Controlled and sustained delivery of siRNA/NPs from hydrogels expedites bone fracture healing

Biomaterials

Volumn 139, Issue , 2017, Pages 127-138

  Wang, Yuchen ^a,b   Malcolm, Dominic W ^a,b   Benoit, Danielle S W ^a,b  

^a University of Rochester   (United States)

^b UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

Drug delivery; Fracture healing; Hydrogels; Nanoparticles; siRNA

Indexed keywords

BIOMECHANICS; BONE; DRUG DELIVERY; FRACTURE; NANOPARTICLES; ORTHOPEDICS; POLYETHYLENE GLYCOLS; RNA;

CONTROLLED RELEASE; FRACTURE HEALING; HYBRID NANOPARTICLE; SIRNA; STRUCTURAL SIMILARITY; THERAPEUTIC EFFICACY; UBIQUITIN-PROTEIN LIGASES; UNTREATED CONTROL;

HYDROGELS;

MACROGOL; NANOPARTICLE; SMALL INTERFERING RNA; UBIQUITIN PROTEIN LIGASE E3; 2-(DIMETHYLAMINO)ETHYL METHACRYLATE; MACROGOL DERIVATIVE; METHACRYLIC ACID DERIVATIVE; UBIQUITIN PROTEIN LIGASE; WWP1 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOMECHANICS; BONE MINERALIZATION; CALLUS; CONTROLLED DRUG RELEASE; CONTROLLED STUDY; CYTOSOL; DRUG EFFICACY; FEMALE; FEMUR DIAPHYSIS; FEMUR FRACTURE; FRACTURE HEALING; GENE; GENE SILENCING; HYDROGEL; IN VIVO STUDY; MOUSE; NONHUMAN; OSSIFICATION; PRIORITY JOURNAL; SUSTAINED DRUG RELEASE; WWP1 GENE; ABSORPTION; ANIMAL; BAGG ALBINO MOUSE; CELL CULTURE; CHEMISTRY; CYTOLOGY; DELAYED RELEASE FORMULATION; DRUG DELIVERY SYSTEM; DRUG EFFECT; FEMUR; GENE KNOCKDOWN; GENETICS; HUMAN; INJURIES; MESENCHYMAL STROMA CELL; METABOLISM; PHARMACOLOGY; TIME FACTOR;

ABSORPTION, PHYSICOCHEMICAL; ANIMALS; BONY CALLUS; CELLS, CULTURED; DELAYED-ACTION PREPARATIONS; DRUG DELIVERY SYSTEMS; FEMALE; FEMORAL FRACTURES; FEMUR; FRACTURE HEALING; GENE KNOCKDOWN TECHNIQUES; GENE SILENCING; HUMANS; HYDROGELS; MESENCHYMAL STROMAL CELLS; METHACRYLATES; MICE; MICE, INBRED BALB C; NANOPARTICLES; POLYETHYLENE GLYCOLS; RNA, SMALL INTERFERING; TIME FACTORS; UBIQUITIN-PROTEIN LIGASES;

EID: 85020297048     PISSN: 01429612     EISSN: 18785905     Source Type: Journal    
DOI: 10.1016/j.biomaterials.2017.06.001     Document Type: Article

References (88)

