《Table 2–Pathological score results of knee cartilage and synovial membrane in papain-induced osteoa

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《Intra-articular delivery of tetramethylpyrazine microspheres with enhanced articular cavity retention for treating osteoarthritis》

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Histologic evaluation was performed by hematoxylin and eosin（H&E）staining and safranin O&fast green staining to observe the morphology of articular cartilage and synovium（Fig.6A）and the staining of cartilage matrix for proteoglycan analysis（Fig.6B）.As shown in the figure，the surface of normal articular cartilage was intact and smooth，chondrocytes were arranged in a regular manner，and the cartilage matrix was well stained with safranin O dye.After 6 weeks of papain induction of OA，untreated cartilage was destroyed，local destruction deep to subchondral bone and replaced by fibrous connective tissue，and fibrous tissue exhibited hyperplasia.Besides，the cartilage matrix showed the loss of safranin O staining and the proteoglycan was depleted.In the treatment group，the cartilage damage was improved compared to the untreated OA model after 2 weeks:the cartilage layer recovered integrity and chondrocytes arranged in normal.However，inflammatory symptoms such as inflammatory cell infiltration，fibrillation and hyperemia were still present.From the 2nd and 3rd weeks of HE-stained joint cavity photos we can see that TMP microspheres had a better anti-inflammatory effect compared to the TMP solution group and the fibrous exudates were less than the solution group.These results may be due to high local drug concentration in the joint cavity of the microspheres.Six weeks after the first administration，it could be observed that the morphology of cartilage and synovium was normal and the density of the safranin O staining was enhanced，indicating that TMP microspheres and TMP solution have prominent therapeutic effect on papain-induced OA model rats.The histologic scores of the 4 groups sections are shown in Table 2.Each item of the scores had a high grade in the osteoarthritis model rats.After 3 weeks of treatment，the scores of various items of osteoarthritis showed a decreasing trend.And the scores were further reduced to a normal level after6 weeks of treatment.Combined with the dosing regimen，one-third dosage of TMP microspheres achieved the similar or even better therapeutic effect on the treatment of OA compared to the TMP solution，and reduced the number of intraarticular injections to a single injection.Thus，TMP microspheres possess the powerful advantages in decreasing the dosage，reducing the number of injections and even improving the therapeutic effect.