Biodegradable polymers: an update on drug delivery in bone and cartilage diseases

References

• Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003;81(9):646–656.
   PubMed Web of Science ®Google Scholar
• Zhang S, Xing M, Li B. Recent advances in musculoskeletal local drug delivery. Acta Biomater. 2019;19:30063–30067.
   Google Scholar
• Briggs AM, Woolf AD, Dreinhofer K, et al. Reducing the global burden of musculoskeletal conditions. Bull World Health Organ. 2018;96(5):366–368.
   PubMed Web of Science ®Google Scholar
• Liu M, Zeng X, Ma C, et al. Injectable hydrogels for cartilage and bone tissue engineering. Bone Res. 2017;5:17014.
   PubMed Web of Science ®Google Scholar
• Alford AI, Kozloff KM, Hankenson KD. Extracellular matrix networks in bone remodeling. Int J Biochem Cell Biol. 2015;65:20–31.
   PubMed Web of Science ®Google Scholar
• Okamoto K, Nakashima T, Shinohara M, et al. Osteoimmunology: the conceptual framework unifying the immune and skeletal systems. Physiol Rev. 2017;97(4):1295–1349.
   PubMed Web of Science ®Google Scholar
• Goldring SR, Goldring MB. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk. Nat Rev Rheumatol. 2016;12(11):632–644.
   PubMed Web of Science ®Google Scholar
• Lagasse HA, Alexaki A, Simhadri VL, et al. Recent advances in (therapeutic protein) drug development. F1000Res. 2017;6:113.
   PubMedGoogle Scholar
• Caspi RR. Immunotherapy of autoimmunity and cancer: the penalty for success. Nat Rev Immunol. 2008;8(12):970–976.
   PubMed Web of Science ®Google Scholar
• Cui Y, Cui P, Chen B, et al. Monoclonal antibodies: formulations of marketed products and recent advances in novel delivery system. Drug Dev Ind Pharm. 2017;43(4):519–530.
   PubMed Web of Science ®Google Scholar
• Mitragotri S, Burke PA, Langer R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat Rev Drug Discov. 2014;13(9):655–672.
   PubMed Web of Science ®Google Scholar
• Awwad S, Angkawinitwong U. Overview of antibody drug delivery. Pharmaceutics. 2018;10(3):1–24.
   Web of Science ®Google Scholar
• Yin H, Kanasty RL, Eltoukhy AA, et al. Non-viral vectors for gene-based therapy. Nat Rev Genet. 2014;15(8):541–555.
   PubMed Web of Science ®Google Scholar
• Evans CH, Huard J. Gene therapy approaches to regenerating the musculoskeletal system. Nat Rev Rheumatol. 2015;11(4):234–242.
   PubMed Web of Science ®Google Scholar
• Grol MW, Lee BH. Gene therapy for repair and regeneration of bone and cartilage. Curr Opin Pharmacol. 2018;40:59–66.
   PubMed Web of Science ®Google Scholar
• Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303(5665):1818–1822.
   PubMed Web of Science ®Google Scholar
• Strebhardt K, Ullrich A. Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat Rev Cancer. 2008;8(6):473–480.
   PubMed Web of Science ®Google Scholar
• Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases. 2007;2(4):MR17–MR71.
   PubMed Web of Science ®Google Scholar
• Whatmore RW. Nanotechnology—what is it? Should we be worried? Occup Med (Lond). 2006;56(5):295–299.
   PubMed Web of Science ®Google Scholar
• Filipponi L, Sutherland D. EUR 24957 NANOTECHNOLOGIES: principles, applications, implications and hands-on activities. A compendium for educators. Luxembourg: Publications Office of the European Union; 2013.
   Google Scholar
• Bawa R, Bawa SR, Maebius SB, et al. Protecting new ideas and inventions in nanomedicine with patents. Nanomedicine. 2005;1(2):150–158.
   PubMed Web of Science ®Google Scholar
• Lövestam G, Rauscher H, Roebben G, et al. Considerations on a definition of nanomaterial for regulatory purposes. Luxembourg: Publications Office of the European Union; 2010.
   Google Scholar
• Qureshi ZP, Seoane-Vazquez E, Rodriguez-Monguio R, et al. Market withdrawal of new molecular entities approved in the United States from 1980 to 2009. Pharmacoepidemiol Drug Saf. 2011;20:772–777.
   PubMed Web of Science ®Google Scholar
• Kaitin KI, DiMasi JA. Pharmaceutical Innovation in the 21st century: new drug approvals in the first decade, 2000–2009. Clin Pharmacol Ther. 2011;89(2):183–188.
   PubMed Web of Science ®Google Scholar
• Silva R, Ferreira H, Cavaco-Paulo A. Sonoproduction of liposomes and protein particles as templates for delivery purposes. Biomacromolecules. 2011;12:3353–3368.
   PubMed Web of Science ®Google Scholar
• Liechty WB, Kryscio DR, Slaughter BV, et al. Polymers for drug delivery systems. Annu Rev Chem Biomol Eng. 2010;1(1):149–173.
   PubMedGoogle Scholar
• Kost J, Langer R. Responsive polymeric delivery systems. Adv Drug Deliv Rev. 2012;64:327–341.
   Web of Science ®Google Scholar
• Martins A, Ferreira H, Reis RL, et al. Delivery systems made of natural-origin polymers for tissue engineering and regenerative medicine applications. In: Neves NM, Reis, RL, editors. Biomaterials from Nature for Advanced Devices and Therapies. New Jersey (NJ): John Wiley & Sons, Inc; 2016. p. 581-611.
   Google Scholar
• Nair LS, Laurencin CT. Biodegradable polymers as biomaterials. Prog Polym Sci. 2007;32(8):762–798.
   Web of Science ®Google Scholar
• Cartaxo AL, Costa-Pinto AR, Martins A, et al. Influence of PDLA nanoparticles size on drug release and interaction with cells. J Biomed Mater Res A. 2019;107(3):482–493.
