising candidates to improve the biointegration of vascular biomaterials. Full article

Osteoarticular pathologies very often require an implementation therapy to favor regeneration processes of bone, cartilage and/or tendons. Clinical approaches performed on osteoarticular complications in dogs constitute an ideal model for human clinical translational applications. The adipose-derived mesenchymal stem cells (ASCs) have already been used to accelerate and facilitate the regenerative process. ASCs can be maintained in vitro and they can be differentiated to osteocytes or chondrocytes offering a good tool for cell replacement therapies in human and veterinary medicine. Although ACSs can be easily obtained from adipose tissue, the amplification process is usually performed by a time consuming process of successive passages. In this work, we use canine ASCs obtained by using a Bioreactor device under GMP cell culture conditions that produces a minimum of 30 million cells within 2 weeks. This method provides a rapid and aseptic method for production of sufficient stem cells with potential further use in clinical applications. We show that plasma rich in growth factors (PRGF) treatment positively contributes to viability and proliferation of canine ASCs into caprolactone 2-(methacryloyloxy) ethyl ester (CLMA) scaffolds. This biomaterial does not need additional modifications for cASCs attachment and proliferation. Here we propose a framework based on a combination of approaches that may contribute to increase the therapeutical capability of stem cells by the use of PRGF and compatible biomaterials for bone and connective tissue regeneration. Full article

Osmotic loading of articular cartilage has been used to study cell-tissue interactions and mechanisms in chondrocyte volume regulation in situ. Since cell volume changes are likely to affect cell’s mechanotransduction, it is important to understand how environmental factors, such as composition of the immersion medium and temperature affect cell volume changes in situ in osmotically challenged articular cartilage. In this study, chondrocytes were imaged in situ with a confocal laser scanning microscope (CLSM) through cartilage surface before and 3 min and 120 min after a hypo-osmotic challenge. Samples were measured either in phosphate buffered saline (PBS, without glucose and Ca²⁺) or in Dulbecco’s modified Eagle’s medium (DMEM, with glucose and Ca²⁺), and at 21 °C or at 37 °C. In all groups, cell volumes increased shortly after the hypotonic challenge and then recovered back to the original volumes. At both observation time points, cell volume changes as a result of the osmotic challenge were similar in PBS and DMEM in both temperatures. Our results indicate that the initial chondrocyte swelling and volume recovery as a result of the hypo-osmotic challenge of cartilage are not dependent on commonly used immersion media or temperature. Full article

This review describes different strategies of surface elaboration for a better control of biomolecule adsorption. After a brief description of the fundamental interactions between surfaces and biomolecules, various routes of surface elaboration are presented dealing with the attachment of functional groups mostly thanks to plasma techniques, with the grafting to and from methods, and with the adsorption of surfactants. The grafting of stimuli-responsive polymers is also pointed out. Then, the discussion is focused on the protein adsorption phenomena showing how their interactions with solid surfaces are complex. The adsorption mechanism is proved to be dependent on the solid surface physicochemical properties as well as on the surface and conformation properties of the proteins. Different behaviors are also reported for complex multiple protein solutions. Full article

The encapsulation of biomolecules in solid materials that retain the native properties of the molecule is a desired feature for the development of biosensors and biocatalysts. In the current study, protein entrapment in silica-based materials is explored using the sol-gel technique. This work surveys the effects of silica confinement on the structure of several model polypeptides, including apomyoglobin, copper-zinc superoxide dismutase, polyglutamine, polylysine, and type I antifreeze protein. Changes in the secondary structure of each protein following encapsulation are monitored by circular dichroism spectroscopy. In many cases, silica confinement reduces the fraction of properly-folded protein relative to solution, but addition of a secondary solute or modification of the silica surface leads to an increase in structure. Refinement of the glass surface by addition of a monosubstituted alkoxysilane during sol-gel processing is shown to be a valuable tool for testing the effects of surface chemistry on protein structure. Because silica entrapment prevents protein aggregation by isolating individual protein molecules in the pores of the glass material, one may monitor aggregation-prone polypeptides under solvent conditions that are prohibited in solution, as demonstrated with polyglutamine and a disease-related variant of superoxide dismutase. Full article

Hydrogels, electrospun fiber mats (EFMs), and their composites have been extensively studied for tissue engineering because of their physical and chemical similarity to native biological systems. However, while chemically similar, hydrogels and electrospun fiber mats display very different topographical features. Here, we examine the influence of surface topography and composition of hydrogels, EFMs, and hydrogel-EFM composites on cell behavior. Materials studied were composed of synthetic poly(ethylene glycol) (PEG) and poly(ethylene glycol)-poly(ε-caprolactone) (PEGPCL) hydrogels and electrospun poly(caprolactone) (PCL) and core/shell PCL/PEGPCL constituent materials. The number of adherent cells and cell circularity were most strongly influenced by the fibrous nature of materials (e.g., topography), whereas cell spreading was more strongly influenced by material composition (e.g., chemistry). These results suggest that cell attachment and proliferation to hydrogel-EFM composites can be tuned by varying these properties to provide important insights for the future design of such composite materials. Full article

Heart valve disease (HVD) is a globally increasing problem and accounts for thousands of deaths yearly. Currently end-stage HVD can only be treated by total valve replacement, however with major drawbacks. To overcome the limitations of conventional substitutes, a new clinical approach based on cell colonization of artificially manufactured heart valves has been developed. Even though this attempt seems promising, a confluent and stable cell layer has not yet been achieved due to the high stresses present in this area of the human heart. This study describes a bioreactor with a new approach to cell conditioning of tissue engineered heart valves. The bioreactor provides a low pulsatile flow that grants the correct opening and closing of the valve without high shear stresses. The flow rate can be regulated allowing a steady and sensitive conditioning process. Furthermore, the correct functioning of the valve can be monitored by endoscope surveillance in real-time. The tubeless and modular design allows an accurate, simple and faultless assembly of the reactor in a laminar flow chamber. It can be concluded that the bioreactor provides a strong tool for dynamic pre-conditioning and monitoring of colonized heart valve prostheses physiologically exposed to shear stress. Full article

The deformation behavior of a pH-sensitive hydrogel micro-fluidic valve system is investigated using inhomogeneous gel deformation theory, in which the fluid-structure interaction (FSI) of the gel solid and fluid flow in the pipe is considered. We use a finite element method with a well adopted hydrogel constitutive equation, which is coded in commercial software, ABAQUS, to simulate the hydrogel valve swelling deformation, while FLUENT is adopted to model the fluid flow in the pipe of the hydrogel valve system. The study demonstrates that FSI significantly affects the gel swelling deformed shapes, fluid flow pressure and velocity patterns. FSI has to be considered in the study on fluid flow regulated by hydrogel microfluidic valve. The study provides a more accurate and adoptable model for future design of new pH-sensitive hydrogel valves, and also gives a useful guideline for further studies on hydrogel fluidic applications. Full article