Hyaluronic Acid Molecules Research Articles

Controlled rheological behaviors of hyaluronic acid solutions through attractive polymeric micelle-mediated interchain association

Herein, we report a facile but straightforward way to control the rheological properties of hyaluronic acid (HA) solutions by taking advantage of the interchain association of electrostatically attractive polymeric micelles (APMs). For this, we synthesized an amphiphilic triblock copolymer, poly(2-aminoethyl methacrylate)-block-poly(3-caprolactone)-block-poly(2-aminoethyl methacrylate) (PAMA-b-PCL-b-PAMA), via atomic transfer radical polymerization and co-assembled it with amphiphilic poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) to produce APMs with cationic charges. The incorporation of the APMs into a gel-type HA solution not only readily transitioned the viscous flow to elastic flow but also easily led to the deformation of the gel microstructure in response to the shear rate, which is comparable to the case of a linear HA solution. We identified that the unique rheological behavior of the gel-type HA solutions stemmed from the APM-mediated particulate crosslinking. Finally, we demonstrated that the fine tuning of the interchain association by manipulation of the electrostatic interaction between APMs and HA molecules enabled the diversification of the rheological properties of HA solutions, making this system a promising hydrogel rheology controller.

Preparation and characterisation of a novel silk fibroin/hyaluronic acid/sodium alginate scaffold for skin repair.

To mimic the natural structure of tissue extracellular matrix, a novel silk fibroin (SF)/hyaluronic acid (HA)/sodium alginate (SA) composite scaffold (92% in porosity) was prepared by freeze-drying. Fourier-transform infrared spectroscopy and Raman spectra indicated interactions among SF, HA, and SA molecules. Scanning electron microscopy showed that the prepared SF/HA/SA scaffold had soft, elastic characteristics, with an average pore diameter of 93 μm. Mechanical property, thermogravimetric analyses and degradation results indicated that the SF/HA/SA scaffold had good physical stability in body fluid and mechanical movement-related environments. Cell proliferation, morphological, and live-dead analyses showed that NIH-3T3 fibroblast cells were better able to attach, grow, and proliferate on the SF/HA/SA scaffold compared with SF, SF/HA, and SF/SA scaffolds. We evaluated the wound healing effects in a rat full-thickness burn model. The hematoxylin-eosin (H&E) and Masson's trichrome staining results from SF/HA/SA scaffold showed that improved re-epithelialization, enhanced extracellular matrix remodeling. Our findings showed that the prepared SF/HA/SA scaffold can provide a potential way as a wound dressing for skin repair.

A versatile theranostic nanoplatform based on mesoporous silica

A versatile of mesoporous silica is designed and operated, including ion doping, surface modify and pore adsorption, based on aqueous well-dispersed. Thus, a multifunctional theranostic nanoplatform is obtained through endowing some functional materials. Detailedly, Gd ions is introduced to mesoporous silica (GM nanoparticles) via a co-assemble process, which is used as prime carrier with MRI. Furthermore, the surface graft of hyaluronic acid (HA) molecule makes contribution to lymph system-targeted delivery (GMH nanoparticles). Additionally, the introduction of functional molecules including Iopamidol (IGMH nanoparticles) and DOX (DGMH nanoparticles) could combine the diagnosis and therapy with CT and sustained drug release. We present evidence that the IGMH and DGMH nanoparticles are highly targeted to lymph system in vitro and in vivo, and highlight CT and MR imaging of IGMH nanoparticles in lymph system, and chemotherapy and MR imaging of DGMH nanoparticles in lymph cancer. Our results provide a new universal manufacture for mesoporous silica to obtain a multifunctional theranostic nanoplatform, has great potential for use in biological applications.

Hyaluronic acid selective anchoring to the cytoskeleton: An atomic force microscopy study.

The hyaluronic acid component of the glycocalyx plays a role in cell mechanotransduction by selectively transmitting mechanical signals to the cell cytoskeleton or to the cell membrane. The aim of this study was to evaluate the mechanical link between the hyaluronic acid molecule and the cell cytoskeleton by means of atomic force microscopy single molecule force spectroscopy. Hyaluronic acid molecules on live cells were targeted with probes coated with hyaluronic acid binding protein. Two different types of events were observed when the detachment of the target molecule from the probe occurred, suggesting the presence of cytoskeleton- and membrane-anchored molecules. Membrane-anchored molecules facilitated the formation of tethers when pulled. About 15% of the tested hyaluronic acid molecules were shown to be anchored to the cytoskeleton. When multiple molecules bonded to the probe, specific detachment patterns were observed, suggesting that a cytoskeletal bond needed to be broken to improve the ability to pull tethers from the cell membrane. This likely resulted in the formation of tethering structures maintaining a cytoskeletal core similar to the ones observed for cells over-expressing HA synthases. The different observed rupture events were associated with separate mechanotransductive mechanisms in an analogous manner to that previously proposed for the endothelial glycocalyx. Single cytoskeleton anchored rupture events represent HA molecules linked to the cytoskeleton and therefore transmitting mechanical stimuli into the inner cell compartments. Single membrane tethers would conversely represent the glycocalyx molecules connected to areas of the membrane where an abundance of signalling molecules reside.

