Citation: Xu-Dong Shi, Pei-Jian Sun, Zhi-Hua Gan. Preparation of Porous Polylactide Microspheres and Their Application in Tissue Engineering[J]. Chinese Journal of Polymer Science, ;2018, 36(6): 712-719. doi: 10.1007/s10118-018-2079-x shu

Preparation of Porous Polylactide Microspheres and Their Application in Tissue Engineering

Xu-Dong Shi ^a,b ,
Pei-Jian Sun ^b ,
Zhi-Hua Gan ^b,c,,

a.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
b.
The CAS Key Laboratory of Engineering Plastics, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, China
c.
State Key Laboratory of Organic-inorganic Composites, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China

Corresponding author: Zhi-Hua Gan, zhgan@mail.buct.edu.cn
Received Date: 2 September 2017
Accepted Date: 26 October 2017
Available Online: 19 January 2018

In this study, porous polylactide (PLA) microspheres with different structures were prepared through the multiple emulsion solvent evaporation method. By changing organic solvents (ethyl acetate and chloroform) and adding effervescent salt NH₄HCO₃ in the inner water phase, microspheres with porous capsular, matrix, microcapsular and multivesicular structures were prepared. The protein encapsulation and release, and the cell growth behavior of porous microspheres were further explored. Under the same inner water phase, microspheres prepared with chloroform had higher protein encapsulation efficiency and less protein release rate as compared with those prepared with ethyl acetate. Cell experiments showed that the relatively rough surface of microspheres prepared with chloroform was more favorable for the cell growth in comparison with the smooth surface of microspheres prepared with ethyl acetate. This study shows a simple and effective method to control the protein release and cell growth behaviors of polymer microspheres by tuning their porous structure.
- Polylactide,
- Porous microspheres,
- Drug release,
- Cell,
- Tissue engineering
1. [1]
  Couvreur P., BlancoPrieto M. J., Puisieux F., Roques B., Fattal E.. Multiple emulsion technology for the design of microspheres containing peptides and oligopeptides[J]. Adv. Drug Deliv. Rev., 1997,28(1):85-96. doi: 10.1016/S0169-409X(97)00052-5
2. [2]
  McGlohorn J. B., Grimes L. W., Webster S. S., Burg K. J. L.. Characterization of cellular carriers for use in injectable tissue-engineering composites[J]. J. Biomed. Mater. Res. Part A, 2003,66A(3):441-449. doi: 10.1002/(ISSN)1097-4636
3. [3]
  Hong Y., Gao C. Y., Xie Y., Gong Y. H., Shen J. C.. Collagen-coated polylactide microspheres as chondrocyte microcarriers[J]. Biomaterials, 2005,26(32):6305-6313. doi: 10.1016/j.biomaterials.2005.03.038
4. [4]
  Thissen H., Chang K. Y., Tebb T. A., Tsai W. B., Glattauer V., Ramshaw J. A. M., Werkmeister J. A.. Synthetic biodegradable microparticles for articular cartilage tissue engineering[J]. J. Biomed. Mater. Res. Part A, 2006,77A(3):590-598. doi: 10.1002/(ISSN)1552-4965
5. [5]
  Liu X., Jin X., Ma P. X.. Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair[J]. Nat. Mater., 2011,10(5):398-406. doi: 10.1038/nmat2999
6. [6]
  Lee J. H., Lee C. S., Cho K. Y.. Enhanced cell adhesion to the dimpled surfaces of golf-ball-shaped microparticles[J]. ACS Appl. Mater. Interfaces, 2014,6(19):16493-16497. doi: 10.1021/am505997s
7. [7]
  Kavas A., Keskin D., Altunbas K., Tezcaner A.. Raloxifene-/raloxifene-poly(ethylene glycol) conjugate-loaded microspheres:a novel strategy for drug delivery to bone forming cells[J]. Int. J. Pharm., 2016,510(1):168-183. doi: 10.1016/j.ijpharm.2016.06.053
8. [8]
