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A novel wound healing accelerator: Effect of vitreous gel of cow eyeball on a chronic wound model

Makhmudi A, Wirohadidjojo YW, Gahara E, Noor HZ, Sunardi M, Mahmudah NA, et al.

Med J Malaysia, 2020 11;75(6):698-704.
PMID: 33219180

INTRODUCTION: Several studies have reported the disturbance in the process of wound healing after administration of mitomycin-C, which inhibits granulation tissue formation and collagen synthesis, resulting in chronic wounds. The vitreous gel of cow eyeballs contains a high level of hyaluronic acid, which has a role in inflammation, granulation, re-epithelialization, and remodelling. This study aims to understand the effect of 1% povidone iodine and vitreous gel of cow eyeballs on wound healing after administration of mitomycin-C.
METHODS: This was an in vivo study with quasi-experimental methods on 32 Wistar mice. Full-thickness wounds were made and then treated with mitomicyn-C. The mice were divided into 4 groups: a control group with NaCl 0.9% vitreous gel of cow eyeball (VGCE), 1% povidone-iodine, and a combination of VGCE and 1% povidone-iodine groups. Macroscopic and microscopic observations of the process of wound healing were performed on days 3, 7, and 14.
RESULTS: Vitreous gel administration produced significant wound healing rates within the first three days, and histological analysis revealed an increased number of fibroblasts and polymorphonuclear cells. However, the povidone iodine group and the combination group with vitreous gel did not produce significant results.
CONCLUSION: The single administration of VGCE can accelerate the wound healing process, increase the number of fibroblasts, and reduce inflammation in a chronic wound model.

Matched MeSH terms: Hyaluronic Acid
Amplifying the manganese scavenging potential of Streptococcus zooepidemicus to reactive oxygen species during production of hyaluronic acid

Mashitah MD, Masitah H, Ramachandran KB

Med J Malaysia, 2004 May;59 Suppl B:59-60.
PMID: 15468818

Streptococcus zooepidemicus (SZ) is an aerotolerant bacteria and its ability to survive under reactive oxidant challenge raises the question of the existence of a defense system. Thus growth, hyaluronic acid (HA) and hydrogen peroxide (H2O2) production by SZ in the presence of increasing concentration of Mn2+ were studied. The results suggested that the tested strain supported growth and HA production in cultures treated with 1 and 10 mM of Mn2+ regardless of H2O2 presence in the medium. This showed that SZ have acquired elaborate defense mechanisms to scavenge oxygen toxicity and thus protect cells from direct and indirect effect of this radical. In contrast, cells treated with 25 mM Mn2+ were sensitive, in which, the HA production was reduced considerably. Thus showing that the oxygen scavenger systems of the cells may be fully saturated at this concentration.

Matched MeSH terms: Hyaluronic Acid/biosynthesis*
Arthroscopic Subchondral Drilling Followed by Injection of Peripheral Blood Stem Cells and Hyaluronic Acid Showed Improved Outcome Compared to Hyaluronic Acid and Physiotherapy for Massive Knee Chondral Defects: A Randomized Controlled Trial

Saw KY, Anz AW, Ng RC, Jee CS, Low SF, Dorvault C, et al.

Arthroscopy, 2021 08;37(8):2502-2517.
PMID: 34265388 DOI: 10.1016/j.arthro.2021.01.067

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intra-articular injections of autologous peripheral blood stem cells (PBSCs) plus hyaluronic acid (HA) after arthroscopic subchondral drilling into massive chondral defects of the knee joint and to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than HA plus physiotherapy.
METHODS: This is a dual-center randomized controlled trial (RCT). Sixty-nine patients aged 18 to 55 years with International Cartilage Repair Society grade 3 and 4 chondral lesions (size ≥3 cm2) of the knee joint were randomized equally into (1) a control group receiving intra-articular injections of HA plus physiotherapy and (2) an intervention group receiving arthroscopic subchondral drilling into chondral defects and postoperative intra-articular injections of PBSCs plus HA. The coprimary efficacy endpoints were subjective International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS)-pain subdomain measured at month 24. The secondary efficacy endpoints included all other KOOS subdomains, Numeric Rating Scale (NRS), and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores.
RESULTS: At 24 months, the mean IKDC scores for the control and intervention groups were 48.1 and 65.6, respectively (P < .0001). The mean for KOOS-pain subdomain scores were 59.0 (control) and 86.0 (intervention) with P < .0001. All other KOOS subdomain, NRS, and MOCART scores were statistically significant (P < .0001) at month 24. Moreover, for the intervention group, 70.8% of patients had IKDC and KOOS-pain subdomain scores exceeding the minimal clinically important difference values, indicating clinical significance. There were no notable adverse events that were unexpected and related to the study drug or procedures.
CONCLUSIONS: Arthroscopic marrow stimulation with subchondral drilling into massive chondral defects of the knee joint followed by postoperative intra-articular injections of autologous PBSCs plus HA is safe and showed a significant improvement of clinical and radiologic scores compared with HA plus physiotherapy.
LEVEL OF EVIDENCE: Level I, RCT.