1. Levy, O., Ruvinov, E., Reem, T., Granot, Y., Cohen, S., Highly efficient osteogenic differentiation of human mesenchymal stem cells by eradication of STAT3 signaling. Int. J. Biochem. Cell Biol. 42 (2010), 1823–1830.
2. Yau, W.W., Rujitanaroj, P.O., Lam, L., Chew, S.Y., Directing stem cell fate by controlled RNA interference. Biomaterials 33 (2012), 2608–2628.
3. Whitehead, K.A., Langer, R., Anderson, D.G., Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8 (2009), 129–138.
4. Wittrup, A., Lieberman, J., Knocking down disease: a progress report on siRNA therapeutics. Nat. Rev. Genet. 16 (2015), 543–552.
5. Aigner, A., Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo. Appl. Microbiol. Biotechnol. 76 (2007), 9–21.
6. Khormaee, S., Choi, Y., Shen, M.J., Xu, B., Wu, H., Griffiths, G.L., et al. Endosomolytic anionic polymer for the cytoplasmic delivery of siRNAs in localized in vivo applications. Adv. Funct. Mater., 2013, 23.
7. Liang, S., Yang, X.Z., Du, X.J., Wang, H.X., Li, H.J., Liu, W.W., et al. Optimizing the size of micellar nanoparticles for efficient siRNA delivery. Adv. Funct. Mater. 25 (2015), 4778–4787.
8. Liu, X., Bone site-specific delivery of siRNA. J. Biomed. Res., 30, 2015.
9. Ghadakzadeh, S., Mekhail, M., Aoude, A., Hamdy, R., Tabrizian, M., Small players ruling the hard game: siRNA in bone regeneration. J. Bone Miner. Res. 31 (2016), 475–487.
10. Andersson, G.B.J., Bouchard, J., Bozic, K.J., Campbell, R.M. Jr., Cisternas, M.G., Correa, A., et al. United States Bone and Joint Decade: the Burden of Musculoskeletal Diseases in the United States. 2008, American Academy of Orthopaedic Surgeons, Rosemont, IL, 97–161.
11. Zhang, G., Guo, B., Wu, H., Tang, T., Zhang, B.T., Zheng, L., et al. A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy. Nat. Med. 18 (2012), 307–314.
12. Zhang, J., Tu, Q., Bonewald, L.F., He, X., Stein, G., Lian, J., et al. Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1. Journal of bone and mineral research. Official J. Am. Soc. Bone Miner. Res. 26 (2011), 1953–1963.
13. Lietman, S.A., Reduction in Gsalpha induces osteogenic differentiation in human mesenchymal stem cells. Clin. Orthop. Relat. Res., 2005, 231–238.
14. Schoolmeesters, A., et al. Functional profiling reveals critical role for miRNA in differentiation of human mesenchymal stem cells. PLoS One, 4, 2009, e5605.
15. Slaughter, B.V., Khurshid, S.S., Fisher, O.Z., Khademhosseini, A., Peppas, N.A., Hydrogels in regenerative medicine. Adv. Mater. 21 (2009), 3307–3329.
16. Shapira, K., Dikovsky, D., Habib, M., Gepstein, L., Seliktar, D., Hydrogels for cardiac tissue regeneration. Bio Med. Mater. Eng. 18 (2008), 309–314.
17. Peppas, N.A., Bures, P., Leobandung, W., Ichikawa, H., Hydrogels in pharmaceutical formulations. European journal of pharmaceutics and biopharmaceutics. Official J. Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik eV 50 (2000), 27–46.
18. Krebs, M.D., Alsberg, E., Localized, targeted, and sustained siRNA delivery. Chemistry 17 (2011), 3054–3062.
19. Nguyen, K., Dang, P.N., Alsberg, E., Functionalized, biodegradable hydrogels for control over sustained and localized siRNA delivery to incorporated and surrounding cells. Acta Biomater. 9 (2013), 4487–4495.
20. Han, H.D., Mora, E.M., Roh, J.W., Nishimura, M., Lee, S.J., Stone, R.L., et al. Chitosan hydrogel for localized gene silencing. Cancer Biol. Ther. 11 (2011), 839–845.
21. Nelson, C.E., Kim, A.J., Adolph, E.J., Gupta, M.K., Yu, F., Hocking, K.M., et al. Tunable delivery of siRNA from a biodegradable scaffold to promote angiogenesis in vivo. Adv. Mater. 26 (2014), 607–614.
22. Kim, Y.M., Park, M.R., Song, S.C., Injectable polyplex hydrogel for localized and long-term delivery of siRNA. ACS Nano 6 (2012), 5757–5766.
23. Zhang, X., Li, Y., Chen, Y.E., Chen, J., Ma, P.X., Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects. Nat. Commun., 7, 2016, 10376.
24. Shu, L., Zhang, H., Boyce, B.F., Xing, L., Ubiquitin E3 ligase Wwp1 negatively regulates osteoblast function by inhibiting osteoblast differentiation and migration. Journal of bone and mineral research. Official J. Am. Soc. Bone Miner. Res. 28 (2013), 1925–1935.
