Skip to main content
SpringerLink
Log in

Drug Delivery Systems for Cartilage

  • Chapter
  • First Online:
Drug Delivery Systems for Musculoskeletal Tissues

  • 38 Accesses

Abstract

A dense network of extracellular matrix and lack of vascularization pose a major challenge in the delivery of therapeutics in the cartilage. Recent advances in material science and nanotechnology have shown the potential to overcome these barriers in cartilage. This chapter focuses on the pathophysiology of cartilage and discusses various drug delivery systems applied in cartilage for various cartilage-associated diseases and cartilage tissue regeneration. These drug delivery systems are majorly classified into nanoparticles, microparticles, hydrogels, and transdermal platforms, which follow different routes of entry.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. L. Wachsmuth, S. Söder, Z. Fan, F. Finger, T. Aigner, Immunolocalization of matrix proteins in different human cartilage subtypes, Histol. Histopathol. 21 (2006) 477–485. https://doi.org/10.14670/HH-21.477.

    CAS  PubMed  Google Scholar 

  2. Y. Krishnan, A.J. Grodzinsky, Cartilage diseases, Matrix Biol. 71–72 (2018) 51–69. https://doi.org/10.1016/j.matbio.2018.05.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. A.J. Sophia Fox, A. Bedi, S.A. Rodeo, The basic science of articular cartilage: Structure, composition, and function, Sports Health. 1 (2009) 461–468. https://doi.org/10.1177/1941738109350438.

    Article  Google Scholar 

  4. K.L. Bauer, J.D. Polousky, Management of Osteochondritis Dissecans Lesions of the Knee, Elbow and Ankle, Clin. Sports Med. 36 (2017) 469–487. https://doi.org/10.1016/j.csm.2017.02.005.

    Article  PubMed  Google Scholar 

  5. L. Andriolo, D.C. Crawford, D. Reale, S. Zaffagnini, C. Candrian, A. Cavicchioli, G. Filardo, Osteochondritis Dissecans of the Knee: Etiology and Pathogenetic Mechanisms. A Systematic Review, Cartilage. 11 (2020) 273–290. https://doi.org/10.1177/1947603518786557.

  6. J.J. Nepple, M.D. Milewski, K.G. Shea, Research in Osteochondritis Dissecans of the Knee: 2016 Update, J. Knee Surg. 29 (2016) 533–538. https://doi.org/10.1055/s-0036-1586723.

  7. B. Ytrehus, C.S. Carlson, S. Ekman, Etiology and pathogenesis of osteochondrosis, Vet. Pathol. 44 (2007) 429–448. https://doi.org/10.1354/vp.44-4-429.

    Article  CAS  PubMed  Google Scholar 

  8. T. Lahmer, M. Treiber, A. von Werder, F. Foerger, A. Knopf, U. Heemann, K. Thuermel, Relapsing polychondritis: An autoimmune disease with many faces, Autoimmun. Rev. 9 (2010) 540–546. https://doi.org/10.1016/j.autrev.2010.02.016.

    Article  CAS  PubMed  Google Scholar 

  9. L. Longo, A. Greco, A. Rea, V.R. Lo Vasco, A. De Virgilio, M. De Vincentiis, Relapsing polychondritis: A clinical update, Autoimmun. Rev. 15 (2016) 539–543. https://doi.org/10.1016/j.autrev.2016.02.013.

    Article  PubMed  Google Scholar 

  10. P. Richette, T. Bardin, M. Doherty, An update on the epidemiology of calcium pyrophosphate dihydrate crystal deposition disease, Rheumatology. 48 (2009) 711–715. https://doi.org/10.1093/rheumatology/kep081.

    Article  PubMed  Google Scholar 

  11. S.A. Qasem, B.R. DeYoung, Cartilage-forming tumors, Semin. Diagn. Pathol. 31 (2014) 10–20. https://doi.org/10.1053/j.semdp.2014.01.006.

    Article  PubMed  Google Scholar 

  12. S. Zhou, T.S. Thornhill, F. Meng, L. Xie, J. Wright, J. Glowacki, Influence of osteoarthritis grade on molecular signature of human cartilage, J. Orthop. Res. 34 (2016) 454–462. https://doi.org/10.1002/jor.23043.

    Article  CAS  PubMed  Google Scholar 

  13. F. Berenbaum, Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!), Osteoarthr. Cartil. 21 (2013) 16–21. https://doi.org/10.1016/j.joca.2012.11.012.

    Article  CAS  Google Scholar 

  14. Y. Li, D. Tong, P. Liang, E. Lönnblom, J. Viljanen, B. Xu, K.S. Nandakumar, R. Holmdahl, Cartilage-binding antibodies initiate joint inflammation and promote chronic erosive arthritis, Arthritis Res. Ther. 22 (2020) 1–14. https://doi.org/10.1186/s13075-020-02169-0.

    Article  CAS  Google Scholar 

  15. H. Huang, Z. Lou, S. Zheng, J. Wu, Q. Yao, R. Chen, L. Kou, D. Chen, Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage, Drug Deliv. 29 (2022) 767–791. https://doi.org/10.1080/10717544.2022.2048130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. J. Fábio dos Santos Duarte Lana, B. Lima Rodrigues, Osteoarthritis as a Chronic Inflammatory Disease: A Review of the Inflammatory Markers, Osteoarthr. Biomarkers Treat. (2019). https://doi.org/10.5772/intechopen.82565.

  17. J. Barranco-Trabi, V. Mank, J. Roberts, D.P. Newman, Atypical Costochondritis: Complete Resolution of Symptoms After Rib Manipulation and Soft Tissue Mobilization, Cureus. 13 (2021) 1–10. https://doi.org/10.7759/cureus.14369.

    Article  Google Scholar 

  18. P. Lama, U. Zehra, C. Balkovec, H.A. Claireaux, L. Flower, I.J. Harding, P. Dolan, M.A. Adams, Significance of cartilage endplate within herniated disc tissue, Eur. Spine J. 23 (2014) 1869–1877. https://doi.org/10.1007/s00586-014-3399-3.

    Article  PubMed  Google Scholar 

  19. R.M. Pauli, Achondroplasia: A comprehensive clinical review, Orphanet Journal of Rare Diseases, 2019. https://doi.org/10.1186/s13023-018-0972-6.

  20. D.M. Ornitz, L. Legeai-mallet, F. Growth, F. Receptor, D. Ornitz, L. Legeai-mallet, Review Developmental Dynamics DOI 10.1002/dvdy. 24479 Achondroplasia: Development, Pathogenesis, and Therapy, (2016) 1–41. https://doi.org/10.1002/dvdy.

  21. L. Gao, L.K.H. Goebel, P. Orth, M. Cucchiarini, H. Madry, Subchondral drilling for articular cartilage repair: A systematic review of translational research, DMM Dis. Model. Mech. 11 (2018). https://doi.org/10.1242/DMM.034280/265026/AM/SUBCHONDRAL-DRILLING-FOR-ARTICULAR-CARTILAGE.

  22. M.F. Sommerfeldt, R.A. Magnussen, T.E. Hewett, C.C. Kaeding, D.C. Flanigan, Microfracture of articular cartilage, JBJS Rev. 4 (2016). https://doi.org/10.2106/JBJS.RVW.15.00005.

  23. W. Xing, D. Mu, Q. Wang, S. Fu, M. Xin, J. Luan, Improvement of Fat Graft Survival with Autologous Bone Marrow Aspirate and Bone Marrow Concentrate: A One-Step Method, Plast. Reconstr. Surg. 137 (2016) 676e-686e. https://doi.org/10.1097/PRS.0000000000001993.

    Article  CAS  PubMed  Google Scholar 

  24. Y. Matsusue, T. Yamamuro, H. Hama, Arthroscopic multiple osteochondral transplantation to the chondral defect in the knee associated with anterior cruciate ligament disruption, Arthrosc. J. Arthrosc. Relat. Surg. 9 (1993) 318–321. https://doi.org/10.1016/S0749-8063(05)80428-1.

    Article  CAS  Google Scholar 

  25. D.L. Richter, J.A. Tanksley, M.D. Miller, Osteochondral Autograft Transplantation: A Review of the Surgical Technique and Outcomes, Sports Med. Arthrosc. 24 (2016) 74–78. https://doi.org/10.1097/JSA.0000000000000099.

    Article  PubMed  Google Scholar 

  26. R. Gudas, R. Simonaityte, E. Čekanauskas, R. Tamošiunas, A prospective, randomized clinical study of osteochondral autologous transplantation versus microfracture for the treatment of osteochondritis dissecans in the knee joint in children, J. Pediatr. Orthop. 29 (2009) 741–748. https://doi.org/10.1097/BPO.0B013E3181B8F6C7.

    Article  PubMed  Google Scholar 

  27. A. Hennig, J. Abate, Osteochondral allografts in the treatment of articular cartilage injuries of the knee, Sports Med. Arthrosc. 15 (2007) 126–132. https://doi.org/10.1097/JSA.0B013E31812E5373.

    Article  PubMed  Google Scholar 

  28. F. Yamashita, K. Sakakida, F. Suzu, S. Takai, The transplantation of an autogeneic osteochondral fragment for osteochondritis dissecans of the knee., Clin. Orthop. Relat. Res. NO. 201 (1985) 43–50. https://doi.org/10.1097/00003086-198512000-00007.

    Article  Google Scholar 

  29. C.M. Wixted, T.J. Dekker, S.B. Adams, Particulated juvenile articular cartilage allograft transplantation for osteochondral lesions of the knee and ankle, https://doi.org/10.1080/17434440.2020.1733973. 17 (2020) 235–244. https://doi.org/10.1080/17434440.2020.1733973.

  30. B.B. Hinckel, D. Thomas, E.E. Vellios, K.J. Hancock, J.G. Calcei, S.L. Sherman, C.D. Eliasberg, T.L. Fernandes, J. Farr, C. Lattermann, A.H. Gomoll, Algorithm for Treatment of Focal Cartilage Defects of the Knee: Classic and New Procedures, Cartilage. 13 (2021) 473S–495S. https://doi.org/10.1177/1947603521993219/ASSET/IMAGES/LARGE/10.1177_1947603521993219-FIG2.JPEG.

    Article  PubMed  PubMed Central  Google Scholar 

  31. J.M. Woodmass, H.P. Melugin, I.T. Wu, D.B.F. Saris, M.J. Stuart, A.J. Krych, Viable Osteochondral Allograft for the Treatment of a Full-Thickness Cartilage Defect of the Patella, Arthrosc. Tech. 6 (2017) e1661–e1665. https://doi.org/10.1016/J.EATS.2017.06.034.