  Garkhal K., Verma S., Tikoo K., Kumar N.. Surface modified poly(L-lactide-co-epsilon-caprolactone) microspheres as scaffold for tissue engineering[J]. J. Biomed. Mater. Res. Part A, 2007,82A(3):747-756. doi: 10.1002/(ISSN)1552-4965
9. [9]
  Lee S. H., Shin H.. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering[J]. Adv. Drug Deliv. Rev., 2007,59(4-5):339-359. doi: 10.1016/j.addr.2007.03.016
10. [10]
  Luciani A., Coccoli V., Orsi S., Ambrosio L., Netti P. A.. PCL microspheres based functional scaffolds by bottom-up approach with predefined microstructural properties and release profiles[J]. Biomaterials, 2008,29(36):4800-4807. doi: 10.1016/j.biomaterials.2008.09.007
11. [11]
  Bae S. E., Choi D. H., Han D. K., Park K.. Effect of temporally controlled release of dexamethasone on in vivo chondrogenic differentiation of mesenchymal stromal cells[J]. J. Control. Release, 2010,143(1):23-30. doi: 10.1016/j.jconrel.2009.12.024
12. [12]
  Le Ray A. M., Chiffoleau S., Iooss P., Grimandi G., Gouyette A., Daculsi G., Merle C.. Vancomycin encapsulation in biodegradable poly(ε-caprolactone) microparticles for bone implantation.Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility[J]. Biomaterials, 2003,24(3):443-449. doi: 10.1016/S0142-9612(02)00357-5
13. [13]
  Bae S. E., Son J. S., Park K., Han D. K.. Fabrication of covered porous PLGA microspheres using hydrogen peroxide for controlled drug delivery and regenerative medicine[J]. J. Control. Release, 2009,133(1):37-43. doi: 10.1016/j.jconrel.2008.09.006
14. [14]
  Malda J., Frondoza C. G.. Microcarriers in the engineering of cartilage and bone[J]. Trends Biotechnol., 2006,24(7):299-304. doi: 10.1016/j.tibtech.2006.04.009
15. [15]
  Crotts G., Park T. G.. Preparation of porous and nonporous biodegradable polymeric hollow microspheres[J]. J. Control. Release, 1995,35(2-3):91-105. doi: 10.1016/0168-3659(95)00010-6
16. [16]
  Hong S. J., Yu H. S., Kim H. W.. Tissue engineering polymeric microcarriers with macroporous morphology and bone-bioactive surface[J]. Macromol. Biosci., 2009,9(7):639-645. doi: 10.1002/mabi.v9:7
17. [17]
  Fan J. B., Song Y. Y., Wang S. T., Jiang L., Zhu M. Q., Guo X. L.. A synergy effect between the hydrophilic PEG and rapid solvent evaporation induced formation of tunable porous microspheres from a triblock copolymer[J]. RSC Adv., 2014,4(2):629-633. doi: 10.1039/C3RA44197K
18. [18]
  Kim T. K., Yoon J. J., Lee D. S., Park T. G.. Gas foamed open porous biodegradable polymeric microspheres[J]. Biomaterials, 2006,27(2):152-159. doi: 10.1016/j.biomaterials.2005.05.081
19. [19]
  Kang S. W., Yang H. S., Seo S. W., Han D. K., Kim B. S.. Apatite-coated poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for bone tissue engineering[J]. J. Biomed. Mater. Res. Part A, 2008,85A(3):747-756. doi: 10.1002/(ISSN)1552-4965
20. [20]
  Wu D., Wang C., Yang J., Wang H., Han H., Zhang A., Yang Y., Li Q.. Improving the intracellular drug concentration in lung cancer treatment through the codelivery of doxorubicin and mir-519c mediated by porous PLGA microparticle[J]. Mol. Pharm., 2016,13(11):3925-3933. doi: 10.1021/acs.molpharmaceut.6b00702
21. [21]
  Iqbal M., Zafar N., Fessi H., Elaissari A.. Double emulsion solvent evaporation techniques used for drug encapsulation[J]. Int.J. Pharm., 2015,496(2):173-190. doi: 10.1016/j.ijpharm.2015.10.057
22. [22]
  Shi X. D., Sun L., Jiang J., Zhang X. L., Ding W. J., Gan Z. H.. Biodegradable polymeric microcarriers with controllable porous structure for tissue engineering[J]. Macromol. Biosci., 2009,9(12):1211-1218. doi: 10.1002/mabi.v9:12
23. [23]
  Shi X. D., Sun L., Gan Z. H.. Formation mechanism of solvent-induced porous PLA microspheres[J]. Acta Polymerica Sinica (in Chinese), 2011(8):866-873.
