Narrow Results

Microcapsules comprising alginate and hyaluronic acid that can be decomposed by radiation are under development. Previously, we observed that radiation efficiently decomposes microcapsules comprising alginate and hyaluronic acid in the ratio 2:1 by weight. In this study, Yttrium (Y) was added to these microcapsules to improve their decomposition by radiation.

Hyaluronic acid solutions (0.1% weight/volume) were mixed into 0.2% alginate solution, and carboplatin (0.2 mmol) was added; the resultant was used for capsule preparation. Capsules were prepared by spraying the material into mixtures of 4.34% CaCl₂ solution supplemented with Y at final concentrations from 0 to 1.0 × 10⁻²%.

These capsules were irradiated by a single dose of 0.5, 1.0, 1.5, or 2 Gy with ⁶⁰Co γ-rays. Immediately after irradiation, we observed the release of the core contents of the microcapsule using a micro Particle Induced X-ray Emission (PIXE) camera.

The mean diameter of the microcapsules was 37.3 ± 7.8 μm. Maximum content of radiation-induced release was observed for liquid-core microcapsules prepared by polymerization in a 4.34% CaCl₂ solution supplemented with 5.5 × 10⁻³% Y.

Hyaluronic acid (HA) is present in high concentrations in the intercellular spaces of the epidermis and the connective tissues of the dermis. It is associated with many beneficial biological activities including water retention, maintenance of various cellular functions, and skin homeostasis. Puerariae Radix (PR), a Chinese herb and a popular food in Asia, is used for various medicinal purposes including anti-hypertension, anti-angina pectoris and anti-dipsotropic. PR is rich in isoflavone glycosides like genistin and daidzin as soya. In this study, Bifidobactericum breve CCRC 14061 and CCRC 11846 were used for the fermentation of PR; moreover, acid was used to hydrolyze PR decoction. Genistein and daidzein in the hydrolysate were determined by HPLC. The HA production in normal human epidermal keratinocytes (NHEK) was measured after 48 hours incubation with PR and its hydrolysate, respectively. HA was assayed by enzyme-linked immunosorbent assay (ELISA), and retinoic acid was used as the positive control. After fermentation with Bifidobactericum breve, the contents of daidzein and genistein were increased 785% and 1,010% by CCRC 14061, and 192% and 406% by CCRC 11846, respectively, whereas after acid hydrolysis, only daidzein was increased by 990%. The production of HA in NHEK was increased after incubation with the fermentation product of CCRC 14061, acid hydrolysate, PR decoction and retinoic acid (22± 0.2%), whereas no increase of HA concentration was found after incubation with the fermentation product of CCRC 11846. Furthermore, the PR hydrolysate stimulated the HA production of NHEK, and the effect was dose-dependent (18.6%–83.9%). In conclusion, PR preparations would stimulate HA production in NHEK cells which might be used as a new cosmetic ingredient in moisturizers and an anti-aging agent.

This pilot study retrospectively compares the efficacy and side effects reported with sodium hyaluronate and hylan G-F 20 (hylan) in the treatment of knee pain associated with osteoarthritis (OA). Patients responded to a questionnaire that assessed pain at rest, pain with weight bearing, mobility, frequency of night-time awakenings, medication use, and side effects pre- and post-injection of sodium hyaluronate (n = 42) or hylan (n = 57). Pain at rest and with activity, mobility, and night-time awakenings were significantly improved with both treatments. Hylan was significantly better than sodium hyaluronate in improving mobility (p = 0.052), relieving pain with weight bearing (p = 0.017), and reducing frequency of night-time awakenings (p = 0.002). When controlling for baseline pain, the latter two variables (p = 0.03 and 0.005, respectively) remained better with hylan than sodium hyaluronate. Post-injection pain was the predominant side effect (sodium hyaluronate 21%; hylan 18%) and was similar between treatments. While both therapies benefited patients with similar tolerability, patients reported greater efficacy with hylan than sodium hyaluronate in relieving pain with weight bearing, reducing night-time awakenings, and improving mobility in OA of the knee.