Matched MeSH terms: Hyaluronic Acid
Articular cartilage regeneration with autologous marrow aspirate and hyaluronic Acid: an experimental study in a goat model

Saw KY, Hussin P, Loke SC, Azam M, Chen HC, Tay YG, et al.

Arthroscopy, 2009 Dec;25(12):1391-400.
PMID: 19962065 DOI: 10.1016/j.arthro.2009.07.011

PURPOSE: The purpose of the study was to determine whether postoperative intra-articular injections of autologous marrow aspirate (MA) and hyaluronic acid (HA) after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring.
METHODS: In a goat model we created a 4-mm full-thickness articular cartilage defect in the stifle joint (equivalent to 1.6 cm in the human knee) and conducted subchondral drilling. The animals were divided into 3 groups: group A (control), no injections; group B (HA), weekly injection of 1 mL of sodium hyaluronate for 3 weeks; and group C (HA + MA), similar to group B but with 2 mL of autologous MA in addition to HA. MA was obtained by bone marrow aspiration, centrifuged, and divided into aliquots for cryopreservation. Fifteen animals were equally divided between the groups and sacrificed 24 weeks after surgery, when the joint was harvested, examined macroscopically and histologically.
RESULTS: Of the 15 animals, 2 from group A had died of non-surgery-related complications and 1 from group C was excluded because of a joint infection. In group A the repair constituted mainly scar tissue, whereas in group B there was less scar tissue, with small amounts of proteoglycan and type II collagen at the osteochondral junction. In contrast, repair cartilage from group C animals showed almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology assessed by Gill scoring was significantly better in group C with 1-way analysis of variance yielding an F statistic of 10.611 with a P value of .004, which was highly significant.
CONCLUSIONS: Postoperative intra-articular injections of autologous MA in combination with HA after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring in a goat model.
CLINICAL RELEVANCE: After arthroscopic subchondral drilling, this novel technique may result in better articular cartilage regeneration.

Matched MeSH terms: Hyaluronic Acid/administration & dosage*
Articular cartilage regeneration with autologous peripheral blood progenitor cells and hyaluronic acid after arthroscopic subchondral drilling: a report of 5 cases with histology

Saw KY, Anz A, Merican S, Tay YG, Ragavanaidu K, Jee CS, et al.

Arthroscopy, 2011 Apr;27(4):493-506.
PMID: 21334844 DOI: 10.1016/j.arthro.2010.11.054

PURPOSE: The purpose of this study was to evaluate the quality of articular cartilage regeneration after arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous peripheral blood progenitor cells (PBPCs) in combination with hyaluronic acid (HA).
METHODS: Five patients underwent second-look arthroscopy with chondral core biopsy. These 5 patients are part of a larger pilot study in which 180 patients with International Cartilage Repair Society grade III and IV lesions of the knee joint underwent arthroscopic subchondral drilling followed by postoperative intra-articular injections. Continuous passive motion was used on the operated knee 2 hours per day for 4 weeks. Partial weight bearing was observed for the first 6 to 8 weeks. Autologous PBPCs were harvested 1 week after surgery. One week after surgery, 8 mL of the harvested PBPCs in combination with 2 mL of HA was injected intra-articularly into the operated knee. The remaining PBPCs were divided into vials and cryopreserved. A total of 5 weekly intra-articular injections were given.
RESULTS: Second-look arthroscopy confirmed articular cartilage regeneration, and histologic sections showed features of hyaline cartilage. Apart from the minimal discomfort of PBPC harvesting and localized pain associated with the intra-articular injections, there were no other notable adverse reactions.
CONCLUSIONS: Articular hyaline cartilage regeneration is possible with arthroscopic subchondral drilling followed by postoperative intraarticular injections of autologous PBPCs in combination with HA.
LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Matched MeSH terms: Hyaluronic Acid/administration & dosage; Hyaluronic Acid/therapeutic use*
Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: a randomized controlled trial

Saw KY, Anz A, Jee CSY, Merican S, Ching-Soong Ng R, Roohi SA, et al.

