Meniscal Replacement With a Silk Fibroin Scaffold Reduces Contact Stresses in the Human Knee.

The aim of the current study was to verify if a previously developed silk fibroin scaffold for meniscal replacement is able to restore the physiological distribution of contact pressure (CP) over the articulating surfaces in the human knee joint, thereby reducing peak loads occurring after partial meniscectomy. The pressure distribution on the medial tibial articular surface of seven human cadaveric knee joints was analysed under continuous flexion-extension movements and under physiological loads up to 2,500 N at different flexion angles. Contact area (CA), maximum tibiofemoral CP, maximum pressure under the meniscus and the pressure distribution were analysed for the intact meniscus, after partial meniscectomy as well as after partial medial meniscal replacement using the silk fibroin scaffold. Implantation of the silk fibroin scaffold considerably improved tibiofemoral contact mechanics after partial medial meniscectomy. While the reduced CA after meniscectomy was not fully restored by the silk fibroin scaffold, clinically relevant peak pressures on the articular cartilage surface occurring after partial meniscectomy were significantly reduced. Nevertheless, at high flexion angles static testing demonstrated that normal pressure distribution comparable to the intact meniscus could not be fully achieved. The current study demonstrates that the silk fibroin implant possesses attributes that significantly improve tibiofemoral CPs within the knee joint following partial meniscectomy. However, the failure to fully recapitulate the CAs and pressures observed in the intact meniscus, particularly at high flexion angles, indicates that the implant's biomechanical properties may require further improvement to completely restore tibiofemoral contact mechanics. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2583-2592, 2019.

Articular cartilage and meniscus reveal higher friction in swing phase than in stance phase under dynamic gait conditions.

Most previous studies investigated the remarkably low and complex friction properties of meniscus and cartilage under constant loading and motion conditions. However, both load and relative velocity within the knee joint vary considerably during physiological activities. Hence, the question arises how friction of both tissues is affected by physiological testing conditions occurring during gait. As friction properties are of major importance for meniscal replacement devices, the influence of these simulated physiological testing conditions was additionally tested for a potential meniscal implant biomaterial. Using a dynamic friction testing device, three different friction tests were conducted to investigate the influence of either just varying the motion conditions or the normal load and also to replicate the physiological gait conditions. It could be shown for the first time that the friction coefficient during swing phase was statistically higher than during stance phase when varying both loading and motion conditions according to the physiological gait pattern. Further, the friction properties of the exemplary biomaterial were also higher, when tested under dynamic gait parameters compared to static conditions, which may suggest that static conditions can underestimate the friction coefficient rather than reflecting the in vivo performance.

The challenge of implant integration in partial meniscal replacement: an experimental study on a silk fibroin scaffold in sheep.

PURPOSE: To restore meniscal function after excessive tissue damage, a silk fibroin implant for partial meniscal replacement was developed and investigated in an earlier sheep model. After 6 months implantation, it showed promising results in terms of chondroprotection and biocompatibility. To improve surgical fixation, the material was subjected to optimisation and a fibre mesh was integrated into the porous matrix. The aim of the study was the evaluation of this second generation of silk fibroin implants in a sheep model. METHODS: Nine adult merino sheep received subtotal meniscal replacement using the silk fibroin scaffold. In nine additional animals, the defect was left untreated. Sham surgery was performed in another group of nine animals. After 6 months of implantation macroscopic, biomechanical and histological evaluations of the scaffold, meniscus, and articular cartilage were conducted. RESULTS: Macroscopic evaluation revealed no signs of inflammation of the operated knee joint and most implants were located in the defect. However, there was no solid connection to the remaining peripheral meniscal rim and three devices showed a radial rupture at the middle zone. The equilibrium modulus of the scaffold increased after 6 months implantation time as identified by biomechanical testing (before implantation 0.6 ± 0.3 MPa; after implantation: 0.8 ± 0.3 MPa). Macroscopically and histologically visible softening and fibrillation of the articular cartilage in the meniscectomy- and implant group were confirmed biomechanically by indentation testing of the tibial cartilage. CONCLUSIONS: In the current study, biocompatibility of the silk fibroin scaffold was reconfirmed. The initial mechanical properties of the silk fibroin implant resembled native meniscal tissue. However, stiffness of the scaffold increased considerably after implantation. This might have prevented integration of the device and chondroprotection of the underlying cartilage. Furthermore, the increased stiffness of the material is likely responsible for the partial destruction of some implants. Clinically, we learn that an inappropriate replacement device might lead to similar cartilage damage as seen after meniscectomy. Given the poor acceptance of the clinically available partial meniscal replacement devices, it can be speculated that development of a total meniscal replacement device might be the less challenging option.

Peptide-directed spatial organization of biomolecules in dynamic gradient scaffolds.

Specific binding peptides are used to spatially organize biomolecule gradients within an electrospun fiber scaffold. Different biomolecule-binding peptide-polymer conjugates are sequentially co-electrospun with a fiber-forming host polymer to generate opposing gradients of peptide functionalization. The binding peptides specifically and non-covalently guide the spatial arrangement of biomolecules into dynamic gradients within the scaffold, mimicking biological gradients found in native tissues.

Responsive poly (γ-glutamic acid) fibres for biomedical applications.

A novel responsive system using a protein-based biopolymer was designed to undergo structural, geometric, and chemical changes upon temperature change or solvent interaction. Poly(γ-glutamic acid) (γ-PGA) is an attractive candidate for various biomedical applications as it is naturally produced, biocompatible and enzymatically degradable. The responsive material was fabricated using an electrospun modified γ-PGA to create a sub-micron fibrous mat. By modulating the environment responsive behaviour in a controlled manner, exciting applications such as wound dressing, compression materials and self-tightening knots are envisaged.