The clinical significance of hyaluronan (HA) levels in the cerebrospinal fluid (CSF) of patients with spinal tumor (ST) was evaluated in order to clarify whether HA concentrations in the CSF of patients with ST differ according to such factors as the tumor site and histopathological diagnosis. CSF samples were obtained from 40 patients with ST who had undergone myelography and CSF examinations retrospectively. The HA levels were determined using a sandwich-binding protein assay. The total protein (TP) levels were also determined. The HA and TP concentrations in CSF were significantly higher in patients with extramedullary tumor than in patients with intramedullary tumor. There was a significant correlation between HA and TP concentrations in CSF patients with ST. A HA assay for CSF is therefore considered to be potentially useful for estimating the localization of ST.

Photopolymerized hydrogel based on poly(ethylene glycol) diacrylate (PEGDA) was applied to periosteum-derived periosteal stem cell (PSC) encapsulation and orthopedic tissue engineering. To provide support for cell adhesion, hyaluronic acid (HA) was incorporated into the PEGDA solution prior to photopolymerization. HA can be utilized to mimic the extracellular matrix composition as well as control cell growth and differentiation. In vitro studies have demonstrated its ability to encapsulate PSCs to form bone-like tissue in a photopolymerized hydrogel. Osteointegration of a tendon graft within the bone tunnel is a primary concern when employing tendon grafts for ligament reconstruction. This study presents a novel technique for fabricating injectable hydrogel–photoencapsulated PSCs in a bone tunnel to enhance tendon–bone healing. A total of 21 adult New Zealand white rabbits were used. The long extensor digitorum tendon was transplanted into a bone tunnel of the proximal tibia. The tendon was pulled through a drill hole in the proximal tibia and attached to the medial aspect of the tibia. Hydrogel suspension containing PSCs at a concentration of 20 million/mL was injected into the bone tunnel. Histological examination of the tendon–bone interface and biomechanical testing for maximal pull-out load were evaluated at postoperative weeks 3 and 6. Histological analysis of the tendon–bone interface showed an interface fibrous layer formed by the photoencapsulation of PSCs between the tendon and the bone. This layer became progressive integrated with the tendon–bone surface during the healing process. Biomechanical testing revealed higher maximal pull-out strength in experimental groups with a statistically significant difference at 3 and 6 weeks. These results suggest that photopolymerizable PEGDA and HA hydrogels are promising for tissue-engineered stem cell therapy to enhance tendon–bone healing.

The objective of this paper was to study in vitro transfection of tendon cells and adherence of transfected cells to different tendon surfaces. Achilles tendon fibroblasts from 2-month-old New Zealand white rabbits were cultured to confluence, after which the cells were transfected by an adenovirus carrying either the β-galactosidase reporter gene or the green fluorescent protein (GFP) gene at multiplicities of infection (MOIs) of 50, 100, or 500. Two days later, the cells were transplanted onto the surfaces of rabbit Achilles, peroneus brevis, flexor profundus, and extensor longus tendons. The tendons were assessed by X-gal staining after 9 days, and by GFP fluorescence at 7, 14, and 21 days. Twenty percent to 50% of the treated cells stained for β-galactosidase at an MOI of 500. The GFP-labeled cells showed nearly 100% fluorescence at an MOI of 50. No positive cells were visible in the control group. The β-galactosidase and GFP-expressing cells remained viable for as long as 3 weeks. It is possible to introduce foreign genes into rabbit tendon cells, transplant the cells onto tendon surfaces, and maintain viability of the cell/tendon construct for several weeks.