   PubMed Web of Science ®Google Scholar
• Faraday M. The bakerian lecture: experimental relations of gold (and other metals) to light. Philos Trans R Soc Lond. 1847;147:159.
   Google Scholar
• Bazylińska U, Lewińska A, Lamch Ł, et al. Polymeric nanocapsules and nanospheres for encapsulation and long sustained release of hydrophobic cyanine-type photosensitizer. Colloids Surf A Physicochem Eng Asp. 2014;442:42–49.
   Web of Science ®Google Scholar
• Deshmukh AS, Chauhan PN, Noolvi MN, et al. Polymeric micelles: basic research to clinical practice. Int J Pharmaceut. 2017;532(1):249–268.
   PubMed Web of Science ®Google Scholar
• McBain JW. Mobility of highly charged micelles. Trans. Faraday Soc. 1913;9:99.
   Google Scholar
• Sherje AP, Jadhav M, Dravyakar BR, et al. Dendrimers: A versatile nanocarrier for drug delivery and targeting. Int J Pharmaceut. 2018;548(1):707–720.
   PubMed Web of Science ®Google Scholar
• Buhleier E, Wehner W, Vogtle F. Cascade-chain-like and nonskid-chain-like syntheses of molecular cavity topologies. Synthesis-Stuttgart. 1978;2:155–158.
   Web of Science ®Google Scholar
• Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8(1):102.
   PubMed Web of Science ®Google Scholar
• Bangham AD, Horne RW. Negative staining of phospholipids + their structural modification by-surface active agents as observed in electron microscope. J Mol Biol. 1964;8(5):660.
   PubMed Web of Science ®Google Scholar
• Hadinoto K, Sundaresan A, Cheow WS. Lipid–polymer hybrid nanoparticles as a new generation therapeutic delivery platform: A review. Eur J Pharm Biopharm. 2013;85(3,Part A):427–443.
   PubMed Web of Science ®Google Scholar
• Torchilin VP. Drug targeting. Eur J Pharm Sci. 2000;11:S81–S91.
   PubMed Web of Science ®Google Scholar
• Farrell KB, Karpeisky A, Thamm DH, et al. Bisphosphonate conjugation for bone specific drug targeting. Bone Rep. 2018;9:47–60.
   PubMedGoogle Scholar
• Rotman SG, Grijpma DW, Richards RG, et al. Drug delivery systems functionalized with bone mineral seeking agents for bone targeted therapeutics. J Control Release. 2018;269:88–99.
   PubMed Web of Science ®Google Scholar
• Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008;83(9):1032–1045.
   PubMed Web of Science ®Google Scholar
• Russell RGG. Bisphosphonates: mode of action and pharmacology. Pediatrics. 2007;119(Supplement 2):S150–S162.
   PubMedGoogle Scholar
• Sangaonkar GM, Pawar KD. Garcinia indica mediated biogenic synthesis of silver nanoparticles with antibacterial and antioxidant activities. Colloids Surf B. 2018;164:210–217.
   PubMed Web of Science ®Google Scholar
• Xie Y, Tan X, Huang J, et al. Atorvastatin-loaded micelles with bone-targeted ligand for the treatment of osteoporosis. Drug Deliv. 2017;24(1):1067–1076.
   PubMed Web of Science ®Google Scholar
• Perrin DD. Binding of tetracyclines to bone. Nature. 1965;208(5012):787–788.
   PubMed Web of Science ®Google Scholar
• Wang H, Liu J, Tao S, et al. Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system. Int J Nanomed. 2015;10:5671–5685.
   PubMed Web of Science ®Google Scholar
• Cheng W, Yue Y, Fan W, et al. Effects of tetracyclines on bones: an ambiguous question needs to be clarified. Pharmazie. 2012;67(5):457–459.
   PubMed Web of Science ®Google Scholar
• Bhan A, Qiu S, Rao SD. Bone histomorphometry in the evaluation of osteomalacia. Bone Rep. 2018;8:125–134.
   PubMedGoogle Scholar
• Payne JB, Golub LM. Using tetracyclines to treat osteoporotic/osteopenic bone loss: from the basic science laboratory to the clinic. Pharmacol Res. 2011;63(2):121–129.
   PubMed Web of Science ®Google Scholar
• Zhang G, Guo B, Wu H, et al. A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nat Med. 2012;18(2):307–314.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Wei L, Miron RJ, et al. Anabolic bone formation via a site-specific bone-targeting delivery system by interfering with semaphorin 4D expression. J Bone Miner Res. 2015;30(2):286–296.
   PubMed Web of Science ®Google Scholar
• Wang X, Yang Y, Jia H, et al. Peptide decoration of nanovehicles to achieve active targeting and pathology-responsive cellular uptake for bone metastasis chemotherapy. Biomater Sci. 2014;2(7):961–971.
   PubMed Web of Science ®Google Scholar
• Wang Y, Yang J, Liu H, et al. Osteotropic peptide-mediated bone targeting for photothermal treatment of bone tumors. Biomaterials. 2017;114:97–105.
   PubMed Web of Science ®Google Scholar
• Tavafoghi M, Cerruti M. The role of amino acids in hydroxyapatite mineralization. J R Soc Interface. 2016;13(123):20160462.
   Web of Science ®Google Scholar
• Wang D, Miller SC, Shlyakhtenko LS, et al. Osteotropic peptide that differentiates functional domains of the skeleton. Bioconjugate Chem. 2007;18(5):1375–1378.
   PubMed Web of Science ®Google Scholar
• Wang D, Sima M, Mosley RL, et al. Pharmacokinetic and biodistribution studies of a bone-targeting drug delivery system based on N-(2-hydroxypropyl)methacrylamide copolymers. Mol Pharm. 2006;3(6):717–725.