24. [24]
  Wang S. Y., Shi X. D., Gan Z. H., Wang F.. Preparation of PLGA microspheres with different porous morphologies[J]. Chinese J. Polym. Sci., 2015,33(1):128-136. doi: 10.1007/s10118-014-1507-9
25. [25]
  Odonnell P. B., McGinity J. W.. Preparation of microspheres by the solvent evaporation technique[J]. Adv. Drug Deliv. Rev., 1997,28(1):25-42. doi: 10.1016/S0169-409X(97)00049-5
26. [26]
  Meng F. T., Ma G. H., Qiu W., Su Z. G.. W/O/W double emulsion technique using ethyl acetate as organic solvent:effects of its diffusion rate on the characteristics of microparticles[J]. J. Control. Release, 2003,91(3):407-416. doi: 10.1016/S0168-3659(03)00273-6
27. [27]
  Zheng Y. H., Cheng Y. L., Chen J. J., Ding J. X., Li M. Q., Li C., Wang J.C., Chen X. S.. Injectable hydrogel-microsphere construct with sequential degradation for locally synergistic chemotherapy[J]. ACS Appl. Mater. Interfaces, 2017,9(4):3487-3496. doi: 10.1021/acsami.6b15245
28. [28]
  Zhang J., Liu H., Ding J. X., Wu J., Zhuang X. L., Chen X. S., Wang J. C., Yin J. B., Li Z. M.. High-pressure compression-molded porous resorbable polymer/hydroxyapatite composite scaffold for cranial bone regeneration[J]. ACS Biomater. Sci. Eng., 2016,2(9):1471-1482. doi: 10.1021/acsbiomaterials.6b00202
29. [29]
  Liu D. H., Ding J. X., Xu W. G., Song X. F., Zhuang X. L., Chen X. S.. Stereocomplex micelles based on 4-armed poly(ethylene glycol)-polylactide enantiomeric copolymers for drug delivery[J]. Acta Polymerica Sinica (in Chinese), 2014(9):1265-1273.
