Aims. A local injection may be used as an early option in the treatment of Morton’s neuroma, and can be performed using various medications. The aim of this study was to compare the effects of injections of hyaluronic acid compared with corticosteroid in the treatment of this condition. Methods. A total of 91 patients were assessed for this trial, of whom 45 were subsequently included and randomized into two groups. One patient was lost to follow-up, leaving 22 patients (24 feet) in each group. The patients in the hyaluronic acid group were treated with three ultrasound-guided injections (one per week) of hyaluronic acid (Osteonil Plus). Those in the corticosteroid group were treated with three ultrasound-guided injections (also one per week) of triamcinolone (Triancil). The patients were evaluated before treatment and at one, three, six, and 12 months after treatment. The primary outcome measure was the visual analogue scale for pain (VAS). Secondary outcome measures included the American Orthopaedic Foot and Ankle Society (AOFAS) score, and complications. Results. Both groups showed significant improvement in VAS and AOFAS scores (p < 0.05) after 12 months. The corticosteroid group had a significantly greater reduction in VAS and increase in AOFAS scores compared with the hyaluronic acid group, at one, three, and six months, but with no significant difference at 12 months. There were no complications in the hyaluronic acid group. There were minor local complications in six patients (six feet) (25.0%) in the corticosteroid group, all with discolouration of the skin at the site of the injection. These minor complications might have been due to the three weekly injections of a relatively high dose of corticosteroid. No patient subsequently underwent excision of the neuroma. Conclusion. An ultrasound-guided corticosteroid injection showed statistically significantly better functional and pain outcomes than an ultrasound-guided injection of hyaluronic acid for the treatment of a Morton’s neuroma at many timepoints. Thus, a corticosteroid injection should be regarded as a primary option in the treatment of these patients, and the only indication for an injection of hyaluronic acid might be in patients in whom corticosteroid is contraindicated. Cite this article: Bone Joint J 2024;106-B(10):1093–1099

The use of stem cells transplanted into the intervertebral disc (IVD) is a promising regenerative approach to treat intervertebral disc degeneration (IDD). The aim of this study was to assess the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) loaded with human mesenchymal stem cells (hMSCs), on IVD extracellular matrix synthesis and nucleus pulposus (NP) marker expression in a whole IVD culture model. HA was blended with batroxobin (BTX), a gelling agent activated in presence of PRP to construct a hydrogel. Bovine IVDs (n=25) were nucleotomised and filled with 1×10. 6. or 2×10. 6. hMSCs suspended in ∼150 mL of the PRP/HA/BTX hydrogel. IVDs harvested at day 0 and nucleotomised IVDs with no hMSCs and/or hydrogel were used as controls. hMSCs alone or encapsulated in the hydrogel were also cultured in well plates to examine the effect of the IVD microenvironment on hMSCs. After 1 week, tissue structure, scaffold integration and gene expression of anabolic (collagen type I, collagen type II and aggrecan), catabolic (matrix metalloproteinase 3 – MMP-3 –, MMP-13 and a disintegrin and metalloproteinase with thrombospondin motifs 4) and NP cell (cytokeratin 19, carbonic anhydrase 12, cluster of differentiation 24) markers were assessed. Histological analysis showed a good integration of the scaffold within the NP area with cell repopulation. At the gene expression level, the hMSC-loaded hydrogels demonstrated to increase disc cell anabolic and catabolic marker expression and promoted hMSC differentiation towards a NP cell phenotype. This study demonstrated that the HA/PRP/BTX may represent a valid carrier for hMSCs being capable of stimulating cell activity and NP marker expression as well as achieving a good integration with the surrounding tissues

