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研究生: 許雨晴
Yu-Ching Hsu
論文名稱: 通過多孔型光固化複合支架控制藥物釋放
Controlled drug delivery by using photocured composites scaffolds with various porous structures
指導教授: 何明樺
Ming-Hua Ho
口試委員: 糜福龍
Fwu-Long Mi
蕭偉文
Wei-Wen Hsiao
呂憲宗
Hsien-Tsung Lu
學位類別: 碩士
Master
系所名稱: 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年: 2022
畢業學年度: 110
語文別: 中文
論文頁數: 83
中文關鍵詞: 多孔結構骨支撐材藥物釋放光固化樹酯3D列印
外文關鍵詞: porous structure, bone scaffolds, drug delivery, photo-resin, 3D-printing
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  • 本研究中,我們製備多孔型水膠/光固化樹酯複合支架,目的是以和藥
    物相容性高且釋放率高的水膠作為藥物載體進行藥物釋放,藉由光固化樹 酯支架有效的控制孔洞結構進而影響物質的釋放行為。
    許多研究結果顯示結構的孔徑與孔隙率會影響藥物釋放,然而通過傳 統多孔結構製備方法難以精確控制結構的孔徑和孔隙率。在本研究中,我們 使用光固化 3D 列印技術開發具有高精細度的孔洞結構支架,並將水膠作為 藥物載體填入光固化樹酯支架中進行藥物釋放,以系統化地分析結構因子 對藥物釋放的影響。在這項研究中,設計了兩種支架結構(直通道和相互連 接的孔洞),同時分別使用了三種孔徑(分別為 4mm、3.46mm 和 2.83 mm)、 三種孔隙率(分別為 52.6%,62.9%和 80.2%)以及三種扭曲率(分別為 1m/m,1.2m/m 和 1.5m/m)作為設計參數,將含有亞甲基藍的水凝膠填充到 支架中,並在各個時間點測量釋放曲線,從釋放曲線來看,與無支架的水凝 膠直接釋放相比,釋放速率和爆發釋放降低至約 40%和 60%,此結果顯示 多孔結構有效地延長了釋放時間。
    接著統計及分析各孔洞參數對釋放速率的影響,結果顯示在前期的釋放 中,釋放速率隨結構孔徑與孔隙度而增加,中期的釋放速率略隨孔隙度的上 升而下降,而後期釋放時程則明顯地因扭曲度的上升而拉長。我們進一步建
    I
    立出一套數學模型,可利用此模型設計所需要的釋放行為,並且在結構上增 加了導管設計,可以優化在臨床應用上更換藥物或填補含藥水膠的便利性。
    作為骨移植材料,結構需要一定的機械強度,而本研究設計的多孔結構 支架在使用 PC 寡聚物時其楊氏係數為 0.4 GPa 至 0.8 GPa,機械性能非常 接近鬆質骨,且此材料具有良好的生物相容性,這表明本研究開發的具有藥 物遞送系統的支架在骨組織工程中具有很高的潛力。


    In this research, porous hydrogel/photo-resin composite scaffolds were prepared. The hydrogel with high drug compatibility and excellent releasing behaviors were applied to encapsulate and release drugs, and 3D printed photoresin would provide precise porous structures for controlled delivery.
    It was indicated that the pore sizes and porosity of carriers would affect the drug delivery in previous studies. However, it was difficult to control porous structures precisely by using convectional processes. The photo-curing 3D printing technique was applied in this study to create well-designed porous structures, and the hydrogel pore-fillers were used for drug release. Thus, the effect of structure parameters can be systematically investigated. We designed two structures (straight and interconnected structures), three pore sizes (4, 3.46 and 2.83 mm), three porosities (52.6, 62.9, and 80.2%) and three tortuosity (1, 1.2 and 1.5 m/m) for 3D printed scaffolds. The hydrogel containing methyl blue was then filled into resin scaffolds and the released amount was measured at various time points. The profile presented that the delivery rate and burst release were decreased by about 40% and 60%. It proved that the porous structures effectively prolong the releasing period.