   PubMed Web of Science ®Google Scholar
• Yarbrough DK, Hagerman E, Eckert R, et al. Specific binding and mineralization of calcified surfaces by small peptides. Calcif Tissue Int. 2010;86(1):58–66.
   PubMed Web of Science ®Google Scholar
• Sun Y, Ye X, Cai M, et al. Osteoblast-targeting-peptide modified nanoparticle for siRNA/microRNA delivery. Acs Nano. 2016;10(6):5759–5768.
   PubMed Web of Science ®Google Scholar
• Stapleton M, Sawamoto K, Almeciga-Diaz CJ, et al. Development of bone targeting drugs. Int J Mol Sci. 2017;18(7):1345.
   PubMed Web of Science ®Google Scholar
• Liang C, Guo B, Wu H, et al. Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference–based bone anabolic strategy. Nat Med. 2015;21:288.
   PubMed Web of Science ®Google Scholar
• Evans CH, Kraus VB, Setton LA. Progress in intra-articular therapy. Nat Rev Rheumatol. 2014;10(1):11–22.
   PubMed Web of Science ®Google Scholar
• Giannoni P, Narcisi R. Nano-approaches in cartilage repair. J Appl Biomater Biomech.2009;7(1):1–12.
   Google Scholar
• Ng L, Grodzinsky AJ, Patwari P, et al. Individual cartilage aggrecan macromolecules and their constituent glycosaminoglycans visualized via atomic force microscopy. J Struct Biol. 2003;143(3):242–257.
   PubMed Web of Science ®Google Scholar
• Bajpayee AG, Wong CR, Bawendi MG, et al. Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis. Biomaterials. 2014;35(1):538–549.
   PubMed Web of Science ®Google Scholar
• Elsaid KA, Ferreira L, Truong T, et al. Pharmaceutical nanocarrier association with chondrocytes and cartilage explants: influence of surface modification and extracellular matrix depletion. Osteoarthr Cartilage. 2013;21(2):377–384.
   PubMed Web of Science ®Google Scholar
• Rothenfluh DA, Bermudez H, O’Neil CP, et al. Biofunctional polymer nanoparticles for intra-articular targeting and retention in cartilage. Nat Mater. 2008;7:248.
   PubMed Web of Science ®Google Scholar
• Torchilin VP. Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers. Adv Drug Deliv Rev. 2008;60(4–5):548–558.
   PubMed Web of Science ®Google Scholar
• Cheung CS, Lui JC, Baron J. Identification of chondrocyte-binding peptides by phage display. J Orthop Res. 2013;31(7):1053–1058.
   PubMed Web of Science ®Google Scholar
• Loffredo FS, Pancoast JR, Cai L, et al. Targeted delivery to cartilage is critical for in vivo efficacy of insulin-like growth factor 1 in a rat model of osteoarthritis. Arthritis Rheumatol. 2014;66(5):1247–1255.
   PubMed Web of Science ®Google Scholar
• Chen M, Daddy JCK, Xiao Y, et al. Advanced nanomedicine for rheumatoid arthritis treatment: focus on active targeting. Expert Opin Drug Deliv. 2017;14(10):1141–1144.
   PubMed Web of Science ®Google Scholar
• Yuan FL, Li X, Lu WG, et al. Epidermal growth factor receptor (EGFR) as a therapeutic target in rheumatoid arthritis. Clin Rheumatol. 2013;32(3):289–292.
   PubMed Web of Science ®Google Scholar
• Leblond A, Allanore Y, Avouac J. Targeting synovial neoangiogenesis in rheumatoid arthritis. Autoimmun Rev. 2017;16(6):594–601.
   PubMed Web of Science ®Google Scholar
• Varghese B, Vlashi E, Xia W, et al. Folate receptor-beta in activated macrophages: ligand binding and receptor recycling kinetics. Mol Pharm. 2014;11(10):3609–3616.
   PubMedGoogle Scholar
• Graversen JH, Svendsen P, Dagnaes-Hansen F, et al. Targeting the hemoglobin scavenger receptor CD163 in macrophages highly increases the anti-inflammatory potency of dexamethasone. Mol Ther. 2012;20(8):1550–1558.
   PubMed Web of Science ®Google Scholar
• Kamperidis P, Kamalati T, Ferrari M, et al. Development of a novel recombinant biotherapeutic with applications in targeted therapy of human arthritis. Arthritis Rheum. 2011;63(12):3758–3767.
   PubMed Web of Science ®Google Scholar
• Sullivan T, Benjamin CG, Kempf PW, et al. Cetuximab in the treatment of rheumatoid arthritis. J Clin Rheumatol. 2010;16(1):32–33.
   PubMed Web of Science ®Google Scholar
• Martins IM, Reis RL, Azevedo HS. Phage display technology in biomaterials engineering: progress and opportunities for applications in regenerative medicine. ACS Chem Biol. 2016;11(11):2962–2980.
   PubMed Web of Science ®Google Scholar
• Delgado M, Abad C, Martinez C, et al. Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases. J Mol Med (Berl). 2002;80(1):16–24.
   PubMed Web of Science ®Google Scholar
• Bar-Shavit Z, Stabinsky Y, Fridkin M, et al. Tuftsin-macrophage interaction: specific binding and augmentation of phagocytosis. J Cell Physiol. 1979;100(1):55–62.
   PubMed Web of Science ®Google Scholar
• Mi Z, Lu X, Mai JC, et al. Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium. Mol Ther. 2003;8(2):295–305.
   PubMed Web of Science ®Google Scholar
• Li Z, Zhao R, Wu X, et al. Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics. Faseb J. 2005;19(14):1978–1985.
   PubMed Web of Science ®Google Scholar
• Tu KN, Lie JD, Wan CKV, et al. Osteoporosis: a review of treatment options. P T. 2018;43(2):92–104.