Arthroscopy, 2013 Apr;29(4):684-94.
PMID: 23380230 DOI: 10.1016/j.arthro.2012.12.008

PURPOSE: The purpose of this study was to compare histologic and magnetic resonance imaging (MRI) evaluation of articular cartilage regeneration in patients with chondral lesions treated by arthroscopic subchondral drilling followed by postoperative intra-articular injections of hyaluronic acid (HA) with and without peripheral blood stem cells (PBSC).
METHODS: Fifty patients aged 18 to 50 years with International Cartilage Repair Society (ICRS) grade 3 and 4 lesions of the knee joint underwent arthroscopic subchondral drilling; 25 patients each were randomized to the control (HA) and the intervention (PBSC + HA) groups. Both groups received 5 weekly injections commencing 1 week after surgery. Three additional injections of either HA or PBSC + HA were given at weekly intervals 6 months after surgery. Subjective IKDC scores and MRI scans were obtained preoperatively and postoperatively at serial visits. We performed second-look arthroscopy and biopsy at 18 months on 16 patients in each group. We graded biopsy specimens using 14 components of the International Cartilage Repair Society Visual Assessment Scale II (ICRS II) and a total score was obtained. MRI scans at 18 months were assessed with a morphologic scoring system.
RESULTS: The total ICRS II histologic scores for the control group averaged 957 and they averaged 1,066 for the intervention group (P = .022). On evaluation of the MRI morphologic scores, the control group averaged 8.5 and the intervention group averaged 9.9 (P = .013). The mean 24-month IKDC scores for the control and intervention groups were 71.1 and 74.8, respectively (P = .844). One patient was lost to follow-up. There were no notable adverse events.
CONCLUSIONS: After arthroscopic subchondral drilling into grade 3 and 4 chondral lesions, postoperative intra-articular injections of autologous PBSC in combination with HA resulted in an improvement of the quality of articular cartilage repair over the same treatment without PBSC, as shown by histologic and MRI evaluation.
LEVEL OF EVIDENCE: Level II, randomized controlled trial (RCT).

Matched MeSH terms: Hyaluronic Acid/administration & dosage*
Bioactive Metabolites of Lactiplantibacillus plantarum K014 Against Methicillin-Resistant Staphylococcus aureus ATCC43300 and In Vitro Evaluation of Its Antibacterial, Antioxidant and Anti-inflammatory Activities

Mlambo LK, Abbasiliasi S, Tang HW, Ng ZJ, Parumasivam T, Hanafiah KM, et al.

Curr Microbiol, 2022 Oct 17;79(12):359.
PMID: 36251092 DOI: 10.1007/s00284-022-03038-6

This study aims to evaluate the effects of bioactive metabolites produced by lactic acid bacteria against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. A total of six lactic acid bacteria (LAB) were selected to evaluate the antimicrobial activity against MRSA ATCC 43300, a skin pathogen that is highly resistant to most antibiotics. The K014 isolate from a fermented vegetable recorded the highest inhibition against MRSA ATCC 43300 at 91.93 ± 0.36%. 16S rRNA sequencing revealed the K014 isolate is closely related to L. plantarum and the sequence was subsequently deposited in the GenBank database with an accession number of MW180960, named as Lactiplantibacillus plantarum K014. The cell-free supernatant (CFS) of L. plantarum K014 had tolerance to high temperature as well as acidic pH. The bioactive metabolites, such as hydrogen peroxide, lactic acid and hyaluronic acid, were produced by L. plantarum K014. Result from ABTS assay showed higher antioxidant activity (46.28%) as compared to that obtained by DPPH assay (2.97%). The CFS had showed anti-inflammatory activity for lipoxygenase (LOX) assay at 43.66%. The bioactive metabolites of L. plantarum K014 showed very promising potential to be used topical skin pathogens.