Purpose: This study was conducted to histopathologically compare the results of the administration of intra-articular PDRN and HA injections in experimentally induced OA in rats. Methods: Osteoarthritis of the knee joints was induced in a total of 30 rats. Rats were randomly divided into three groups; polydeoxyribonucleic (PDRN) acid group, hyaluronic acid (HA) group, and saline group. The PDRN group was injected with 12 mg/0.05 ccPDRN acid. The HA group was injected with 12 mg/0.05 ccHA, whereas the saline group was injected with 50 $\mu$l (0.05 cc) of 0.9% sodium chloride solution. All rats were sacrificed on postinjection day 29, and the right knee joints were prepared and evaluated histologically using the Mankin scoring system. Results: Total Mankin scores showed a significant difference among all groups ($p$ = 0.001). According to bilateral comparisons performed to identify the group that showed a difference, the total Mankin scores of the PDRN acid and HA groups were found to be significantly lower than those of the saline group. In PDRN acid group, tidemark continuity wasobserved in all specimen. Conclusion: Intra-articular injections of PDRN acid resulted in greater chondroprotective effects and less degeneration than those of HA and saline in experimentally induced OA of the knee joints in rats.

Nanject: Drug Delivery Cancer Cells Detection.

Potential Thrills and Perils of Synthetic Biology.

A Novel Technology to Protect from Airborne Viruses.

Creating A New, Safer Generation of Hyaluronic Acid for Pharmaceutical Applications.

The Benefits of Refractive Index Detection for UHPLC.

This work presents the process of physical crosslinking of hyaluronic acid (HA) in the presence of phospholipids (PL) as applied to the lubrication in articular cartilage system. Three time scales of the process have been studied using Molecular Dynamics simulation: 2ps, 200ps and 20ns. The simulations were carried out for long and short chains of HA in the presence and in the absence of PL. We show that in contrast to the macroscopic thermal (white) noise, the short-time noise on the molecular scale has the properties of color noise with the power spectrum distribution proportional to the inverse of frequency, $\mathrm{\text{PSD}}\sim 1∕f^{\alpha }$. The long-time simulations are characterized by a power spectrum similar to that of white noise.

The number of drug-resistant bacteria is increasing significantly. To combat such issues, antimicrobial PDT (aPDT) provides an efficient way to eliminate these species efficiently, cost-effectively, and more importantly, without the associated mechanism of resistance. The hemisynthesis and synthesis of photosensitizers such as polyaminated chlorin-p6 and 5-(4-aminophenyl)-10,15,20-tris(4-$N$-methylpyridinium)porphyrin triiodide and their water stable and soluble formulation with hyaluronic acid bio-polymer (PS-HA) is reported. Structures of porphyrin-HA formulations were characterized by IR, DSC, DLS, zeta potential, SEM imaging, UV-vis analysis and rheological evaluation confirming the covalent conjugation of PSs on conjugate platform (hyaluronic acid). These conjugate formulations were tested against the Gram-negative Escherichia coli (CIP 53.126) and Gram-positive Staphylococcus aureus (CIP 76.25) bacteria for their potency for aPDT.

Hyaluronic acid (HA) concentration is an important parameter in fermentation process. Currently, carbazole assay is widely used for HA content determination in routine analysis. However, this method is time-consuming, environment polluting and has the risk of microbial contamination, as well as the results lag behind fermentation process. This paper attempted the feasibility to predict the concentration of HA in fermentation broth by using near infrared (NIR) spectroscopy in transmission mode. In this work, a total of 56 samples of fermentation broth from 7 batches were analyzed, which contained HA in the range of 2.35–9.69 g/L. Different data preprocessing methods were applied to construct calibration models. The final optimal model was obtained with first derivative using Savitzky–Golay smoothing (9 points window, second-order polynomial) and partial least squares (PLS) regression with leave-one-block-out cross validation. The correlation coefficient and Root Mean Square Error of prediction set is 0.98 and 0.43 g/L, respectively, which show the possibility of NIR as a rapid method for microanalysis and to be a promising tool for a rapid assay in HA fermentation.

