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      A pH-responsive mesoporous silica nanoparticles-based drug delivery system with controlled release of andrographolide for OA treatment

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          Abstract

          Andrographolide (AG) has favorable anti-inflammatory and antioxidative capacity. However, it has low bioavailability due to high lipophilicity and can be easily cleared by the synovial fluid after intra-articular injection, leading to low therapeutic efficiency in osteoarthritis (OA). Herein, we designed a nano-sized pH-responsive drug delivery system (DDS) for OA treatment by using modified mesoporous silica nanoparticles (MSNs) with pH-responsive polyacrylic acid (PAA) for loading of AG to form AG@MSNs-PAA nanoplatform. The nanoparticles have uniform size (∼120 nm), high drug loading efficiency (22.38 ± 0.71%) and pH-responsive properties, beneficial to sustained release in OA environment. Compared with AG, AG@MSNs-PAA showed enhanced antiarthritic efficacy and chondro-protective capacity based on IL-1β-stimulated chondrocytes and anterior cruciate ligament transection-induced rat OA model, as demonstrated by lower expression of inflammatory factors and better prevention of proteoglycan loss. Therefore, the AG@MSNs-PAA nanoplatform may be developed as a promising OA-specific and on-demand DDS.

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          Osteoarthritis cartilage histopathology: grading and staging.

          Current osteoarthritis (OA) histopathology assessment methods have difficulties in their utility for early disease, as well as their reproducibility and validity. Our objective was to devise a more useful method to assess OA histopathology that would have wide application for clinical and experimental OA assessment and would become recognized as the standard method. An OARSI Working Group deliberated on principles, standards and features for an OA cartilage pathology assessment system. Using current knowledge of the pathophysiology of OA morphologic features, a proposed system was presented at OARSI 2000. Subsequently, this was widely circulated for comments amongst experts in OA pathology. An OA cartilage pathology assessment system based on six grades, which reflect depth of the lesion and four stages reflecting extent of OA over the joint surface was developed. The OARSI cartilage OA histopathology grading system appears consistent and simple to apply. Further studies are required to confirm the system's utility.
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            OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines.

            To develop concise, patient-focussed, up to date, evidence-based, expert consensus recommendations for the management of hip and knee osteoarthritis (OA), which are adaptable and designed to assist physicians and allied health care professionals in general and specialist practise throughout the world. Sixteen experts from four medical disciplines (primary care, rheumatology, orthopaedics and evidence-based medicine), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. A systematic review of existing guidelines for the management of hip and knee OA published between 1945 and January 2006 was undertaken using the validated appraisal of guidelines research and evaluation (AGREE) instrument. A core set of management modalities was generated based on the agreement between guidelines. Evidence before 2002 was based on a systematic review conducted by European League Against Rheumatism and evidence after 2002 was updated using MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Library and HTA reports. The quality of evidence was evaluated, and where possible, effect size (ES), number needed to treat, relative risk or odds ratio and cost per quality-adjusted life years gained were estimated. Consensus recommendations were produced following a Delphi exercise and the strength of recommendation (SOR) for propositions relating to each modality was determined using a visual analogue scale. Twenty-three treatment guidelines for the management of hip and knee OA were identified from the literature search, including six opinion-based, five evidence-based and 12 based on both expert opinion and research evidence. Twenty out of 51 treatment modalities addressed by these guidelines were universally recommended. ES for pain relief varied from treatment to treatment. Overall there was no statistically significant difference between non-pharmacological therapies [0.25, 95% confidence interval (CI) 0.16, 0.34] and pharmacological therapies (ES=0.39, 95% CI 0.31, 0.47). Following feedback from Osteoarthritis Research International members on the draft guidelines and six Delphi rounds consensus was reached on 25 carefully worded recommendations. Optimal management of patients with OA hip or knee requires a combination of non-pharmacological and pharmacological modalities of therapy. Recommendations cover the use of 12 non-pharmacological modalities: education and self-management, regular telephone contact, referral to a physical therapist, aerobic, muscle strengthening and water-based exercises, weight reduction, walking aids, knee braces, footwear and insoles, thermal modalities, transcutaneous electrical nerve stimulation and acupuncture. Eight recommendations cover pharmacological modalities of treatment including acetaminophen, cyclooxygenase-2 (COX-2) non-selective and selective oral non-steroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs and capsaicin, intra-articular injections of corticosteroids and hyaluronates, glucosamine and/or chondroitin sulphate for symptom relief; glucosamine sulphate, chondroitin sulphate and diacerein for possible structure-modifying effects and the use of opioid analgesics for the treatment of refractory pain. There are recommendations covering five surgical modalities: total joint replacements, unicompartmental knee replacement, osteotomy and joint preserving surgical procedures; joint lavage and arthroscopic debridement in knee OA, and joint fusion as a salvage procedure when joint replacement had failed. Strengths of recommendation and 95% CIs are provided. Twenty-five carefully worded recommendations have been generated based on a critical appraisal of existing guidelines, a systematic review of research evidence and the consensus opinions of an international, multidisciplinary group of experts. The recommendations may be adapted for use in different countries or regions according to the availability of treatment modalities and SOR for each modality of therapy. These recommendations will be revised regularly following systematic review of new research evidence as this becomes available.
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              Mesoporous silica nanoparticles in biomedical applications.