    Article  PubMed  PubMed Central  Google Scholar 

  32. M. Krill, N. Early, J.S. Everhart, D.C. Flanigan, Autologous Chondrocyte Implantation (ACI) for Knee Cartilage Defects, JBJS Rev. 6 (2018) E5. https://doi.org/10.2106/JBJS.RVW.17.00078.

    Article  PubMed  Google Scholar 

  33. R. Cugat, G. Samitier, G. Vinagre, M. Sava, E. Alentorn-Geli, M. García-Balletbó, X. Cuscó, R. Seijas, D. Barastegui, J. Navarro, P. Laiz, Particulated Autologous Chondral−Platelet-Rich Plasma Matrix Implantation (PACI) for Treatment of Full-Thickness Cartilage Osteochondral Defects, Arthrosc. Tech. 10 (2021) e539–e544. https://doi.org/10.1016/J.EATS.2020.10.038.

    Article  PubMed  PubMed Central  Google Scholar 

  34. J.P. Benthien, P. Behrens, Autologous matrix-induced chondrogenesis (AMIC): Combining microfracturing and a collagen I/III matrix for articular cartilage resurfacing, Cartilage. 1 (2010) 65–68. https://doi.org/10.1177/1947603509360044/ASSET/IMAGES/LARGE/10.1177_1947603509360044-FIG2.JPEG.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. M. Wiewiorski, A. Barg, V. Valderrabano, Autologous matrix-induced chondrogenesis in osteochondral lesions of the talus, Foot Ankle Clin. 18 (2013) 151–158. https://doi.org/10.1016/j.fcl.2012.12.009.

    Article  PubMed  Google Scholar 

  36. P. Gupta, K. Vermani, S. Garg, Hydrogels: from controlled release to pH-responsive drug delivery, Drug Discov. Today. 7 (2002) 569–579. https://doi.org/10.1016/S1359-6446(02)02255-9.

    Article  CAS  PubMed  Google Scholar 

  37. J. Radhakrishnan, A. Subramanian, U.M. Krishnan, S. Sethuraman, Injectable and 3D Bioprinted Polysaccharide Hydrogels: From Cartilage to Osteochondral Tissue Engineering, Biomacromolecules. 18 (2017) 1–26. https://doi.org/10.1021/ACS.BIOMAC.6B01619/ASSET/IMAGES/LARGE/BM-2016-01619E_0007.JPEG.

    Article  CAS  PubMed  Google Scholar 

  38. M.A. Mohamed, A. Fallahi, A.M.A. El-Sokkary, S. Salehi, M.A. Akl, A. Jafari, A. Tamayol, H. Fenniri, A. Khademhosseini, S.T. Andreadis, C. Cheng, Stimuli-responsive hydrogels for manipulation of cell microenvironment: From chemistry to biofabrication technology, Prog. Polym. Sci. 98 (2019) 101147. https://doi.org/10.1016/J.PROGPOLYMSCI.2019.101147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. C. Wang, N. Feng, F. Chang, J. Wang, B. Yuan, Y. Cheng, H. Liu, J. Yu, J. Zou, J. Ding, X. Chen, Injectable Cholesterol-Enhanced Stereocomplex Polylactide Thermogel Loading Chondrocytes for Optimized Cartilage Regeneration, Adv. Healthc. Mater. 8 (2019) 1900312. https://doi.org/10.1002/ADHM.201900312.

    Article  Google Scholar 

  40. C.H. Hulme, J. Perry, H.S. McCarthy, K.T. Wright, M. Snow, C. Mennan, S. Roberts, Cell therapy for cartilage repair, Emerg. Top. Life Sci. 5 (2021) 575–589. https://doi.org/10.1042/ETLS20210015.

  41. M.F. Pittenger, D.E. Discher, B.M. Péault, D.G. Phinney, J.M. Hare, A.I. Caplan, Mesenchymal stem cell perspective: cell biology to clinical progress, Npj Regen. Med. 4 (2019). https://doi.org/10.1038/s41536-019-0083-6.

  42. J.B. Richardson, K.T. Wright, J. Wales, J.H. Kuiper, H.S. McCarthy, P. Gallacher, P.E. Harrison, S. Roberts, Efficacy and safety of autologous cell therapies for knee cartilage defects (autologous stem cells, chondrocytes or the two): Randomized controlled trial design, Regen. Med. 12 (2017) 493–501. https://doi.org/10.2217/rme-2017-0032.

    Article  CAS  PubMed  Google Scholar 

  43. Z. Wang, G. Schuch, J.K. Williams, S. Soker, Peripheral Blood Stem Cells, Essentials Stem Cell Biol. Third Ed. (2014) 227–244. https://doi.org/10.1016/B978-0-12-409503-8.00017-2.

  44. S. Kulkarni, J. Treleaven, Patient selection: Preliminary interview, screening of patient and donor, Elsevier Ltd, 2009. https://doi.org/10.1016/B978-0-443-10147-2.50024-2.

  45. T. Mori, T. Osumi, Hematopoietic Stem Cell Transplantation, Non-Hodgkin’s Lymphoma Child. Adolesc. (2019) 305–313. https://doi.org/10.1007/978-3-030-11769-6_25.

  46. K.Y. Saw, A. Anz, C. Siew-Yoke Jee, S. Merican, R. Ching-Soong Ng, S.A. Roohi, K. Ragavanaidu, Articular cartilage regeneration with autologous peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial, Arthrosc. – J. Arthrosc. Relat. Surg. 29 (2013) 684–694. https://doi.org/10.1016/j.arthro.2012.12.008.

  47. W.L. Fu, Y.F. Ao, X.Y. Ke, Z.Z. Zheng, X. Gong, D. Jiang, J.K. Yu, Repair of large full-thickness cartilage defect by activating endogenous peripheral blood stem cells and autologous periosteum flap transplantation combined with patellofemoral realignment, Knee. 21 (2014) 609–612. https://doi.org/10.1016/j.knee.2013.10.010.

    Article  PubMed  Google Scholar 

  48. Z. Wang, L. Han, T. Sun, J. Ma, S. Sun, L. Ma, B. Wu, Extracellular matrix derived from allogenic decellularized bone marrow mesenchymal stem cell sheets for the reconstruction of osteochondral defects in rabbits, Acta Biomater. 118 (2020) 54–68. https://doi.org/10.1016/J.ACTBIO.2020.10.022.

    Article  CAS  PubMed  Google Scholar 

  49. A.J. Favreau-Lessard, D.B. Sawyer, Cardiac Regeneration and Stem Cells as Therapy for Heart Disease, Elsevier Inc., 2018. https://doi.org/10.1016/b978-0-12-809657-4.65740-x.

    Book  Google Scholar 

  50. S. Bhat, P. Viswanathan, S. Chandanala, S.J. Prasanna, R.N. Seetharam, Expansion and characterization of bone marrow derived human mesenchymal stromal cells in serum-free conditions, Sci. Rep. 11 (2021) 1–18. https://doi.org/10.1038/s41598-021-83088-1.

    Article  CAS  Google Scholar 

  51. S. Zhang, B. Hu, W. Liu, P. Wang, X. Lv, S. Chen, H. Liu, Z. Shao, Articular cartilage regeneration: The role of endogenous mesenchymal stem/progenitor cell recruitment and migration, Semin. Arthritis Rheum. 50 (2020) 198–208. https://doi.org/10.1016/j.semarthrit.2019.11.001.

    Article  Google Scholar 

  52. J.M. Lee, B.S. Kim, H. Lee, G. Il Im, In vivo tracking of mesechymal stem cells using fluorescent nanoparticles in an osteochondral repair model, Mol. Ther. 20 (2012) 1434–1442. https://doi.org/10.1038/mt.2012.60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. M.S. Park, Y.H. Kim, Y. Jung, S.H. Kim, J.C. Park, D.S. Yoon, S.H. Kim, J.W. Lee, In Situ Recruitment of Human Bone Marrow-Derived Mesenchymal Stem Cells Using Chemokines for Articular Cartilage Regeneration, Cell Transplant. 24 (2015) 1067–1083. https://doi.org/10.3727/096368914X681018.

    Article  PubMed  Google Scholar 

  54. S.J. Baek, S.K. Kang, J.C. Ra, In vitro migration capacity of human adipose tissue-derived mesenchymal stem cells reflects their expression of receptors for chemokines and growth factors, Exp. Mol. Med. 43 (2011) 596–603. https://doi.org/10.3858/emm.2011.43.10.069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. J.D. Miller, S.M. Lankford, K.B. Adler, A.R. Brody, Mesenchymal stem cells require MARCKS protein for directed chemotaxis in vitro, Am. J. Respir. Cell Mol. Biol. 43 (2010) 253–258. https://doi.org/10.1165/rcmb.2010-0015RC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. J. Ringe, S. Strassburg, K. Neumann, M. Endres, M. Notter, G.R. Burmester, C. Kaps, M. Sittinger, Towards in situ tissue repair: Human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2, J. Cell. Biochem. 101 (2007) 135–146. https://doi.org/10.1002/jcb.21172.

    Article  CAS  PubMed  Google Scholar 

  57. A.L. Ponte, E. Marais, N. Gallay, A. Langonné, B. Delorme, O. Hérault, P. Charbord, J. Domenech, The In Vitro Migration Capacity of Human Bone Marrow Mesenchymal Stem Cells: Comparison of Chemokine and Growth Factor Chemotactic Activities, Stem Cells. 25 (2007) 1737–1745. https://doi.org/10.1634/stemcells.2007-0054.

    Article  CAS  PubMed  Google Scholar 

  58. M. Endres, K. Andreas, G. Kalwitz, U. Freymann, K. Neumann, J. Ringe, M. Sittinger, T. Häupl, C. Kaps, Chemokine profile of synovial fluid from normal, osteoarthritis and rheumatoid arthritis patients: CCL25, CXCL10 and XCL1 recruit human subchondral mesenchymal progenitor cells, Osteoarthr. Cartil. 18 (2010) 1458–1466. https://doi.org/10.1016/j.joca.2010.08.003.

    Article  CAS  Google Scholar 

  59. R.F. Martin, V. Murray, G. D’Cunha, M. Pardee, E. Kampouris, A. Haigh, D.P. Kelly, G.S. Hodgson, Rapid communication, Int. J. Radiat. Biol. 57 (1990) 939–946. https://doi.org/10.1080/09553009014551061.

    Article  CAS  PubMed  Google Scholar 

  60. H. Brisby, N. Papadimitriou, E. Runesson, N. Sasaki, A. Lindahl, H.B. Henriksson, Moderate physical exercise results in increased cell activity in articular cartilage of the knee joint in rats, Cells Tissues Organs. 198 (2013) 237–248. https://doi.org/10.1159/000355919.

