AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.3396
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RESEARCH ARTICLE

Dexamethasone-loaded PLGA porous microspheres used as 3D-bioprinted bioink promote tissue-engineered cartilage regeneration

Zhuoqi Chen1 ,  Yanjun Feng1 ,  Yuchen Wang1 ,  Tianfeng Zheng1 ,  Jinshi Zeng1 ,  Wenshuai Liu1 ,  Yue Ma1 ,  Xiaowei Yue1 ,  Tian Li1 ,  Luosha Gu1 ,  Qinghua Yang1* ,  Haiyue Jiang1* ,  Xia Liu1,2*
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1 Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
2 Key Laboratory of External Tissue and Organ Regeneration, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
IJB 2024, 10(5), 3396 https://doi.org/10.36922/ijb.3396
Submitted: 9 April 2024 | Accepted: 3 June 2024 | Published: 27 August 2024
(This article belongs to the Special Issue 3D printing for tissue engineering and regenerative medicine)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The current investigation focused on fabricating and thoroughly analyzing porous microspheres (MPs) comprising poly (lactic-co-glycolic acid, PLGA) encapsulating dexamethasone, by utilizing the water-in-oil-in-water (W/O/W) emulsion solvent evaporation technique. The meticulous characterization encompassed various parameters, including particle size distribution, morphology, and polymer integrity, all of which exhibited consistent attributes across the MPs populations. The analysis of drug content and release kinetics revealed a sustained and controlled liberation of dexamethasone, characterized by an initial burst release within the initial 3 days followed by a gradual, protracted release profile. Subsequent in vivo assessments further validated the potent anti-inflammatory effects of the dexamethasone-loaded PLGA MPs, as evidenced by notable reductions in CD86 immunohistochemical staining intensity, along with the change in membrane thickness. Additionally, the MPs demonstrated an impressive capability to support the maintenance of cartilage phenotype, as indicated by the augmented secretion of cartilage matrix components and elevated glycosaminoglycan content.  

