Osteoarthritis is confronted with a multifaceted pathological microenvironment, and the implementation of palliative pharmacological strategies facilitates the continued progression of osteoarthritis. In this study, a dynamic hydrogel composed of oxidized hyaluronic acid and gelatin was devised for encapsulating and dispensing EGCG to combat inflammation and oxidative stress in the initial phase, stimulating the differentiation of BMSCs to preserve the metabolic equilibrium of the extracellular matrix through the gradual release of KGN-loaded PLGA microspheres. Subsequently, accomplished adhesion and in-situ delivery were achieved through minimally invasive injection into the joint cavity. These hydrogels possess excellent shear-thinning properties and biocompatibility. The design of double-loaded hydrogel is capable of eradicating intracellular reactive oxygen species while fostering cartilage differentiation via controlled release of EGCG and KGN. A double-loaded injectable hydrogel may provide a new idea for early minimally invasive treatment of osteoarthritis.
JeonOHDavidNCampisiJ, et al.Senescent cells and osteoarthritis: a painful connection. J Clin Investig2018; 128(4): 1229–1237.
3.
RichardMJDribanJBMcalindonTE. Pharmaceutical treatment of osteoarthritis. Osteoarthr Cartil2023; 31(4): 458–466.
4.
KloppenburgMBerenbaumF. Osteoarthritis year in review 2019: epidemiology and therapy. Osteoarthr Cartil2020; 28(3): 242–248.
5.
OlivieriID’AngeloSPalazziC, et al.Advances in the management of psoriatic arthritis. Nat Rev Rheumatol2014; 10(9): 531–542.
6.
LeeJSShimDWKangKY, et al.Method categorization of stem cell therapy for degenerative osteoarthritis of the knee: a review. Int J Mol Sci2021; 22(24): 13323.
7.
NiemeyerPAlbrechtDAndereyaS, et al.Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group “Clinical Tissue Regeneration” of the German society of orthopaedics and trauma (DGOU). Knee2016; 23(3): 426.
8.
AngelePZellnerJSchröterS, et al.Biological reconstruction of localized full-thickness cartilage defects of the knee: a systematic review of level 1 studies with a minimum Follow-Up of 5 years. Cartilage2022; 13(4): 5–18.
9.
WeiWMaYYaoX, et al.Advanced hydrogels for the repair of cartilage defects and regeneration. Bioact Mater2021; 6(4): 998–1011.
10.
HuYChenXWangSC, et al.Subchondral bone microenvironment in osteoarthritis and pain. Bone Res2021; 9(1): 20.
11.
SharmaL. Osteoarthritis of the knee. N Engl J Med2021; 384(1): 51–59.
12.
DeyleGDAllenCSAllisonSC, et al.Physical therapy versus glucocorticoid injection for osteoarthritis of the knee. N Engl J Med2020; 382(15): 1420–1429.
13.
LiJZhangHHanY, et al.Targeted and responsive biomaterials in osteoarthritis. Theranostics2023; 13(3): 931–954.
14.
FengQLiQTWenHJ, et al.Injection and self-assembly of bioinspired stem cell-laden gelatin/hyaluronic acid hybrid microgels promote cartilage repair in vivo. Adv Funct Mater2019; 29(50): 1906690.
15.
LuoHTWangZTYuFL, et al.Injectable and microporous microgel assembly with sequential bioactive factor release for the endogenous repair of nucleus pulposus. Adv Funct Mater2024; 34(5): 15592.
16.
LinWFKleinJ. Recent progress in cartilage lubrication. Adv Mater2021; 33(18): e2005513.
17.
HanYYangJLZhaoWW, et al.Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis. Bioact Mater2021; 6(10): 3596–3607.
18.
ZhangWZhengLYanY, et al.Facile preparation of multifunctional hydrogels with sustained resveratrol release ability for bone tissue regeneration. Gels2024; 10(7): 429.
19.
DaiQYLiMCHanXY, et al.Co-delivery of Zn ions and resveratrol via bioactive glass-integrated injectable microspheres for postoperative regeneration of bone tumor defects. Compos Part B-Eng, 2024, p. 272.
20.
HeZCLuoHTWangZT, et al.Injectable and tissue adhesive EGCG-laden hyaluronic acid hydrogel depot for treating oxidative stress and inflammation. Carbohydr Polym2023; 299: 120180.
21.
MokraDJoskovaMMokryJ. Therapeutic effects of green tea polyphenol (-)-Epigallocatechin-3-Gallate (EGCG) in relation to molecular pathways controlling inflammation, oxidative stress, and apoptosis. Int J Mol Sci2023; 24(1): 340.