Objective. To study the effect of hyaluronic acid (HA) on local anaesthetic chondrotoxicity in vitro. Methods. Chondrocytes were harvested from bovine femoral condyle cartilage and isolated using collagenase-containing media. At 24 hours after seeding 15 000 cells per well onto a 96-well plate, chondrocytes were treated with media (DMEM/F12 + ITS), PBS, 1:1 lidocaine (2%):PBS, 1:1 bupivacaine (0.5%):PBS, 1:1 lidocaine (2%):HA, 1:1 bupivacaine (0. 5%):HA, or 1:1 HA:PBS for one hour. Following treatment, groups had conditions removed and 24-hour incubation. Cell viability was assessed using PrestoBlue and confirmed visually using fluorescence microscopy. Results. Media-treated groups had a mean of 1.55×10. 4. cells/well (. sem. 783). All treated cells showed statistically significant reduced viability when compared with media alone (all p < 0.003). Cells treated with bupivacaine + HA (6.70×10. 3. cells/well (. sem. 1.10×10. 3. )) survived significantly more than bupivacaine (2.44×10. 3. cells/well (. sem . 830)) (p < 0.001). Lidocaine + HA (1.45×10. 3. cells/well (. sem. 596)) was not significantly more cytotoxic than lidocaine (2.24×10. 3. cells/well (. sem. 341)) (p = 0.999). There was no statistical difference between the chondrotoxicities of PBS (8.49×10. 3. cells/well (. sem. 730) cells/well) and HA (4.75×10. 3. cells/well (. sem. 886)) (p = 0.294). Conclusions. HA co-administration reduced anaesthetic cytotoxicity with bupivacaine but not lidocaine, suggesting different mechanisms of injury between the two. Co-administered intra-articular injections of HA with bupivacaine, but not lidocaine, may protect articular chondrocytes from local anaesthetic-associated death. Cite this article: Bone Joint Res 2013;2:270–5

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors. Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes. There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism

Hyaluronic acid (HA) is responsible for the viscoelastic properties of synovial fluid and cartilage. Compared to healthy joints, synovial fluid in osteoarthritic joints contains HA of lower concentration and molecular weight. Hyaluronic acid hybrid complexes are composed by long and short HA chains linked by H bonds. These rheological characteristics and viscoelastic properties were produced by thermal patented process without chemical modification. Chondroitin sulfate (CS) is one of the essential components of the articular cartilage matrix and plays a key role in cartilage's mechanical and elastic properties. Biotechnological chondroitin (CB) is produced through fermentative/biotechnological processes and, unlike CS, is not sulfated. It has been shown that CB to play a more significant role in the phenotypic maintenance of chondrocytes than chondroitin sulfate and increases their viability and proliferation. A recent A Single-Arm, Open-Label, Pilot Study was conducted to evaluate the safety and efficacy of a single-dose intra-articular injection of Hybrid Hyaluronic acid and Sodium Chondroitin in the Treatment of Symptomatic Hip Osteoarthritis. A single injection of HS-SC was well tolerated and safe in the treatment of symptomatic hip OA. The treatment demonstrated a rapid significant improvement in pain (VAS) and function (Lequesne's Index) up to 6 months of follow-up

Background. Infiltration is considered the first treatment option for symptomatic Morton's neuroma and can be performed with various medications. The aim of this study was to compare the effects of hyaluronic acid infiltration versus corticosteroid injection in the treatment of Morton's neuroma. Methods. A randomised clinical trial was conducted with 46 patients (50 feet) diagnosed with Morton's neuroma. After randomisation, the control group (CG) received three injections (one per week) of triamcinolone (Triancil®) guided by ultrasound, while the study group (SG) received three applications of hyaluronic acid (Osteonil Plus®). Patients were followed up for six months after the intervention. The primary outcome measure used was the Visual Pain Analog Scale (VAS). Secondary endpoints included patient-reported outcome measures using the American Orthopaedic Foot & Ankle Society (AOFAS) score and complications. Results. Both groups showed significant improvement in VAS and AOFAS scores (p < 0.001). The CG showed greater improvement than the SG in the VAS (p < 0.05) and AOFAS (p < 0.001) variables. Four patients in the CG experienced skin hypochromia at the injection site, while there were no complications in the SG. Conclusion. Ultrasound-guided hyaluronic acid infiltration in Morton's Neuroma proved to be safe, showing improvement in pain and function after six months of follow-up, without major complications, but with a significantly lower improvement when compared to corticosteroid injection. Taking into account cost implications and the potential for longer lasting improvement from viscosupplementation further medium- and long-term studies are needed

Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148

Objectives. To evaluate the in vitro effects of hyaluronic acid (HA) on adipose-derived stem cells (ASC) in order to consider the possibility of their combined used in the treatment of knee arthrosis. Material and methods. The ASC cells were grown both in the presence and absence of AH, and several studies were carried out: proliferation (WST8) and cell viability studies (Alamar Blue and Trypan Blue), possible chondrogenic differentiation (collagen type 2 expression) by RT-PCR, AH receptor expression (CD44) by flow cytometry and RT-QPCR, and expression of inflammatory and anti-inflammatory factors (IL-6, TGFß, IL-10) by RT-QPCR. Results. The number of ASC significantly increased after 7 days with HA (158±39%, p < .05). Additionally, the cell viability of the ASC treated with HA after 1, 3, 5 and 7 days was similar to that of the control cells, being considered non-toxic. There were no changes observed in the expression of CD44 and chondrogenic differentiation. TGFß expression was not modified after AH treatment, but there was a 4-fold decrease in IL-6 expression and IL-10 expression increased up to 2-fold compared to control cells. Conclusions. Hyaluronic acid favours ASC proliferation without causing cellular toxicity, and inducing an anti-inflammatory profile in these cells. Hyaluronic acid appears to be a suitable vehicle for the intra-articular administration of mesenchymal stem cells

Aims. There is conflicting evidence on the safety of intra-articular injections of hyaluronic acid (HA) or corticosteroids (CSs) before total knee arthroplasty (TKA). We performed a meta-analysis of the relationship between intra-articular injections and subsequent infection rates after TKA. Methods. We searched PubMed, EMBASE, and the Cochrane Library for cohort studies that assessed the effect of preoperative injection of drugs into the joint cavity on the infection rate after TKA. The outcomes analyzed included the total infection rate, as well as those for different preoperative injection time periods and different drugs. Results. Eight studies, including 73,880 in the injection group and 126,187 in the control group, met the inclusion criteria. The injection group had a significantly higher postoperative infection rate than the control group (risk ratio (RR) 1.16; 95% confidence interval (CI) 1.07 to 1.27; p < 0.001; I. 2. = 32%). For patients who received injections up to three months preoperatively, the postoperative infection risk was significantly higher than that in the control group (RR 1.26; 95% CI 1.18 to 1.35; p＜0.001; I. 2. = 0%). There was no significant difference in the infection rates between the four-to-six-month injection and control groups (RR 1.12; 95% CI 0.93 to 1.35; p = 0.240; I. 2. = 75%) or between the seven-to-12-month injection and control groups (RR 1.02; 95% CI 0.94 to 1.12; p = 0.600; I. 2. = 0%). Conclusion. Current evidence suggests that intra-articular injections of CSs or HA before TKA increase the risk of postoperative infection. Injections administered more than three months before TKA do not significantly increase the risk of infection. Cite this article: Bone Joint Res 2022;11(3):171–179

Abstract. Introduction. The effectiveness of single intra-articular injections of polyacrylamide hydrogel (iPAAG) and hyaluronic acid (HA) was compared in subgroups of participants from an RCT based on baseline age, BMI or Kellgren-Lawrence (KL) grade. Methodology. 239 participants were randomised to 6 mL iPAAG (Arthrosamid; n=119) or 6 mL HA (Synvisc-One; n=120). Participants continued analgesics (except 48 hours prior to visits) and non-pharmacological therapy. Topical therapies and intra-articular corticosteroids were not allowed. Pre-specified subgroup analyses (age: <70 years, ≥70 years; BMI: normal, overweight, obese; KL grade: 2, 3, 4, 2–3) of change from baseline in WOMAC pain subscale at 52 weeks were based on the least squares means for the treatment-by-week interaction effect using a mixed model for repeated measurement with a restricted maximum likelihood-based approach. Results. Across all patients, change from baseline in WOMAC pain subscale in the iPAAG group was non-inferior to HA at 26 weeks and approached superiority (p=0.0572) at 52 weeks. Treatment differences for change from baseline in WOMAC pain subscale in favour of iPAAG over HA were statistically significant for the age <70 years (p=0.019), BMI normal (p=0.011) and KL grade 2–3 (p=0.033) subgroups. Treatment differences for all other subgroups favoured iPAAG, except for KL grade 4 which favoured HA, without reaching statistical significance. Conclusion. iPAAG approached superiority to HA across all participants at 52weeks, but demonstrated statistical superiority in participants with normal BMI, participants <70 years old or participants with KL score 2–3. iPAAG represents a useful alternative to HA for the treatment of knee OA

