Journal: Acta biomaterialia
Elastin provides structural integrity, biological cues and persistent elasticity to a range of important tissues including the vasculature and lungs. Its critical importance to normal physiology makes it a desirable component of biomaterials that seek to repair or replace these tissues. The recent availability of large quantities of the highly purified elastin monomer, tropoelastin, have allowed for a thorough characterization of the mechanical and biological mechanisms underpinning the benefits of mature elastin. While tropoelastin is a flexible molecule, a combination of optical and structural analyses has defined key regions of the molecule that directly contribute to the elastomeric properties and control the cell interactions of the protein. Insights into the structure and behavior of tropoelastin have translated into increasingly sophisticated elastin-like biomaterials, evolving from classically manufactured hydrogels and fibers to new forms, stabilized in the absence of incorporated cross-linkers. Tropoelastin is also compatible with synthetic and natural co-polymers, expanding the applications of its potential use beyond traditional elastin-rich tissues and facilitating finer control of biomaterial properties and the design of next-generation tailored bioactive materials.
Bioactive glasses are reported to be able to stimulate more bone regeneration than other bioactive ceramics but they lag behind other bioactive ceramics in terms of commercial success. Bioactive glass has not yet reached its potential but research activity is growing. This paper reviews the current state of the art, starting with current products and moving onto recent developments. Larry Hench’s 45S5 Bioglass® was the first artificial material that was found to form a chemical bond with bone, launching the field of bioactive ceramics. In vivo studies have shown that bioactive glasses bond with bone more rapidly than other bioceramics, and in vitro studies indicate that their osteogenic properties are due to their dissolution products stimulating osteoprogenitor cells at the genetic level. However, calcium phosphates such as tricalcium phosphate and synthetic hydroxyapatite are more widely used in the clinic. Some of the reasons are commercial, but others are due to the scientific limitations of the original Bioglass 45S5. An example is that it is difficult to produce porous bioactive glass templates (scaffolds) for bone regeneration from Bioglass 45S5 because it crystallizes during sintering. Recently, this has been overcome by understanding how the glass composition can be tailored to prevent crystallization. The sintering problems can also be avoided by synthesizing sol-gel glass, where the silica network is assembled at room temperature. Process developments in foaming, solid freeform fabrication and nanofibre spinning have now allowed the production of porous bioactive glass scaffolds from both melt- and sol-gel-derived glasses. An ideal scaffold for bone regeneration would share load with bone. Bioceramics cannot do this when the bone defect is subjected to cyclic loads, as they are brittle. To overcome this, bioactive glass polymer hybrids are being synthesized that have the potential to be tough, with congruent degradation of the bioactive inorganic and the polymer components. Key to this is creating nanoscale interpenetrating networks, the organic and inorganic components of which have covalent coupling between them, which involves careful control of the chemistry of the sol-gel process. Bioactive nanoparticles can also now be synthesized and their fate tracked as they are internalized in cells. This paper reviews the main developments in the field of bioactive glass and its variants, covering the importance of control of hierarchical structure, synthesis, processing and cellular response in the quest for new regenerative synthetic bone grafts. The paper takes the reader from Hench’s Bioglass 45S5 to new hybrid materials that have tailorable mechanical properties and degradation rates.
Porcupines use their lightweight quills, which are strong enough to support significant compression and flexure loads, for defense. Hystrix, with long and thick quills, belongs to the family of Hystricidae (Old World porcupines), while Erethizon, with smaller quills, belongs to the Erethizontidae family (New World porcupines). The objective of this work is to compare the structure and compressive properties of quills from Hystrix and Erethizon. Both quills have a thin keratinous cortex filled with closed-cell foam that has cell diameters decreasing from the center to the cortex. Hystrix quills have stiffeners that extend from the cortex towards the center. The local buckling strength is larger for Hystrix, and very good agreement is found between the predicted values and the experimental ones for both quills. The foam shows extensive deformation, both tensile and compressive, around the buckled cortex.