Matched MeSH terms: Hyaluronic Acid/pharmacology
Fulltext Bioactives from probiotics for dermal health: functions and benefits

Lew LC, Liong MT

J Appl Microbiol, 2013 May;114(5):1241-53.
PMID: 23311666 DOI: 10.1111/jam.12137

Probiotics have been extensively reviewed for decades, emphasizing on improving general gut health. Recently, more studies showed that probiotics may exert other health-promoting effects beyond gut well-being, attributed to the rise of the gut-brain axis correlations. Some of these new benefits include skin health such as improving atopic eczema, atopic dermatitis, healing of burn and scars, skin-rejuvenating properties and improving skin innate immunity. Increasing evidence has also showed that bacterial compounds such as cell wall fragments, their metabolites and dead bacteria can elicit certain immune responses on the skin and improve skin barrier functions. This review aimed to underline the mechanisms or the exact compounds underlying the benefits of bacterial extract on the skin based on evidences from in vivo and in vitro studies. This review could be of help in screening of probiotic strains with potential dermal enhancing properties for topical applications.

Matched MeSH terms: Hyaluronic Acid/pharmacology
Biosynthesis of high molecular weight hyaluronic acid by Streptococcus zooepidemicus using oxygen vector and optimum impeller tip speed

Lai ZW, Rahim RA, Ariff AB, Mohamad R

J Biosci Bioeng, 2012 Sep;114(3):286-91.
PMID: 22608992 DOI: 10.1016/j.jbiosc.2012.04.011

The potential use of n-dodecane and n-hexadecane as oxygen vectors for enhancing hyaluronic acid (HA) biosynthesis by Streptococcus zooepidemicus ATCC 39920 was investigated using a 2-L stirred-tank bioreactor equipped with helical ribbon or Rushton turbine impellers. The volumetric fraction of the oxygen vector influenced the gas-liquid volumetric oxygen transfer coefficient (K(L)a) positively. Batch HA fermentation with 1% (v/v) n-dodecane or 0.5% (v/v) n-hexadecane addition was carried out at different impeller tip speeds. Even though cell growth was lower in the fermentation with oxygen vector addition, the HA productivity and molecular weight were higher when compared to the fermentation without oxygen vector at low impeller tip speed. The highest HA concentration (4.25 gHA/l) and molecular weight (1.54 × 10(7) Da) were obtained when 0.5% (v/v) n-hexadecane and 0.785 m/s impeller tip speed of helical ribbon were used.

Matched MeSH terms: Hyaluronic Acid/biosynthesis*; Hyaluronic Acid/metabolism; Hyaluronic Acid/chemistry*
Chitosan and hyaluronic acid-based nanocarriers for advanced cancer therapy and intervention

Rohtagi P, Garg U, Triveni, Jain N, Pandey M, Amin MCIM, et al.

Biomater Adv, 2024 Feb;157:213733.
PMID: 38118207 DOI: 10.1016/j.bioadv.2023.213733

Cancer has become a major public health issue leading to one of the foremost causes of morbidity and death in the world. Despite the current advances in diagnosis using modern technologies and treatment via surgery or chemo- and radio-therapies, severe side effects or after-effects limit the application of these treatment modalities. Novel drug delivery systems have shown the potential to deliver chemotherapeutics directly to cancer cells, thus minimizing unnecessary exposure to healthy cells. Concurrently, to circumvent difficulties associated with conventional deliveries of cancer therapeutics, natural polysaccharides have gained attention for the fabrication of such deliveries owing to biocompatibility, low toxicity, and biodegradability. It has been exhibited that natural polysaccharides can deliver high therapeutic concentrations of the entrapped drug to the target cells by sustained and targeted release. Considering the immense potential of natural polymers, the present work focuses on naturally generated biopolymer carriers based on chitosan and hyaluronic acid. This review delineated on the role of chitosan and its derivation from renewable resources as a biocompatible, biodegradable, nonimmunogenic material with notable antitumor activity as a drug delivery carrier in oncotherapy. Moreover, hyaluronic acid, itself by its structure or when linked with other molecules contributes to developing promising pharmaceutical delivery systems to setback the restrictions related to conventional cancer treatment.