Keywords
Cartilage repair
Porous microspheres
Dexamethasone
PLGA porous microspheres
Targeted drug delivery
3D bioprinting
Funding
This work was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-052, 2017-I2M-1-007), and the Natural Science Foundation of China (82371796, 82302832).
Conflict of interest
The authors declare no competing financial interests.
References
  1. Wilkes GH, Wong J, Guilfoyle R. Microtia reconstruction. Plast Reconstr Surg. 2014;134(3):464e-479e. doi: 10.1097/prs.0000000000000526
  2. Griffith LG, Naughton G. Tissue engineering--current challenges and expanding opportunities. Science. 2002;295(5557):1009-1014. doi: 10.1126/science.1069210
  3. Havla JB, Lotz AS, Richter E, et al. Cartilage tissue engineering for auricular reconstruction: in vitro evaluation of potential genotoxic and cytotoxic effects of scaffold materials. Toxicol In Vitro. 2010;24(3):849-853. doi: 10.1016/j.tiv.2009.12.005
  4. Di Gesù R, Acharya AP, Jacobs I, Gottardi R. 3D printing for tissue engineering in otolaryngology. Connect Tissue Res. 2020;61(2):117-136. doi: 10.1080/03008207.2019.1663837
  5. Haudenschild AK, Sherlock BE, Zhou X, et al. Non-destructive detection of matrix stabilization correlates with enhanced mechanical properties of self-assembled articular cartilage. J Tissue Eng Regen Med. 2019;13(4):637-648. doi: 10.1002/term.2824
  6. Alhattab DM, Khan Z, Alshehri S, Susapto HH, Hauser CAE. 3D bioprinting of ultrashort self-assembling peptides to engineer scaffolds with different matrix stiffness for chondrogenesis. Int J Bioprint. 2023;9(4):719. doi: 10.18063/ijb.719
  7. Murphy MP, Koepke LS, Lopez MT, et al. Articular cartilage regeneration by activated skeletal stem cells. Nat Med. 2020;26(10):1583-1592. doi: 10.1038/s41591-020-1013-2
  8. Li M, Yin H, Yan Z, et al. The immune microenvironment in cartilage injury and repair. Acta Biomater. 2022;140:23-42. doi: 10.1016/j.actbio.2021.12.006
  9. Bonato A, Fisch P, Ponta S, et al. Engineering inflammation-resistant cartilage: bridging gene therapy and tissue engineering. Adv Healthc Mater. 2023;12(17):e2202271. doi: 10.1002/adhm.202202271
  10. Vahdati A, Zhao Y, Ovaert TC, Wagner DR. Computational investigation of fibrin mechanical and damage properties at the interface between native cartilage and implant. J Biomech Eng. 2012;134(11):111004. doi: 10.1115/1.4007748
  11. Zhou K, Ding R, Tao X, et al. Peptide-dendrimer-reinforced bioinks for 3D bioprinting of heterogeneous and biomimetic in vitro models. Acta Biomater. 2023;169:243-255. doi: 10.1016/j.actbio.2023.08.008
  12. Bayindir-Buchhalter I, Göbel U, Stimson L. Biofabrication, biomedical devices, nanomedicine, and tissue engineering – advanced materials in healthcare. Adv Healthc Mater. 2018;7(1):1701399. doi: 10.1002/adhm.201701399
  13. Liu J, Tagami T, Ozeki T. Fabrication of 3D-printed fish-gelatin-based polymer hydrogel patches for local delivery of PEGylated liposomal doxorubicin. Mar Drugs. 2020;18(6):325. doi: 10.3390/md18060325
  14. Steijvers E, Ghei A, Xia Z. Manufacturing artificial bone allografts: a perspective. Biomater Transl. 2022;3(1):65-80. doi: 10.12336/biomatertransl.2022.01.007
  15. Bian L, Stoker AM, Marberry KM, Ateshian GA, Cook JL, Hung CT. Effects of dexamethasone on the functional properties of cartilage explants during long-term culture. Am J Sports Med. 2010;38(1):78-85. doi: 10.1177/0363546509354197
  16. Stefani RM, Lee AJ, Tan AR, et al. Sustained low-dose dexamethasone delivery via a PLGA microsphere-embedded agarose implant for enhanced osteochondral repair. Acta Biomater. 2020;102:326-340. doi: 10.1016/j.actbio.2019.11.052
  17. Polderman JA, Farhang-Razi V, Van Dieren S, et al. Adverse side effects of dexamethasone in surgical patients. Cochrane Database Syst Rev. 2018;8(8):Cd011940. doi: 10.1002/14651858.CD011940.pub2
  18. Polderman JA, Farhang-Razi V, Van Dieren S, et al. Adverse side effects of dexamethasone in surgical patients. Cochrane Database Syst Rev. 2018;11(11):CD011940. doi: 10.1002/14651858.CD011940.pub3
  19. Salem R, Padia SA, Lam M, et al. Clinical, dosimetric, and reporting considerations for Y-90 glass microspheres in hepatocellular carcinoma: updated 2022 recommendations from an international multidisciplinary working group. Eur J Nucl Med Mol Imaging. 2023;50(2):328-343. doi: 10.1007/s00259-022-05956-w