   PubMedGoogle Scholar
• Rosen CJ. The epidemiology and pathogenesis of osteoporosis. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext. South Dartmouth (MA): MDText.com, Inc.; 2000.
   Google Scholar
• Boche M, Pokharkar V. Positive effect of alendronate on bone turnover in ovariectomised rats’ osteoporosis: comparison of transdermal lipid-based delivery with conventional oral administration. Drug Deliv Transl Res. 2018;8(5):1078–1089.
   PubMed Web of Science ®Google Scholar
• Rawat P, Manglani K, Gupta S, et al. Design and development of bioceramic based functionalized PLGA nanoparticles of risedronate for bone targeting: in-vitro characterization and pharmacodynamic evaluation. Pharm Res-Dordr. 2015;32(10):3149–3158.
   PubMed Web of Science ®Google Scholar
• Rawat P, Ahmad I, Thomas SC, et al. Revisiting bone targeting potential of novel hydroxyapatite based surface modified PLGA nanoparticles of risedronate: pharmacokinetic and biochemical assessment. Int J Pharmaceut. 2016;506(1–2):253–261.
   PubMed Web of Science ®Google Scholar
• Dave JR, Dewle AM, Mhaske ST, et al. Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy. Nanomedicine. 2019;15(1):218–230.
   PubMed Web of Science ®Google Scholar
• Yang Y, Aghazadeh-Habashi A, Panahifar A, et al. Bone-targeting parathyroid hormone conjugates outperform unmodified PTH in the anabolic treatment of osteoporosis in rats. Drug Deliv Transl Res. 2017;7(4):482–496.
   PubMed Web of Science ®Google Scholar
• Dang M, Koh AJ, Jin X, et al. Local pulsatile PTH delivery regenerates bone defects via enhanced bone remodeling in a cell-free scaffold. Biomaterials. 2017;114:1–9.
   PubMed Web of Science ®Google Scholar
• Quinlan E, Thompson EM, Matsiko A, et al. Functionalization of a collagen-hydroxyapatite scaffold with osteostatin to facilitate enhanced bone regeneration. Adv Healthc Mater. 2015;4(17):2649–2656.
   PubMed Web of Science ®Google Scholar
• Lv BH, Tan W, Zhu CC, et al. Properties of a stable and sustained-release formulation of Recombinant Human Parathyroid Hormone (rhPTH) with chitosan and silk fibroin microparticles. Med Sci Monit. 2018;24:7532–7540.
   PubMed Web of Science ®Google Scholar
• Baskaran R, Lee CJ, Kang SM, et al. Poly(lactic-co-glycolic acid) microspheres containing a Recombinant Parathyroid Hormone (1-34) for sustained release in a rat model. Indian J Pharm Sci. 2018;80(5):837–843.
   Web of Science ®Google Scholar
• Naito C, Katsumi H, Suzuki T, et al. Self-dissolving microneedle arrays for transdermal absorption enhancement of human parathyroid hormone (1-34). Pharmaceutics. 2018;10(4):215.
   PubMed Web of Science ®Google Scholar
• Ji X, Chen X, Yu XJ. MicroRNAs in osteoclastogenesis and function: potential therapeutic targets for osteoporosis. Int J Mol Sci. 2016;17(3):349.
   Web of Science ®Google Scholar
• Cai M, Yang L, Zhang S, et al. A bone-resorption surface-targeting nanoparticle to deliver anti-miR214 for osteoporosis therapy. Int J Nanomed. 2017;12:7469–7482.
   PubMed Web of Science ®Google Scholar
• Zhang YF, Wei LF, Miron RJ, et al. Anabolic bone formation via a site-specific bone-targeting delivery system by interfering with semaphorin 4D expression. J Bone Miner Res. 2015;30(2):286–296.
   PubMed Web of Science ®Google Scholar
• Yang K, Miron RJ, Bian Z, et al. A bone-targeting drug-delivery system based on Semaphorin 3A gene therapy ameliorates bone loss in osteoporotic ovariectomized mice. Bone. 2018;114:40–49.
   PubMed Web of Science ®Google Scholar
• Zhu HM, Qin L, Garnero P, et al. The first multicenter and randomized clinical trial of herbal Fufang for treatment of postmenopausal osteoporosis. Osteoporos Int. 2012;23(4):1317–1327.
   PubMed Web of Science ®Google Scholar
• Zhang G, Qin L, Shi Y. Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial. J Bone Miner Res. 2007;22(7):1072–1079.
   PubMed Web of Science ®Google Scholar
• Sun X, Wei J, Lyu J, et al. Bone-targeting drug delivery system of biomineral-binding liposomes loaded with icariin enhances the treatment for osteoporosis. J Nanobiotechnology. 2019;17(1):10.
   PubMed Web of Science ®Google Scholar
• Huang L, Wang X, Cao H, et al. A bone-targeting delivery system carrying osteogenic phytomolecule icaritin prevents osteoporosis in mice. Biomaterials. 2018;182:58–71.
   PubMed Web of Science ®Google Scholar
• Brennan-Olsen SL, Cook S, Leech MT, et al. Prevalence of arthritis according to age, sex and socioeconomic status in six low and middle income countries: analysis of data from the World Health Organization study on global AGEing and adult health (SAGE) Wave 1. Bmc Musculoskel Dis. 2017;18(1):271–283.
   PubMed Web of Science ®Google Scholar
• Theis KA, Roblin DW, Helmick CG, et al. Prevalence and causes of work disability among working-age US adults, 2011-2013, NHIS. Disabil Health J. 2018;11(1):108–115.
   PubMed Web of Science ®Google Scholar
• Eichaker LR, Cho HS, Duvall CL, et al. Future nanomedicine for the diagnosis and treatment of osteoarthritis. Nanomedicine-Uk. 2014;9(14):2203–2215.
   PubMed Web of Science ®Google Scholar
• Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023–2038.