    Article  CAS  PubMed  Google Scholar 

  61. M. Honczarenko, Y. Le, M. Swierkowski, I. Ghiran, A.M. Glodek, L.E. Silberstein, Human Bone Marrow Stromal Cells Express a Distinct Set of Biologically Functional Chemokine Receptors, Stem Cells. 24 (2006) 1030–1041. https://doi.org/10.1634/stemcells.2005-0319.

    Article  CAS  PubMed  Google Scholar 

  62. G. Kalwitz, K. Andreas, M. Endres, K. Neumann, M. Notter, J. Ringe, M. Sittinger, C. Kaps, Chemokine profile of human serum from whole blood: Migratory effects of CXCL-10 and CXCL-11 on human mesenchymal stem cells, Connect. Tissue Res. 51 (2010) 113–122. https://doi.org/10.3109/03008200903111906.

    Article  CAS  PubMed  Google Scholar 

  63. Y. Naaldijk, A.A. Johnson, S. Ishak, H.J. Meisel, C. Hohaus, A. Stolzing, Migrational changes of mesenchymal stem cells in response to cytokines, growth factors, hypoxia, and aging, Exp. Cell Res. 338 (2015) 97–104. https://doi.org/10.1016/j.yexcr.2015.08.019.

    Article  CAS  PubMed  Google Scholar 

  64. M. Ullah, J. Eucker, M. Sittinger, J. Ringe, Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express chemokine receptor CCR9 and chemotactically migrate toward CCL25 or serum, Stem Cell Res. Ther. 4 (2013) 1–16. https://doi.org/10.1186/scrt310.

    Article  CAS  Google Scholar 

  65. G. Kalwitz, M. Endres, K. Neumann, K. Skriner, J. Ringe, O. Sezer, M. Sittinger, T. Häupl, C. Kaps, Gene expression profile of adult human bone marrow-derived mesenchymal stem cells stimulated by the chemokine CXCL7, Int. J. Biochem. Cell Biol. 41 (2009) 649–658. https://doi.org/10.1016/j.biocel.2008.07.011.

    Article  CAS  PubMed  Google Scholar 

  66. Y. Wu, M.J. Hoogduijn, C.C. Baan, S.S. Korevaar, R. De Kuiper, L. Yan, L. Wang, N.M.V. Besouw, Adipose Tissue-Derived Mesenchymal Stem Cells Have a Heterogenic Cytokine Secretion Profile, Stem Cells Int. 2017 (2017). https://doi.org/10.1155/2017/4960831.

  67. Y. Mishima, M. Lotz, Chemotaxis of Human Articular Chondrocytes and Mesenchymal Stem Cells, J. Orthop. Res. 26 (2008) 1407–1412. https://doi.org/10.1002/jor.20668.

    Article  PubMed  Google Scholar 

  68. A. Schmidt, D. Ladage, T. Schinköthe, U. Klausmann, C. Ulrichs, F. Klinz, K. Brixius, S. Arnhold, B. Desai, U. Mehlhorn, R.H.G. Schwinger, P. Staib, K. Addicks, W. Bloch, Basic Fibroblast Growth Factor Controls Migration in Human Mesenchymal Stem Cells, Stem Cells. 24 (2006) 1750–1758. https://doi.org/10.1634/stemcells.2005-0191.

    Article  CAS  PubMed  Google Scholar 

  69. Y. Wang, J. Chen, W. Fan, J. Zhang, B. Hua, B. Sun, L. Zhu, X. Niu, Z. Yan, C. Guo, Stromal cell-derived factor-1α and transforming growth factor-β1 synergistically facilitate migration and chondrogenesis of synovium-derived stem cells through MAPK pathways, Am. J. Transl. Res. 9 (2017) 2656–2667.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. A. Mendelson, E. Frank, C. Allred, E. Jones, M. Chen, W. Zhao, J.J. Mao, Chondrogenesis by chemotactic homing of synovium, bone marrow, and adipose stem cells in vitro, FASEB J. 25 (2011) 3496–3504. https://doi.org/10.1096/fj.10-176305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. R. Rollín, F. Marco, E. Camafeita, E. Calvo, L. López-Durán, J.Á. Jover, J.A. López, B. Fernández-Gutiérrez, Differential proteome of bone marrow mesenchymal stem cells from osteoarthritis patients, Osteoarthr. Cartil. 16 (2008) 929–935. https://doi.org/10.1016/j.joca.2007.12.006.

    Article  Google Scholar 

  72. H.L. Holmes, B. Wilson, J.P. Goerger, J.L. Silverberg, I. Cohen, W.R. Zipfel, L.A. Fortier, Facilitated recruitment of mesenchymal stromal cells by bone marrow concentrate and platelet rich plasma, PLoS One. 13 (2018) 1–12. https://doi.org/10.1371/journal.pone.0194567.

    Article  CAS  Google Scholar 

  73. H. Joos, A. Wildner, C. Hogrefe, H. Reichel, R.E. Brenner, Interleukin-1 beta and tumor necrosis factor alpha inhibit migration activity of chondrogenic progenitor cells from non-fibrillated osteoarthritic cartilage, Arthritis Res. Ther. 15 (2013) 1–13. https://doi.org/10.1186/ar4299.

    Article  CAS  Google Scholar 

  74. S. Koelling, J. Kruegel, M. Irmer, J.R. Path, B. Sadowski, X. Miro, N. Miosge, Migratory Chondrogenic Progenitor Cells from Repair Tissue during the Later Stages of Human Osteoarthritis, Cell Stem Cell. 4 (2009) 324–335. https://doi.org/10.1016/j.stem.2009.01.015.

    Article  CAS  PubMed  Google Scholar 

  75. Y. Jiang, C. Hu, S. Yu, J. Yan, H. Peng, H.W. Ouyang, R.S. Tuan, Cartilage stem/progenitor cells are activated in osteoarthritis via interleukin-1β/nerve growth factor signaling, Arthritis Res. Ther. 17 (2015) 1–13. https://doi.org/10.1186/s13075-015-0840-x.

    Article  CAS  Google Scholar 

  76. J.S. Lee, S.K. Kim, B.J. Jung, S.B. Choi, E.Y. Choi, C.S. Kim, Enhancing proliferation and optimizing the culture condition for human bone marrow stromal cells using hypoxia and fibroblast growth factor-2, Stem Cell Res. 28 (2018) 87–95. https://doi.org/10.1016/j.scr.2018.01.010.

    Article  CAS  PubMed  Google Scholar 

  77. H. Chuma, H. Mizuta, S. Kudo, K. Takagi, Y. Hiraki, One day exposure to FGF-2 was sufficient for the regenerative repair of full-thickness defects of articular cartilage in rabbits, Osteoarthr. Cartil. 12 (2004) 834–842. https://doi.org/10.1016/j.joca.2004.07.003.

    Article  CAS  Google Scholar 

  78. B. Awan, D. Turkov, C. Schumacher, A. Jacobo, A. McEnerney, A. Ramsey, G. Xu, D. Park, S. Kalomoiris, W. Yao, L.E. Jao, M.L. Allende, C.B. Lebrilla, F.A. Fierro, FGF2 Induces Migration of Human Bone Marrow Stromal Cells by Increasing Core Fucosylations on N-Glycans of Integrins, Stem Cell Reports. 11 (2018) 325–333. https://doi.org/10.1016/j.stemcr.2018.06.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. H.L. Reesink, R.M. Sutton, C.R. Shurer, R.P. Peterson, J.S. Tan, J. Su, M.J. Paszek, A.J. Nixon, Galectin-1 and galectin-3 expression in equine mesenchymal stromal cells (MSCs), synovial fibroblasts and chondrocytes, and the effect of inflammation on MSC motility, Stem Cell Res. Ther. 8 (2017) 1–12. https://doi.org/10.1186/s13287-017-0691-2.

    Article  CAS  Google Scholar 

  80. A. Barhanpurkar-Naik, S.T. Mhaske, S.T. Pote, K. Singh, M.R. Wani, Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4, Stem Cell Res. Ther. 8 (2017) 1–15. https://doi.org/10.1186/s13287-017-0618-y.

    Article  CAS  Google Scholar 

  81. C. Jiang, P. Ma, B. Ma, Z. Wu, G. Qiu, X. Su, Z. Xia, Z. Ye, Y. Wang, Plasma-derived fibronectin stimulates chondrogenic differentiation of human subchondral cortico-spongious progenitor cells in late-stage osteoarthritis, Int. J. Mol. Sci. 16 (2015) 19477–19489. https://doi.org/10.3390/ijms160819477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. J.P. Krüger, S. Hondke, M. Endres, A. Pruss, A. Siclari, C. Kaps, Human platelet-rich plasma stimulates migration and chondrogenic differentiation of human subchondral progenitor cells, J. Orthop. Res. 30 (2012) 845–852. https://doi.org/10.1002/jor.22005.

    Article  CAS  PubMed  Google Scholar 

  83. P.C. Kreuz, J.P. Krüger, S. Metzlaff, U. Freymann, M. Endres, A. Pruss, W. Petersen, C. Kaps, Platelet-Rich Plasma Preparation Types Show Impact on Chondrogenic Differentiation, Migration, and Proliferation of Human Subchondral Mesenchymal Progenitor Cells, Arthrosc. – J. Arthrosc. Relat. Surg. 31 (2015) 1951–1961. https://doi.org/10.1016/j.arthro.2015.03.033.

    Article  Google Scholar 

  84. J. Amrichová, T. Špaková, J. Rosocha, D. Harvanová, D. Bačenková, M. Lacko, S. Horňák, Effect of PRP and PPP on proliferation and migration of human chondrocytes and synoviocytes in vitro, Cent. Eur. J. Biol. 9 (2014) 139–148. https://doi.org/10.2478/s11535-013-0255-0.

    Article  CAS  Google Scholar 

  85. A. Damerau, A. Lang, M. Pfeiffenberger, F. Buttgereit, T. Gaber, FRI0002 Development of an in vitro multi-component 3d joint model to simulate the pathogenesis of arthritis, (2017) 480.2–480. https://doi.org/10.1136/annrheumdis-2017-eular.5889.

  86. R. Kulawig, J.P. Krüger, O. Klein, Z. Konthur, H. Schütte, J. Klose, C. Kaps, M. Endres, Identification of fibronectin as a major factor in human serum to recruit subchondral mesenchymal progenitor cells, Int. J. Biochem. Cell Biol. 45 (2013) 1410–1418. https://doi.org/10.1016/j.biocel.2013.04.016.