  20. Abdel-Rahman O, Elsayed Z. Yttrium-90 microsphere radioembolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev. 2020;11(11):Cd011313. doi: 10.1002/14651858.CD011313.pub4
  21. Lin X, He J, Li W, et al. Lung-targeting lysostaphin microspheres for methicillin-resistant Staphylococcus aureus pneumonia treatment and prevention. ACS Nano. 2021;15(10):16625-16641. doi: 10.1021/acsnano.1c06460
  22. Kim TK, Yoon JJ, Lee DS, Park TG. Gas foamed open porous biodegradable polymeric microspheres. Biomaterials. 2006;27(2):152-159. doi: 10.1016/j.biomaterials.2005.05.081
  23. Zhou S, Deng X, Li X. Investigation on a novel core-coated microspheres protein delivery system. J Control Release. 2001;75(1-2):27-36. doi: 10.1016/s0168-3659(01)00379-0
  24. Prajapati VD, Jani GK, Kapadia JR. Current knowledge on biodegradable microspheres in drug delivery. Expert Opin Drug Deliv. 2015;12(8):1283-1299. doi: 10.1517/17425247.2015.1015985
  25. Wen H, Guo J, Chang B, Yang W. pH-responsive composite microspheres based on magnetic mesoporous silica nanoparticle for drug delivery. Eur J Pharm Biopharm. 2013;84(1):91-98. doi: 10.1016/j.ejpb.2012.11.019
  26. Lin TH, Wang HC, Cheng WH, Hsu HC, Yeh ML. Osteochondral tissue regeneration using a tyramine-modified bilayered PLGA scaffold combined with articular chondrocytes in a Porcine model. Int J Mol Sci. 2019;20(2):326. doi: 10.3390/ijms20020326
  27. Qian Y, Zhou X, Zhang F, Diekwisch TGH, Luan X, Yang J. Triple PLGA/PCL scaffold modification including silver impregnation, collagen coating, and electrospinning significantly improve biocompatibility, antimicrobial, and osteogenic properties for orofacial tissue regeneration. ACS Appl Mater Interfaces. 2019;11(41):3 7381-37396. doi: 10.1021/acsami.9b07053
  28. Shahverdi M, Seifi S, Akbari A, Mohammadi K, Shamloo A, Movahhedy MR. Melt electrowriting of PLA, PCL, and composite PLA/PCL scaffolds for tissue engineering application. Sci Rep. 2022;12(1):19935. doi: 10.1038/s41598-022-24275-6
  29. Hassanajili S, Karami-Pour A, Oryan A, Talaei-Khozani T. Preparation and characterization of PLA/PCL/HA composite scaffolds using indirect 3D printing for bone tissue engineering. Mater Sci Eng C Mater Biol Appl. 2019;104:109960. doi: 10.1016/j.msec.2019.109960
  30. Jia L, Hua Y, Zeng J, et al. Bioprinting and regeneration of auricular cartilage using a bioactive bioink based on microporous photocrosslinkable acellular cartilage matrix. Bioact Mater. 2022;16:66-81. doi: 10.1016/j.bioactmat.2022.02.032
  31. Lim KS, Galarraga JH, Cui X, Lindberg GCJ, Burdick JA, Woodfield TBF. Fundamentals and applications of photo-cross-linking in bioprinting. Chem Rev. 2020;120(19): 10662-10694. doi: 10.1021/acs.chemrev.9b00812
  32. Kim SH, Hong H, Ajiteru O, et al. 3D bioprinted silk fibroin hydrogels for tissue engineering. Nat Protoc. 2021;16(12):5484-5532. doi: 10.1038/s41596-021-00622-1
  33. Gillispie G, Prim P, Copus J, et al. Assessment methodologies for extrusion-based bioink printability. Biofabrication. 2020;12(2):022003. doi: 10.1088/1758-5090/ab6f0d
  34. Jin S, Xia X, Huang J, et al. Recent advances in PLGA-based biomaterials for bone tissue regeneration. Acta Biomater. 2021;127:56-79. doi: 10.1016/j.actbio.2021.03.067
  35. Park K. Tolerance levels of PLGA microspheres in the eyes. J Control Release. 2017;266:365. doi: 10.1016/j.jconrel.2017.11.010
  36. Jain H, Bairagi A, Srivastava S, Singh SB, Mehra NK. Recent advances in the development of microparticles for pulmonary administration. Drug Discov Today. 2020;25(10): 1865-1872. doi: 10.1016/j.drudis.2020.07.018
  37. Bian J, Cai F, Chen H, et al. Modulation of local overactive inflammation via injectable hydrogel microspheres. Nano Lett. 2021;21(6):2690-2698. doi: 10.1021/acs.nanolett.0c04713
  38. Park JY, Ryu H, Lee B, et al. Development of a functional airway-on-a-chip by 3D cell printing. Biofabrication. 2018;11(1):015002. doi: 10.1088/1758-5090/aae545