22.
ZhangSLChenZHLinDT, et al.Epigallocatechin gallate regulates inflammatory responses and new bone formation through Wnt/β-Catenin/COX-2 pathway in spondyloarthritis. Int Immunopharmacol2021; 98: 107869.
23.
ZhuWRTangHCaoL, et al.Epigallocatechin-3-O-gallate ameliorates oxidative stress-induced chondrocyte dysfunction and exerts chondroprotective effects via the Keap1/Nrf2/ARE signaling pathway. Chem Biol Drug Des2022; 100(1): 108–120.
24.
LeeJHJinHXShimHE, et al.Epigallocatechin-3-gallate inhibits osteoclastogenesis by down-regulating c-Fos expression and suppressing the nuclear factor-kappaB signal. Mol Pharmacol2010; 77(1): 17–25.
25.
HeMJChuTHWangZT, et al.Inhibition of macrophages inflammasome activation autophagic degradation of HMGB1 by EGCG ameliorates HBV-induced liver injury and fibrosis. Front Immunol2023; 14: 1147379.
26.
JohnsonKZhuSTTremblayMS, et al.A stem cell-based approach to cartilage repair. Science2012; 336(6082): 717–721.
27.
XuXLiangYJLiXF, et al.Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration. Biomaterials2021; 269: 120539.
28.
FengQLiDGLiQT, et al.Dynamic nanocomposite microgel assembly with microporosity, injectability, tissue-adhesion, and sustained drug release promotes articular cartilage repair and regeneration. Adv Healthcare Mater2022; 11(8): e2102395.
29.
ChenYRYanXYuanFZ, et al.Kartogenin-conjugated double-network hydrogel combined with stem cell transplantation and tracing for cartilage repair. Adv Sci2022; 9(35): e2105571.
30.
ZarePPezeshki-ModaressMDavachiSM, et al.Alginate sulfate-based hydrogel/nanofiber composite scaffold with controlled kartogenin delivery for tissue engineering. Carbohydr Polym2021; 266: 118123.
31.
ZhaoBZhuSLiuY, et al.Enriching and smart releasing curcumin via phenylboronic acid-anchored bioinspired hydrogel for diabetic wound healing. Advanced NanoBiomed Research2023; 3(5): 2200177.
32.
JingHZhangXLuoK, et al.miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1. Biomaterials2020; 231: 119682.
33.
LvYCCaiFYHeYX, et al.Multi-crosslinked hydrogels with strong wet adhesion, self-healing, antibacterial property, reactive oxygen species scavenging activity, and on-demand removability for seawater-immersed wound healing. Acta Biomater2023; 159: 95–110.
34.
WuJWangXNHeY, et al.Stability evaluation of gardenia yellow pigment in presence of different phenolic compounds. Food Chem2022; 373: 373.
35.
Ford VersyptANPackDWBraatzRD. Mathematical modeling of drug delivery from autocatalytically degradable PLGA microspheres - a review. J Contr Release2013; 165(1): 29–37.
36.
ZhangFXLiuPDingW, et al.Injectable mussel-inspired highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration. Biomaterials2021; 278: 121169.
37.
XuXXuLXiaJ, et al.Harnessing knee joint resident mesenchymal stem cells in cartilage tissue engineering. Acta Biomater2023; 168: 372–387.
38.
GhorbaniFZamanianABehnamghaderA, et al.Bioactive and biostable hyaluronic acid-pullulan dermal hydrogels incorporated with biomimetic hydroxyapatite spheres. Mat Sci Eng C-Mater2020; 112: 110906.
39.
WangZYWangSQWangK, et al.Stimuli-sensitive nanotherapies for the treatment of osteoarthritis. Macromol Biosci2021; 21(11): e2100280.
40.
KapoorMMartel-PelletierJLajeunesseD, et al.Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol2011; 7(1): 33–42.
41.
ZhangSHuPLLiuT, et al.Kartogenin hydrolysis product 4-aminobiphenyl distributes to cartilage and mediates cartilage regeneration. Theranostics2019; 9(24): 7108–7121.
42.
JingHZhangXGaoM, et al.Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and beta-catenin-related pathways. FASEB J2019; 33(4): 5641–5653.
43.
KaidaKHondaYHashimotoY, et al.Application of green tea catechin for inducing the osteogenic differentiation of human dedifferentiated fat cells in vitro. Int J Mol Sci2015; 16(12): 27988–28000.