    Article  CAS  PubMed  Google Scholar 

  87. R.H. Kalkreuth, J.P. Krüger, S. Lau, P. Niemeyer, M. Endres, P.C. Kreuz, C. Kaps, Fibronectin stimulates migration and proliferation, but not chondrogenic differentiation of human subchondral progenitor cells, Regen. Med. 9 (2014) 759–773. https://doi.org/10.2217/rme.14.40.

    Article  CAS  PubMed  Google Scholar 

  88. T. Tao, Y. Li, C. Gui, Y. Ma, Y. Ge, H. Dai, K. Zhang, J. Du, Y. Guo, Y. Jiang, J. Gui, Fibronectin enhances cartilage repair by activating progenitor cells through integrin α5β1 Receptor, 2018. https://doi.org/10.1089/ten.tea.2017.0322.

  89. R. He, B. Wang, M. Cui, Z. Xiong, H. Lin, L. Zhao, Z. Li, Z. Wang, S. Peggrem, Z. Xia, Z. Shao, Link Protein N-Terminal Peptide as a Potential Stimulating Factor for Stem Cell-Based Cartilage Regeneration, Stem Cells Int. 2018 (2018). https://doi.org/10.1155/2018/3217895.

  90. K. Zha, X. Li, Z. Yang, G. Tian, Z. Sun, X. Sui, Y. Dai, S. Liu, Q. Guo, Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application, Npj Regen. Med. 6 (2021). https://doi.org/10.1038/s41536-021-00122-6.

  91. T. Nagamura-Inoue, Umbilical cord-derived mesenchymal stem cells: Their advantages and potential clinical utility, World J. Stem Cells. 6 (2014) 195. https://doi.org/10.4252/wjsc.v6.i2.195.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Y. Shang, H. Guan, F. Zhou, Biological Characteristics of Umbilical Cord Mesenchymal Stem Cells and Its Therapeutic Potential for Hematological Disorders, Front. Cell Dev. Biol. 9 (2021) 1–11. https://doi.org/10.3389/fcell.2021.570179.

  93. I.H. Dilogo, A.F. Canintika, A.L. Hanitya, J.A. Pawitan, I.K. Liem, J. Pandelaki, Umbilical cord-derived mesenchymal stem cells for treating osteoarthritis of the knee: a single-arm, open-label study, Eur. J. Orthop. Surg. Traumatol. 30 (2020) 799–807. https://doi.org/10.1007/s00590-020-02630-5.

    Article  PubMed  Google Scholar 

  94. S. Ceccarelli, P. Pontecorvi, E. Anastasiadou, C. Napoli, C. Marchese, Immunomodulatory Effect of Adipose-Derived Stem Cells: The Cutting Edge of Clinical Application, Front. Cell Dev. Biol. 8 (2020) 1–12. https://doi.org/10.3389/fcell.2020.00236.

  95. Y. Song, H. Du, C. Dai, L. Zhang, S. Li, D.J. Hunter, L. Lu, C. Bao, Human adipose-derived mesenchymal stem cells for osteoarthritis: A pilot study with long-term follow-up and repeated injections, Regen. Med. 13 (2018) 295–307. https://doi.org/10.2217/rme-2017-0152.

    Article  CAS  PubMed  Google Scholar 

  96. F. Slimi, W. Zribi, M. Trigui, R. Amri, N. Gouiaa, C. Abid, M.A. Rebai, T. Boudawara, S. Jebahi, H. Keskes, The effectiveness of platelet-rich plasma gel on full-thickness cartilage defect repair in a rabbit model, https://doi.org/10.1302/2046-3758.103.BJR-2020-0087.R2. 10 (2021) 192–202. https://doi.org/10.1302/2046-3758.103.BJR-2020-0087.R2.

  97. S.G. Boswell, B.J. Cole, E.A. Sundman, V. Karas, L.A. Fortier, Platelet-Rich Plasma: A Milieu of Bioactive Factors, Arthrosc. J. Arthrosc. Relat. Surg. 28 (2012) 429–439. https://doi.org/10.1016/J.ARTHRO.2011.10.018.

    Article  Google Scholar 

  98. R. Alves, R. Grimalt, A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification, Ski. Appendage Disord. 4 (2018) 18–24. https://doi.org/10.1159/000477353.

    Article  Google Scholar 

  99. G.Z. Jin, Current nanoparticle-based technologies for osteoarthritis therapy, Nanomaterials. 10 (2020) 1–20. https://doi.org/10.3390/nano10122368.

    Article  CAS  Google Scholar 

  100. J. Jeevanandam, A. Barhoum, Y.S. Chan, A. Dufresne, M.K. Danquah, Review on nanoparticles and nanostructured materials: History, sources, toxicity and regulations, Beilstein J. Nanotechnol. 9 (2018) 1050–1074. https://doi.org/10.3762/bjnano.9.98.

    Article  PubMed  PubMed Central  Google Scholar 

  101. A. Biswas, I.S. Bayer, A.S. Biris, T. Wang, E. Dervishi, F. Faupel, Advances in top-down and bottom-up surface nanofabrication: Techniques, applications & future prospects, Adv. Colloid Interface Sci. 170 (2012) 2–27. https://doi.org/10.1016/j.cis.2011.11.001.

    Article  CAS  PubMed  Google Scholar 

  102. X. Li, B. Dai, J. Guo, L. Zheng, Q. Guo, J. Peng, J. Xu, L. Qin, Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy, 2021. https://doi.org/10.1007/s40820-021-00670-y.

  103. Z. Shi, Y. Zhou, T. Fan, Y. Lin, H. Zhang, L. Mei, Inorganic nano-carriers based smart drug delivery systems for tumor therapy, Smart Mater. Med. 1 (2020) 32–47. https://doi.org/10.1016/j.smaim.2020.05.002.

    Article  Google Scholar 

  104. L. Valot, M. Maumus, L. Brunel, J. Martinez, M. Amblard, D. Noël, A. Mehdi, G. Subra, A collagen-mimetic organic-inorganic hydrogel for cartilage engineering, Gels. 7 (2021) 1–15. https://doi.org/10.3390/gels7020073.

    Article  CAS  Google Scholar 

  105. M. Zheng, H. Jia, H. Wang, L. Liu, Z. He, Z. Zhang, W. Yang, L. Gao, X. Gao, F. Gao, Application of nanomaterials in the treatment of rheumatoid arthritis, RSC Adv. 11 (2021) 7129–7137. https://doi.org/10.1039/d1ra00328c.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. J. Yang, C.R. Han, J.F. Duan, F. Xu, R.C. Sun, Insitu grafting silica nanoparticles reinforced nanocomposite hydrogels, Nanoscale. 5 (2013) 10858–10863. https://doi.org/10.1039/c3nr04252a.

    Article  CAS  PubMed  Google Scholar 

  107. M.A. Bonifacio, A. Cochis, S. Cometa, A. Scalzone, P. Gentile, G. Procino, S. Milano, A.C. Scalia, L. Rimondini, E. De Giglio, Advances in cartilage repair: The influence of inorganic clays to improve mechanical and healing properties of antibacterial Gellan gum-Manuka honey hydrogels, Mater. Sci. Eng. C. 108 (2020) 110444. https://doi.org/10.1016/j.msec.2019.110444.

    Article  CAS  Google Scholar 

  108. Y. Ao, E. Zhang, Y. Liu, L. Yang, J. Li, F. Wang, Advanced Hydrogels With Nanoparticle Inclusion for Cartilage Tissue Engineering, Front. Bioeng. Biotechnol. 10 (2022) 1–13. https://doi.org/10.3389/fbioe.2022.951513.

  109. N. Amiryaghoubi, M. Fathi, A. Barzegari, J. Barar, H. Omidian, Y. Omidi, Recent advances in polymeric scaffolds containing carbon nanotube and graphene oxide for cartilage and bone regeneration, Mater. Today Commun. 26 (2021) 102097. https://doi.org/10.1016/j.mtcomm.2021.102097.

    Article  CAS  Google Scholar 

  110. P. Liu, G. Chen, J. Zhang, A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives, Molecules. 27 (2022). https://doi.org/10.3390/molecules27041372.

  111. G. Wen, H.F. Deng, W.Z. Bing, S.Z. Luo, Preliminarily experimental study on biological properties of 153Sm-citrate-nano-hydroxyapatite, J. Sichuan Univ. (Medical Sci. Ed.) 38 (2007) 1017–1020.

    CAS  Google Scholar 

  112. G. Gregoriadis, A.T. Florence, Liposomes in Drug Delivery, Drugs. 45 (1993) 15–28. https://doi.org/10.2165/00003495-199345010-00003.

    Article  CAS  PubMed  Google Scholar 

  113. W. Deng, W. Chen, S. Clement, A. Guller, Z. Zhao, A. Engel, E.M. Goldys, Controlled gene and drug release from a liposomal delivery platform triggered by X-ray radiation, Nat. Commun. 9 (2018) 1–11. https://doi.org/10.1038/s41467-018-05118-3.

    Article  CAS  Google Scholar 

  114. A. Akbarzadeh, R. Rezaei-Sadabady, S. Davaran, S.W. Joo, N. Zarghami, Y. Hanifehpour, M. Samiei, M. Kouhi, K. Nejati-Koshki, Liposome: Classification, preparation, and applications, Nanoscale Res. Lett. 8 (2013) 1. https://doi.org/10.1186/1556-276X-8-102.

    Article  CAS  Google Scholar 

  115. O. Craciunescu, M. Icriverzi, P.E. Florian, A. Roseanu, M. Trif, Mechanisms and pharmaceutical action of lipid nanoformulation of natural bioactive compounds as efficient delivery systems in the therapy of osteoarthritis, Pharmaceutics. 13 (2021) 1–24. https://doi.org/10.3390/pharmaceutics13081108.

    Article  CAS  Google Scholar 

  116. W. Lin, R. Goldberg, J. Klein, Poly-phosphocholination of liposomes leads to highly-extended retention time in mice joints, J. Mater. Chem. B. 10 (2022) 2820–2827. https://doi.org/10.1039/d1tb02346b.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. J. Yang, Y. Zhu, F. Wang, L. Deng, X. Xu, W. Cui, Microfluidic liposomes-anchored microgels as extended delivery platform for treatment of osteoarthritis, Chem. Eng. J. 400 (2020) 126004. https://doi.org/10.1016/j.cej.2020.126004.

    Article  CAS  Google Scholar 

  118. R. Gauro, M. Nandave, V.K. Jain, K. Jain, Advances in dendrimer-mediated targeted drug delivery to the brain, J. Nanoparticle Res. 23 (2021). https://doi.org/10.1007/s11051-021-05175-8.