The aim of this study was to evaluate the effect of hyaluronic acid on the stability of the functional spinal unit (FSU) after discectomy. The study included 20 Cercopithecus monkeys. Through a left retroperitoneal approach, four FSUs were exposed and nucleotomy performed. On one level a simple nucleotomy was done, while hyaluronic acid was inserted into one space, hylaform into another, and hylaform and bone morphogenetic protein (BMP)-2 into the fourth. The specimens were evaluated radiologically and histologically at the University of Marburg, Germany. The vertebral height of all segments remained mostly unchanged. Insertion of hylaform with BMP-2 led to ossification in 30%. There was no ossification after insertion of hyaluronic acid alone or in 10% of simple nucleotomies. The insertion of hyaluronic acid shows a promising capability of preventing disc collapse after nucleotomy and may enhance the favourable outcome of minimally invasive procedures

The use of intra-articular hyaluronic acid injections for the treatment of early osteoarthritis is in widespread clinical use. Hyaluronate (HA) is a major component of connective tissue. 1. and is available commercially for the intra-articular injective treatment of osteoarthritis of the knee and periarthritis of the shoulder. Although it is known to improve intra-articular lubrication it is also thought to promote articular cartilage structure and prevent catabolism of matrix proteoglycans in osteoarthritis. Clinical studies have shown beneficial effects lasting for many months after cessation of therapy unlike anti-inflammatory drugs that have relatively short term relieving effects. 2,. 3. . Documentation of the true chondroprotective effects of hyaluronic acid (HA) at the cellular level is lacking and therefore this study aimed to identify the effects of HA on chondrocytes cultured in vitro. Bovine articular chondrocytes were isolated by sequential digestion with pronase and collagenase and seeded in 2% alginate at 1x10. 7. cells/ml. The constructs were cultured for up to 14 days in standard culture medium (DMEM + 20% Fetal calf serum) containing varying concentrations of HA (Sigma), including doses equivalent to those found in vivo. The medium was replaced every 3 days and representative constructs were removed from culture, digested and assayed for DNA, glycosaminoglycans and Collagen. Further constructs were fixed in 4% paraformaldehyde for standard histology and immunolocalisation of collagen types I, II and chondroitin-6-sulphate. Chondrocytes cultured in the HA system proliferated (increase in DNA) at a faster rate than the controls. There was a 2.2 fold increase in cell concentration at 14 days compared to a 1.2 fold increase in the controls. Total GAG levels at each time point were significantly greater for cells cultured in HA than in controls. Histologically, constructs were characterised by extensive cell cluster formation and intense Safranin-O staining. The newly synthesised matrix also stained positive for type II collagen. By contrast, control constructs exhibited minimal cluster formation, Safranin-O and type II collagen staining. Cells maintained with HA exhibited a significantly greater rate of proliferation and matrix production. The presence of matrix rich in type II collagen indicates maintenance of chondrocytic phenotype. By contrast, cells cultured without HA did not show these features. These results support the use of intra-articular injections for the treatment of osteoarthritis. The benefits of HA injections may be due to cellular mechanisms as well as mechanical