Matched MeSH terms: Hyaluronic Acid/therapeutic use
Curcumin-laden hyaluronic acid-co-Pullulan-based biomaterials as a potential platform to synergistically enhance the diabetic wound repair

Shah SA, Sohail M, Minhas MU, Khan S, Hussain Z, Mahmood A, et al.

Int J Biol Macromol, 2021 Aug 31;185:350-368.
PMID: 34171251 DOI: 10.1016/j.ijbiomac.2021.06.119

Injectable hydrogel with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report hyaluronic acid and Pullulan-based injectable hydrogel loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade compared to other treatment groups. The physical interaction and self-assembly of hyaluronic acid-Pullulan-grafted-pluronic F127 injectable hydrogel were confirmed using nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The CUR-laden hyaluronic acid-Pullulan-g-F127 injectable hydrogel promptly undergoes a sol-gel transition and has proved to potentiate wound healing in a streptozotocin-induced diabetic rat model by promoting 93% of wound closure compared to other groups having 35%, 38%, and 62%. The comparative in vivo study and histological examination was conducted which demonstrated an expeditious recovery rate by significantly reducing the wound healing days i.e. 35 days in a control group, 33 days in the CUR suspension group, 21 days in unloaded injectable, and 13 days was observed in CUR loaded hydrogel group. Furthermore, we suggest that the injectable hydrogel laden with CUR showed a prompt wound healing potential by increasing the cell proliferation and serves as a drug delivery platform for sustained and targeted delivery of hydrophobic moieties.

Matched MeSH terms: Hyaluronic Acid/administration & dosage*; Hyaluronic Acid/pharmacology; Hyaluronic Acid/chemistry
Fulltext Diffuse alveolar haemorrhage and myocardial infarction: life-threatening effects from self-injected hyaluronic acid dermal filler

Che Ani AA, Mohd Akhir S, Chiang Li-Xue W, Shahidan NZ, Abd Hamid A

Monaldi Arch Chest Dis, 2021 Jul 22;91(4).
PMID: 34296835 DOI: 10.4081/monaldi.2021.1845

Hyaluronic acid (HA) is a widely used dermal filler for soft tissue augmentation. We described a case of a 38-year-old transwoman who presented with sudden onset of severe respiratory distress following self-injection of HA dermal filler. She developed multiple episodes of pulmonary haemorrhage, and her chest X-ray showed diffuse ground-glass opacities consistent with diffuse alveolar haemorrhage (DAH). There were no relevant drugs or past medical histories. Anti-nuclear antibodies and rheumatoid factor were negative. Initially, the pulmonary haemorrhage episodes and ventilation requirement improved with systemic steroid, however she subsequently developed acute myocardial infarction with progressive clinical deterioration leading to death. To the best of our knowledge, this is the first HA-related DAH with myocardial infarction reported with a fatal outcome. This case highlights the importance of awareness and the necessity of having a high suspicion of DAH in patients with history of illicit HA dermal filler use.

Matched MeSH terms: Hyaluronic Acid/adverse effects
Fulltext Effect of intra-articular hyaluronic injection on postural stability and risk of fall in patients with bilateral knee osteoarthritis

Khalaj N, Abu Osman NA, Mokhtar AH, George J, Abas WA

ScientificWorldJournal, 2014;2014:815184.
PMID: 25136689 DOI: 10.1155/2014/815184

Knee osteoarthritis is a common cause of disability which influences the quality of life. It is associated with impaired knee joint proprioception, which affects postural stability. Postural stability is critical for mobility and physical activities. Different types of treatment including nonsurgical and surgical are used for knee osteoarthritis. Hyaluronic acid injection is a nonsurgical popular treatment used worldwide. The aim of this study was to demonstrate the effect of hyaluronic acid injections on postural stability in individuals with bilateral knee osteoarthritis. Fifty patients aged between 50 and 70 years with mild and moderate bilateral knee osteoarthritis participated in our study. They were categorized into treatment (n = 25) and control (n = 25) groups. The treatment group received five weekly hyaluronic acid injections for both knees, whereas the control group did not receive any treatment. Postural stability and fall risk were assessed using the Biodex Stability System and clinical "Timed Up and Go" test. All the participants completed the study. The treatment group showed significant decrease in postural stability and fall risk scores after five hyaluronic acid injections. In contrast, the control group showed significant increase. This study illustrated that five intra-articular hyaluronic acid injections could significantly improve postural stability and fall risk in bilateral knee osteoarthritis patients. This trial is registered with: NCT02063373.