   PubMed Web of Science ®Google Scholar
• Pap T, Korb-Pap A. Cartilage damage in osteoarthritis and rheumatoid arthritis-two unequal siblings. Nat Rev Rheumatol. 2015;11(10):606–615.
   PubMed Web of Science ®Google Scholar
• Krishnan Y, Grodzinsky AJ. Cartilage diseases. Matrix Biol. 2018;71–72:51–69.
   PubMed Web of Science ®Google Scholar
• Jones IA, Togashi R, Wilson ML, et al. Intra-articular treatment options for knee osteoarthritis. Nat Rev Rheumatol. 2019;15(2):77–90.
   PubMed Web of Science ®Google Scholar
• Maudens P, Jordan O, Allemann E. Recent advances in intra-articular drug delivery systems for osteoarthritis therapy. Drug Discov Today. 2018;23(10):1761–1775.
   PubMed Web of Science ®Google Scholar
• Wang Q, Li Y, Chen XY, et al. Optimized in vivo performance of acid-liable micelles for the treatment of rheumatoid arthritis by one single injection. Nano Res. 2019;12(2):421–428.
   Web of Science ®Google Scholar
• Zhang N, Xu CY, Li N, et al. Folate receptor-targeted mixed polysialic acid micelles for combating rheumatoid arthritis: in vitro and in vivo evaluation. Drug Deliv. 2018;25(1):1182–1191.
   PubMed Web of Science ®Google Scholar
• Assali M, Shawahna R, Dayyeh S, et al. Dexamethasone-diclofenac loaded polylactide nanoparticles: preparation, release and anti-inflammatory activity. Eur J Pharm Sci. 2018;122:179–184.
   PubMed Web of Science ®Google Scholar
• Chiesa E, Pisani S, Colzani B, et al. Intra-articular formulation of GE11-PLGA conjugate-based NPs for dexamethasone selective targeting-in vitro evaluation. Int J Mol Sci. 2018;19(8):2304.
   Web of Science ®Google Scholar
• Colzani B, Speranza G, Dorati R, et al. Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs: synthesis, preparation and in vitro/ex vivo characterization. Int J Pharmaceut. 2016;511(2):1112–1123.
   PubMed Web of Science ®Google Scholar
• Vanniasinghe AS, Manolios N, Schibeci S, et al. Targeting fibroblast-like synovial cells at sites of inflammation with peptide targeted liposomes results in inhibition of experimental arthritis. Clin Immunol. 2014;151(1):43–54.
   PubMed Web of Science ®Google Scholar
• Kumar A, Bendele AM, Blanks RC, et al. Sustained efficacy of a single intra-articular dose of FX006 in a rat model of repeated localized knee arthritis. Osteoarthr Cartilage. 2015;23(1):151–160.
   PubMed Web of Science ®Google Scholar
• Bodick N, Lufkin J, Willwerth C, et al. Prolonged joint residency of triamcinolone acetonide after an intra-articular injection of FX006, a sustained release formulation for the treatment of osteoarthritis. Osteoarthr Cartilage. 2015;23:A360–A361.
   Web of Science ®Google Scholar
• Bodick N, Lufkin J, Willwerth C, et al. An intra-articular, extended-release formulation of triamcinolone acetonide prolongs and amplifies analgesic effect in patients with osteoarthritis of the knee: a randomized clinical trial. J Bone Joint Surg Am. 2015;97(11):877–888.
   PubMed Web of Science ®Google Scholar
• Conaghan P, Strand V, Hunter D, et al. an intra-articular, extended release formulation of triamcinolone (FX006) affords clinically relevant improvements in pain and function of knee osteoarthritis: post-hoc pooled analyses of 3 randomized controlled trials. Osteoarthr Cartilage. 2017;25:S432–S433.
   Web of Science ®Google Scholar
• Joshi N, Yan J, Levy S, et al. Towards an arthritis flare-responsive drug delivery system. Nat Commun. 2018;9(1):1275.
   Web of Science ®Google Scholar
• Yang MD, Ding JX, Feng XR, et al. Scavenger receptor-mediated targeted treatment of collagen-induced arthritis by dextran sulfate-methotrexate prodrug. Theranostics. 2017;7(1):97–105.
   PubMed Web of Science ®Google Scholar
• Yang MD, Ding JX, Zhang Y, et al. Activated macrophage-targeted dextran-methotrexate/folate conjugate prevents deterioration of collagen-induced arthritis in mice. J Mater Chem B. 2016;4(12):2102–2113.
   PubMed Web of Science ®Google Scholar
• Xu XL, Li WS, Wang XJ, et al. Endogenous sialic acid-engineered micelles: a multifunctional platform for on-demand methotrexate delivery and bone repair of rheumatoid arthritis. Nanoscale. 2018;10(6):2923–2935.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Zhou Y, Chen H, et al. The efficacy and safety of certolizumab pegol (CZP) in the treatment of active rheumatoid arthritis (RA): a meta-analysis from nine randomized controlled trials. Int J Clin Exp Med. 2014;7(11):3870–3880.
   PubMed Web of Science ®Google Scholar
• Horton S, Walsh C, Emery P. Certolizumab pegol for the treatment of rheumatoid arthritis. Expert Opin Biol Ther. 2012;12(2):235–249.
   PubMed Web of Science ®Google Scholar
• Lee H, Lee MY, Bhang SH, et al. Hyaluronate-gold nanoparticle/tocilizumab complex for the treatment of rheumatoid arthritis. Acs Nano. 2014;8(5):4790–4798.
   PubMed Web of Science ®Google Scholar
• Lima AC, Cunha C, Carvalho A, et al. Interleukin-6 Neutralization by Antibodies Immobilized at the Surface of Polymeric Nanoparticles as a Therapeutic Strategy for Arthritic Diseases. Acs Appl Mater Inter. 2018;10(16):13839–13850.