Aims: Comparison of the effectiveness of the injection of hyaluronic acid (Ostenil¨) and cortisone (Volon¨) into the facet joints in the treatment of facet joint syndrome. Methods: 60 patients suffering from low back pain due to degenerative arthritis of the facet joints were included in this randomized, controlled, double-blinded, clinical trial. 30 patients received intra-articular injections of hyaluronic acid (Ostenil¨) and 30 patients received intra-articular injections of 10mg triamcinolon-hexacetonid (Volon 10¨). The facet joints of the spinal segments L3/L4, L4/L5, and L5/S1 were injected bilaterally with computed tomography guidance in intervals of one week each. Clinical evaluation was carried out one week prior þrst injection, at the day of þrst injection, after one, two, and three weeks, and after three and six months. Clinical assessment was carried out using the visual analog scale for pain, the Roland Morris Questionnaire, and the Oswestry Disability Questionnaire. Quality of life was assessed using the SF-36 health questionnaire. Radiological assessment was done according to Kellgren. Results: Pain reduction was achieved faster in the Volon 10¨group. After three months the Ostenil¨group reached better pain reduction and this effect lasted for a longer period. The Roland Morris score, the Oswestry Disability Questionaire, as well as the Low Back Pain Outcome Score showed signiþcantly better results in the Ostenil¨group after 3 and 6 months follow-up. Conclusion: Even though no signiþcant difference was found in the short-term follow-up, the results in the Ostenil¨group were comparable to the Volon 10¨group, and were signiþcantly better in the long-term follow up. Thus the intra-articular injection of hyal-uronic acid (Ostenil¨) is an effective alternative in the treatment of low back pain caused by facet joint syndrome, avoiding the known side effects of cortisone

Introduction and Objective. Hyaluronic acid (HA) is an effective option for the treatment of osteoarthritis (OA) patients due to several properties such as normalization of the mechanical and rheological properties of the synovial fluid and amelioration of OA symptoms and joints function by promoting cartilage nutrition. Since OA progression is also significantly related to oxidative stress and reactive oxygen species (ROS), sodium succinate (SS) is envisioned as a promising compound for cartilage treatment by providing antioxidant defense able to normalize intracellular metabolism and tissue respiration via mitochondrial mechanism of action. The scope of this study was to investigate on an in vitro inflammatory model the efficacy of Diart. ®. product, a combination of HA and SS. Materials and Methods. Donor-matched chondrocytes and synoviocytes were obtained from KL 3–4 OA patients undergoing total knee replacement. At passage 4, inflammation was promoted with 1 ng/ml IL-1B for 48 hours in absence and presence of Diart. ®. at 1:3 dilution rate. Nitric oxide (NO) from cell culture supernatant was measured by Griess reaction. Mitochondrial and cytoplasmatic ROS evaluation was assessed by flow cytometry with MitoSox and dichlorodihydrofluorescein diacetate (DCFDA) assays. Gene expression of inflammation/oxidative stress-related transcripts (MMP1/MMP3/INOS/COX2) was evaluated by qRT-PCR using TBP as reference. Results. NO was detected only in inflamed chondrocytes and Diart® was able to abolish its levels. NO was not detected in synoviocytes in all conditions. IL-1B reduced both cytoplasmic (−66%) and mitochondrial (−68%) ROS in chondrocytes, with Diart® partially restoring (+40%) mitochondrial levels. In synoviocytes, IL-1B did not alter ROS, with Diart® modestly increasing (+27%) mitochondrial levels. Inflammation was able to increase transcript levels of all tested markers, with the exception of INOS in synoviocytes. In chondrocytes, Diart® significantly (p < 0.05) reduced COX2 (−75%) and MMP1 (−33%). In synoviocytes, Diart® significantly reduced COX2 (−77%) and MMP3 (−84%), with MMP1 53% decreased albeit without reaching statistical significance. Conclusions. Diart. ®. biochemical and physiologic properties in the tested in vitro model of inflammation on donor-matched chondrocytes and synoviocytes allowed reducing inflammation and oxidative stress-related markers, prompting the use of this combination as successful strategy to manage OA-related symptoms