30. [30]
  Shen K. X., Li D., Guan J. J., Ding J. X., Wang Z. T., Gu J. K., Liu T. J., Chen X. S.. Targeted sustained delivery of antineoplastic agent with multicomponent polylactide stereocomplex micelle[J]. Nanomed. Nanotechnol. Biol. Med., 2017,13(3):1279-1288. doi: 10.1016/j.nano.2016.12.022
31. [31]
  Feng X. R., Ding J. X., Gref R., Chen X. S.. Poly(b-cyclodextrin)-mediated polylactide-cholesterol stereocomplex micelles for controlled drug delivery[J]. Chinese J. Polym. Sci., 2017,35(6):693-699. doi: 10.1007/s10118-017-1932-7
32. [32]
  Wang J. X., Xu W. G., Ding J. X., Lu S. F., Wang X. Q., Wang C. X., Chen X. S.. Cholesterol-enhanced polylactide-based stereocomplex micelle for effective delivery of doxorubicin[J]. Materials, 2015,8(1):216-230. doi: 10.3390/ma8010216
33. [33]
  Ho M. L., Fu Y. C., Wang G. J., Chen H. T., Chang J. K., Tsai T. H., Wang C. K.. Controlled release carrier of BSA made by W/O/W emulsion method containing PLGA and hydroxyapatite[J]. J. Control. Release, 2008,128(2):142-148. doi: 10.1016/j.jconrel.2008.02.012
34. [34]
  Sturesson C., Carlfors J.. Incorporation of protein in PLG-microspheres with retention of bioactivity[J]. J. Control. Release, 2000,67(2-3):171-178. doi: 10.1016/S0168-3659(00)00205-4
35. [35]
  Florence A. T., Whitehill D.. The formulation and stability of multiple emulsions[J]. Int. J. Pharm., 1982,11:277-308. doi: 10.1016/0378-5173(82)90080-1
36. [36]
  Sah H. K., Smith M. S., Chern R. T.. A novel method of preparing PLGA microcapsules utilizing methylethyl ketone[J]. Pharm. Res., 1996,13(3):360-367. doi: 10.1023/A:1016080123176
37. [37]
  Schugens C., Laruelle N., Nihant N., Grandfils C., Jerome R., Teyssie P.. Effect of the emulsion stability on the morphology and porosity of semicrystalline poly(L-lactide) microparticles prepared by W/O/W double emulsion-evaporation[J]. J. Control. Release, 1994,32(2):161-176. doi: 10.1016/0168-3659(94)90055-8
38. [38]
  Rezwan K., Chen Q. Z., Blaker J. J., Boccaccini A. R.. Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering[J]. Biomaterials, 2006,27(18):3413-3431. doi: 10.1016/j.biomaterials.2006.01.039
39. [39]
  Bodmeier R., McGinity J.W.. Solvent selection in the preparation of poly(DL-lactide) microspheres prepared by the solvent evaporation method[J]. Int. J. Pharm., 1988,43(1-2):179-186. doi: 10.1016/0378-5173(88)90073-7
40. [40]
  Kojima R., Yoshida T., Tasaki H., Umejima H., Maeda M., Higashi Y., Watanabe S., Oku N.. Release mechanisms of tacrolimus-loaded PLGA and PLA microspheres and immunosuppressive effects of the microspheres in a rat heart transplantation model[J]. Int. J. Pharm., 2015,492(1-2):20-27. doi: 10.1016/j.ijpharm.2015.07.004
41. [41]
  Wei G. B., Pettway G. J., McCauley L. K., Ma P. X.. The release profiles and bioactivity of parathyroid hormone from poly(lactic-co-glycolic acid) microspheres[J]. Biomaterials, 2004,25(2):345-352. doi: 10.1016/S0142-9612(03)00528-3
42. [42]
  Jones K. H., Senft J. A.. An improved method to determine cell viability by simultaneous staining with fluorescein diacetate propidium iodide[J]. J. Histochem. Cytochem., 1985,33(1):77-79. doi: 10.1177/33.1.2578146
43. [43]
