Adhesive liposomes loaded onto an injectable, self-healing and antibacterial hydrogel for promoting bone reconstruction
Source abstract
Abstract
Abstract Loading hydrogels with bioactive agents is an important method for expanding the functional application of hydrogels. However, how to improve the local administration and slow release of drugs from a hydrogel is a challenge when using hydrogels loaded with drugs. In this paper, we first developed adhesive liposomes (A-LIP) loaded with BMP-2. Then, we incorporated the A-LIP into PEG hydrogels based on the coordinated cross-linking principle of SH-PEG and Ag+, fabricating an injectable, antibacterial and self-healing multifunctional drug delivery system. The adhesive lipo-hydrogel (A-LIP-PEG) fabricated by mixing PEG hydrogels and adhesive liposomes can be locally injected into an osteoporotic fracture and bone marrow cavity, where A-LIP-PEG can release adhesive liposomes that adhere to the bone injury area and promote bone reconstruction. Based on the principle of electrostatic attraction, tissue nonspecific A-LIP were fabricated by grafting octadecylamine onto liposomes. Because of the coordination and cross-linking of thiolated polyethylene (SH-PEG) and Ag+, the A-LIP-PEG showed excellent injectability and self-healing properties; further, because of the presence of Ag+, the A-LIP-PEG showed effective inhibition of S. aureus and Escherichia coli. The liposomes released by the A-LIP-PEG were able to adhere to tissue. In vitro studies showed that A-LIP-PEG significantly promoted osteogenic differentiation and had no significant effect on cell proliferation. Compared with common lipo-hydrogel (LIP-PEG), the A-LIP-PEG had better tissue adhesion in vivo, which led to better osteogenic differentiation and faster local bone remodeling of osteoporotic fractures in rats. This research developed a novel hydrogel system with adhesive liposomes to expand the application of hydrogels.
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Research context
OpenAlex topics: 3D Printing in Biomedical Research · Hydrogels: synthesis, properties, applications · Nanoparticle-Based Drug Delivery
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (53)
Show source-provided references
1. Kim, B. & Mooney, D. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol. 16, 224 (1998).10.1016/S0167-7799(98)01191-3 ↗
2. Kim, S. H. et al. Hydrogel-laden paper scaffold system for origami-based tissue engineering. Proc. Natl Acad. Sci. USA 112, 15426–15431 (2015).10.1073/pnas.1504745112 ↗
3. Khademhosseini, A. & Langer, R. Microengineered hydrogels for tissue engineering. Biomaterials 28, 5087–5092 (2007).10.1016/j.biomaterials.2007.07.021 ↗
4. Fan, Z. et al. A new class of biological materials: cell membrane-derived hydrogel scaffolds. Biomaterials 197, 244–254 (2019).10.1016/j.biomaterials.2019.01.020 ↗
5. Yu, Y. et al. Nanostructured lipid carrier-based pH and temperature dual-responsive hydrogel composed of carboxymethyl chitosan and poloxamer for drug delivery. Int. J. Biol. Macromol. 114, 462–469 (2018).10.1016/j.ijbiomac.2018.03.117 ↗
6. Hong, S. et al. Supramolecular metallo-bioadhesive for minimally invasive use. Adv. Mater. 28, 8675–8680 (2016).10.1002/adma.201602606 ↗
7. Wang, K. & Han, Z. Injectable hydrogels for ophthalmic applications. J. Control. Release 268, 212–224 (2017).10.1016/j.jconrel.2017.10.031 ↗
8. Hsieh, F. Y. et al. Non-viral delivery of an optogenetic tool into cells with self-healing hydrogel. Biomaterials 174, 31–40 (2018).10.1016/j.biomaterials.2018.05.014 ↗
9. Gan, D. et al. Mussel‐inspired contact‐active antibacterial hydrogel with high cell affinity, toughness, and recoverability. Adv. Funct. Mater. 29, 1805964 (2019).10.1002/adfm.201805964 ↗
10. Derycke, A. S. L. Witte PAMD. Liposomes for photodynamic therapy. Adv. Drug Deliv. Rev. 56, 17–30 (2004).10.1016/j.addr.2003.07.014 ↗
11. Gradauer, K. et al. Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats. J. Control. Release 172, 872–878 (2013).10.1016/j.jconrel.2013.10.011 ↗
12. Kim, K., Kim, K., Ryu, J. H. & Lee, H. Chitosan-catechol: a polymer with long-lasting mucoadhesive properties. Biomaterials 52, 161–170 (2015).10.1016/j.biomaterials.2015.02.010 ↗