  119. K. Jain, P. Kesharwani, U. Gupta, N.K. Jain, Dendrimer toxicity: Let’s meet the challenge, Int. J. Pharm. 394 (2010) 122–142. https://doi.org/10.1016/j.ijpharm.2010.04.027.

    Article  CAS  PubMed  Google Scholar 

  120. M. Mariyam, K. Ghosal, S. Thomas, N. Kalarikkal, M.S. Latha, Dendrimers: General Aspects, Applications and Structural Exploitations as Prodrug/Drug-delivery Vehicles in Current Medicine, Mini-Reviews Med. Chem. 18 (2017) 439–457. https://doi.org/10.2174/1389557517666170512095151.

    Article  CAS  Google Scholar 

  121. S. Sadekar, H. Ghandehari, Transepithelial transport and toxicity of PAMAM dendrimers: Implications for oral drug delivery, Adv. Drug Deliv. Rev. 64 (2012) 571–588. https://doi.org/10.1016/j.addr.2011.09.010.

    Article  CAS  PubMed  Google Scholar 

  122. L.P. Mendes, J. Pan, V.P. Torchilin, Dendrimers as nanocarriers for nucleic acid and drug delivery in cancer therapy, Molecules. 22 (2017) 1–21. https://doi.org/10.3390/molecules22091401.

    Article  CAS  Google Scholar 

  123. C.A. Razzino, V. Serafín, M. Gamella, M. Pedrero, A. Montero-Calle, R. Barderas, M. Calero, A.O. Lobo, P. Yáñez-Sedeño, S. Campuzano, J.M. Pingarrón, An electrochemical immunosensor using gold nanoparticles-PAMAM-nanostructured screen-printed carbon electrodes for tau protein determination in plasma and brain tissues from Alzheimer patients, Biosens. Bioelectron. 163 (2020) 112238. https://doi.org/10.1016/j.bios.2020.112238.

    Article  CAS  PubMed  Google Scholar 

  124. A. Janaszewska, J. Lazniewska, P. Trzepiński, M. Marcinkowska, B. Klajnert-Maculewicz, Cytotoxicity of dendrimers, Biomolecules. 9 (2019) 1–23. https://doi.org/10.3390/biom9080330.

    Article  CAS  Google Scholar 

  125. B.C. Geiger, S. Wang, R.F. Padera, A.J. Grodzinsky, P.T. Hammond, Cartilage-penetrating nanocarriers improve delivery and efficacy of growth factor treatment of osteoarthritis, Sci. Transl. Med. 10 (2018) 1–13. https://doi.org/10.1126/scitranslmed.aat8800.

    Article  CAS  Google Scholar 

  126. F. Liu, X. Wang, Y. Li, M. Ren, P. He, L. Wang, J. Xu, S. Yang, P. Ji, Dendrimer-modified gelatin methacrylate hydrogels carrying adipose-derived stromal/stem cells promote cartilage regeneration, Stem Cell Res. Ther. 13 (2022) 1–15. https://doi.org/10.1186/s13287-022-02705-6.

    Article  CAS  Google Scholar 

  127. L. Degoricija, P.N. Bansal, S.H.M. Söntjens, N.S. Joshi, M. Takahashi, B. Snyder, M.W. Grinstaff, Hydrogels for osteochondral repair based on photocrosslinkable carbamate dendrimers, Biomacromolecules. 9 (2008) 2863–2872. https://doi.org/10.1021/bm800658x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. H.M. Aliabadi, A. Lavasanifar, Polymeric micelles for drug delivery, Expert Opin. Drug Deliv. 3 (2006) 139–162. https://doi.org/10.1517/17425247.3.1.139.

    Article  CAS  PubMed  Google Scholar 

  129. L.C. Nelemans, L. Gurevich, Drug delivery with polymeric nanocarriers-cellular uptake mechanisms, Materials (Basel). 13 (2020) 1–21. https://doi.org/10.3390/ma13020366.

    Article  CAS  Google Scholar 

  130. D. Maysinger, J. Lovrić, A. Eisenberg, R. Savić, Fate of micelles and quantum dots in cells, Eur. J. Pharm. Biopharm. 65 (2007) 270–281. https://doi.org/10.1016/j.ejpb.2006.08.011.

    Article  CAS  PubMed  Google Scholar 

  131. Y. Wei, L. Yan, L. Luo, T. Gui, B. Jang, A. Amirshaghaghi, T. You, A. Tsourkas, L. Qin, Z. Cheng, Phospholipase A2 inhibitor-loaded micellar nanoparticles attenuate inflammation and mitigate osteoarthritis progression, Sci. Adv. 7 (2021). https://doi.org/10.1126/SCIADV.ABE6374.

  132. L. Ma, X. Zheng, R. Lin, A.R. Sun, J. Song, Z. Ye, D. Liang, M. Zhang, J. Tian, X. Zhou, L. Cui, Y. Liu, Y. Liu, Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems, (2022).

    Google Scholar 

  133. Q. Wang, H. Jiang, Y. Li, W. Chen, H. Li, K. Peng, Z. Zhang, X. Sun, Targeting NF-kB signaling with polymeric hybrid micelles that co-deliver siRNA and dexamethasone for arthritis therapy, Biomaterials. 122 (2017) 10–22. https://doi.org/10.1016/j.biomaterials.2017.01.008.

    Article  CAS  PubMed  Google Scholar 

  134. X. Wu, P. Li, J. Cheng, Q. Xu, B. Lu, C. Han, W. Huo, ROS-Sensitive Nanoparticles Co-delivering Dexamethasone and CDMP-1 for the Treatment of Osteoarthritis Through Chondrogenic Differentiation Induction and Inflammation Inhibition, Front. Bioeng. Biotechnol. 9 (2021) 1–11. https://doi.org/10.3389/fbioe.2021.608150.

  135. L. An, Z. Li, L. Shi, L. Wang, Y. Wang, L. Jin, X. Shuai, J. Li, Inflammation-Targeted Celastrol Nanodrug Attenuates Collagen-Induced Arthritis through NF-κB and Notch1 Pathways, Nano Lett. 20 (2020) 7728–7736. https://doi.org/10.1021/acs.nanolett.0c03279.

    Article  CAS  PubMed  Google Scholar 

  136. J. Li, Y. Long, R. Guo, K. Ren, Z. Lu, M. Li, X. Wang, Y. Wang, Z. Zhang, Q. He, Shield and sword nano-soldiers ameliorate rheumatoid arthritis by multi-stage manipulation of neutrophils, J. Control. Release. 335 (2021) 38–48. https://doi.org/10.1016/j.jconrel.2021.05.008.

    Article  CAS  PubMed  Google Scholar 

  137. N. Zhang, C. Xu, N. Li, S. Zhang, L. Fu, X. Chu, H. Hua, X. Zeng, Y. Zhao, Folate receptor-targeted mixed polysialic acid micelles for combating rheumatoid arthritis: In vitro and in vivo evaluation, Drug Deliv. 25 (2018) 1182–1191. https://doi.org/10.1080/10717544.2018.1472677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. G. Seetharaman, A.R. Kallar, V.M. Vijayan, J. Muthu, S. Selvam, Design, preparation and characterization of pH-responsive prodrug micelles with hydrolyzable anhydride linkages for controlled drug delivery, J. Colloid Interface Sci. 492 (2017) 61–72. https://doi.org/10.1016/j.jcis.2016.12.070.

    Article  CAS  PubMed  Google Scholar 

  139. A. Chenxian Zhu, A. Zhongxing Zhang, Y. Wen, A. Xia Song, J. Zhu, Y. Yao, and J. Li, Cationic micelles as nanocarriers for enhancing intra-cartilage drug penetration and retention, J. Mater. Chem. B. 10 (2021) 4118. https://doi.org/10.1039/D2TB02050E.

    Article  Google Scholar 

  140. M. Jaiswal, R. Dudhe, P.K. Sharma, Nanoemulsion: an advanced mode of drug delivery system, 3 Biotech. 5 (2015) 123–127. https://doi.org/10.1007/s13205-014-0214-0.

  141. F.U. Rehman, K.U. Shah, S.U. Shah, I.U. Khan, G.M. Khan, A. Khan, From nanoemulsions to self-nanoemulsions, with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS), Expert Opin. Drug Deliv. 14 (2017) 1325–1340. https://doi.org/10.1080/17425247.2016.1218462.

    Article  CAS  PubMed  Google Scholar 

  142. J. Tudela, M. Martínez, R. Valdivia, J. Romo, M. Portillo, R. Rangel, Enhanced Reader.pdf, Nature. 388 (2010) 539–547.

    Google Scholar 

  143. E.B. Souto, A. Cano, C. Martins-Gomes, T.E. Coutinho, A. Zielińska, A.M. Silva, Microemulsions and Nanoemulsions in Skin Drug Delivery, Bioengineering. 9 (2022) 1–22. https://doi.org/10.3390/bioengineering9040158.

    Article  CAS  Google Scholar 

  144. J. Yoo, C. Park, G. Yi, D. Lee, H. Koo, Active targeting strategies using biological ligands for nanoparticle drug delivery systems, Cancers (Basel). 11 (2019). https://doi.org/10.3390/cancers11050640.

  145. C. Li, X. Chen, X. Luo, H. Wang, Y. Zhu, G. Du, W. Chen, Z. Chen, X. Hao, Z. Zhang, X. Sun, Nanoemulsions Target to Ectopic Lymphoids in Inflamed Joints to Restore Immune Tolerance in Rheumatoid Arthritis, Nano Lett. 21 (2021) 2551–2561. https://doi.org/10.1021/acs.nanolett.0c05110.

    Article  CAS  PubMed  Google Scholar 

  146. J.P. Gokhale, H.S. Mahajan, S.S. Surana, Quercetin loaded nanoemulsion-based gel for rheumatoid arthritis: In vivo and in vitro studies, Biomed. Pharmacother. 112 (2019) 108622. https://doi.org/10.1016/j.biopha.2019.108622.

    Article  CAS  PubMed  Google Scholar 

  147. R. Hamed, M. Basil, T. AlBaraghthi, S. Sunoqrot, O. Tarawneh, Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies, Pharm. Dev. Technol. 21 (2016) 980–989. https://doi.org/10.3109/10837450.2015.1086372.

    Article  CAS  PubMed  Google Scholar 

  148. J. Kousalová, T. Etrych, Polymeric nanogels as drug delivery systems, Physiol. Res. 67 (2018) s305–s317. https://doi.org/10.33549/physiolres.933979.