Tissue engineering strategies for regenerating damaged cartilage using hydrogels have garnered significant attention due to the limited self-healing capacity of damaged cartilage tissue and the restrictions of current medical treatment methods. In particular, using human mesenchymal stem cells (hMSCs) as the cell source has shown the potential to differentiate along a chondrogenic lineage. Hydrogels, whether made of synthetic polymers, natural polymers, or combinations, are widely explored as scaffolding materials mimicking the natural cartilage environment. Based on the understanding of the importance of surface nanotopographies and mechanical stiffness, hydrogels have been presented in various forms and tested for the differentiation of hMSCs. The primary focus of this review is to provide a summary of recent advances in physically and chemically modified hydrogels promoting the chondrogenesis of hMSCs. Advances in micromachining have helped in forming surfaces with the required roughness or an array of micropillars of defined architecture. Hydrogels have been combined with various stimulants such as small peptides, growth factors, and many modified matrix elements. Creating anisotropic hydrogels mimicking the extracellular matrix of cartilage has also been reported. These studies show promising results and identify a niche for in-vitro differentiation of chondrocytes from hMSCs.

Background: Dupuytren disease (DD) is characterised by increased myofibroblast/fibroblast activity and type3/type1 collagen ratios. Hyaluronic acid (HA) is major component of the extracellular matrix and some studies have showed that HA limits myofibroblast activity and decreases type3/type1 collagen ratio. The aim of this study is to determine the effect of the ex-vivo application of HA on cultured fibroblasts obtained from normal and diseased tissue from patients with DD. This is the initial step towards defining the use of HA as a new approach for medical treatment of DD.

Methods: Tissue samples were obtained from both healthy forearm (C) and unhealthy palmar (D) fascia of patients undergoing surgery for DD. Tissue samples were cultured and divided into four groups depending on the addition of HA [C(HA−), C(HA+), D(HA−) and D(HA+)]. The tissues were evaluated using Western blot to detect effect of HA on myofibroblast (by measuring alpha smooth muscle actin [α-SMA) and on the ratio of type3/type1 collagen by measuring collagen type1 alpha 1 Chain (COL1A1) and collagen type3 alpha 1 Chain (COL3A1).

Results: The rate of the average α-SMA value in the D(HA+) group was significantly lower compared to that of the D(HA−) group. The average ratio of type3/type1 collagen in the D(HA+) group was significantly lower compared to the D(HA−) group.

Conclusions: The ex-vivo application of HA on cultured fibroblasts obtained from patients with DD resulted in a decrease in myofibroblast/fibroblast activity and type3/type1 collagen ratios. This may pave the way for clinical application of HA in the treatment of DD.

Background: Hyaluronan (HA) sperm selection, utilizing the affinity of mature sperm for HA, has emerged as a technique to enhance the selection of sperm for intracytoplasmic sperm injection (ICSI). However, conflicting evidence exists regarding the impact of HA-ICSI on clinical outcomes including fertilization, embryo utilization, and pregnancy rates. The study aimed to compare clinical outcomes including fertilization, utilization, and pregnancy rates between paired ICSI and HA-ICSI cycles within patients, particularly for male factor and low utilization subgroups.

Methods: A retrospective study from 3,988 ICSI treatment cycles was conducted between January 2018 and March 2022. A HA-ICSI cycle was paired with the preceding ICSI cycle from the same patient. Fertilization, utilization, and clinical pregnancy rates were compared based on infertility diagnosis and utilization rate (UR) from the initial ICSI cycle.

Results: There were no differences in fertilization, utilization, embryo quality, euploidy, or pregnancy rates between ICSI and HA-ICSI in all paired cycles. However, for patients with male factor infertility UR increased from 25.0% to 38.5% in their HA-ICSI cycle ($p=0.014$). There was no difference observed for female factor infertility patients. HA-ICSI use was of particular benefit for male factor infertility patients with low ($<40\%$) embryo utilization in their initial ICSI cycle, evident by an increased utilization from 14.3% to 25.0% in their HA cycle ($p=0.006$).