   PubMed Web of Science ®Google Scholar
• Giulbudagian M, Yealland G, Honzke S, et al. Breaking the barrier - potent anti-inflammatory activity following efficient topical delivery of etanercept using thermoresponsive nanogels. Theranostics. 2018;8(2):450–463.
   PubMed Web of Science ®Google Scholar
• Aldayel AM, O’Mary HL, Valdes SA, et al. Lipid nanoparticles with minimum burst release of TNF-alpha siRNA show strong activity against rheumatoid arthritis unresponsive to methotrexate. J Control Release. 2018;283:280–289.
   PubMed Web of Science ®Google Scholar
• Jain S, Tran TH, Amiji M. Macrophage repolarization with targeted alginate nanoparticles containing IL-10 plasmid DNA for the treatment of experimental arthritis. Biomaterials. 2015;61:162–177.
   PubMed Web of Science ®Google Scholar
• Fan Z, Li J, Liu J, et al. Anti-inflammation and joint lubrication dual effects of a novel hyaluronic acid/curcumin nanomicelle improve the efficacy of rheumatoid arthritis therapy. ACS Appl Mater Interfaces. 2018;10(28):23595–23604.
   PubMed Web of Science ®Google Scholar
• American Cancer Society. Facts & figures. Atlanta, Ga: American Cancer Society; 2019.
   Google Scholar
• Croucher PI, McDonald MM, Martin TJ. Bone metastasis: the importance of the neighbourhood. Nat Rev Cancer. 2016;16:373.
   PubMed Web of Science ®Google Scholar
• Abarrategi A, Tornin J, Martinez-Cruzado L, et al. Osteosarcoma: cells-of-origin, cancer stem cells, and targeted therapies. Stem Cells Int. 2016;2016:3631764.
   PubMed Web of Science ®Google Scholar
• Gui K, Zhang X, Chen F, et al. Lipid-polymer nanoparticles with CD133 aptamers for targeted delivery of all-trans retinoic acid to osteosarcoma initiating cells. Biomed Pharmacother. 2019;111:751–764.
   PubMed Web of Science ®Google Scholar
• Feng S, Wu Z-X, Zhao Z, et al. Engineering of bone- and CD44-dual-targeting redox-sensitive liposomes for the treatment of orthotopic osteosarcoma. Acs Appl Mater Inter. 2019;11(7):7357–7368.
   PubMed Web of Science ®Google Scholar
• Magalhães M, Almeida M, Tavares-da-Silva E, et al. miR-145-loaded micelleplexes as a novel therapeutic strategy to inhibit proliferation and migration of osteosarcoma cells. Eur J Pharm Sci. 2018;123:28–42.
   PubMed Web of Science ®Google Scholar
• Grünewald TGP, Cidre-Aranaz F, Surdez D, et al. Ewing sarcoma. Nat Rev Dis Primers. 2018;4(1):5.
   PubMedGoogle Scholar
• Rao DD, Jay C, Wang Z, et al. Preclinical justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing’s Sarcoma. Mol Ther. 2016;24(8):1412–1422.
   PubMed Web of Science ®Google Scholar
• Kang MH, Wang J, Makena MR, et al. Activity of MM-398, nanoliposomal irinotecan (nal-IRI), in Ewing’s family tumor xenografts is associated with high exposure of tumor to drug and high SLFN11 expression. Clin Cancer Res. 2015;21(5):1139–1150.
   PubMed Web of Science ®Google Scholar
• Chu W, Huang Y, Yang C, et al. Calcium phosphate nanoparticles functionalized with alendronate-conjugated polyethylene glycol (PEG) for the treatment of bone metastasis. Int J Pharmaceut. 2017;516(1):352–363.
   PubMed Web of Science ®Google Scholar
• Wang M, Cai X, Yang J, et al. A targeted and pH-responsive bortezomib nanomedicine in the treatment of metastatic bone tumors. Acs Appl Mater Inter. 2018;10(48):41003–41011.
   PubMed Web of Science ®Google Scholar
• Petriceks AH, Salmi D. Educational case: primary osteosarcoma. Acad Pathol. 2019;6:2374289518820337.
   Web of Science ®Google Scholar
• Jamil N, Howie S, Salter DM. Therapeutic molecular targets in human chondrosarcoma. Int J Exp Pathol. 2010;91(5):387–393.
   PubMed Web of Science ®Google Scholar
• Boehme KA, Schleicher SB, Traub F, et al. Chondrosarcoma: a rare misfortune in aging human cartilage? the role of stem and progenitor cells in proliferation, malignant degeneration and therapeutic resistance. Int J Mol Sci. 2018;19(1):311.
   PubMed Web of Science ®Google Scholar
• Peyrode C, Weber V, Voissière A, et al. Proteoglycans as target for an innovative therapeutic approach in chondrosarcoma: preclinical proof of concept. Mol Cancer Ther. 2016;15(11):2575–2585.
   PubMed Web of Science ®Google Scholar
• Mithoefer K, McAdams T, Williams RJ, et al. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: anevidence-based systematic analysis. Am J Sports Med. 2009;37(10):2053–2063.
   PubMed Web of Science ®Google Scholar
• Steadman JR, Rodkey WG, Briggs KK. Microfracture to treat full-thickness chondral defects: surgical technique, rehabilitation, and outcomes. J Knee Surg. 2002;15(3):170–176.
   PubMedGoogle Scholar
• Ahmad J, Jones K. Comparison of osteochondral autografts and allografts for treatment of recurrent or large talar osteochondral lesions. Foot Ankle Int. 2016;37(1):40–50.
   PubMed Web of Science ®Google Scholar
• Hangody L, Dobos J, Balo E, et al. Clinical experiences with autologous osteochondral mosaicplasty in an athletic population: a 17-year prospective multicenter study. Am J Sports Med. 2010;38(6):1125–1133.