    Article  PubMed  Google Scholar 

  149. G. Soni, K.S. Yadav, Nanogels as potential nanomedicine carrier for treatment of cancer: A mini review of the state of the art, Saudi Pharm. J. 24 (2016) 133–139. https://doi.org/10.1016/j.jsps.2014.04.001.

    Article  PubMed  Google Scholar 

  150. Z. An, Q. Qiu, G. Liu, Synthesis of architecturally well-defined nanogels via RAFT polymerization for potential bioapplications, Chem. Commun. 47 (2011) 12424–12440. https://doi.org/10.1039/c1cc13955j.

    Article  CAS  Google Scholar 

  151. M. Suhail, J.M. Rosenholm, M.U. Minhas, S.F. Badshah, A. Naeem, K.U. Khan, M. Fahad, Nanogels as drug-delivery systems: A comprehensive overview, Ther. Deliv. 10 (2019) 697–717. https://doi.org/10.4155/tde-2019-0010.

    Article  CAS  PubMed  Google Scholar 

  152. F. Sultana, Manirujjaman, Imran-Ul-Haque, M. Arafat, S. Sharmin, An overview of nanogel drug delivery system, J. Appl. Pharm. Sci. 3 (2013) 95–105. https://doi.org/10.7324/JAPS.2013.38.S15.

    Article  CAS  Google Scholar 

  153. K. Mizuno, Y. Ikeuchi-Takahashi, Y. Hattori, H. Onishi, Preparation and evaluation of conjugate nanogels of glycyl-prednisolone with natural anionic polysaccharides as anti-arthritic delivery systems, Drug Deliv. 28 (2021) 144–152. https://doi.org/10.1080/10717544.2020.1865478.

    Article  CAS  PubMed  Google Scholar 

  154. T. Adachi, N. Miyamoto, H. Imamura, T. Yamamoto, E. Marin, W. Zhu, M. Kobara, Y. Sowa, Y. Tahara, N. Kanamura, K. Akiyoshi, O. Mazda, I. Nishimura, G. Pezzotti, Three-Dimensional Culture of Cartilage Tissue on Nanogel-Cross-Linked Porous Freeze-Dried Gel Scaffold for Regenerative Cartilage Therapy: A Vibrational Spectroscopy Evaluation, Int. J. Mol. Sci. 23 (2022). https://doi.org/10.3390/ijms23158099.

  155. N. Feng, M. Yang, X. Feng, Y. Wang, F. Chang, J. Ding, Reduction-Responsive Polypeptide Nanogel for Intracellular Drug Delivery in Relieving Collagen-Induced Arthritis, ACS Biomater. Sci. Eng. 4 (2018) 4154–4162. https://doi.org/10.1021/acsbiomaterials.8b00738.

    Article  CAS  PubMed  Google Scholar 

  156. S. Bale, A. Khurana, A.S.S. Reddy, M. Singh, C. Godugu, Overview on therapeutic applications of microparticulate drug delivery systems, Crit. Rev. Ther. Drug Carrier Syst. 33 (2016) 309–361. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2016015798.

    Article  PubMed  Google Scholar 

  157. N.A. Ballesteros, M. Alonso, S.R. Saint-Jean, S.I. Perez-Prieto, An oral DNA vaccine against infectious haematopoietic necrosis virus (IHNV) encapsulated in alginate microspheres induces dose-dependent immune responses and significant protection in rainbow trout (Oncorrhynchus mykiss), Fish Shellfish Immunol. 45 (2015) 877–888. https://doi.org/10.1016/j.fsi.2015.05.045.

    Article  CAS  PubMed  Google Scholar 

  158. Y.M. Yoon, J.S. Lewis, M.R. Carstens, M. Campbell-Thompson, C.H. Wasserfall, M.A. Atkinson, B.G. Keselowsky, A combination hydrogel microparticle-based vaccine prevents type 1 diabetes in non-obese diabetic mice, Sci. Rep. 5 (2015) 1–13. https://doi.org/10.1038/srep13155.

    Article  CAS  Google Scholar 

  159. A. Sheikh Hasan, A. Sapin, C. Damgé, P. Leroy, M. Socha, P. Maincent, Reduction of the in vivo burst release of insulin-loaded microparticles, J. Drug Deliv. Sci. Technol. 30 (2015) 486–493. https://doi.org/10.1016/j.jddst.2015.06.020.

    Article  CAS  Google Scholar 

  160. J. Castro-Rosas, C.R. Ferreira-Grosso, C.A. Gómez-Aldapa, E. Rangel-Vargas, M.L. Rodríguez-Marín, F.A. Guzmán-Ortiz, R.N. Falfan-Cortes, Recent advances in microencapsulation of natural sources of antimicrobial compounds used in food – A review, Food Res. Int. 102 (2017) 575–587. https://doi.org/10.1016/j.foodres.2017.09.054.

    Article  CAS  PubMed  Google Scholar 

  161. N. Choudhury, M. Meghwal, K. Das, Microencapsulation: An overview on concepts, methods, properties and applications in foods, Food Front. 2 (2021) 426–442. https://doi.org/10.1002/fft2.94.

    Article  CAS  Google Scholar 

  162. H. Yu, C. Huang, X. Kong, J. Ma, P. Ren, J. Chen, X. Zhang, H. Luo, G. Chen, Nanoarchitectonics of Cartilage-Targeting Hydrogel Microspheres with Reactive Oxygen Species Responsiveness for the Repair of Osteoarthritis, ACS Appl. Mater. Interfaces. 14 (2022) 40711–40723. https://doi.org/10.1021/acsami.2c12703.

    Article  CAS  PubMed  Google Scholar 

  163. R.J. Kulchar, B.R. Denzer, B.M. Chavre, M. Takegami, J. Patterson, A review of the use of microparticles for cartilage tissue engineering, Int. J. Mol. Sci. 22 (2021). https://doi.org/10.3390/ijms221910292.

  164. S. Cosenza, M. Ruiz, K. Toupet, C. Jorgensen, D. Noël, Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis, Sci. Rep. 7 (2017) 1–12. https://doi.org/10.1038/s41598-017-15376-8.

    Article  CAS  Google Scholar 

  165. J. Zhang, X. Zhang, Y. Hong, Q. Fu, Q. He, A. Mechakra, Q. Zhu, F. Zhou, R. Liang, C. Li, Y. Hu, Y. Zou, S. Zhang, H. Ouyang, Tissue-Adhesive Paint of Silk Microparticles for Articular Surface Cartilage Regeneration, ACS Appl. Mater. Interfaces. 12 (2020) 22467–22478. https://doi.org/10.1021/acsami.0c01776.

    Article  CAS  PubMed  Google Scholar 

  166. M. Li, M.J. Mondrinos, X. Chen, M.R. Gandhi, F.K. Ko, P.I. Lelkes, Elastin Blends for Tissue Engineering Scaffolds, J. Biomed. Mater. Res. Part A. 79 (2006) 963–73. https://doi.org/10.1002/jbm.a.

    Article  Google Scholar 

  167. K. Peh, T. Khan, H. Ch’ng, Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing., J. Pharm. Pharm. Sci. 3 (2000) 303–311.

    Google Scholar 

  168. J. Di, S. Yao, Y. Ye, Z. Cui, J. Yu, T.K. Ghosh, Y. Zhu, Z. Gu, Stretch-Triggered Drug Delivery from Wearable Elastomer Films Containing Therapeutic Depots, ACS Nano. 9 (2015) 9407–9415. https://doi.org/10.1021/acsnano.5b03975.

    Article  CAS  PubMed  Google Scholar 

  169. J. Li, W.R.K. Illeperuma, Z. Suo, J.J. Vlassak, Hybrid hydrogels with extremely high stiffness and toughness, ACS Macro Lett. 3 (2014) 520–523. https://doi.org/10.1021/mz5002355.

    Article  CAS  PubMed  Google Scholar 

  170. J. Li, D.J. Mooney, Designing hydrogels for controlled drug delivery, Nat. Rev. Mater. 1 (2016) 1–18. https://doi.org/10.1038/natrevmats.2016.71.

    Article  CAS  Google Scholar 

  171. W. Liu, M. Griffith, F. Li, Alginate microsphere-collagen composite hydrogel for ocular drug delivery and implantation, J. Mater. Sci. Mater. Med. 19 (2008) 3365–3371. https://doi.org/10.1007/s10856-008-3486-2.

    Article  CAS  PubMed  Google Scholar 

  172. L. Yu, J. Ding, Injectable hydrogels as unique biomedical materials, Chem. Soc. Rev. 37 (2008) 1473–1481. https://doi.org/10.1039/b713009k.

    Article  CAS  PubMed  Google Scholar 

  173. T. Nii, 38. Honary, S.; Zahir, F. Effect of zeta potential on the properties of nano-drug delivery systems, Molecules. 26 (2021) 1–45.

    Google Scholar 

  174. K.D. Ngadimin, A. Stokes, P. Gentile, A.M. Ferreira, Biomimetic hydrogels designed for cartilage tissue engineering, Biomater. Sci. 9 (2021) 4246–4259. https://doi.org/10.1039/d0bm01852j.

    Article  CAS  PubMed  Google Scholar 

  175. M.R. Prausnitz, R. Langer, Nihms121685, Nat Biotechnol. 26 (2009) 1261–1268. https://doi.org/10.1038/nbt.1504.Transdermal.

    Article  Google Scholar 

  176. M.T.C. Mccrudden, B.M. Torrisi, M.J. Garland, T. Raghu, R. Singh, R.F. Donnelly, Microneedles for intradermal and transdermal delivery, Eur. J. Pharm. Sci. 50 (2013) 623–637. https://doi.org/10.1016/j.ejps.2013.05.005.Microneedles.

    Article  PubMed  PubMed Central  Google Scholar 

  177. A. Tucak, M. Sirbubalo, L. Hindija, O. Rahić, J. Hadžiabdić, K. Muhamedagić, A. Čekić, E. Vranić, Microneedles: Characteristics, materials, production methods and commercial development, Micromachines. 11 (2020) 1–30. https://doi.org/10.3390/mi11110961.

    Article  Google Scholar 

  178. P.S. Kumbhar, T.P. Jadhav, S.S. Chopade, T.T. Gavade, R.C. Sorate, T.U. Shinde, P.P. Maske, J.I. Disouza, A.S. Manjappa, Microneedles: An advanced approach for transdermal delivery of biologics, Asian J. Pharm. Res. 11 (2021) 46–54. https://doi.org/10.5958/2231-5691.2021.00010.1.