The Application of Biomaterials to Tissue Engineering Neural Retina and Retinal Pigment Epithelium.

The prevalence of degenerative retinal disease is ever increasing as life expectancy rises globally. The human retina fails to regenerate and the use of human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) to engineer retinal tissue is of particular interest due to the limited availability of suitable allogeneic or autologous tissue. Retinal tissue and its development are well characterized, which have resulted in robust assays to assess the development of tissue-engineered retina. Retinal tissue can be generated in vitro from hESCs and hiPSCs without biomaterial scaffolds, but despite advancements, protocols remain slow, expensive, and fail to result in mature functional tissue. Several recent studies have demonstrated the potential of biomaterial scaffolds to enhance generation of hESC/hiPSC-derived retinal tissue, including synthetic polymers, silk, alginate, hyaluronic acid, and extracellular matrix molecules. This review outlines the advances that have been made toward tissue-engineered neural retina and retinal pigment epithelium (RPE) for clinical application in recent years, including the success of clinical trials involving transplantation of cells and tissue to promote retinal repair; and the evidence from in vitro and animal studies that biomaterials can enhance development and integration of retinal tissue.

Redox- and enzyme-responsive fluorescent porous silica nanocarriers for drug delivery

In this work, redox/enzyme-responsive fluorescent porous silica (pSiO2) nanoparticles (NPs) were constructed for drug delivery. The resultant pSiO2 NPs have large-pore core and mesoporous shell with size of 75 nm and present high specific surface area (605 m2 g−1). Oxidized glutathione (GSSG) as linker was conjugated on the surfaces of amino-functionalized porous silica (pSiO2-NH2) NPs by the amide bonds for redox-responsive drug release. Dox is served as model drugs to evaluate the release performance of carriers. After loading Dox molecules, both carbon dots (CDs) as fluorescent label and hyaluronic acid (HA) as gatekeepers are capped on the surface of carries (pSiO2-ss-CDs/HA) so as to endow the delivery system with fluorescent monitoring and enzyme-responsive properties. The pSiO2-ss-CDs/HA carriers displayed redox/enzyme-responsive and sustained release behavior. The controlled release of drug from the pSiO2-ss-CDs/HA delivery system was realized by the reduction of disulfide bonds in GSSG linker and degrading HA molecules. The incorporated CDs presented novel redox-dependent fluorescence, which could be used to trace the drug release.

Capstan-like mechanism in hyaluronan–phospholipid systems

Functionality of articular cartilage results from complex interactions between its molecular components. Among many biomolecules, two are of prime importance for lubrication: hyaluronic acid (HA) and phospholipids (PL). The purpose of this study is to discuss a mechanism of interaction between these two components and how their synergies contribute to nanobiolubrication of articular cartilage. Preliminary molecular dynamics simulations have been performed to investigate these interactions by adopting a capstan-like mechanism of action. By applying a constant pulling force to both ends of a HA molecule, wrapped around a PL micelle, we viewed the rotation of the PL micelle. The simulations were performed upon two physicochemical constraints: force- and solvent-dependency. The results show the efficiency of rotation from intermolecular bond creation and annihilation. We found a direct relation between the available surface of the micelle and the magnitude of the force, which varies significantly through the unwinding. The movement of the attached molecules is characterized by a slide-to-roll relation, which is affected by the viscosity of the surrounding medium. As a consequence, two solvents were studied for specific force conditions and the molecular dynamics simulation exhibited double the slide-to-roll coefficient for the viscous solvent as compared to its low-viscosity limit.

Fabrication of dihydroxyflavone-conjugated hyaluronic acid nanogels for targeted antitumoral effect.