    The structure effects on release rates were statistically analyzed. The results revealed that the early release rate increased with pore sizes and porosity, the release rate in the middle stage decayed with the increase in porosity, and the late release was prolonged with the increase in tortuosity. Based on the statistical analysis, a mathematical model was developed, which was applicable in customizing drug delivery. Besides, the in vitro injection channel developed in this study would be able to promote the convenience in adding or replacing the hydrogel clinically.
    As a bone graft, the Young’s modulus of porous scaffolds developed in this research was about 0.4 -0.8 GPa, which was close to the sponge bones. Moreovet, the biocompatibility of photo-resin and hydrogel were high. The results identified the potential of hydrogel/photoresin composite scaffolds in bone tissue engineering.

    摘要 I Abstract III 致謝 V 圖目錄 XI 表目錄 XIV 方程式目錄 XV 專有名詞縮寫 XVI 第一章 緒論 1 第二章 文獻回顧 3 2-1 骨組織工程 3 2-2 骨填補材料 4 2-2.1 自然骨填補材料 5 2-2.2 人工合成骨填補材料 6 2-3 骨填補支架的製備方法 9 2-3.1 傳統工法 9 2-3.2 積層製造 10 2-4 多孔結構支架系統 11 2-4.1 多孔結構對機械強度的影響 11 2-4.2 多孔結構對細胞貼附的影響 12 2-4.3 多孔結構對釋放的影響 12 2-4.4 複合材料藥物釋放 13 第三章 實驗材料與方法 15 3-1 實驗藥品 15 3-2 實驗儀器 17 3-3 實驗步驟 19 3-3.1 光固化樹酯支架製備 19 3-3.2 水膠/光固化樹酯支架製備 20 3-3.3 多孔結構支架釋放系統 20 3-4 光固化材料性質檢測 21 3-4.1 黏度測試 21 3-4.2 結構孔洞化壓縮測試 21 3-4.3 多孔結構孔隙度分析 24 3-5 水膠材料分析 25 3-5.1 黏度測試 25 3-5.2 水膠物質釋放測試 25 3-6 水膠/光固化複合支架物性分析 26 3-6.1 複合支架表面型態分析 26 3-6.2 物質釋放實驗 26 3-7 體外細胞實驗 27 3-7.1 光固化材料試片製作 27 3-7.2 生物相容性檢測方式與操作 28 3-7.3 細胞來源 29 3-7.4 細胞培養 30 3-7.5 細胞冷凍保存 31 3-7.6 細胞解凍及培養 31 3-7.7 細胞計數 32 3-7.8 粒線體活性測試 34 第四章 結果與討論 37 4-1 支架設計與機械性質調控 37 4-1.1 多孔結構支架精細度 37 4-1.2 孔隙度與孔洞尺寸對壓縮性質影響 39 4-1.3 往復壓縮支架測定回復性 42 4-2 水膠性質與交聯時間分析 45 4-2.1 溫度對水膠流變性之影響 45 4-2.2 水膠配方與成膠時間影響 49 4-3 水膠與釋放速率分析 51 4-3.1 酸鹼值於水膠釋放速率比較 52 4-3.2 溫度對水膠釋放速率之影響 53 4-4 多孔型支架釋放速率分析 54 4-4.1 孔洞直徑對釋放速率之影響 55 4-4.2 孔隙度對釋放速率之影響 56 4-4.3 扭曲度對釋放速率之影響 57 4-4.4 不同孔洞結構對釋放速率之影響 59 4-4.5 模型出口孔洞大小對釋放速率的影響 62 4-5 建立支架參數數學模型 63 4-5.1 單一變數與釋放速率的相關性 63 4-5.2 多變數下與釋放速率的相關性 66 4-6 外部環境與釋放物質改變時支架的釋放變化 67 4-6.1 酸鹼值對複合支架釋放速率的影響 67 4-6.2 不同分子物質於釋放速率的比較 69 4-7 導管式注入水膠支架設計 70 4-7.1 導管支架有效黏度範圍 70 4-7.2 雙材料注射針筒的可行性 71 4-8 支架材料生物性質檢測 73 4-8.1 光固化樹酯與水膠對生物相容性之影響 73 第五章 結論 74 第六章 參考文獻 76

    1. Wang, X., Ao, Q., Tian X., Fan J., Wei Y. and Hou W., '“3D bioprinting technologies for hard tissue and organ engineering.” Materials, 2016. 9(10): p. 802.