    Article  Google Scholar 

  179. P. Zhou, C. Chen, X. Yue, J. Zhang, C. Huang, S. Zhao, A. Wu, X. Li, Y. Qu, C. Zhang, Strategy for osteoarthritis therapy: Improved the delivery of triptolide using liposome-loaded dissolving microneedle arrays, Int. J. Pharm. 609 (2021) 121211. https://doi.org/10.1016/j.ijpharm.2021.121211.

    Article  CAS  PubMed  Google Scholar 

  180. M. PISUTTANAWAT, S.S. Khuangsirikul, D. Heebthamai, O. Phruetthiphat, T. Chotanaphuti;, Effect of transdermal microneedle patch with NSAID in Osteoarthritis knee, Osteoarthr. Cartil. 28 (2020) S499. https://doi.org/10.1016/j.joca.2020.02.783.

  181. D. Javelaud, A. Mauviel, Mammalian transforming growth factor-βs: Smad signaling and physio-pathological roles, Int. J. Biochem. Cell Biol. 36 (2004) 1161–1165. https://doi.org/10.1016/S1357-2725(03)00255-3.

    Article  CAS  PubMed  Google Scholar 

  182. G.S. Anusuya, M. Kandasamy, S.A.J. Raja, S. Sabarinathan, P. Ravishankar, B. Kandhasamy, Bone morphogenetic proteins: Signaling periodontal bone regeneration and repair, J. Pharm. Bioallied Sci. 8 (2016) S39–S41. https://doi.org/10.4103/0975-7406.191964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. C. Wen, L. Xu, X. Xu, D. Wang, Y. Liang, L. Duan, Insulin-like growth factor-1 in articular cartilage repair for osteoarthritis treatment, Arthritis Res. Ther. 23 (2021). https://doi.org/10.1186/S13075-021-02662-0.

  184. M.J. Cross, J. Dixelius, T. Matsumoto, L. Claesson-Welsh, VEGF-receptor signal transduction, Trends Biochem. Sci. 28 (2003) 488–494. https://doi.org/10.1016/S0968-0004(03)00193-2.

    Article  CAS  PubMed  Google Scholar 

  185. O.K. Hwang, Y.W. Noh, J.T. Hong, J.W. Lee, Hypoxia Pretreatment Promotes Chondrocyte Differentiation of Human Adipose-Derived Stem Cells via Vascular Endothelial Growth Factor, Tissue Eng. Regen. Med. 2020 173. 17 (2020) 335–350. https://doi.org/10.1007/S13770-020-00265-5.

  186. Z. Jia, S. Wang, Y. Liang, Q. Liu, Combination of kartogenin and transforming growth factor-β3 supports synovial fluid-derived mesenchymal stem cell-based cartilage regeneration, Am. J. Transl. Res. 11 (2019) 2056–2069.

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Y. Zhao, B. Teng, X. Sun, Y. Dong, S. Wang, Y. Hu, Z. Wang, X. Ma, Q. Yang, Synergistic Effects of Kartogenin and Transforming Growth Factor-β3 on Chondrogenesis of Human Umbilical Cord Mesenchymal Stem Cells In Vitro, Orthop. Surg. 12 (2020) 938–945. https://doi.org/10.1111/OS.12691.

    Article  PubMed  PubMed Central  Google Scholar 

  188. J. Lin, L. Wang, J. Lin, Q. Liu, W. Lin, L. Zhu, D. Raucher, Dual Delivery of TGF-β3 and Ghrelin in Microsphere/Hydrogel Systems for Cartilage Regeneration, Mol. 2021, Vol. 26, Page 5732. 26 (2021) 5732. https://doi.org/10.3390/MOLECULES26195732.

  189. Y. Li, Y. Liu, Q. Guo, Silk fibroin hydrogel scaffolds incorporated with chitosan nanoparticles repair articular cartilage defects by regulating TGF-β1 and BMP-2, Arthritis Res. Ther. 23 (2021) 1–11. https://doi.org/10.1186/S13075-020-02382-X/FIGURES/6.

    Article  Google Scholar 

  190. T. Zhou, X. Li, G. Li, T. Tian, S. Lin, S. Shi, J. Liao, X. Cai, Y. Lin, Injectable and thermosensitive TGF-β1-loaded PCEC hydrogel system for in vivo cartilage repair, Sci. Reports 2017 71. 7 (2017) 1–13. https://doi.org/10.1038/s41598-017-11322-w.

  191. Y. Chen, T. Wu, S. Huang, C.W.W. Suen, X. Cheng, J. Li, H. Hou, G. She, H. Zhang, H. Wang, X. Zheng, Z. Zha, Sustained Release SDF-1α/TGF-β1-Loaded Silk Fibroin-Porous Gelatin Scaffold Promotes Cartilage Repair, ACS Appl. Mater. Interfaces. 11 (2019) 14608–14618. https://doi.org/10.1021/ACSAMI.9B01532/ASSET/IMAGES/LARGE/AM-2019-015322_0007.JPEG.

    Article  CAS  PubMed  Google Scholar 

  192. T. Wu, Y. Chen, W. Liu, K.L. Tong, C.W.W. Suen, S. Huang, H. Hou, G. She, H. Zhang, X. Zheng, J. Li, Z. Zha, Ginsenoside Rb1/TGF-β1 loaded biodegradable silk fibroin-gelatin porous scaffolds for inflammation inhibition and cartilage regeneration, Mater. Sci. Eng. C. 111 (2020) 110757. https://doi.org/10.1016/J.MSEC.2020.110757.

    Article  CAS  Google Scholar 

  193. W. Ye, Z. Yang, F. Cao, H. Li, T. Zhao, H. Zhang, Z. Zhang, S. Yang, J. Zhu, Z. Liu, J. Zheng, H. Liu, G. Ma, Q. Guo, X. Wang, Articular cartilage reconstruction with TGF-β1-simulating self-assembling peptide hydrogel-based composite scaffold, Acta Biomater. 146 (2022) 94–106. https://doi.org/10.1016/J.ACTBIO.2022.05.012.

    Article  CAS  PubMed  Google Scholar 

  194. R. Vayas, R. Reyes, M.R. Arnau, C. Évora, A. Delgado, Injectable Scaffold for Bone Marrow Stem Cells and Bone Morphogenetic Protein-2 to Repair Cartilage, Cartilage. 12 (2021) 293–306. https://doi.org/10.1177/1947603519841682/ASSET/IMAGES/LARGE/10.1177_1947603519841682-FIG2.JPEG.

    Article  CAS  PubMed  Google Scholar 

  195. T. Taniyama, T. Masaoka, T. Yamada, X. Wei, H. Yasuda, T. Yoshii, Y. Kozaka, T. Takayama, M. Hirano, A. Okawa, S. Sotome, Repair of osteochondral defects in a rabbit model using a porous hydroxyapatite collagen composite impregnated with bone morphogenetic protein-2, Artif. Organs. 39 (2015) 529–535. https://doi.org/10.1111/AOR.12409.

    Article  CAS  PubMed  Google Scholar 

  196. A.C. Kuo, J.J. Rodrigo, A.H. Reddi, S. Curtiss, E. Grotkopp, M. Chiu, Microfracture and bone morphogenetic protein 7 (BMP-7) synergistically stimulate articular cartilage repair, Osteoarthr. Cartil. 14 (2006) 1126–1135. https://doi.org/10.1016/J.JOCA.2006.04.004.

    Article  CAS  Google Scholar 

  197. S. Odabas, G.A. Feichtinger, P. Korkusuz, I. Inci, E. Bilgic, A.S. Yar, T. Cavusoglu, S. Menevse, I. Vargel, E. Piskin, Auricular cartilage repair using cryogel scaffolds loaded with BMP-7-expressing primary chondrocytes, J. Tissue Eng. Regen. Med. 7 (2013) 831–840. https://doi.org/10.1002/TERM.1634.

    Article  CAS  PubMed  Google Scholar 

  198. R. Kuroda, A. Usas, S. Kubo, K. Corsi, H. Peng, T. Rose, J. Cummins, F.H. Fu, J. Huard, Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells, Arthritis Rheum. 54 (2006) 433–442. https://doi.org/10.1002/ART.21632.

    Article  CAS  PubMed  Google Scholar 

  199. H.J. Kim, M.A. Han, J.Y. Shin, J.H. Jeon, S.J. Lee, M.Y. Yoon, H.J. Kim, E.J. Choi, S.H. Do, V.C. Yang, H. He, Y. Il Yang, Intra-articular delivery of synovium-resident mesenchymal stem cells via BMP-7-loaded fibrous PLGA scaffolds for cartilage repair, J. Control. Release. 302 (2019) 169–180. https://doi.org/10.1016/J.JCONREL.2019.04.002.

    Article  CAS  PubMed  Google Scholar 

  200. K. Gavenis, N. Heussen, M. Hofman, S. Andereya, U. Schneider, B. Schmidt-Rohlfing, Cell-free repair of small cartilage defects in the Goettinger minipig: The effects of BMP-7 continuously released by poly(lactic-co-glycolid acid) microspheres, https://doi.org/10.1177/0885328213491440. 28 (2013) 1008–1015. https://doi.org/10.1177/0885328213491440.

  201. H. Wu, Z. Peng, Y. Xu, Z. Sheng, Y. Liu, Y. Liao, Y. Wang, Y. Wen, J. Yi, C. Xie, X. Chen, J. Hu, B. Yan, H. Wang, X. Yao, W. Fu, H. Ouyang, Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development, Stem Cell Res. Ther. 13 (2022) 1–15. https://doi.org/10.1186/S13287-021-02695-X/FIGURES/7.

    Article  Google Scholar 

  202. H. Cho, J. Kim, S. Kim, Y.C. Jung, Y. Wang, B.J. Kang, K. Kim, Dual delivery of stem cells and insulin-like growth factor-1 in coacervate-embedded composite hydrogels for enhanced cartilage regeneration in osteochondral defects, J. Control. Release. 327 (2020) 284–295. https://doi.org/10.1016/J.JCONREL.2020.08.002.

    Article  CAS  PubMed  Google Scholar 

  203. S. Morscheid, J.K. Venkatesan, A. Rey-Rico, M. Cucchiarini, G. Schmitt, Remodeling of Human Osteochondral Defects via rAAV-Mediated Co-Overexpression of TGF-β and IGF-I from Implanted Human Bone Marrow-Derived Mesenchymal Stromal Cells, J. Clin. Med. 2019, Vol. 8, Page 1326. 8 (2019) 1326. https://doi.org/10.3390/JCM8091326.