   PubMed Web of Science ®Google Scholar
• Levy YD, Gortz S, Pulido PA, et al. Do fresh osteochondral allografts successfully treat femoral condyle lesions? Clin Orthop Relat Res. 2013;471(1):231–237.
   PubMed Web of Science ®Google Scholar
• Klement M, Luzzi AJ, Siddiqi A, et al. Intra-articular corticosteroid injection following total knee arthroplasty: is it effective? J Arthroplasty. 2018;34(2):303–308.
   PubMed Web of Science ®Google Scholar
• Rönn K, Reischl N, Gautier E, et al. Current surgical treatment of knee osteoarthritis. Arthritis. 2011;2011:454873.
   PubMedGoogle Scholar
• Wylde V, Dieppe P, Hewlett S, et al. Total knee replacement: is it really an effective procedure for all? Knee. 2007;14(6):417–423.
   PubMed Web of Science ®Google Scholar
• Steinwachs MR, Guggi T, Kreuz PC. Marrow stimulation techniques. Injury. 2008;39(Suppl 1):S26–31.
   PubMedGoogle Scholar
• Filardo G, Kon E, Perdisa F, et al. Autologous osteochondral transplantation for the treatment of knee lesions: results and limitations at two years’ follow-up. Int Orthop. 2014;38(9):1905–1912.
   PubMed Web of Science ®Google Scholar
• Mistry H, Connock M, Pink J, et al. Autologous chondrocyte implantation in the knee: systematic review and economic evaluation. 2017.
   Google Scholar
• Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994;331(14):889–895.
   PubMed Web of Science ®Google Scholar
• Gille J, Behrens P, Schulz AP, et al. Matrix-associated autologous chondrocyte implantation: a clinical follow-up at 15 years. Cartilage. 2016;7(4):309–315.
   PubMed Web of Science ®Google Scholar
• Marlovits S, Striessnig G, Kutscha-Lissberg F, et al. Early postoperative adherence of matrix-induced autologous chondrocyte implantation for the treatment of full-thickness cartilage defects of the femoral condyle. Knee Surg Sports Traumatol Arthrosc. 2005;13(6):451–457.
   PubMed Web of Science ®Google Scholar
• Brix MO, Stelzeneder D, Chiari C, et al. Treatment of full-thickness chondral defects with hyalograft c in the knee: long-term results. Am J Sports Med. 2014;42(6):1426–1432.
   PubMed Web of Science ®Google Scholar
• Filardo G, Andriolo L, Balboni F, et al. Cartilage failures. Systematic literature review, critical survey analysis, and definition. Knee Surg Sports Traumatol Arthrosc. 2015;23(12):3660–3669.
   PubMed Web of Science ®Google Scholar
• Gobbi A, Karnatzikos G, Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med. 2014;42(3):648–657.
   PubMed Web of Science ®Google Scholar
• Kon E, Filardo G. A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years. Knee Surg Sports Traumatol Arthrosc. 2018;26(9):2704–2715.
   PubMed Web of Science ®Google Scholar
• Kon E, Filardo G, Perdisa F, et al. A one-step treatment for chondral and osteochondral knee defects: clinical results of a biomimetic scaffold implantation at 2 years of follow-up. J Mater Sci Mater Med. 2014;25(10):2437–2444.
   PubMed Web of Science ®Google Scholar
• Costa-Pinto AR, Correlo VM, Sol PC, et al. Chitosan–poly(butylene succinate) scaffolds and human bone marrow stromal cells induce bone repair in a mouse calvaria model. J Tissue Eng Regen M. 2012;6(1):21–28.
   PubMed Web of Science ®Google Scholar
• Shive MS, Stanish WD, McCormack R, et al. BST-CarGel® treatment maintains cartilage repair superiority over microfracture at 5 years in a multicenter randomized controlled trial. Cartilage. 2015;6(2):62–72.
   PubMed Web of Science ®Google Scholar
• Pina S, Canadas RF, Jimenez G, et al. Biofunctional ionic-doped calcium phosphates: silk fibroin composites for bone tissue engineering scaffolding. Cells Tissues Organs. 2017;204(3–4):150–163.
   PubMed Web of Science ®Google Scholar
• Ribeiro JFM, Oliveira SM, Alves JL, et al. Structural monitoring and modeling of the mechanical deformation of three-dimensional printed poly(epsilon-caprolactone) scaffolds. Biofabrication. 2017;9(2):025015.
   PubMed Web of Science ®Google Scholar
• Canadas RF, Ren T, Marques AP, et al. Biochemical gradients to generate 3D heterotypic-like tissues with isotropic and anisotropic architectures. Adv Funct Mater. 2018;28(48):1804148.
   Web of Science ®Google Scholar
• Malafaya PB, Reis RL. Bilayered chitosan-based scaffolds for osteochondral tissue engineering: influence of hydroxyapatite on in vitro cytotoxicity and dynamic bioactivity studies in a specific double-chamber bioreactor. Acta Biomater. 2009;5(2):644–660.
   PubMed Web of Science ®Google Scholar
• Faia-Torres AB, Charnley M, Goren T, et al. Osteogenic differentiation of human mesenchymal stem cells in the absence of osteogenic supplements: A surface-roughness gradient study. Acta Biomater. 2015;28:64–75.
   PubMed Web of Science ®Google Scholar
• Faia-Torres AB, Guimond-Lischer S, Rottmar M, et al. Differential regulation of osteogenic differentiation of stem cells on surface roughness gradients. Biomaterials. 2014;35(33):9023–9032.
   PubMed Web of Science ®Google Scholar
• Robotti F, Bottan S, Fraschetti F, et al. A micron-scale surface topography design reducing cell adhesion to implanted materials. Sci Rep-Uk. 2018;8(1):10887.
   PubMedGoogle Scholar
• Rostam HM, Singh S, Salazar F, et al. The impact of surface chemistry modification on macrophage polarisation. Immunobiology. 2016;221(11):1237–1246.
