Traditional Chinese Medicine(TCM) Compound Delivery System For Treatment Of Osteoarthritis

Owing to continuing demographic and life style changes,degenerative disorders have become an enormous medical and socio-economic challenge.Musculoskeletal diseases are the most prevalent degenerative burden.Particularly,osteoarthritis(OA)affects millions of patients worldwide without effective and standardized treatment for the repair and prevention of this disease.Controlling inflammation,regenerating damaged cartilage,and restoring the subchondral bone are effective approaches for the treatment of OA.In the present study,compounds isolated from traditional Chinese medicine(TCM)with anti-inflammatory and regenerative potential,will be combined with biomimetic delivery systems to address these challenges.Part One Screening for active small molecules with anti-inflammatory and osteogenic formation from TCM JingShu KeLi.Enzyme-linked immunosorbent assay(Elisa)was used to analyze the expression of tumor necrosis factor-alpha(TNF-?),interleukin 6(IL-6)and interleukin 8(IL-8)in MH7 A cells induced by lipopolysaccharides(LPS).The anti-inflammatory ingredients in JingShu KeLi were identified as Cinnamomi Cortex,Radix Angelicae Sinensis and Carthami Flos.Moreover,cinnamaldehyde was identified as the main component responsible for the anti-inflammatory effect of Cinnamomi cortex.The anti-inflammatory effect of cinnamaldehyde(CIN)was associated with JAK/STAT signaling pathway.CIN could also promote mineralization of MC3T3-E1 cells.Part Two Biphasic scaffold(PK/PTC)that consisted of poly lactic-co-glycolic acid(PLGA)with kartogenin(a molecule for promoting chondrogenesis,KGN)for cartilage repair and poly lactic-co-glycolic acid and tricalcium phosphate(P-T)with CIN for subchondral bone repair,was fabricated via low temperature 3D printing technology.The morphology,porosity,mechanical properties,degradation characteristics in vitro and biocompatibility of the biphasic scaffolds were tested respectively.The cartilage layer and the subchondral bone layer of the biphasic scaffold which was fabricated via low temperature 3D printing technology are tightly combined.The pore size and porosity of the biphasic scaffold is suitable for cell migration and growth.Moreover,the scaffold with mechanical properties degrades slowly in vivo,thus providing mechanical support for cell growth.The BMSCs cells have good adhesion on the surface of the biphasic scaffold detected by SEM and DAPI staining.Part Three The repair effect of the biphasic scaffolds was evaluated by implanting it into a rabbit osteoarthritis model with osteochondral defects.The papain-induced rabbit knee arthritis model was used to make osteochondral defects at the femoral trochlear center.After 16 weeks of implantation,glycosaminoglycan(GAG)and collagen II of the new cartilage in the defect site were evaluated via histological staining,polarized light and immunohistochemistry.The results showed that the neo-cartilage of the PK/PTC group was better than the PTP group.This indicates that KGN may promote the expression of GAG and collagen II.The bone mass of the new bone at the defect was evaluated by histological staining,micro-CT,and dual fluorescent labeling.The BV/TV and the Tb.N in the PK/PTC group were greater than those in the control group and the PTP group.However,the Tb.Th and Tb.Sp in the PK/PTC group were lower than in the control and PTP groups.The mineralization deposition rate of new bone in PK/PTC group was higher than that in PTP group.The osteoblast activity of the PK/PTC group is stronger,indicating that CIN may promote osteoblast mineralization and new bone formation.In summary,the biphasic scaffold with bioactive molecules was established to promote the regeneration of cartilage and subchondral bone in osteoarthritis.It provides an important theoretical basis for clinical treatment of OA-induced osteochondral defects.