  39. Long J, Yao Z, Zhang W, et al. Regulation of osteoimmune microenvironment and osteogenesis by 3D-printed PLAG/ black phosphorus scaffolds for bone regeneration. Adv Sci (Weinh). 2023;10(28):e2302539. doi: 10.1002/advs.202302539
  40. Yang F, Niu X, Gu X, Xu C, Wang W, Fan Y. Biodegradable magnesium-incorporated poly(l-lactic acid) microspheres for manipulation of drug release and alleviation of inflammatory response. ACS Appl Mater Interfaces. 2019;11(26):23546-23557. doi: 10.1021/acsami.9b03766
  41. Aymard G, Warot D, Démolis P, et al. Comparative pharmacokinetics and pharmacodynamics of intravenous and oral Nefopam in healthy volunteers*. Pharmacol Toxicol. 2003;92(6):279-286. doi: 10.1034/j.1600-0773.2003.920605.x
  42. Loew D, Schuster O, Graul EH. Dose-dependent pharmacokinetics of dexamethasone. Eur J Clin Pharmacol. 1986;30(2):225-230. doi: 10.1007/bf00614309
  43. Yang J, Wu H, Zhang P, Hou DM, Chen J, Zhang SG. The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration. Acta Otolaryngol. 2008;128(5):496-504. doi: 10.1080/00016480701558906
  44. Wang H, Zhao P, Su W, et al. PLGA/polymeric liposome for targeted drug and gene co-delivery. Biomaterials. 2010;31(33):8741-8748. doi: 10.1016/j.biomaterials.2010.07.082
  45. Jin L, Pan Y, Pham AC, Boyd BJ, Norton RS, Nicolazzo JA. Prolonged plasma exposure of the Kv1.3-inhibitory peptide HsTX1[R14A] by subcutaneous administration of a poly(Lactic-co-Glycolic Acid) (PLGA) microsphere formulation. J Pharm Sci. 2021;110(3):1182-1188. doi: 10.1016/j.xphs.2020.10.014
  46. Kato Y, Gospodarowicz D. Stimulation by glucocorticoid of the synthesis of cartilage-matrix proteoglycans produced by rabbit costal chondrocytes in vitro. J Biol Chem. 1985;260(4):2364-2373.
  47. Lu YC, Evans CH, Grodzinsky AJ. Effects of short-term glucocorticoid treatment on changes in cartilage matrix degradation and chondrocyte gene expression induced by mechanical injury and inflammatory cytokines. Arthritis Res Ther. 2011;13(5):R142. doi: 10.1186/ar3456
  48. Cardone DA, Tallia AF. Joint and soft tissue injection. Am Fam Physician. 2002;66(2):283-289.
  49. Li D, Guo G, Fan R, et al. PLA/F68/dexamethasone implants prepared by hot-melt extrusion for controlled release of anti-inflammatory drug to implantable medical devices: I. Preparation, characterization and hydrolytic degradation study. Int J Pharm. 2013;441(1-2): 365-372. doi: 10.1016/j.ijpharm.2012.11.019
  50. Kagaya F, Usui T, Kamiya K, et al. Intraocular dexamethasone delivery system for corneal transplantation in an animal model. Cornea. 2002;21(2):200-202. doi: 10.1097/00003226-200203000-00015
  51. Caratti G, Desgeorges T, Juban G, et al. Macrophagic AMPKα1 orchestrates regenerative inflammation induced by glucocorticoids. EMBO Rep. 2023;24(2):e55363. doi: 10.15252/embr.202255363
  52. Agarwal R, García AJ. Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair. Adv Drug Deliv Rev. 2015;94:53-62. doi: 10.1016/j.addr.2015.03.013
  53. Tsiapla AR, Karagkiozaki V, Bakola V, et al. Biomimetic and biodegradable cellulose acetate scaffolds loaded with dexamethasone for bone implants. Beilstein J Nanotechnol. 2018;9:1986-1994. doi: 10.3762/bjnano.9.189
  54. Yoo BW, Kong YT, Chae SW, Kim KN, Song B, Kim J. Comparison of the characteristics of three acellular dermal matrices subjected to distinct processing methods using five types of histochemical staining. Aesthetic Plast Surg. 2023;47(4):1315-1323. doi: 10.1007/s00266-023-03318-x
  55. Fang W, Yang F, Li W, et al. Dexamethasone microspheres and celecoxib microcrystals loaded into injectable gels for enhanced knee osteoarthritis therapy. Int J Pharm. 2022;622:121802. doi: 10.1016/j.ijpharm.2022.121802
  56. Li J, Li L, Wu T, et al. An injectable thermosensitive hydrogel containing resveratrol and dexamethasone-loaded carbonated hydroxyapatite microspheres for the regeneration of osteoporotic bone defects. Small Methods. 2024;8(1):e2300843. doi: 10.1002/smtd.202300843
  57. Ren X, Wang J, Wu Y, et al. One-pot synthesis of hydroxyapatite hybrid bioinks for digital light processing 3D printing in bone regeneration. J Mater Sci Technol. 2024;188:84-97. doi: 10.1016/j.jmst.2024.01.00

 

 

 

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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