   PubMed Web of Science ®Google Scholar
• McNally AK, Anderson JM. Phenotypic expression in human monocyte-derived interleukin-4-induced foreign body giant cells and macrophages in vitro: dependence on material surface properties. J Biomed Mater Res A. 2015;103(4):1380–1390.
   PubMed Web of Science ®Google Scholar
• Bao X, Zhu L, Huang X, et al. 3D biomimetic artificial bone scaffolds with dual-cytokines spatiotemporal delivery for large weight-bearing bone defect repair. Sci Rep-Uk. 2017;7(1):7814.
   PubMedGoogle Scholar
• Zhang X, Li Y, Chen YE, et al. Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects. Nat Commun. 2016;7:10376.
   PubMed Web of Science ®Google Scholar
• Birt MC, Anderson DW, Toby EB, et al. Osteomyelitis: recent advances in pathophysiology and therapeutic strategies. J Orthop. 2017;14(1):45–52.
   PubMed Web of Science ®Google Scholar
• Nandi SK, Bandyopadhyay S, Das P, et al. Understanding osteomyelitis and its treatment through local drug delivery system. Biotechnol Adv. 2016;34(8):1305–1317.
   PubMed Web of Science ®Google Scholar
• Dorati R, DeTrizio A, Modena T, et al. Biodegradable scaffolds for bone regeneration combined with drug-delivery systems in osteomyelitis therapy. Pharmaceuticals. 2017;10(4):96.
   Web of Science ®Google Scholar
• Hassani Besheli N, Mottaghitalab F, Eslami M, et al. Sustainable release of vancomycin from silk fibroin nanoparticles for treating severe bone infection in rat tibia osteomyelitis model. Acs Appl Mater Inter. 2017;9(6):5128–5138.
   PubMed Web of Science ®Google Scholar
• Dorati R, De Trizio A, Genta I, et al. Formulation and in vitro characterization of a composite biodegradable scaffold as antibiotic delivery system and regenerative device for bone. J Drug Deliv Sci Technol. 2016;35:124–133.
   Google Scholar
• Dorati R, De Trizio A, Genta I, et al. Gentamicin-loaded thermosetting hydrogel and moldable composite scaffold: formulation study and biologic evaluation. J Pharm Sci-Us. 2017;106(6):1596–1607.
   PubMed Web of Science ®Google Scholar
• Ter Boo GA, Arens D, Metsemakers WJ, et al. Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model. Acta Biomater. 2016;43:185–194.
   PubMed Web of Science ®Google Scholar
• Wang C, Hou W, Guo X, et al. Two-phase electrospinning to incorporate growth factors loaded chitosan nanoparticles into electrospun fibrous scaffolds for bioactivity retention and cartilage regeneration. Mater Sci Eng C Mater Biol Appl. 2017;79:507–515.
   PubMed Web of Science ®Google Scholar
• Man Z, Yin L, Shao Z, et al. The effects of co-delivery of BMSC-affinity peptide and rhTGF-β1 from coaxial electrospun scaffolds on chondrogenic differentiation. Biomaterials. 2014;35(19):5250–5260.
   PubMed Web of Science ®Google Scholar
• Huang H, Zhang X, Hu X, et al. A functional biphasic biomaterial homing mesenchymal stem cells for in vivo cartilage regeneration. Biomaterials. 2014;35(36):9608–9619.
   PubMed Web of Science ®Google Scholar
• Sridhar BV, Brock JL, Silver JS, et al. Development of a cellularly degradable PEG hydrogel to promote articular cartilage extracellular matrix deposition. Adv Healthc Mater. 2015;4(5):702–713.
   PubMed Web of Science ®Google Scholar
• Gugjoo MB, Amarpal, Abdelbaset-Ismail A, et al. Mesenchymal stem cells with IGF-1 and TGF- β1 in laminin gel for osteochondral defects in rabbits. Biomed Pharmacother. 2017;93:1165–1174.
   PubMed Web of Science ®Google Scholar
• Hung K-C, Tseng C-S, Dai L-G, et al. Water-based polyurethane 3D printed scaffolds with controlled release function for customized cartilage tissue engineering. Biomaterials. 2016;83:156–168.
   PubMed Web of Science ®Google Scholar
• Chen P, Tao J, Zhu S, et al. Radially oriented collagen scaffold with SDF-1 promotes osteochondral repair by facilitating cell homing. Biomaterials. 2015;39:114–123.
   PubMed Web of Science ®Google Scholar
• Algul D, Gokce A, Onal A, et al. In vitro release and In vivo biocompatibility studies of biomimetic multilayered alginate-chitosan/β-TCP scaffold for osteochondral tissue. J Biomater Sci Polym Ed. 2016;27(5):431–440.
   PubMed Web of Science ®Google Scholar
• Lu S, Lam J, Trachtenberg JE, et al. Dual growth factor delivery from bilayered, biodegradable hydrogel composites for spatially-guided osteochondral tissue repair. Biomaterials. 2014;35(31):8829–8839.
   PubMed Web of Science ®Google Scholar
• Lee Y-H, Wu H-C, Yeh C-W, et al. Enzyme-crosslinked gene-activated matrix for the induction of mesenchymal stem cells in osteochondral tissue regeneration. Acta Biomater. 2017;63:210–226.
   PubMed Web of Science ®Google Scholar
• Needham CJ, Shah SR, Dahlin RL, et al. Osteochondral tissue regeneration through polymeric delivery of DNA encoding for the SOX trio and RUNX2. Acta Biomater. 2014;10(10):4103–4112.
   PubMed Web of Science ®Google Scholar
• Wang W, Sun L, Zhang P, et al. An anti-inflammatory cell-free collagen/resveratrol scaffold for repairing osteochondral defects in rabbits. Acta Biomater. 2014;10(12):4983–4995
   PubMed Web of Science ®Google Scholar