25. Benoit, D.S., Boutin, M.E., Controlling mesenchymal stem cell gene expression using polymer-mediated delivery of siRNA. Biomacromolecules 13 (2012), 3841–3849.
26. Benoit, D.S., Convertine, A.J., Duvall, C.L., Hoffman, A.S., Stayton, P.S., Development of a novel endosomolytic diblock copolymer for siRNA delivery. J. Controll. Release Official J. Control. Release Soc. 133 (2009), 221–229.
27. Malcolm, D.W., Sorrells, J.E., Van Twisk, D., Thakar, J., Benoit, D.S., Evaluating side effects of nanoparticle-mediated siRNA delivery to mesenchymal stem cells using next generation sequencing and enrichment analysis. Bioeng. Transl. Med. 1 (2016), 193–206.
28. D.W. Malcolm, M.A.T. Freeberg, Y. Wang, K.R. Sims, H.A. Awad, and D.S. Benoit,Diblock copolymer hydrophobicity facilitates efficient gene silencing and cytocompatible nanoparticle-mediated siRNA delivery to musculoskeletal cell types. Submitted. 2017.
29. Liu, W., Saint, D.A., A new quantitative method of real time reverse transcription polymerase chain reaction assay based on simulation of polymerase chain reaction kinetics. Anal. Biochem. 302 (2002), 52–59.
30. Pfaffl, M.W., A new mathematical model for relative quantification in real-time RT–PCR. Nucleic Acids Res., 29C, 2001, e45.
31. Hoffman, M.D., Xie, C., Zhang, X., Benoit, D.S., The effect of mesenchymal stem cells delivered via hydrogel-based tissue engineered periosteum on bone allograft healing. Biomaterials 34 (2013), 8887–8898.
32. Hoffman, M.D., Van Hove, A.H., Benoit, D.S., Degradable hydrogels for spatiotemporal control of mesenchymal stem cells localized at decellularized bone allografts. Acta Biomater. 10 (2014), 3431–3441.
33. Fairbanks, B.D., Schwartz, M.P., Bowman, C.N., Anseth, K.S., Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2, 4, 6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials 30 (2009), 6702–6707.
34. Flory, P.J., Rehner, J. Jr., Statistical mechanics of cross-linked polymer networks II. Swelling. J. Chem. Phys. 11 (2004), 521–526.
35. Reynolds, D.G., Shaikh, S., Papuga, M.O., Lerner, A.L., O'Keefe, R.J., Schwarz, E.M., et al. μCT-Based measurement of cortical bone graft-to-host union. J. Bone Miner. Res. 24 (2009), 899–907.
36. Zhang, L., Chang, M., Beck, C.A., Schwarz, E.M., Boyce, B.F., Analysis of new bone, cartilage, and fibrosis tissue in healing murine allografts using whole slide imaging and a new automated histomorphometric algorithm. Bone Res., 4, 2016.
37. Cowin, S.C., Bone Mechanics Handbook. 2001, CRC Press.
38. Reynolds, D.G., Hock, C., Shaikh, S., Jacobson, J., Zhang, X., Rubery, P.T., et al. Micro-computed tomography prediction of biomechanical strength in murine structural bone grafts. J. Biomech. 40 (2007), 3178–3186.
39. Benoit, D.S., Henry, S.M., Shubin, A.D., Hoffman, A.S., Stayton, P.S., pH-responsive polymeric sirna carriers sensitize multidrug resistant ovarian cancer cells to doxorubicin via knockdown of polo-like kinase 1. Mol. Pharm. 7 (2010), 442–455.
40. Arany, S., Benoit, D.S., Dewhurst, S., Ovitt, C.E., Nanoparticle-mediated gene silencing confers radioprotection to salivary glands in vivo. Molecular therapy. J. Am. Soc. Gene Ther. 21 (2013), 1182–1194.
41. Benoit, D.S., Srinivasan, S., Shubin, A.D., Stayton, P.S., Synthesis of folate-functionalized RAFT polymers for targeted siRNA delivery. Biomacromolecules 12 (2011), 2708–2714.
42. Fu, Y., Kao, W.J., Drug release kinetics and transport mechanisms from semi-interpenetrating networks of gelatin and poly (ethylene glycol) diacrylate. Pharm. Res. 26 (2009), 2115–2124.
43. Lin, C.-C., Metters, A.T., Hydrogels in controlled release formulations: network design and mathematical modeling. Adv. drug Deliv. Rev. 58 (2006), 1379–1408.
44. Zustiak, S.P., Leach, J.B., Hydrolytically degradable poly (ethylene glycol) hydrogel scaffolds with tunable degradation and mechanical properties. Biomacromolecules 11 (2010), 1348–1357.