Aims: A mounting research effort has recently been devoted to design a biocompatible, sterile and safe material as nucleus polposus substitute. Several chemical modifications of Hyaluronic acid (HA), a biodegradable linear polysaccharide, have been devised to provide mechanically and chemically robust materials in medical applications. This study was specially designed to assess whether such a kind of materials are capable to substitute natural NP by suitable viscoelastic properties. Methods: The NPs were obtained from pigs (L4-L5, L6-L7). Bromide of 2-Hydroxy-4-hydroxyethoxy-2-methyl-propriophenone ester of HA (50% of degree of esterification, cross-linked gel) (HYAFF120p50A8) and dodecylic amide of Hyaluronic acid (11% of carboxyl group substitution of 200 kDa HA) (HYADD3A8) solutions, supplied by FAB, were studied at different ionic strength (0 and 0.15M). Small amplitude oscillatory shear tests were performed to study linear viscoelastic properties by using a strain controlled rheometer (Bohlin VOR). In particular, the elastic modulus (G’) and the viscous modulus G’’ were evaluated. Results: Porcine NP showed a rheological behaviour typical of “weak gel”. Indeed, G’ values were always higher than G” ones all over the frequency range and both moduli were almost frequency independent. In particular, at 1 Hz G’ and G” values were respectively 310 and 81 Pa. The same rheological behaviour was observed for all HA derivatives. In particular, G’ and G’’ were respectively equal to 400 and 91Pa for HYADD3A8 solutions at 1Hz and at 20mg/ml (0,15M), and 210 and 51Pa for HYAFF120p50A8 at 50 mg/ml(0M). Conclusions: HYADD3A8 and HYAFF120p50A8 solutions seem promising candidates as NP substitute from a viscoelastic point of view. In particular, HYADD3A8 (20mg/ml,0.15M solution) properly matched the rheological behaviour of porcine NPs

The rheological properties of synovial fluid (SF) are largely attributed to the presence of high molecular weight hyaluronic acid (HA). In normal SF, HA has been shown to be an anti-inflammatory molecule able to increase the viscosity and promote endogenous production of HA. The aim of the present report was to investigate the possible effect of HA concentration in rheological properties (elastic modulus, G´ and viscous modulus, G´´) of osteoarthritic equine SF. For this purpose, SF from intercarpal, metacarpophalangeal and distal interphalangeal joint was aspirated by aseptic arthrocentesis from 60 Warmblood horses. For determining HA concentrations in equine SF samples, a commercially available ELISA kit was used. Additionally, full rheological sample characterization was carried out with an AR-G2 rheometer (TA Instruments Ltd., UK) in order to measure the elastic G´ and viscous G´´ moduli, at horse's body (37.5 ºC) temperature. The ANOVA findings revealed statistically significant main effects of the factors Joint Type (p = 0.001), and main effects of covariates Age (p = 0.019) and HA (p < 0.001) on the mean values of logG” and logG' measurements. Interpreting the coefficients of the covariate HA, a positive correlation of HA was detected on the response logG” and logG' measurements. Collectively, these data illustrate the role of HA in equine pathological SF

The extracellular matrix (ECM)-based biomaterials provide a platform to mimic the disc microenvironment in facilitating stem cell transplantation for tissue regeneration. However, little is known about in vitro preconditioning human umbilical cord Wharton Jelly-derived mesenchymal stem cells (MSCs) on 3D hyaluronic acid (HA)/type II collagen (COLII) hydrogel for nucleus pulposus (NP) phenotype and pain modulation. We developed a tuneable 3D HA/COLII by fabricating HA/COLII hydrogel at 2 mg/ml COLII and various weight ratios of HA:COLII, 1:9 and 4.5:9. The hydrogel was characterized for degradability, stability, and swelling capacity. The viability of hWJ-MSC encapsulated on hydrogel supplemented with TGF-β3 was assessed. The implantation of HA/COLII hydrogel was done in surgically induced disc injury model of pain in the rat tail. The general health status in rats was monitored. The nociceptive behaviour in rats was performed for mechanical allodynia using von Frey test. The HA/COLII 4.5:9 hydrogel showed higher swelling capacity than weight ratio 1:9, suggesting that a higher amount of HA can absorb a large amount of water. Both HA/COLII 4.5:9 and 1:9 hydrogel formulations had a similar degradation profile, stable to the hydrolytic process. The hWJ-MSC-encapsulated on hydrogel marked higher cell viability with round morphology shape of cells in vitro. The surgically induced disc injury in the rat tail evoked mechanical allodynia, without affecting general health status in rats. The implantation of HA/COLII 1:9 hydrogel was observed to slightly alleviate injury-induced mechanical allodynia. Fine-tuning HA/COLII-based hydrogel provides the optimal swelling capacity, stability, degradability, and non-cytotoxic, mimicking the 3D NP niche in guiding hWJ-MSCs towards NP phenotype. The HA/COLII hydrogel could be employed as an advanced cell delivery system in facilitating stem cell transplantation for intervertebral disc regeneration targeting pain