We prepared hyaluronic acid (HA)-based nanogels conjugated with dihydroxyflavone (DHF) and evaluated their cellular uptake and antitumoral efficiency. 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was used as a conjugation agent for esterification between DHF and HA as well as crosslinking among HA. The conjugations were confirmed by nuclear magnetic resonance spectroscopy, UV/vis spectroscopy, and high-performance liquid chromatography. The size and Zeta-potential of the DHF/HA nanogels were reduced with an increase in the concentration of DMTMM due to the involvement of more HA molecules for the conjugation reactions. The DHF/HA nanogel with a smaller size was greatly taken up by two kinds of tumor cells (HeLa and HepG2), compared to NIH3T3. The cell viabilities were reduced to approximately 60% for HeLa and HepG2 cells after 48 h post treatment with DHF/HA nanogels.

Systematic clinical evidence review of NASHA (Durolane hyaluronic acid) for the treatment of knee osteoarthritis.

BackgroundPain and limitations in joint mobility associated with knee osteoarthritis (OA) are clinically challenging to manage, and advanced progression of disease can often lead to total knee arthroplasty. Intra-articular injection of hyaluronic acid (HA), also referred to as viscosupplementation, is a non-surgical treatment approach for OA, the effectiveness of which may depend on the HA composition, and the length of time over which it resides in the joint. One of the available options for such therapies includes NASHA (Durolane HA), a non-animal, biofermentation-derived product, which is manufactured using a process that stabilizes the HA molecules to slow down their rate of degradation and produce a unique formulation with a terminal half-life of ~1 month. The objectives of the current review were to assess, in patients with OA of the knee, the efficacy and safety of intra-articular treatment with NASHA relative to control (saline) injections, other HA products, and other injectables (corticosteroids, platelet-rich plasma, mesenchymal stem cells).MethodsThis systematic evidence review examines patient outcomes following NASHA treatment as described in published data from studies conducted in subjects with knee OA. A Preferred Reporting Items for Systematic Reviews and Meta-analyses-compliant literature search strategy yielded 11 eligible clinical studies with a variety of comparator arms. Outcomes assessed at various time points following intra-articular treatment included measures of pain, function, quality of life, and incidence of treatment-related adverse events (AEs).ResultsThe available evidence reported for the clinical studies assessed demonstrates sustained and effective relief of knee OA symptoms following a single injection of NASHA. In addition, an excellent biocompatibility profile is observed for NASHA as an intra-articular therapy for OA, as reflected by the low rate of AEs associated with treatment.ConclusionTreatment with NASHA is an effective and safe single-injection procedure, which can be beneficial in the clinical management of knee OA.

Advances in Tribology of Lubricin and Lubricin-Like Synthetic Polymer Nanostructures

Articular cartilage surrounds the ends of diarthrodial joints (most common movable joints) and during motion, it experiences a wide range of loading conditions while remaining under exceedingly low-friction and wear-free conditions. This remarkable tribological performance stems from complex interactions between the synovial fluid and articular cartilage. In fact, lubricin and hyaluronic acid (HA) that are part of the synovial fluid are now known to be the key contributors to effective joint lubrication and wear protection. Studies involving animal models and artificial systems suggest that lubricin and HA molecules may work in tandem to produce a highly synergistic effect for lubrication. However, latest observations suggest that lubricin has significant potential for protecting the articular joints, probably more than HA. Recently, lurbicin-related friction regulation in soft eye tissues, where much lower forces are involved compared to knee joints for instance, has been shown to be related to dry eye disease and contact lens discomfort. As such, lubricin’s role in natural friction regulation is very complex. Moreover, partially unresolved water-lubricin interactions are essential for lubrication and load carrying function in the joints. The chemical structure of lubricin has inspired several chemists to synthesize new copolymers and polymer brushes that function just like lubricin in order to design new synthetic or bio-based lubricants with ultra-low-friction coefficients. Hence, lubricin has emerged as a key natural molecule for bioinspired tribology. The aim of this review is to present the latest advances in understanding of lubricin’s function in joint lubrication and in soft tissue friction (i.e., human eye) and document what has been achieved so far in transforming this biomedical knowledge into new polymer design for advanced engineering tribology. It is hoped that this review will catalyze research and development efforts in obtaining very stable and high load-bearing polymer-based ultra-low-friction surfaces via biomimicry.