              This tutorial review provides an outlook on nanomaterials that are currently being used for theranostic purposes, with a special focus on mesoporous silica nanoparticle (MSNP) based materials. MSNPs with large surface area and pore volume can serve as efficient carriers for various therapeutic agents. The functionalization of MSNPs with molecular, supramolecular or polymer moieties, provides the material with great versatility while performing drug delivery tasks, which makes the delivery process highly controllable. This emerging area at the interface of chemistry and the life sciences offers a broad palette of opportunities for researchers with interests ranging from sol-gel science, the fabrication of nanomaterials, supramolecular chemistry, controllable drug delivery and targeted theranostics in biology and medicine.
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                Author and article information

                Journal
                Regen Biomater
                Regen Biomater
                rb
                Regenerative Biomaterials
                Oxford University Press
                2056-3418
                2056-3426
                August 2021
                30 June 2021
                30 June 2021
                : 8
                : 4
                : rbab020
                Affiliations
                [1 ] Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University , No. 22 Shuangyong Road, Qingxiu District, Nanning 530021, China
                [2 ] Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University , No. 22 Shuangyong Road, Qingxiu District, Nanning 530021, China
                [3 ] Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University , No. 6 Shuangyong Road, Qingxiu District, Nanning 530021, China
                Author notes
                Correspondence address. Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, No.22 Shuangyong Road, Qingxiu District, Nanning 530021, China. Tel: +86-07715540585; E-mail: zhenhuilu1989@ 123456163.com (Z.H.L); Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Qingxiu District, Nanning 530021, China. Tel: +86-07715359001; E-mail: weiqingjungxnn@ 123456163.com (Q.J.W); Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, No.22 Shuangyong Road, Qingxiu District, Nanning 530021, China. Tel: +86-07715358132; E-mail: zhengli224@ 123456163.com (L.Z)

                Mingwei He, Zainen Qin, Xiaonan Liang contributed as first authors.

                Article
                rbab020
                10.1093/rb/rbab020
                8242227
                34221446
                5d4b52a6-446f-4b5f-b5a8-040c72d4b024
                © The Author(s) 2021. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 December 2020
                : 08 April 2021
                : 16 April 2021
                Page count
                Pages: 10
                Funding
                Funded by: The National key research and development program of China;
                Award ID: 2016YFB0700800
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 81972120
                Funded by: Guangxi Science and Technology Base and Talent Special Project;
                Award ID: GuikeAD19254003
                Funded by: Seventh Batch of Special Experts in Guangxi (Professor Wei Yao);
                Categories
                Research Article
                AcademicSubjects/MED00010
                AcademicSubjects/SCI01410

                osteoarthritis,mesoporous silica nanoparticles,polyacrylic acid,ph-response,andrographolide

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