Functionalized poly(γ-Glutamic Acid) fibrous scaffolds for tissue engineering.

Poly(γ-glutamic acid) (γ-PGA) is a biocompatible, enzymatically-degradable, natural polymer with a higher resistance to hydrolysis than polyesters commonly used for tissue engineering scaffolds such as poly(L-lactide) (PLLA). Notably, γ-PGA's free carboxyl side groups allow for simple chemical functionalization, making it a versatile candidate for producing scaffolds. Here, a series of water-resistant fibrous scaffolds were engineered from ethyl (Et), propyl (Pr) and benzyl (Bn) esterifications of γ-PGA. All scaffolds were non-cytotoxic and γ-PGA-Bn showed an increase in cell adhesion of hMSCs compared to γ-PGA-Et and γ-PGA-Pr. Moreover, cells on γ-PGA-Bn showed three-fold higher viability at day 14 and significantly higher adhesion when compared with PLLA scaffolds, despite having a similar hydrophobicity. Cell attachment decreased by 40% when the polymer was only partially modified with benzyl groups (γ-PGA-Bn-77%), but was restored when integrin-binding RGD peptide was conjugated to the remaining free carboxylic groups, indicating the peptide was accessible and able to bind integrins. The mechanism behind the cell-material interactions on γ-PGA-Bn scaffolds was further investigated through protein adsorption and fibronectin conformation experiments. These results, in addition to the cell-adhesion studies, suggest an inherent effect of the benzyl modification in the mechanism of cell attachment to γ-PGA-Bn scaffolds. Finally, γ-PGA-Bn scaffolds cultured in osteogenic media were also efficient in supporting hMSCs differentiation towards an osteogenic lineage as determined by alkaline phosphatase and Runx2 gene expression. Taken together these data suggest that esterified γ-PGA polymer scaffolds are new and versatile candidates for tissue engineering applications and that, intriguingly, aromatic functionality plays a key role in the cell-scaffold interaction.

Self-organization of mixtures of fluorocarbon and hydrocarbon amphiphilic thiolates on the surface of gold nanoparticles.

Self-assembled monolayers composed of a mixture of thiolate molecules, featuring hydrocarbon or perfluorocarbon chains (H- and F-chains) terminating with a short poly(oxoethylene) (PEG) moiety, are the most extreme example of surfactant immiscibility on gold nanoparticles reported so far. The phase segregation between H-chains and F-chains and the consequent, peculiar folding of PEG chains are responsible for the increased affinity of a selected radical probe for the fluorinated region, which increases as the size of the fluorinated domains decrease, independently of the shape of such domains. This feature has been revealed by ESR measurements and an in silico innovative multiscale molecular simulations approach in explicit water. Our results reveal an underlying mechanism of a transmission of the organization of the monolayer from the inner region close to the gold surface toward the external hydrophilic PEG region. Moreover, this study definitively proves that a mixed monolayer is a complex system with properties markedly different from those characterizing the parent homoligand monolayers.

Formation of patches on 3D SAMs driven by thiols with immiscible chains observed by ESR spectroscopy.

Beyond stripes: The extreme lipophobicity of perfluorinated chains attached to amphiphilic thiolates triggers the formation of "stars" (or patches) surrounded by amphiphilic alkylthiolates in three-dimensional self-assembled monolayers. This strategy led to the first example of a water-soluble multicompartment monolayer wrapped around a gold core.

Water-soluble gold nanoparticles protected by fluorinated amphiphilic thiolates.

The preparation and the properties of gold nanoparticles (Au NPs) protected by perfluorinated amphiphiles are described. The thiols were devised to form a perfluorinated region close to the gold surface and to have a hydrophilic portion in contact with the bulk solvent to impart solubility in water. The monolayer protected clusters were prepared, in an homogeneous phase using sodium thiolates because of the low nucleophilicity of the alpha-perfluorinated thiols, and fully characterized with (1)H, (19)F NMR spectrometry, IR and UV-vis absorption spectroscopies, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). Au NPs with core diameters ranging from 1.6 to 2.9 nm, depending on the reaction conditions, were obtained. Water-soluble NPs (MPC-F8-PEGs) were obtained with the thiol HS-F8-PEG ending with a short poly(ethylene glycol) unit (PEG-OMe 550), whereas thiols with shorter PEG chains give rise to NPs insoluble in water. MPC-F8-PEGs undergo an exchange reaction with amphiphilic alkyl thiols. ESR investigations, using a hydrophobic radical probe, indicate that the MPC-F8-PEG monolayer shows a greater hydrophobicity compared to the analogous hydrogenated monolayer.

Effect of core size on the partition of organic solutes in the monolayer of water-soluble nanoparticles: an ESR investigation.

ESR spectroscopy has been used to study the interaction of para-pentylbenzyl hydroxyalkyl nitroxide with the monolayer of water-soluble protected gold clusters having a core diameter ranging from 1.6 to 5.3 nm. The solubilization of the nitroxide probe in the more hydrophobic environment of the monolayer strongly depends on the size of the gold core. In particular, the partition equilibrium constant increases as the nanoparticle diameter decreases. These results have been attributed to the different packing of the chains in the monolayer resulting from the different radius of curvature of the investigated nanoparticles. This represents, to the best of our knowledge, the first report demonstrating that the core size of metallic nanoparticles affects the solvating properties of the protective organic monolayer.