45. Granéli, C., Thorfve, A., Ruetschi, U., Brisby, H., Thomsen, P., Lindahl, A., et al. Novel markers of osteogenic and adipogenic differentiation of human bone marrow stromal cells identified using a quantitative proteomics approach. Stem Cell Res. 12 (2014), 153–165.
46. Harwood, P.J., Newman, J.B., Michael, A.L., An update on fracture healing and non-union. Orthop. Trauma 24 (2010), 9–23.
47. Jahagirdar, R., Scammell, B.E., Principles of fracture healing and disorders of bone union. Surg. Oxf. 27 (2009), 63–69.
48. Newman, M.R., Benoit, D.S., Local and targeted drug delivery for bone regeneration. Curr. Opin. Biotechnol. 40 (2016), 125–132.
49. Hadjiargyrou, M., O'Keefe, R.J., The convergence of fracture repair and stem cells: interplay of genes, aging, environmental factors and disease. Journal of bone and mineral research. Official J. Am. Soc. Bone Miner. Res. 29 (2014), 2307–2322.
50. Wang, J., Lu, Z., Wientjes, M.G., Au, J.L.-S., Delivery of siRNA therapeutics: barriers and carriers. AAPS J. 12 (2010), 492–503.
51. Van de Water, F.M., Boerman, O.C., Wouterse, A.C., Peters, J.G., Russel, F.G., Masereeuw, R., Intravenously administered short interfering RNA accumulates in the kidney and selectively suppresses gene function in renal proximal tubules. Drug metabol. Dispos. 34 (2006), 1393–1397.
52. Castanotto, D., Rossi, J.J., The promises and pitfalls of RNA-interference-based therapeutics. Nature 457 (2009), 426–433.
53. Soutschek, J., Akinc, A., Bramlage, B., Charisse, K., Constien, R., Donoghue, M., et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432 (2004), 173–178.
54. Lorenzer, C., Dirin, M., Winkler, A.-M., Baumann, V., Winkler, J., Going beyond the liver: progress and challenges of targeted delivery of siRNA therapeutics. J. Contr. Release 203 (2015), 1–15.
55. Chao, L., Zhang, G., Guo, B.S., Wu, H., Zhang, L.Q., Lu, A.P., Aptamer-functionalized lipid nanoparticles (LNPs) targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. J. Bone Miner. Res. 29 (2014), S36–S38.
56. Sun, Y., Ye, X., Cai, M., Liu, X., Xiao, J., Zhang, C., et al. Osteoblast-targeting-peptide modified nanoparticle for siRNA/microRNA delivery. ACS Nano, 2016.
57. Li, B.-j., Tang, Q., Cheng, D., Qin, C., Xie, F.Y., Wei, Q., et al. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque. Nat. Med. 11 (2005), 944–951.
58. DiFiglia, M., Sena-Esteves, M., Chase, K., Sapp, E., Pfister, E., Sass, M., et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc. Natl. Acad. Sci. 104 (2007), 17204–17209.
59. Tan, P., Yang, L., Shih, H., Lan, K., Cheng, J., Gene knockdown with intrathecal siRNA of NMDA receptor NR2B subunit reduces formalin-induced nociception in the rat. Gene Ther. 12 (2005), 59–66.
60. Lingor, P., Koeberle, P., Kügler, S., Bähr, M., Down-regulation of apoptosis mediators by RNAi inhibits axotomy-induced retinal ganglion cell death in vivo. Brain: J. Neurol. 128 (2005), 550–558.
61. Arany, S., Xu, Q., Hernady, E., Benoit, D.S., Dewhurst, S., Ovitt, C.E., Pro-apoptotic gene knockdown mediated by nanocomplexed siRNA reduces radiation damage in primary salivary gland cultures. J. Cell. Biochem. 113 (2012), 1955–1965.
62. Xue, H.Y., Liu, S., Wong, H.L., Nanotoxicity: a key obstacle to clinical translation of siRNA-based nanomedicine. Nanomed. Nanotechnol. Biol. Med. 9 (2014), 295–312.
63. Landesman-Milo, D., Peer, D., Toxicity profiling of several common RNAi-based nanomedicines: a comparative study. Drug Deliv. Transl. Res. 4 (2014), 96–103.
64. Tokatlian, T., Cam, C., Siegman, S.N., Lei, Y., Segura, T., Design and characterization of microporous hyaluronic acid hydrogels for in vitro gene transfer to mMSCs. Acta Biomater. 8 (2012), 3921–3931.
65. Gerecht, S., Burdick, J.A., Ferreira, L.S., Townsend, S.A., Langer, R., Vunjak-Novakovic, G., Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 11298–11303.
66. Sun, G., Zhang, X., Shen, Y.I., Sebastian, R., Dickinson, L.E., Fox-Talbot, K., et al. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 20976–20981.
67. Kisiday, J., Jin, M., Kurz, B., Hung, H., Semino, C., Zhang, S., et al. Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: implications for cartilage tissue repair. Proc. Natl. Acad. Sci. U. S. A. 99 (2002), 9996–10001.