Highly stretchable HA/SA hydrogels for tissue engineering

A highly stretchable hyaluronic acid (HA)/sodium alginate (SA) hydrogel was developed in this study based on an interpenetrating polymer network. HA/SA hydrogels were prepared by mixing two polysaccharides followed by covalent crosslinking via epoxy groups on HA molecules and ionic crosslinking via divalent ions on SA chains sequentially. The effect of HA/SA ratio on the pore size and distribution, swelling ratio, elongation and rheological properties as well as protein loading and release properties of HA/SA hydrogels was explored. Moreover, a surface modification method, layer-by-layer (LBL) assembly technique, was applied to modify the hydrogel to evaluate the hydrogel’s tenability in varying biological performance. It was then shown that the hydrogels had the pore sizes ranging from 100 to 50 μm. With the increase in SA content of the resulting hydrogels, the pore size, swelling ratio, and storage modulus (G′) and loss modulus (G″) of the hydrogel all decreased, whereas the in vitro bulk weight loss was fastened. Moreover, elongation at break (EB) value increased first, reached a peak value and then decreased, that is HA8/SA1 (HA:SA = 8:1) had the highest EB value of 417%. This hydrogel could retain 33.2% of the pre-loaded protein even after 72 h, which could be further attenuated when LBL was used to shell the hydrogel. The growth of fibroblasts on HA8/SA1 hydrogel gave preliminary assessment on its suitability as a cellular carrier, while the LBL modified HA8/SA1 hydrogel also favored the anchoring of keratinocytes, further enhancing its cell carrier role for tissue regeneration, especially skin engineering.

Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications

Hyaluronic acid (HA) is a natural linear polysaccharide that has been used extensively in the biomedical field as it is a biocompatible, biodegradable, nontoxic and non-immunogenic polymer with high water affinity. Besides, the presence of multiple acid and hydroxyl groups in the HA molecule makes it an ideal candidate for chemical modification. The present paper describes the synthesis and characterization of HA-based hydrogels. For this purpose, aqueous mixtures containing 5% (w/w) of HA and different concentrations of Gantrez S97 (GAN) (1, 3 and 5% w/w) were used to prepare HA-based hydrogels. The mixtures were dried and the hydrogels were obtained after heating the solid material at 80°C for 24h. GAN is the acid form of an methylvinylether and maleic anhydride copolymer and contains multiple acid groups that can form ester bonds when reacting with the multiple hydroxyl groups present in HA chains. The method described here present potential to be applied for the preparation of HA-based biomaterials with a defined form as the crosslinking reaction between HA and the crosslinker takes place in solid phase. Besides, the method can be considered an environmental-friendly process as no organic solvents or potentially toxic substances were used. The esterification reaction was confirmed by infrared spectroscopy and dynamic scanning calorimetry measurements. The loading and release capabilities of the hydrogels were evaluating by using methylene blue (MB) as a model molecule. The hydrogels showed a high affinity for MB showing loadings up to 0.35mg MB per mg of hydrogel. Moreover, the hydrogels were capable of sustaining the MB release over two days. The use of microwave radiation was evaluated to reduce the crosslinking time from 24h to 1h, but this procedure needs to be optimized in future studies. As the crosslinking procedure takes place in solid state, the HA/GAN hydrogels were used to prepare micro-engineered device, microneedle arrays. Finally, the antimicrobial properties of the hydrogels were evaluated. The results showed that the hydrogels presented anti-infective properties.

Human hyaluronic acid synthase-1 promotes malignant transformation via epithelial-to-mesenchymal transition, micronucleation and centrosome abnormalities

BackgroundHuman hyaluronic acid (HA) molecules are synthesized by three membrane spanning Hyaluronic Acid Synthases (HAS1, HAS2 and HAS3). Of the three, HAS1 is found to be localized more into the cytoplasmic space where it synthesizes intracellular HA. HA is a ubiquitous glycosaminoglycan, mainly present in the extracellular matrix (ECM) and on the cell surface, but are also detected intracellularly. Accumulation of HA in cancer cells, the cancer-surrounding stroma, and ECM is generally considered an independent prognostic factors for patients. Higher HA production also correlates with higher tumor grade and more genetic heterogeneity in multiple cancer types which is known to contribute to drug resistance and results in treatment failure. Tumor heterogeneity and intra-tumor clonal diversity are major challenges for diagnosis and treatment. Identification of the driver pathway(s) that initiate genomic instability, tumor heterogeneity and subsequent phenotypic/clinical manifestations, are fundamental for the diagnosis and treatment of cancer. Thus far, no evidence was shown to correlate intracellular HA status (produced by HAS1) and the generation of genetic diversity in tumors.MethodsWe tested different cell lines engineered to induce HAS1 expression. We measured the epithelial traits, centrosomal abnormalities, micronucleation and polynucleation of those HAS1-expressing cells. We performed real-time PCR, 3D cell culture assay, confocal microscopy, immunoblots and HA-capture methods.ResultsOur results demonstrate that overexpression of HAS1 induces loss of epithelial traits, increases centrosomal abnormalities, micronucleation and polynucleation, which together indicate manifestation of malignant transformation, intratumoral genetic heterogeneity, and possibly create suitable niche for cancer stem cells generation.ConclusionsThe intracellular HA produced by HAS1 can aggravate genomic instability and intratumor heterogeneity, pointing to a fundamental role of intracellular HA in cancer initiation and progression.