Corneal endothelial diseases lead to severe vision impairment, motivating the transplantation of donor corneae or corneal endothelial lamellae, which is, however, impeded by endothelial cell loss during processing. Therefore, one prioritized aim in corneal tissue engineering is the generation of transplantable human corneal endothelial cell (HCEC) layers. Thermo-responsive cell culture carriers are widely used for non-enzymatic harvest of cell sheets. The current study presents a novel thermo-responsive carrier based on simultaneous electron beam immobilization and cross-linking of poly(vinyl methyl ether) (PVME) on polymeric surfaces, which allows one to adjust layer thickness, stiffness, switching amplitude and functionalization with bioactive molecules to meet cell type specific requirements. The efficacy of this approach for HCEC, which require elaborate cell culture conditions and are strongly adherent to the substratum, is demonstrated. The developed method may pave the way to tissue engineering of corneal endothelium and significantly improve therapeutic options.
Pore size and porosity control rate and depth of cellular migration in electrospun vascular fabrics and thereby have a strong impact on long-term graft success. In this study we investigated the effect of graft porosity on cell migration in-vitro and in-vivo. Polyetherurethane (PU) grafts were fabricated by electrospinning as fine mesh, low porosity grafts [void fraction (VF): 53%] and coarse mesh, high porosity grafts [VF: 80%]. The fabricated grafts were evaluated in-vitro for endothelial cell attachment and proliferation. Prostheses were investigated in a rat model for either 7 days, 1, 3 or 6 months (n=7 per time point) and analyzed after retrieval by biomechanical analysis and various histological techniques. Cell migration was calculated by computer-assisted morphometry. In vitro, fine pore mesh favored early cell attachment. In-vivo, coarse mesh grafts revealed significantly higher cell populations at all time points in all areas of the conduit wall. Biomechanical tests indicated sufficient compliance, tensile and suture retention strength before and after implantation. Increased porosity improves host cell ingrowth and survival in electrospun conduits. These conduits show successful natural host vessel reconstitution without limitation of biomechanical properties.
The influence of cellulose ethers additives (CEAs) on the performance of final calcium phosphate cement (CPC) products is thoroughly investigated. Four CEAs were added into the liquid phase of apatitic CPCs based on the hydrolysis of α-tricalcium phosphate (α-TCP), to investigate the influence of both molecular weight and degree of substitution on the CPCs' properties, including handling properties (e.g. injectability, cohesion, washout resistance and setting time), microstructure (e.g. porosity and micromorphology) and mechanical properties (e.g. fracture toughness and compressive strength). The results showed that even a small amount of CEAs have modified most of these CPCs' features depending on the structural parameters of CEAs. The CEAs dramatically improved injectability, cohesion and washout resistance of the pastes, prolonged the final setting time and increased the porosity of CPCs. Moreover, the CEAs had an evident toughening effect on CPCs, and this effect become more significant with increasing molecular weight and mass fraction of CEAs, inducing also a significant tolerance to damage. Overall, the molecular weight of CEAs played a major role compared to their degree of substitution in CPCs' performances.
The major required functions for load-bearing orthopaedic implants are load-bearing and mechanical or biological fixation with the surrounding bone. Porous materials with appropriate mechanical properties and adequate pore structure for fixation are promising load-bearing implant material candidates. In our preceding work, we developed a novel titanium (Ti) foam sheet with 1-2 mm thickness by an original slurry foaming method. In the present work, we developed novel Ti foam with mechanical properties compatible with cortical bone and biological fixation capabilities by layer-by-layer stacking of different foam sheets having volumetric porosities of 80% and 17%. The resulting multilayer Ti foam exhibited a Young’s modulus of 11-12 GPa and yield strength of 150-240 MPa in compression tests. In vitro cell culture on the sample revealed good cell penetration in the higher porosity foam (80% volumetric porosity) which reaches to 1.2 mm for 21 d of incubation. Cell penetration into the high porosity layers of multilayer sample was good and not influenced by the lower porosity layers. Calcification is also observed in the high porosity foam suggesting that our Ti foam does not inhibit bone formation. Contradictory requirements for high volumetric porosity and high strength were attained by role-sharing between the foam sheets of different porosities. The unique characteristics of the present multilayer Ti foam make them attractive for application in the field of orthopaedics.