68. Holloway, J.L., Spiller, K.L., Lowman, A.M., Palmese, G.R., Analysis of the in vitro swelling behavior of poly(vinyl alcohol) hydrogels in osmotic pressure solution for soft tissue replacement. Acta Biomater. 7 (2011), 2477–2482.
69. Studenovska, H., Slouf, M., Rypacek, F., Poly(HEMA) hydrogels with controlled pore architecture for tissue regeneration applications. J. Mater. Sci. Mater. Med. 19 (2008), 615–621.
70. Hoffman, M.D., Benoit, D.S., Emulating native periosteum cell population and subsequent paracrine factor production to promote tissue engineered periosteum-mediated allograft healing. Biomaterials 52 (2015), 426–440.
71. Van Hove, A.H., Beltejar, M.J., Benoit, D.S., Development and in vitro assessment of enzymatically-responsive poly(ethylene glycol) hydrogels for the delivery of therapeutic peptides. Biomaterials 35 (2014), 9719–9730.
72. Shubin, A.D., Felong, T.J., Graunke, D., Ovitt, C.E., Benoit, D.S., Development of poly(ethylene glycol) hydrogels for salivary gland tissue engineering applications. Tissue Eng. Part A 21 (2015), 1733–1751.
73. Ashley, G.W., Henise, J., Reid, R., Santi, D.V., Hydrogel drug delivery system with predictable and tunable drug release and degradation rates. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 2318–2323.
74. Shubin, A.D., Felong, T.J., Schutrum, B.E., SLJ, D., Ovitt, C.E., SWB, D., Encapsulation of primary salivary gland cells in enzymatically degradable poly(ethylene glycol) hydrogels promotes acinar cell characteristics. Acta Biomater., 2016.
75. Van Hove, A.H., Wilson, B.D., Benoit, D.S., Microwave-assisted functionalization of poly(ethylene glycol) and on-resin peptides for use in chain polymerizations and hydrogel formation. Journal of visualized experiments. JoVE, 2013, e50890.
76. Van Hove, A.H., Burke, K., Antonienko, E., Brown, E. 3rd, Benoit, D.S., Enzymatically-responsive pro-angiogenic peptide-releasing poly(ethylene glycol) hydrogels promote vascularization in vivo. Journal of controlled release. Official J. Control. Release Soc. 217 (2015), 191–201.
77. Fairbanks, B.D., Schwartz, M.P., Halevi, A.E., Nuttelman, C.R., Bowman, C.N., Anseth, K.S., A versatile synthetic extracellular matrix mimic via thiol-norbornene photopolymerization. Adv. Mater. 21 (2009), 5005–5010.
78. Hsu, C.W., Olabisi, R.M., Olmsted-Davis, E.A., Davis, A.R., West, J.L., Cathepsin K-sensitive poly (ethylene glycol) hydrogels for degradation in response to bone resorption. J. Biomed. Mater. Res. Part A 98 (2011), 53–62.
79. Einhorn, T.A., Gerstenfeld, L.C., Fracture healing: mechanisms and interventions. Nat. Rev. Rheumatol. 11 (2015), 45–54.
80. Bishop, G.B., Einhorn, T.A., Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery. Int. Orthop. 31 (2007), 721–727.
81. Benglis, D., Wang, M.Y., Levi, A.D., A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery. Neurosurgery 62 (2008), ONS423–ONS431.
82. Shen, J., Velasco, O., Khadarian, K., Asatrian, G., Hwang, A., Zhang, Y., et al. A mouse femoral defect model demonstrates the clinically relevant side effects of BMP-2. Int. J. Orthop. 2 (2015), 468–475.
83. Bhandari, D., Robia, S.L., Marchese, A., The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction. Mol. Biol. Cell 20 (2009), 1324–1339.
84. Rapp, A.E., Bindl, R., Recknagel, S., Erbacher, A., Müller, I., Schrezenmeier, H., et al. Fracture healing is delayed in immunodeficient NOD/scid- IL2Rγ c null Mice. PLoS One, 11, 2016, e0147465.
85. Zhi, X., Chen, C., WWP1: a versatile ubiquitin E3 ligase in signaling and diseases. Cellular and molecular life sciences. CMLS 69 (2012), 1425–1434.
86. Lam, J.K., Chow, M.Y., Zhang, Y., Leung, S.W., siRNA versus miRNA as therapeutics for gene silencing. Mol. Ther. Nucleic Acids, 4, 2015, e252.
87. Price, S., Bone: novel microRNA expressed in osteoblasts promotes bone formation. Nat. Rev. Rheumatol., 6, 2010, 64.
88. Li, Y., Fan, L., Liu, S., Liu, W., Zhang, H., Zhou, T., et al. The promotion of bone regeneration through positive regulation of angiogenic–osteogenic coupling using microRNA-26a. Biomaterials 34 (2013), 5048–5058.