    2. Ruchholtz, S., G. Tager, and D. Nast-Kolb,“The periprosthetic total hip infection.” Der Unfallchirurg, 2004. 107(4): p. 307-319.
    3. Harris, W.H. and C.B. Sledge,“ Total hip and total knee replacement. ”New England Journal of Medicine, 1990. 323(11): p. 725-731.
    4. Muñoz, N., Galvis, S., Patiño, O., & Moneriz, C., “Cranial osteomyelitis as a complication of furuncular myiasis.” Revista Paulista de Pediatria, 2021. 39.
    5. Wang, Y., D.W. Malcolm, and D.S. Benoit, “Controlled and sustained delivery of siRNA/NPs from hydrogels expedites bone fracture healing. ”Biomaterials, 2017. 139: p. 127-138.
    6. Sui, B. D., Hu, C. H., Liu, A. Q., Zheng, C. X., Xuan, K., & Jin, Y., “Stem cell-based bone regeneration in diseased microenvironments: challenges and solutions.” Biomaterials, 2019. 196: p. 18-30.
    7. Zhu, Y., Zhang, K., Zhao, R., Ye, X., Chen, X., Xiao, Z. & Zhang, X., “Bone regeneration with micro/nano hybrid-structured biphasic calcium phosphate bioceramics at segmental bone defect and the induced immunoregulation of MSCs.” Biomaterials, 2017. 147: p. 133-144.
    8. Lai, Y., Cao, H., Wang, X., Chen, S., Zhang, M., Wang, N., Qin, L., “Porous composite scaffold incorporating osteogenic phytomolecule icariin for promoting skeletal regeneration in challenging osteonecrotic bone in rabbits.” Biomaterials, 2018. 153: p. 1-13.
    9. Mathieu, L. M., Mueller, T. L., Bourban, P. E., Pioletti, D. P., Müller, R., & Månson, J. A. E., “Architecture and properties of anisotropic polymer composite scaffolds for bone tissue engineering. ”Biomaterials, 2006. 27(6): p. 905-916.
    10. Li, X. and Q. Feng,“Porous poly-L-lactic acid scaffold reinforced by chitin fibers.” Polymer Bulletin, 2005. 54(1): p. 47-55.
    11. Cao, H. and N. Kuboyama, “A biodegradable porous composite scaffold of PGA/β-TCP for bone tissue engineering.” Bone, 2010. 46(2): p. 386-395.
    12. Yu, J. C., Xu, A., Zhang, L., Song, R., & Wu, L., “Synthesis and characterization of porous magnesium hydroxide and oxide nanoplates.” The Journal of Physical Chemistry B, 2004. 108(1): p. 64-70.
    13. Butscher, A., Bohner, M., Hofmann, S., Gauckler, L., & Müller, R., “Structural and material approaches to bone tissue engineering in powder-based three-dimensional printing. ”Acta biomaterialia, 2011. 7(3): p. 907-920.
    14. Lee, J., “Educational testing: Measuring and remedying achievement gaps.” Emerging Trends in the Social and Behavioral Sciences, 2015: p. 1-14.
    15. Bose, S., S. Vahabzadeh, and A. “Bandyopadhyay, Bone tissue engineering using 3D printing.” Materials today, 2013. 16(12): p. 496-504.