13. Ponchel, G. & Irache, J. M. Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv. Drug Deliv. Rev. 34, 191–219 (1998).10.1016/S0169-409X(98)00040-4 ↗
14. Lavelle, E. C., Grant, G., Pusztai, A., Pfüller, U. & O’Hagan, D. T. Mucosal immunogenicity of plant lectins in mice. Immunology 99, 30–37 (2000).10.1046/j.1365-2567.2000.00932.x ↗
15. Miyake, K., Tanaka, T. & McNeil, P. L. Lectin-based food poisoning: a new mechanism of protein toxicity. PLoS ONE. 2, e687 (2007).10.1371/journal.pone.0000687 ↗
16. Lee, S. et al. Enhanced therapeutic neovascularization by CD31-expressing cells and embryonic stem cell-derived endothelial cells engineered with chitosan hydrogel containing VEGF-releasing microtubes. Biomaterials 63, 158–167 (2015).10.1016/j.biomaterials.2015.06.009 ↗
17. Yue, K. et al. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials 73, 254–271 (2015).10.1016/j.biomaterials.2015.08.045 ↗
18. He, Q., Huang, Y. & Wang, S. Hofmeister effect-assisted one step fabrication of ductile and strong gelatin hydrogels. Adv. Funct. Mater. 28, 1705069 (2018).10.1002/adfm.201705069 ↗
19. Cheng, R. et al. Mechanically enhanced lipo-hydrogel with controlled release of multi-type drugs for bone regeneration. Appl. Mater. Today 12, 294–308 (2018).10.1016/j.apmt.2018.06.008 ↗
20. Pérez-San, V. A. et al. Self-healing dynamic hydrogel as injectable shock-absorbing artificial nucleus pulposus. Biomacromolecules 18, 2360–2370 (2017).10.1021/acs.biomac.7b00566 ↗
21. Cummings, S. R. & Melton, L. J. Epidemiology and outcomes of osteoporotic fractures. Lancet 359, 1761–1767 (2002).10.1016/S0140-6736(02)08657-9 ↗
22. Li, Y., He, S., Hua, Y. & Hu, J. Effect of osteoporosis on fixation of osseointegrated implants in rats. J. Biomed. Mater. Res. B Appl. Biomater. 105, 2426–2432 (2016).10.1002/jbm.b.33787 ↗
23. Becker, W, Hujoel, P. P., Becker, B. E. & Willingham, H. Osteoporosis and implant failure: an exploratory case-control study. J. Periodontol. 71, 625–631 (2000).10.1902/jop.2000.71.4.625 ↗
24. Barbu, H. M. et al. Dental implant placement in patients with osteoporosis. J. Craniofac. Surg. 26, e558 (2015).10.1097/SCS.0000000000001958 ↗
25. Bertoni, S. et al. pH and reactive oxygen species-sequential responsive nano-in-micro composite for targeted therapy of inflammatory bowel disease. Adv. Funct. Mater. 28, 1806175 (2018).10.1002/adfm.201806175 ↗
26. Guo, J. et al. Development of tannin-inspired antimicrobial bioadhesives. Acta Biomater. 72, 35–44 (2018).10.1016/j.actbio.2018.03.008 ↗
27. Guo, J. et al. Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives. Biomaterials 85, 204–217 (2016).10.1016/j.biomaterials.2016.01.069 ↗
28. Tan, L. et al. Rapid biofilm eradication on bone implants using red phosphorus and near-infrared light. Adv. Mater. 30, 1801808 (2018).10.1002/adma.201801808 ↗
29. Li, Y. et al. Eradicating multidrug-resistant bacteria rapidly using a multi functional g-C3N4@ Bi2S3 nanorod heterojunction with or without antibiotics. Adv. Funct. Mater. 29, 1900946 (2019).10.1002/adfm.201900946 ↗
30. Quan, H. et al. Chemical self-assembly of multi-functional hydroxyapatite with coral-like nanostructure for osteoporotic bone reconstruction. ACS Appl. Mater. Interfaces 10, 25547–25560 (2018).10.1021/acsami.8b09879 ↗
31. Low, S. A., Galliford, C. V., Jiyuan, Y., Low, P. S. & Kopeček, J. Biodistribution of fracture-targeted GSK3β inhibitor-loaded micelles for improved fracture healing. Biomacromolecules 16, 3145 (2015).10.1021/acs.biomac.5b00777 ↗
32. Jia, Z. et al. Simvastatin prodrug micelles target fracture and improve healing. J. Control. Release 200, 23–34 (2015).10.1016/j.jconrel.2014.12.028 ↗
33. Hauptstein, S., Dezorzi, S., Prüfert, F., Matuszczak, B. & Bernkop-Schnürch, A. Synthesis and in vitro characterization of a novel S-protected thiolated alginate. Carbohydr. Polym. 124, 1–7 (2015).10.1016/j.carbpol.2015.01.049 ↗
34. Chen, H. et al. The potential use of novel chitosan-coated deformable liposomes in an ocular drug delivery system. Colloids Surf. B Biointerfaces 143, 455–462 (2016).10.1016/j.colsurfb.2016.03.061 ↗
35. Hoogenboom, R., Schubert, U., Fischer, D. C. & Knop, F. K. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew. Chem. Int. Ed. Engl. 42, 6288–6308 (2011).