Conclusions: This is the first study to focus on the impact of HA-ICSI on embryo utilization, particularly in patients with male factor infertility. The efficacy of HA-ICSI as a sperm selection tool appears to be limited to improving UR in patients with male factor infertility, particularly those with low utilization in a previous ICSI cycle, with no significant effect on fertilization or pregnancy rates.

Conclusion: HA-ICSI may be useful for sperm selection at the time of ICSI for a select subgroup of patients. Male factor infertility patients, who have previously undertaken an ICSI cycle with less than 40% utilization, should be considered as candidates for treatment.

Synovial fluid functions as a biological lubricant and lubricates articular cartilage to reduce friction and wear. Lubricin and hyaluronic acid are the primary components of synovial fluid responsible for its lubricating properties. The loss of properties in synovial fluid and articular cartilage due to aging and activities can restrict mobility in synovial joints, resulting in the degradation of articular cartilage and ultimately leading to pathological synovial joints, which is a major cause of disability. Thus, research on synovial joints remains crucial, and despite previous investigations on synovial joint lubrication, there are several issues related to squeeze film lubrication that require further attention. The Newtonian model of squeeze film lubrication in synovial joints needs to be extensively studied. In this study, lubrication and other related properties of synovial fluid are studied theoretically. In this paper, we have studied the flow of synovial fluid in the diseased synovial joint. Further, we have studied the effect of the viscosity of the synovial fluid, the permeability of articular cartilage, thickness of articular cartilage, and fluid film thickness on the characteristic of the squeeze film formed between the articular cartilages of the diseased human knee joint. The flow of synovial fluid is modeled by considering it as a viscous, incompressible and Newtonian fluid. We have derived the modified Reynolds equation using the principle of hydrodynamic lubrication and continuum mechanics theory and solved it by applying the suitable boundary conditions according to the physical considerations. Subsequently, we obtained the expression for pressure distribution in fluid film, load-bearing capacity, and squeeze time and have done the theoretical analysis on these properties for different parameters. Pressure increases with squeeze velocity and viscosity of the synovial fluid and decreases with permeability and fluid film thickness. Human knee joint becomes diseased due to excessive pressure, and the mobility of the knee joint decreases. The load capacity increases with viscosity and squeeze velocity and decreases with permeability resulting in the reduction of the load-carrying capacity of the knee joint in diseased conditions. Moreover, the squeeze time also increased in the diseased state of the joint.

Injectable filler, which is often applied in minimally invasive surgery, has been widely-used in facial rejuvenation. Because of its convenience, effective usage and less downtime after treatment for the patients, it becomes one of the most popular treatment methods at present. The currently available products containing collagen base have been proven to have much satisfactory safety and effectiveness, but one of its disadvantages is the lack of long-term volume persistence. We have previously prepared the reconstituted collagen fibrils with hyaluronic acid (HA) by modifying the fibril surface. This study is to evaluate the potential of these materials as injectable filler in vitro. A preparation of collagen fibrils with a diameter of 100–150 nm was used. The modification rate of HA on the fibril surface was 20%. In assessment of the biocompatibility, it was proven that the collagen fibril and HA-collagen fibril treated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) had no cytotoxicity or inhibitory actions. In interactions between these materials and cells, it was found that the existence of HA could improve the migration ability of L929 fibroblasts and breast cancer cells (MDA-MB 435s). In conclusion, collagen fibril and HA-collagen fibril have the potential to be developed into an injection as a soft tissue filler for biomedical applications.

Aim. Macroporous sponge-like gelatin–hyaluronic acid (Gl–HA) scaffolds cross-linked by EDC were produced using cryogelation technology, which allows for the preparation of highly porous scaffolds without compromising their mechanical properties, and is a more cost-efficient process than freeze drying. The aim of this study is to evaluate the osteogenic potential of porcine adipose-derived stem cells (PADSCs) in GI–HA cryogel.