Hyaluronate dots for highly efficient photodynamic therapy

Nanoscale particles, such as quantum dots and carbon dots, are important materials for use in sensing and treating irregular biological events, but their versatility for biomedical applications are usually limited by their undesirable properties such toxicity and non-degradability. Here, we report biofunctional hyaluronic acid (HA) dots containing biodegradable/biocompatible HA. HA dots were prepared by conjugating multiple HA molecules to C60 (used as a base dot) without any hydrothermal treatment. The hydroxyl groups of HA completely linked to all π-π carbon bonds in C60. The chemically synthesized HA dots (Mn=16.1kDa) were 2nm in diameter, soluble in aqueous solution, and possessed multiple functional (carboxyl) groups. The HA dots were biofunctional, enabling highly efficient binding to CD44 receptors overexpressed on in vitro/in vivo tumors. With light illumination, we demonstrated that the HA dots bearing a photosensitizing model drug (chlorin e6: Ce6) resulted in a significant enhancement in in vitro/in vivo tumor cell ablation. We believe that this approach offers a new strategy to create biopolymer dots.

Molecular Dynamic Analysis of Hyaluronic Acid and Phospholipid Interaction in Tribological Surgical Adjuvant Design for Osteoarthritis.

Tribological surgical adjuvants constitute a therapeutic discipline made possible by surgical advances in the treatment of damaged articular cartilage beyond palliative care. The purpose of this study is to analyze interactions between hyaluronic acid and phospholipid molecules, and the formation of geometric forms, that play a role in the facilitated lubrication of synovial joint organ systems. The analysis includes an evaluation of the pathologic state to detail conditions that may be encountered by adjuvants during surgical convalescence. The synovial fluid changes in pH, hyaluronic acid polydispersity, and phospholipid concentration associated with osteoarthritis are presented as features that influence the lubricating properties of adjuvant candidates. Molecular dynamic simulation studies are presented, and the Rouse model is deployed, to rationalize low molecular weight hyaluronic acid behavior in an osteoarthritic environment of increased pH and phospholipid concentration. The results indicate that the hyaluronic acid radius of gyration time evolution is both pH- and phospholipid concentration-dependent. Specifically, dipalmitoylphosphatidylcholine induces hydrophobic interactions in the system, causing low molecular weight hyaluronic acid to shrink and at high concentration be absorbed into phospholipid vesicles. Low molecular weight hyaluronic acid appears to be insufficient for use as a tribological surgical adjuvant because an increased pH and phospholipid concentration induces decreased crosslinking that prevents the formation of supramolecular lubricating forms. Dipalmitoylphosphatidylcholine remains an adjuvant candidate for certain clinical situations. The need to reconcile osteoarthritic phenotypes is a prerequisite that should serve as a framework for future adjuvant design and subsequent tribological testing.

Noninvasive penetration of 5nm hyaluronic acid molecules across the epidermal barrier (in vitro) and its interaction with human skin cells.

Hyaluronic acid represents one of the major components of the extracellular environment. The main challenge remains in the ability to deliver these molecules noninvasively across the skin barrier, which can be overcome by the reduction in size to an extent that allows these molecules to pass across the skin barrier. The aim of this study was to measure the penetration and bioavailability of low molecular weight hyaluronic acid to cross an epidermal barrier model. Determining the quantity of hyaluronic acid in the test solutions was carried with method of photocolorimetry analysis. Investigation of the interaction of cells with LMWHA was studied with a confocal microscope. The study showed that LMWHA is able to cross the epidermis. Most effective penetration level is during the first 6hours reaching 75%, and then the concentration started to decline and reached the equilibrium state within the following 2hours. Confocal laser microscopy demonstrated different distribution and behavior of these molecules among the keratinocytes and fibroblasts. Reducing the size of hyaluronic acid to 5nm enhance their transport across the epidermal layer. The concentration of hyaluronic acid molecules was higher on the fibroblast surface in comparison to their extracellular environment.