Matched MeSH terms: Hyaluronic Acid/administration & dosage*; Hyaluronic Acid/therapeutic use*
Effectiveness of hyaluronic acid and its derivatives on chronic wounds: a systematic review

Shaharudin A, Aziz Z

J Wound Care, 2016 Oct 02;25(10):585-592.
PMID: 27681589 DOI: 10.12968/jowc.2016.25.10.585

OBJECTIVE: Hyaluronic acid (HA) and its derivatives are used for chronic wounds, but evidence of their effectiveness remains unclear. The aim of this study was to provide more updated evidence for the effectiveness of HA (or its derivatives) compared with placebo or other agents for promoting healing in chronic wounds.
METHOD: The Cochrane Central Register of Controlled Trials, MEDLINE via Ovid Online, CINAHL and the EMBASE via EBSCO host databases were searched. Drug companies and experts in wounds were also contacted. Randomised controlled trials of HA (or its derivatives) compared with control were eligible for inclusion.
RESULTS: We identified nine randomised controlled trials involving 865 participants with chronic wounds were included in the review. The reporting for mixed arterial and venous ulcers seems to be better quality than that for venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs). Studies provided little evidence regarding the claimed effects of HA or its derivaties on healing of chronic wounds. However, there is some evidence on their effectiveness for reducing pain intensity for mixed arterial and venous ulcers, which involved 255 patients (MD=-6.78 [95% CI: -11.10 to -2.46]).
CONCLUSION: Evidence to guide decisions regarding the use of HA or its derivatives to promote wound healing is still limited. More good-quality randomised controlled trials are warranted.
KEYWORDS: assessment bias; chronic ulcers; hyaluronan; meta-analysis

Matched MeSH terms: Hyaluronic Acid/therapeutic use*
Fulltext Efficacy of intra-articular injection of hyaluronic acid in the treatment of knee osteoarthritis

Narayanan SS, Suhail A, Harjeet S, Shahril Y, Masbah O

Malays Orthop J, 2009;3(1):19-23.
MyJurnal

This study was conducted to evaluate the efficacy of intra-articular injection of hyaluronic acid for the treatment of knee osteoarthritis. Patients with knee osteoarthritis were followed for a period of six months to assess the efficacy of intra-articular injection of hyaluronic acid given three times in three consecutive weeks. Fifty patients were reviewed at two, eight and 24 weeks post-injection. The average age was 60.9 years and female to male ratio was 3:1. Patients were assessed using the Lequesne Algofunctional Index for function, and the visual analogue score for pain and side effects. We found that the knee pain reduced and the function improved in most patients and these beneficial effects maintained for till the last follow up. The only side effect noted was one case of acute non-septic joint effusion after the 3rd injection. We concluded that intra-articular injection of hyaluronic acid can produce pain relief and functional improvement for up to 6 months.

Matched MeSH terms: Hyaluronic Acid
Fe2+ and Cu2+ increase the production of hyaluronic acid by lactobacilli via affecting different stages of the pentose phosphate pathway

Choi SB, Lew LC, Hor KC, Liong MT

Appl Biochem Biotechnol, 2014 May;173(1):129-42.
PMID: 24648139 DOI: 10.1007/s12010-014-0822-5

This study aimed at optimizing the production of hyaluronic acid by Lactobacillus acidophilus FTDC 1231 using response surface methodology and evaluating the effects of divalent metal ions along the production pathway using molecular docking. Among different divalent metal ions that were screened, only iron (II) sulphate and copper (II) sulphate significantly (P acid. Subsequent optimization yielded hyaluronic acid at concentration of 0.6152 mg/mL in the presence of 1.24 mol L(-1) iron (II) sulphate and 0.16 mol L(-1) of copper (II) sulphate (103 % increase compared to absence of divalent metal ions). Data from molecular docking showed Fe(2+) improved the binding affinity of UDP-pyrophophorylase towards glucose-1-phosphate, while Cu(2+) contributed towards the interaction between UDP-glucose dehydrogenase and UDP-glucose. We have demonstrated that lactobacilli could produce hyaluronic acid at increased concentration upon facilitation by specific divalent metal ions, via specific targets of enzymes and substrates along pentose phosphate pathway.