The excursion resistance between the tendon and pulley is an important factor contributing to the limitation of function after surgery to the hand. The administration of hyaluronic acid (HA) in the early rehabilitation after tendon grafting may help to prevent adhesions. We evaluated changes in the excursion resistance between potential sources of flexor tendon grafts and the annular pulley in a canine model after administration of HA. The intrasynovial and extrasynovial tendons were soaked in 10 mg/ml of HA for five minutes. The excursion resistance between these tendons and the annular pulley of an intact proximal phalanx and that of the same tendons of the opposite foot without administration of HA were evaluated. The tendon of flexor digitorum profundus of the second toe without administration of HA was used as a control. The gliding resistance of canine tendons was significantly decreased after the administration of HA especially in the extrasynovial tendons. Our findings suggest that the administration of HA may improve the gliding function of a flexor tendon graft

Objectives: Hyaluronic acid (HA) is used in osteoarthritis especially for the control of pain. In this animal study, we investigated the effects of HA on the early stage of osteoarthritis. Methods: The experimental osteoarthritis model was constituted on 10 rabbits by the way of anterior cruciate ligament transection. In HA group, HA was injected 0.6 ml (15mg/ml) dosage per week for 3 weeks in right knees of ten rabbits and in SF group, saline was injected 0.6 ml dosage per week for 3 weeks in left knees of rabbits. Because three rabbits died in experimental period, fourteen knees of seven rabbits were taken into account for the study. The knees of rabbits, which were sacrified at 12th weeks after index operation, were measured according to cartilage area and Mankin scale. Results: The mean cartilage area of HA and SF groups were measured 1.097 mm2 and 0.477 mm2, respectively. The difference of mean cartilage area between HA and SF groups was statistically significant (p< 0.05). According to Mankin scale, the mean total point of scale was measured 3.57 in HA group and 11.14 in SF group and the difference between mean total points of groups was significant (p< 0.05). Although, there is no significant difference in cellular abnormality, matrix staining, and tidemark continuity criteries of scale, we found the significant difference between total point and structure of cartilage criteria of scale. Conclusions: HA has a retarder effect on progression of cartilage injury in early stage osteoarthritis

Tissue engineering is a promising approach to regenerate damaged skeletal tissues. In particular, the use of injectable hydrogels alleviates common issues of poor cell viability and engraftment. However, uncontrolled cell fate, resulting from unphysiological environments and degradation rates, still remain a hurdle and impedes tissue healing. We thus aim at developing a new platform of injectable hyaluronic acid (HA) hydrogels with a large panel of properties (stiffness, degradation…) matching those of skeletal tissues. Hence, HA with different molecular weights were functionalized with silylated moieties. Upon injection, these hydrogels formed through a sol-gel chemistry within 5 to 20 minutes in physiological conditions, as demonstrated by rheological characterization. By varying the crosslinking density and concentration, we obtained hydrogels spanning a large range of elastic moduli (E = 0.1–20 kPa), similar to those of native ECMs, with tunable biodegradation rates (from 24 hours to > 50 days) and swelling ratios (500 to 5000% (w/w)). Cell viability was confirmed by Live/Dead assays and will be completed by in vivo subcutaneous implantations in mice to study the foreign body reaction and degradation rate. We further developed hybrid HA/biphasic calcium phosphate granules hydrogels and demonstrated a strong mechanical reinforcement (E = 0.1 MPa) and a faster relaxation behaviour (τ. 1/2. < 400s), with similar degradation rates. Ongoing in vitro differentiation assays and in vivo implantations in a rabbit femur model will further assess their ability to drive bone regeneration. Collectively, these results suggest that this hydrogel platform offers promising outcomes for improved strategies in skeletal tissue engineering