  Webb K., Hlady V., Tresco P. A.. Relative importance of surface wettability and charged functional groups on NIH 3T3 fibroblast attachment, spreading, and cytoskeletal organization[J]. J. Biomed. Mater. Res., 1998,41(3):422-430. doi: 10.1002/(ISSN)1097-4636
44. [44]
  Kim H. K., Chung H. J., Park T. G.. Biodegradable polymeric microspheres with "open/closed" pores for sustained release of human growth hormone[J]. J. Control. Release, 2006,112(2):167-174. doi: 10.1016/j.jconrel.2006.02.004
45. [45]
  Lee J., Lee K. Y.. Injectable microsphere/hydrogel combination systems for localized protein delivery[J]. Macromol. Biosci., 2009,9(7):671-676. doi: 10.1002/mabi.v9:7
46. [46]
  Zhang Y., Sun L., Jiang J. A., Zhang X. L., Ding W. J., Gan Z. H.. Biodegradation-induced surface change of polymer microspheres and its influence on cell growth[J]. Polym. Degrad. Stab., 2010,95(8):1356-1364. doi: 10.1016/j.polymdegradstab.2010.01.025
1. [1]
  Yunan Yuan , Zhimin Luo , Jie Chen , Chaoliang He , Kai Hao , Huayu Tian . Constructing thermoresponsive PNIPAM-based microcarriers for cell culture and enzyme-free cell harvesting. Chinese Chemical Letters, 2024, 35(7): 109549-. doi: 10.1016/j.cclet.2024.109549
2. [2]
  Shihong Wu , Ronghui Zhou , Hang Zhao , Peng Wu . Sonoafterglow luminescence for in vivo deep-tissue imaging. Chinese Chemical Letters, 2024, 35(10): 110026-. doi: 10.1016/j.cclet.2024.110026
3. [3]
  Kun-Heng Li , Hong-Yang Zhao , Dan-Dan Wang , Ming-Hui Qi , Zi-Jian Xu , Jia-Mi Li , Zhi-Li Zhang , Shi-Wen Huang . Mitochondria-targeted nano-AIEgens as a powerful inducer for evoking immunogenic cell death. Chinese Chemical Letters, 2024, 35(5): 108882-. doi: 10.1016/j.cclet.2023.108882
4. [4]
  Yang Liu , Yan Liu , Kaiyin Yang , Zhiruo Zhang , Wenbo Zhang , Bingyou Yang , Hua Li , Lixia Chen . A selective HK2 degrader suppresses SW480 cancer cell growth by degrading HK2. Chinese Chemical Letters, 2024, 35(8): 109264-. doi: 10.1016/j.cclet.2023.109264
5. [5]
  Boran Cheng , Lei Cao , Chen Li , Fang-Yi Huo , Qian-Fang Meng , Ganglin Tong , Xuan Wu , Lin-Lin Bu , Lang Rao , Shubin Wang . Fluorine-doped carbon quantum dots with deep-red emission for hypochlorite determination and cancer cell imaging. Chinese Chemical Letters, 2024, 35(6): 108969-. doi: 10.1016/j.cclet.2023.108969
6. [6]
  Jing Chen , Peisi Xie , Pengfei Wu , Yu He , Zian Lin , Zongwei Cai . MALDI coupled with laser-postionization and trapped ion mobility spectrometry contribute to the enhanced detection of lipids in cancer cell spheroids. Chinese Chemical Letters, 2024, 35(4): 108895-. doi: 10.1016/j.cclet.2023.108895
7. [7]
  Yanjing Li , Jiayin Li , Yuqi Chang , Yunfeng Lin , Lei Sui . Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell. Chinese Chemical Letters, 2024, 35(9): 109414-. doi: 10.1016/j.cclet.2023.109414
8. [8]
  Zhixue Liu , Haiqi Chen , Lijuan Guo , Xinyao Sun , Zhi-Yuan Zhang , Junyi Chen , Ming Dong , Chunju Li . Luminescent terphen[3]arene sulfate-activated FRET assemblies for cell imaging. Chinese Chemical Letters, 2024, 35(9): 109666-. doi: 10.1016/j.cclet.2024.109666
9. [9]
  Ying Gao , Rong Zhou , Qiwen Wang , Shaolong Qi , Yuanyuan Lv , Shuang Liu , Jie Shen , Guocan Yu . Natural killer cell membrane doped supramolecular nanoplatform with immuno-modulatory functions for immuno-enhanced tumor phototherapy. Chinese Chemical Letters, 2024, 35(10): 109521-. doi: 10.1016/j.cclet.2024.109521