Method. The character of the GI–HA cryogel was evaluated. The pore size and the microstructure were observed using scanning electron microscope (SEM). The swelling ratio was measured. The PADSCs were harvested and isolated from pig inguinal area. Then, the GI–HA cryogel was seeded with PADSCs. The cryogel/ASCs mixture was cultured in osteogenic medium for 0, 3, 7, 14, and 21 days. The cell proliferation was measured by MTS. The RT-PCR of specific osteogenic gene expression such as osteocalcin (OC), RUNX2 was used to assess the osteogenic ability. The SEM was used to observe the interaction between scaffold and cells. Energy dispersive spectrum (EDS) was used to analyze the mineralization around cells.

Results. The pore size was variable between 200 and 369 μm. The swelling ratio was around 8.67 ± 1.669%. The cell proliferation was increasing along with the increase of induction periods. The expression of early gene of RUNX2 and late gene of OC mean that the PADSCs were differentiated well into osteoblasts within the cryogels. The SEM detailed that the PADSCs cell can proliferate well in the pore of GI–HA scaffold. The EDS also demonstrated the mineralization of PADSCs in GI–HA scaffold after induction.

Conclusions. To conclude, the PADSCs can proliferate and differentiate well into osteoblasts in the three-dimensional, porous, GI–HA cryogel.

This study examined the biocompatibility of blood vessels and a biodegradable drug-loaded vascular stent. The Traditional Chinese Medicine System Laboratory of Chung Yuan Christian University prepared the vascular stent, and our study verified the sustained release of drugs from the stent when it was within blood vessels. A platelet adhesion experiment revealed that stents with less surface roughness resulted in a reduction in the number of adhered platelets and decreased fibrinogen accumulation. The results of a hemolysis experiment verified that the hemolysis index was between 1% and 1.4%, within the range of no hemolysis and would not cause hypoxia. Subsequently, a drug release rate experiment indicated that the amount of released everolimus increased with time. The greatest amount of drug that was released occurred at 8h, with a release rate of 36.95%. A swelling rate experiment revealed that the degree of swelling of the hyaluronic acid (HA) that contained everolimus was 10 times less than that of the original HA; therefore, the use of a material with a low swelling rate in vascular stents did not immediately cause an obstruction in blood vessels. A lactate dehydrogenase (LDH) toxicity experiment revealed that the percentage of LDH released was 13–18%. This indicated that the cell viability was not affected and that there was no cytotoxicity; thus, the stent was suitable for use in blood vessels. This study proved that the prepared biodegradable drug-loaded vascular stent had favorable blood compatibility, no cytotoxicity, and a suitable drug release rate. Moreover, the drug release material was made from a material with a low degree of swelling. As a result of our findings, this new type of stent is suitable for application in blood vessels.

Natural methacrylate polysaccharides and proteins represent a versatile group of modified macromolecules. The methacrylic group is capable of undergoing a gelling process through a photo-crosslinking polymerization into the macromolecule backbone. This chapter presents an overview of the methacrylation reaction of biopolymers, such as chitosan, laminarin, hyaluronic acid, dextran, gellan gum, gelatin and platelet lysates, developed by our research group. The biomedical applications, such as tissue engineering, therapeutic delivery and stem cells modulation, are highlighted.

Toll-like receptor (TLRs) is cell surface receptor family discovered in recent years, which belongs to the first line weapon for immune system to rapidly fight against microbial infection and plays an important role in triggering natural immunity and affecting acquired immunity. High molecular weight hyaluronic acid (HMW-HA) is important component in extracellular matrix. It can be degraded into low molecular weight hyaluronic acid (LMW-HA) by reactive oxygen molecules (ROS). The later can coordinate with ROS to activate the immune system and induce inflammation reaction through toll-like receptors. Hyaluronic acid, as internal signal of tissue damage, can be recognized by TLRs and TLRs can be activated, thereby producing a series of physiological and biochemical reaction. Different kinds of TLRs can make different reactions on hyaluronic acid in segments of different sizes. Study of relationship between hyaluronic acid and toll-like receptors can provide new concept and means for physiological and pathological mechanism of immune response and inflammatory response.