36. Lee, A. L. Z., Ng, V. W. L., Gao, S., Hedrick, J. L. & Yang, Y. Y. Injectable hydrogels from triblock copolymers of vitamin E-functionalized polycarbonate and poly(ethylene glycol) for subcutaneous delivery of antibodies for cancer therapy. Adv. Funct. Mater. 24, 1538–1550 (2014).10.1002/adfm.201301307 ↗
37. Dimatteo, R., Darling, N. J. & Segura, T. In situ forming injectable hydrogels for drug delivery and wound repair. Adv. Drug Deliv. Rev. 127, 167–184 (2018).10.1016/j.addr.2018.03.007 ↗
38. Li, L., Yan, B., Yang, J., Chen, L. & Zeng, H. Novel mussel-inspired injectable self-healing hydrogel with anti-biofouling property. Adv. Mater. 27, 1294–1299 (2015).10.1002/adma.201405166 ↗
39. Tseng, T.-C. et al. An injectable, self-healing hydrogel to repair the central nervous system. Adv. Mater. 27, 3518–3524 (2015).10.1002/adma.201500762 ↗
40. Hsu, R. S. et al. Adaptable microporous hydrogels of propagating NGF-gradient by injectable building blocks for accelerated axonal outgrowth. Adv. Sci. 6, 1900520 (2019).
41. Chen, H. et al. An injectable self-healing coordinative hydrogel with antibacterial and angiogenic properties for diabetic skin wound repair. NPG Asia Mater. 11, 3 (2019).
42. Wang, H. et al. Cell-laden photocrosslinked GelMA–DexMA copolymer hydrogels with tunable mechanical properties for tissue engineering. J. Mater. Sci. Mater. Med. 25, 2173–2183 (2014).10.1007/s10856-014-5261-x ↗
43. Ruth, P. et al. Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties. Int. J. Nanomed. 7, 2523–2534 (2012).
44. Fan, B. et al. Revealing the assembly mechanism of an octadecylamine based supramolecular complex on mild steel in condensate water: correlative experimental and theoretical studies. J. Mol. Liq. 292, 111446 (2019).
45. Huang, Y., Leobandung, W., Foss, A. & Peppas, N. A. Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces. J. Control. Release 65, 63–71 (2000).10.1016/S0168-3659(99)00233-3 ↗
46. Johnson, C. T. et al. Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing. Proc. Natl Acad. Sci. USA 115, 201801013 (2018).10.1073/pnas.1815820115 ↗
47. Xu, Z. et al. Tannic acid/Fe3 + /Ag nanofilm exhibiting superior photodynamic and physical antibacterial activity. ACS Appl. Mater. Interfaces 9, 39657–39671 (2017).10.1021/acsami.7b10818 ↗
48. Liu, J., Sonshine, D. A., Shervani, S. & Hurt, R. H. Controlled release of biologically active silver from nanosilver surfaces. ACS Nano 4, 6903–6913 (2010).10.1021/nn102272n ↗
49. He, M., Wang, Q., Zhang, J., Zhao, W. & Zhao, C. Substrate-independent Ag-nanoparticle-loaded hydrogel coating with regenerable bactericidal and thermoresponsive antibacterial properties. ACS Appl. Mater. Interfaces 9, 44782–44791 (2017).10.1021/acsami.7b13238 ↗
50. Paustovskaia, V. V., Rozhkovskaia, G. P., Rappoport, M. B., Anina, I. A. & Pasternak, G. A. Biological action of 4,4'-diaminodicyclohexylmethane carbonate and octadecylamine. Gig. Sanit. 38, 31–35 (1973).
51. MacDonald, W. E., Deichmann, W. B., Radomski, J. L. & Austin, B. S. The chronic toxicity of octadecylamine in the rat—a supplemental report. Toxicol. Appl. Pharmacol. 4, 610–612 (1962).10.1016/0041-008X(62)90087-X ↗
52. Xu, Y. et al. A novel lipoprotein-mimic nanocarrier composed of the modified protein and lipid for tumor cell targeting delivery. J. Control. Release 146, 299–308 (2010).10.1016/j.jconrel.2010.05.022 ↗
53. Kim, H. Y. et al. Sustained release of BMP-2 from porous particles with leaf-stacked structure for bone regeneration. ACS Appl. Mater. Interfaces 10, 21091–21102 (2018).10.1021/acsami.8b02141 ↗