10. [10]
  Lixian Fu , Yiyun Tan , Yue Ding , Weixia Qing , Yong Wang . Water–soluble and polarity–sensitive near–infrared fluorescent probe for long–time specific cancer cell membranes imaging and C. Elegans label. Chinese Chemical Letters, 2024, 35(4): 108886-. doi: 10.1016/j.cclet.2023.108886
11. [11]
  Jisheng Liu , Junli Chen , Xifeng Zhang , Yin Wu , Xin Qi , Jie Wang , Xiang Gao . Red blood cell membrane-coated FLT3 inhibitor nanoparticles to enhance FLT3-ITD acute myeloid leukemia treatment. Chinese Chemical Letters, 2024, 35(9): 109779-. doi: 10.1016/j.cclet.2024.109779
12. [12]
  Jianqiu Li , Yi Zhang , Songen Liu , Jie Niu , Rong Zhang , Yong Chen , Yu Liu . Cucurbit[8]uril-based non-covalent heterodimer realized NIR cell imaging through topological transformation from nanowire to nanorod. Chinese Chemical Letters, 2024, 35(10): 109645-. doi: 10.1016/j.cclet.2024.109645
13. [13]
  Linghui Zou , Meng Cheng , Kaili Hu , Jianfang Feng , Liangxing Tu . Vesicular drug delivery systems for oral absorption enhancement. Chinese Chemical Letters, 2024, 35(7): 109129-. doi: 10.1016/j.cclet.2023.109129
14. [14]
  Fengjie Liu , Fansu Meng , Zhenjiang Yang , Huan Wang , Yuehong Ren , Yu Cai , Xingwang Zhang . Exosome-biomimetic nanocarriers for oral drug delivery. Chinese Chemical Letters, 2024, 35(9): 109335-. doi: 10.1016/j.cclet.2023.109335
15. [15]
  Hao Wang , Meng-Qi Pan , Ya-Fei Wang , Chao Chen , Jian Xu , Yuan-Yuan Gao , Chuan-Song Qi , Wei Li , Xian-He Bu . Post-synthetic modifications of MOFs by different bolt ligands for controllable release of cargoes. Chinese Chemical Letters, 2024, 35(10): 109581-. doi: 10.1016/j.cclet.2024.109581
16. [16]
  Lishan Xiong , Xinyuan Li , Xiaojie Lu , Zhendong Zhang , Yan Zhang , Wen Wu , Chenhui Wang . Inhaled multilevel size-tunable, charge-reversible and mucus-traversing composite microspheres as trojan horse: Enhancing lung deposition and tumor penetration. Chinese Chemical Letters, 2024, 35(9): 109384-. doi: 10.1016/j.cclet.2023.109384
17. [17]
  Chengde Wang , Liping Huang , Shanshan Wang , Lihao Wu , Yi Wang , Jun Dong . A distinction of gliomas at cellular and tissue level by surface-enhanced Raman scattering spectroscopy. Chinese Chemical Letters, 2024, 35(5): 109383-. doi: 10.1016/j.cclet.2023.109383
18. [18]
  Xing Tian , Di Wu , Wanheng Wei , Guifu Dai , Zhanxian Li , Benhua Wang , Mingming Yu . A lipid droplets-targetable fluorescent probe for polarity detection in cells of iron death, inflammation and fatty liver tissue. Chinese Chemical Letters, 2024, 35(6): 108912-. doi: 10.1016/j.cclet.2023.108912
19. [19]
  Ziyi Zhu , Yang Cao , Jun Zhang . CO2-switched porous metal-organic framework magnets. Chinese Journal of Structural Chemistry, 2024, 43(2): 100241-100241. doi: 10.1016/j.cjsc.2024.100241
20. [20]
  Chao Ma , Cong Lin , Jian Li . MicroED as a powerful technique for the structure determination of complex porous materials. Chinese Journal of Structural Chemistry, 2024, 43(3): 100209-100209. doi: 10.1016/j.cjsc.2023.100209

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(593)
HTML views(1)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142