High-throughput generation of hyaluronic acid microgels via microfluidics-assisted enzymatic crosslinking and/or Diels–Alder click chemistry for cell encapsulation and delivery

Cell encapsulation in 3D microgels offers unique advantages to meet the complicated requirements in tissue engineering, regenerative medicine and cell therapy. Herein we report high-throughput microfluidic generation of cell-laden microgels based on a new hyaluronic acid (HA) derivative, i.e. furylamine and tyramine grafted HA molecules, which can be crosslinked via either enzymatic crosslinking, or Diels–Alder click chemistry, or both. Compared with traditional photoinitiated free radical polymerization and Michael conjugate addition reaction, enzymatic crosslinking and click chemistry crosslinking show higher chemical selectivity and milder reaction conditions. More importantly, the switching of crosslinking strategy in the same molecule makes it possible to fabricate microgels with almost the same composition but variable gelation time and elasticity. Using ATDC-5 cells as model cells, three types of cell-laden microgels were generated in high-throughput manner and their potentials as cell carriers were evaluated in detail by comparing their mechanical elasticity, gelation time, microgel size, swelling ratio, cell viability, enzymatic degradation and bioactivity of released cells. Our results reveal that the new HA-derived microgels crosslinked by enzymatic crosslinking and Diels–Alder click chemistry are very promising candidate for cell encapsulation and delivery.

Enhanced hyluronic acid production in Streptococcus zooepidemicus by over expressing HasA and molecular weight control with Niscin and glucose

Hyaluronic acid (HA) is a high molecular weight linear polysaccharide, endowed with unique physiological and biological properties. Given its unique properties, HA have unprecedented applications in the fields of medicine and cosmetics. The ever growing demand for HA production is the driving force behind the need for finding and developing novel and amenable sources of the HA producers. Microbial fermentation of Streptococcus zooepidemicus deemed as one the most expeditious and pervasive methods of HA production. Herein, a wild type Streptococcus zooepidemicus, intrinsically expressing high levels of HA, was selected and optimized for HA production. HasA gene was amplified and introduced into the wild type Streptococcus zooepidemicus, under the control of Nisin promoter. The HasA over-expression increased the HA production, while the molecular weight was decreased. In order to compensate for molecular weight loss, the glucose concentration was increased to an optimum amount of 90g/L. It is hypostatizes that excess glucose would rectify the distribution of the monomers and each HasA molecule would be provided with sufficient amount of substrates to lengthen the HA molecules. Arriving at an improved strain and optimized cultivating condition would pave the way for industrial grade HA production with high quality and quantity.

Cytoprotective Self-assembled RGD Peptide Nanofilms for Surface Modification of Viable Mesenchymal Stem Cells

Intravenous administration of mesenchymal stem cells (MSCs) has served as a clinical intervention for inflammatory diseases. Once entered to blood circulation, MSCs are exposed to a harsh environment which sharply decreases cell viability due to the fact that injected cells, being susceptible to shear stress, are subjected to the high velocities of the bloodstream and lack of proper mechanical support that keeping them in an attachment-deprived state. Here, we coated the nanofilm onto viable MSCs by depositing poly-l-lysine and hyaluronic acid molecules along with arginine-glycine-aspartic acid (RGD peptide) as building blocks to protect cells from shear stress and stabilize them in a single cell, suspension state. In this article, we found that nanofilm-coated cells showed significantly increased cell survival in vitro and in vivo, which was also supported by the activation of survival-related protein, Akt. The coated nanofilm did not interfere with the stemness of MSCs which was determined based on the ...

Computational Model for the Generalised Dispersion of Synovial Fluid

The metabolic function of synovial fluid is important to understand normal and abnormal synovial joint motion, especially if one seeks some leading causes of the degenerative joint disease. The concentration of hyaluronic acid molecules and other high molecular weight substances in the synovial fluid may be responsible to disperse the nutrients into the cartilage. The theoretical study of the convective diffusion mechanism occurring in the knee joint is presented. A flow model has been analyzed for better understanding of the convective diffusion of the viscous flow in between the articular surfaces. The governing system of partial differential equations has been solved for the Newtonian fluid with suitable matching and conditions. The analytical solution for the unsteady dispersion problem has been obtained for the better understand the phenomena of nutritional transport to synovial joint. The contributions of (convection + diffusion) on the dispersion of nutrients are investigated in detail. The dispersion coefficient has been computed for different values of the viscosity parameter. The results show that the average concentration has a negative correlation with the axial distance and the time.