  204. X.B. Peng, Y. Zhang, Y.Q. Wang, Q. He, Q. Yu, IGF-1 and BMP-7 synergistically stimulate articular cartilage repairing in the rabbit knees by improving chondrogenic differentiation of bone-marrow mesenchymal stem cells, J. Cell. Biochem. 120 (2019) 5570–5582. https://doi.org/10.1002/JCB.27841.

    Article  CAS  PubMed  Google Scholar 

  205. S. Shi, B.J. Kelly, C. Wang, K. Klingler, A. Chan, G.J. Eckert, S.B. Trippel, Human IGF-I propeptide A promotes articular chondrocyte biosynthesis and employs glycosylation-dependent heparin binding, Biochim. Biophys. Acta – Gen. Subj. 1862 (2018) 567–575. https://doi.org/10.1016/J.BBAGEN.2017.11.017.

    Article  Google Scholar 

  206. M.B. Gugjoo, Amarpal, A. Abdelbaset-Ismail, H.P. Aithal, P. Kinjavdekar, A.M. Pawde, G.S. Kumar, G.T. Sharma, Mesenchymal stem cells with IGF-1 and TGF- β1 in laminin gel for osteochondral defects in rabbits, Biomed. Pharmacother. 93 (2017) 1165–1174. https://doi.org/10.1016/J.BIOPHA.2017.07.032.

    Article  CAS  PubMed  Google Scholar 

  207. C. Alemdar, I. Yücel, B. Erbil, H. Erdem, R. Atiç, E. Özku, Effect of insulin-like growth factor-1 and hyaluronic acid in experimentally produced osteochondral defects in rats, Indian J. Orthop. 2016 504. 50 (2016) 414–420. https://doi.org/10.4103/0019-5413.185607.

  208. Z. Zhou, W. Song, G. Zhang, S. Zhan, Z. Cai, W. Yu, Y. He, The recombinant human fibroblast growth factor-18 (sprifermin) improves tendon-to-bone healing by promoting chondrogenesis in a rat rotator cuff repair model, J. Shoulder Elb. Surg. 31 (2022) 1617–1627. https://doi.org/10.1016/J.JSE.2022.01.137.

    Article  Google Scholar 

  209. L.T. Kuhn, T. Peng, G. Gronowicz, M.M. Hurley, Endogenous FGF-2 levels impact FGF-2/BMP-2 growth factor delivery dosing in aged murine calvarial bone defects, J. Biomed. Mater. Res. Part A. 109 (2021) 2545–2555. https://doi.org/10.1002/JBM.A.37249.

    Article  CAS  Google Scholar 

  210. Y.P. Morscheid, J.K. Venkatesan, G. Schmitt, P. Orth, D. Zurakowski, S. Speicher-Mentges, M.D. Menger, M.W. Laschke, M. Cucchiarini, H. Madry, rAAV-Mediated Human FGF-2 Gene Therapy Enhances Osteochondral Repair in a Clinically Relevant Large Animal Model Over Time In Vivo, https://doi.org/10.1177/0363546521988941. 49 (2021) 958–969. https://doi.org/10.1177/0363546521988941.

  211. S. Zhou, Z. Wang, J. Tang, W. Li, J. Huang, W. Xu, F. Luo, M. Xu, J. Wang, X. Wen, L. Chen, H. Chen, N. Su, Y. Shen, X. Du, Y. Xie, L. Chen, Exogenous fibroblast growth factor 9 attenuates cartilage degradation and aggravates osteophyte formation in post-traumatic osteoarthritis, Osteoarthr. Cartil. 24 (2016) 2181–2192. https://doi.org/10.1016/J.JOCA.2016.07.005.

    Article  CAS  Google Scholar 

  212. P. Orth, G. Kaul, M. Cucchiarini, D. Zurakowski, M.D. Menger, D. Kohn, H. Madry, Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo, Knee Surg. Sports Traumatol. Arthrosc. 19 (2011) 2119–2130. https://doi.org/10.1007/S00167-011-1448-6.

    Article  PubMed  Google Scholar 

  213. H. Madry, P. Orth, G. Kaul, D. Zurakowski, M.D. Menger, D. Kohn, M. Cucchiarini, Acceleration of articular cartilage repair by combined gene transfer of human insulin-like growth factor I and fibroblast growth factor-2 in vivo, Arch. Orthop. Trauma Surg. 130 (2010) 1311–1322. https://doi.org/10.1007/S00402-010-1130-3.

    Article  PubMed  Google Scholar 

  214. H. Maehara, S. Sotome, T. Yoshii, I. Torigoe, Y. Kawasaki, Y. Sugata, M. Yuasa, M. Hirano, N. Mochizuki, M. Kikuchi, K. Shinomiya, A. Okawa, Repair of large osteochondral defects in rabbits using porous hydroxyapatite/collagen (HAp/Col) and fibroblast growth factor-2 (FGF-2), J. Orthop. Res. 28 (2010) 677–686. https://doi.org/10.1002/JOR.21032.

    Article  CAS  PubMed  Google Scholar 

  215. J. Ide, K. Kikukawa, J. Hirose, K. ichi Iyama, H. Sakamoto, H. Mizuta, The Effects of Fibroblast Growth Factor-2 on Rotator Cuff Reconstruction With Acellular Dermal Matrix Grafts, Arthrosc. J. Arthrosc. Relat. Surg. 25 (2009) 608–616. https://doi.org/10.1016/J.ARTHRO.2008.11.011.

    Article  Google Scholar 

  216. J.S. Lee, P. Guo, K. Klett, M. Hall, K. Sinha, S. Ravuri, J. Huard, W.L. Murphy, VEGF-attenuated platelet-rich plasma improves therapeutic effect on cartilage repair, Biomater. Sci. 10 (2022) 2172–2181. https://doi.org/10.1039/D1BM01873F.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. H. Utsunomiya, X. Gao, H. Cheng, Z. Deng, G. Nakama, R. Mascarenhas, J.L. Goldman, S.K. Ravuri, J.W. Arner, J.J. Ruzbarsky, W.R. Lowe, M.J. Philippon, J. Huard, Intra-articular Injection of Bevacizumab Enhances Bone Marrow Stimulation–Mediated Cartilage Repair in a Rabbit Osteochondral Defect Model, https://doi.org/10.1177/03635465211005102. 49 (2021) 1871–1882. https://doi.org/10.1177/03635465211005102.

  218. R. Chung, B.K. Foster, C.J. Xian, The potential role of VEGF-induced vascularisation in the bony repair of injured growth plate cartilage, J. Endocrinol. 221 (2014) 63–75. https://doi.org/10.1530/JOE-13-0539.

    Article  CAS  PubMed  Google Scholar 

  219. F. Geiger, H. Bertram, I. Berger, H. Lorenz, O. Wall, C. Eckhardt, H.G. Simank, W. Richter, Vascular endothelial growth factor gene-activated matrix (VEGF165-GAM) enhances osteogenesis and angiogenesis in large segmental bone defects, J. Bone Miner. Res. 20 (2005) 2028–2035. https://doi.org/10.1359/JBMR.050701.

    Article  CAS  PubMed  Google Scholar 

  220. R. Becker, T. Pufe, S. Kulow, N. Giessmann, W. Neumann, R. Mentlein, W. Petersen, Expression of vascular endothelial growth factor during healing of the meniscus in a rabbit model, J. Bone Joint Surg. Br. 86 (2004) 1082–1087. https://doi.org/10.1302/0301-620X.86B7.14349.

    Article  CAS  PubMed  Google Scholar 

  221. T. Tarkka, A. Sipola, T. Jämsä, Y. Soini, S. Ylä-Herttuala, J. Tuukkanen, T. Hautala, Adenoviral VEGF-A gene transfer induces angiogenesis and promotes bone formation in healing osseous tissues, J. Gene Med. 5 (2003) 560–566. https://doi.org/10.1002/JGM.392.

    Article  CAS  PubMed  Google Scholar 

  222. X. Li, G. Su, J. Wang, Z. Zhou, L. Li, L. Liu, M. Guan, Q. Zhang, H. Wang, Exogenous bFGF promotes articular cartilage repair via up-regulation of multiple growth factors, Osteoarthr. Cartil. 21 (2013) 1567–1575. https://doi.org/10.1016/J.JOCA.2013.06.006.

    Article  CAS  Google Scholar 

  223. Y. Hong, N. Liu, R. Zhou, X. Zhao, Y. Han, F. Xia, J. Cheng, M. Duan, Q. Qian, X. Wang, W. Cai, H. Zreiqat, D. Feng, J. Xu, D. Cui, Combination Therapy Using Kartogenin-Based Chondrogenesis and Complex Polymer Scaffold for Cartilage Defect Regeneration, ACS Biomater. Sci. Eng. 6 (2020) 6276–6284. https://doi.org/10.1021/ACSBIOMATERIALS.0C00724.

    Article  CAS  PubMed  Google Scholar 

  224. N. Asgari, F. Bagheri, M.B. Eslaminejad, M.H. Ghanian, F.A. Sayahpour, A.M. Ghafari, Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration, Stem Cell Res. Ther. 11 (2020). https://doi.org/10.1186/S13287-020-01797-2.

  225. W.N. Zeng, Y. Zhang, D. Wang, Y.P. Zeng, H. Yang, J. Li, C.P. Zhou, J.L. Liu, Q.J. Yang, Z.L. Deng, Z.K. Zhou, Intra-articular Injection of Kartogenin-Enhanced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis in a Rat Model, Am. J. Sports Med. 49 (2021) 2795–2809. https://doi.org/10.1177/03635465211023183.

    Article  PubMed  Google Scholar 

  226. B.C. Geiger, A.J. Grodzinsky, P. Hammond, Designing drug delivery systems for articular joints, Chem. Eng. Prog. 114 (2018).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER) – Ahmedabad, Gandhinagar, Gujarat, India

    Akash Yadav & Raghavendra Dhanenawar

  2. Department of Medical Devices, National Institute of Pharmaceutical Education and Research (NIPER) – Ahmedabad, Gandhinagar, Gujarat, India

    Akshay Srivastava

Authors
  1. Akash Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raghavendra Dhanenawar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akshay Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akshay Srivastava .

Editor information

Editors and Affiliations

  1. School of Biosciences & Bioengineering, Indian Institute of Technology Mandi, Mandi, Himachal Pradesh, India

    Sumit Murab

Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yadav, A., Dhanenawar, R., Srivastava, A. (2024). Drug Delivery Systems for Cartilage. In: Murab, S. (eds) Drug Delivery Systems for Musculoskeletal Tissues. Springer, Cham. https://doi.org/10.1007/978-3-031-55653-1_3

Download citation

Publish with us

Policies and ethics

Search

Navigation