Matched MeSH terms: Hyaluronic Acid/biosynthesis*
Fulltext Growth optimization of Lactobacillus rhamnosus FTDC 8313 and the production of putative dermal bioactives in the presence of manganese and magnesium ions

Lew LC, Liong MT, Gan CY

J Appl Microbiol, 2013 Feb;114(2):526-35.
PMID: 23082775 DOI: 10.1111/jam.12044

AIMS: The study aimed to optimize the growth and evaluate the production of putative dermal bioactives from Lactobacillus rhamnosus FTDC 8313 using response surface methodology, in the presence of divalent metal ions, namely manganese and magnesium.
METHODS AND RESULTS: A central composite design matrix (alpha value of ± 1.414) was generated with two independent factors, namely manganese sulphate (MnSO(4) ) and magnesium sulphate (MgSO(4) ). The second-order regression model indicated that the quadratic model was significant (P < 0.01), suggesting that the model accurately represented the data in the experimental region. Three-dimensional response surfaces predicted an optimum point with maximum growth of 10.59 log(10) CFU ml(-1) . The combination that produced the optimum point was 0.80 mg ml(-1) MnSO(4) and 1.09 mg ml(-1) MgSO(4) . A validation experiment was performed, and data obtained showed a deviation of 0.30% from the predicted value, ascertaining the predictions and the reliability of the regression model used. Effects of divalent metal ions on the production of putative dermal bioactives, namely hyaluronic acid, diacetyl, peptidoglycan, lipoteichoic acid and organic acids in the region of optimized growth, were evaluated using 3D response surfaces generated. Evaluation based on the individual and interaction effects showed that both manganese and magnesium played an important role in the production of these putative bioactives.
CONCLUSIONS: Optimum growth of Lact. rhamnosus FTDC 8313 in reconstituted skimmed milk was achieved at 10.59 log(10) CFU ml(-1) in the presence of MnSO(4) (0.80 mg ml(-1) ) and MgSO(4) (1.09 mg ml(-1) ). Production of putative dermal bioactive and inhibitory compounds including hyaluronic acid, diacetyl, peptidoglycan, lipoteichoic acid and organic acids at the regions of optimized growth showed potential dermal applications.
SIGNIFICANT AND IMPACT OF THE STUDY: This research can serve as a fundamental study to further evaluate the potential of Lactobacillus strains in non-gut-related roles such as dermal applications.

Matched MeSH terms: Hyaluronic Acid/biosynthesis
High tibial osteotomy in combination with chondrogenesis after stem cell therapy: a histologic report of 8 cases

Saw KY, Anz A, Jee CS, Ng RC, Mohtarrudin N, Ragavanaidu K

Arthroscopy, 2015 Oct;31(10):1909-20.
PMID: 26008951 DOI: 10.1016/j.arthro.2015.03.038

PURPOSE: To histologically evaluate the quality of articular cartilage regeneration from the medial compartment after arthroscopic subchondral drilling followed by postoperative intra-articular injections of autologous peripheral blood stem cells (PBSCs) and hyaluronic acid with concomitant medial open-wedge high tibial osteotomy (HTO) in patients with varus deformity of the knee joint.
METHODS: Eight patients with varus deformity of the knee joint underwent arthroscopic subchondral drilling of International Cartilage Repair Society (ICRS) grade 4 bone-on-bone lesions of the medial compartment with concomitant HTO. These patients were part of a larger pilot study in which 18 patients underwent the same procedure. PBSCs were harvested and cryopreserved preoperatively. At 1 week after surgery, 8 mL of PBSCs was mixed with 2 mL of hyaluronic acid and injected intra-articularly into the knee joint; this was repeated once a week for 5 consecutive weeks. Three additional intra-articular injections were administered weekly at intervals of 6, 12, and 18 months postoperatively. Informed consent was obtained at the time of hardware removal for opportunistic second-look arthroscopy and chondral biopsy. Biopsy specimens were stained with H&E, safranin O, and immunohistochemical staining for type I and II collagen. Specimens were graded using the 14 components of the ICRS Visual Assessment Scale II, and a total score was obtained.
RESULTS: Second-look arthroscopy showed satisfactory healing of the regenerated cartilage. Histologic analysis showed significant amounts of proteoglycan and type II collagen. The total ICRS Visual Assessment Scale II histologic scores comparing the regenerated articular cartilage (mean, 1,274) with normal articular cartilage (mean, 1,340) indicated that the repair cartilage score approached 95% of the normal articular cartilage score. There were no infections, delayed unions, or nonunions.
CONCLUSIONS: Chondrogenesis with stem cells in combination with medial open-wedge HTO for varus deformity correction of the knee joint regenerates cartilage that closely resembles the native articular cartilage.
LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Matched MeSH terms: Hyaluronic Acid/administration & dosage
Fulltext Hyaluronic Acid-Mediated Drug Delivery System Targeting for Inflammatory Skin Diseases: A Mini Review