Bioactive glasses (BG) are known for their unique ability to bond to living bone. Consequently, the incorporation of BG into calcium phosphate cement (CPC) was hypothesized to be a feasible approach to improve the biological performance of CPC. Previously, it has been demonstrated that BG can successfully be introduced into CPC, with or without PLGA-microparticles. Although, an in vitro physicochemical study on the introduction of BG into CPC was encouraging, the biocompatibility and in vivo bone response to these formulations are still unknown. Therefore, the present study aimed to evaluate the in vivo performance of BG supplemented CPC, either pure or supplemented with PLGA-microparticles, via both ectopic and orthotopic implantation models in rats. Pre-set scaffolds in 4 different formulations (1: CPC; 2: CPC/BG; 3: CPC/PLGA; and 4: CPC/PLGA/BG) were implanted subcutaneously and into femoral condyle defects of rats for 2 and 6 weeks. Upon ectopic implantation, incorporation of BG into CPC improved the soft tissue response by improving capsule and interface quality. Additionally, the incorporation of BG into CPC and CPC/PLGA showed an 1.8- and 4.7-fold higher degradation and a 2.2- and 1.3-fold higher bone formation in a femoral condyle defect in rats compared to pure CPC and CPC/PLGA, respectively. Consequently, these results highlight the potential of BG to be used as an additive to CPC to improve the biological performance for bone regeneration applications. Nevertheless, further confirmation is necessary regarding long-term in vivo studies, which also have to be performed under compromised wound healing conditions.
One key for the successful integration of implants into the human body is the control of protein adsorption by adjusting surface properties at different length scales. This is particularly important for titanium oxide constituting one of the most common biomedical interfaces. As for titania (TiO(2)) the interface is largely defined by its crystal surface structure it is crucial to understand how the surface crystallinity affects the structure, properties and function of protein layers mediating the subsequent biological reaction. For rutile TiO(2) we demonstrate that the conformation and relative amount of human plasma fibrinogen (HPF) and the structure of adsorbed HPF layers depend on the crystal surface nanostructure by employing thermally etched multi-faceted TiO(2) surfaces. Thermal etching of polycrystalline TiO(2) facilitates a nanoscale crystal faceting and, thus, the creation of different surface nanostructures on a single specimen surface. Atomic force microscopy shows that HPF arranges into networks and thin globular layers on flat and irregular crystal grain surfaces, respectively. On a third, faceted category we observed an alternating conformation of HPF on neighboring facets. The bulk grain orientation obtained from electron back scatter diffraction and thermodynamic mechanisms of surface reconstruction during thermal etching suggest the grain and facet surface specific arrangement and relative amount of adsorbed proteins to depend on the associated on-site free crystal surface energy. Implications for potentially favorable TiO(2) crystal facets regarding the inflammatory response and hemostasis are discussed in view of an advanced surface design of future implants.
The formation of grain boundary (GB) brittle carbides with a complex three-dimensional (3D) morphology can be detrimental to both the fatigue properties and corrosion resistance of a biomedical titanium alloy. A detailed microscopic study has been performed on an as-sintered biomedical Ti-15Mo alloy containing 0.032 wt.% C. A noticeable presence of a carbon-enriched phase has been observed along the GB, although the carbon content is well below the maximum carbon limit of 0.1 wt.% specified by ASTM Standard F2066. Transmission electron microscopy (TEM) identified that the carbon-enriched phase is fcc-Ti2C. 3D tomography reconstruction revealed that the Ti2C structure has morphology similar to primary α-Ti. Nanoindentation confirmed the high hardness and high Young’s modulus of the GB Ti2C phase. To avoid GB carbide formation in Ti-15Mo, the carbon content should be limited to 0.006 wt.% by Thermo-Calc predictions. Similar analyses and characterisation of the carbide formation in biomedical unalloyed Ti, Ti-6Al-4V and Ti-16Nb have also been performed.