How KN, Yap WH, Lim CLH, Goh BH, Lai ZW

Front Pharmacol, 2020;11:1105.
PMID: 32848737 DOI: 10.3389/fphar.2020.01105

Hyaluronic acid (HA), a major component of extracellular matrix has been widely applied in pharmaceutical and cosmetic industries due to its reported pharmacological properties. Various types of HA drug delivery system including nanoparticles, cryogel-based formulations, microneedle patches, and nano-emulsions were developed. There are studies reporting that several HA-based transdermal delivery systems exhibit excellent biocompatibility, enhanced permeability and efficient localized release of anti-psoriasis drugs and have shown to inhibit psoriasis-associated skin inflammation. Similarly HA is found in abundant at epidermis of atopic dermatitis (AD) suggesting its role in atopic AD pathology. Anti-allergenic effect of atopic eczema can be achieved through the inhibition of CD44 and protein kinase C alpha (PKCα) interaction by HA. Herein, we aim to evaluate the current innovation on HA drug delivery system and the other potential applications of HA in inflammatory skin diseases, focusing on atopic dermatitis and psoriasis. HA is typically integrated into different delivery systems including nanoparticles, liposomes, ethosomes and microneedle patches in supporting drug penetration through the stratum corneum layer of the skin. For instance, ethosomes and microneedle delivery system such as curcumin-loaded HA-modified ethosomes were developed to enhance skin retention and delivery of curcumin to CD44-expressing psoriatic cells whereas methotrexate-loaded HA-based microneedle was shown to enhance skin penetration of methotrexate to alleviate psoriasis-like skin inflammation. HA-based nanoparticles and pluronic F-127 based dual responsive (pH/temperature) hydrogels had been described to enhance drug permeation through and into the intact skin for AD treatment.

Matched MeSH terms: Hyaluronic Acid
Hyaluronic acid decorated tacrolimus-loaded nanoparticles: Efficient approach to maximize dermal targeting and anti-dermatitis efficacy

Zhuo F, Abourehab MAS, Hussain Z

Carbohydr Polym, 2018 Oct 01;197:478-489.
PMID: 30007638 DOI: 10.1016/j.carbpol.2018.06.023

Nano-delivery systems have gained remarkable recognition for targeted delivery of therapeutic payload, reduced off-target effects, and improved biopharmaceutical profiles of drugs. Therefore, we aimed to fabricate polymeric nanoparticles (NPs) to deliver tacrolimus (TCS) to deeper layers of the skin in order to alleviate its systemic toxicity and improved therapeutic efficacy against atopic dermatitis (AD). To further optimize the targeting efficiency, TCS-loaded NPs were coated with hyaluronic acid (HA). Following the various physicochemical optimizations, the prepared HA-TCS-CS-NPs were tested for in vitro drug release kinetics, drug permeation across the stratum corneum, percentage of drug retained in the epidermis and dermis, and anti-AD efficacy. Results revealed that HA-TCS-CS-NPs exhibit sustained release profile, promising drug permeation ability, improved skin retention, and pronounced anti-AD efficacy. Conclusively, we anticipated that HA-based modification of TCS-CS-NPs could be a promising therapeutic approach for rationalized management of AD, particularly in children as well as in adults having steroid phobia.

Matched MeSH terms: Hyaluronic Acid/administration & dosage; Hyaluronic Acid/pharmacology*; Hyaluronic Acid/chemistry

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