    16. Brunello, G., Sivolella, S., Meneghello, R., Ferroni, L., Gardin, C., Piattelli, A., ... & Bressan, E., “Powder-based 3D printing for bone tissue engineering.” Biotechnology advances, 2016. 34(5): p. 740-753.
    17. Guvendiren, M., Molde, J., Soares, R. M., & Kohn, J., “Designing biomaterials for 3D printing. ”ACS biomaterials science & engineering, 2016. 2(10): p. 1679-1693.
    18. Derby, B., “Printing and prototyping of tissues and scaffolds.” science, 2012. 338(6109): p. 921-926.
    19. Wu, C., Fan, W., Zhou, Y., Luo, Y., Gelinsky, M., Chang, J., & Xiao, Y., “3D-printing of highly uniform CaSiO 3 ceramic scaffolds: preparation, characterization and in vivo osteogenesis.” Journal of Materials Chemistry, 2012. 22(24): p. 12288-12295.
    20. Chen, S. H., Lei, M., Xie, X. H., Zheng, L. Z., Yao, D., Wang, X. L., ... & Qin, L., “PLGA/TCP composite scaffold incorporating bioactive phytomolecule icaritin for enhancement of bone defect repair in rabbits. ”Acta biomaterialia, 2013. 9(5): p. 6711-6722.
    21. Qin, L., Yao, D., Zheng, L., Liu, W. C., Liu, Z., Lei, M., ... & Cheng, C. Y., “Phytomolecule icaritin incorporated PLGA/TCP scaffold for steroid-associated osteonecrosis: proof-of-concept for prevention of hip joint collapse in bipedal emus and mechanistic study in quadrupedal rabbits. ”Biomaterials, 2015. 59: p. 125-143.
    22. Chen, S. H., Zheng, L. Z., Xie, X. H., Wang, X. L., Lai, Y. X., Chen, S. K., ... & Qin, L., “Comparative study of poly (lactic-co-glycolic acid)/tricalcium phosphate scaffolds incorporated or coated with osteogenic growth factors for enhancement of bone regeneration. ”Journal of Orthopaedic Translation, 2014. 2(2): p. 91-104.
    23. Zhang, P., Hong, Z., Yu, T., Chen, X., & Jing, X., “In vivo mineralization and osteogenesis of nanocomposite scaffold of poly (lactide-co-glycolide) and hydroxyapatite surface-grafted with poly (L-lactide).” Biomaterials, 2009. 30(1): p. 58-70.
    24. Wang, C., Lai, J., Li, K., Zhu, S., Lu, B., Liu, J., ... & Wei, Y., “Cryogenic 3D printing of dual-delivery scaffolds for improved bone regeneration with enhanced vascularization.” Bioactive Materials, 2021. 6(1): p. 137-145.
    25. Park, J. Y., Shim, J. H., Choi, S. A., Jang, J., Kim, M., Lee, S. H., & Cho, D. W., “3D printing technology to control BMP-2 and VEGF delivery spatially and temporally to promote large-volume bone regeneration.” Journal of Materials Chemistry B, 2015. 3(27): p. 5415-5425.
    26. Lanza, R., Langer, R., Vacanti, J. P., & Atala, A. (Eds.)., “Principles of tissue engineering.”Academic press, 2020.
    27. Salgado, A.J., O.P. Coutinho, and R.L. “Reis, Bone tissue engineering: state of the art and future trends.” Macromolecular bioscience, 2004. 4(8): p. 743-765.
    28. Hollinger, J.O. and S.A. Guelcher, “An introduction to biomaterials.”CRC Press/Taylor & Francis Boca Raton, Florida. USA, 2012.
    29. Naujoks, C., Meyer, U., Wiesmann, H. P., Jäsche-Meyer, J., Hohoff, A., Depprich, R., & Handschel, J., “Principles of cartilage tissue engineering in TMJ reconstruction.” Head & Face Medicine, 2008. 4(1): p. 1-7.
    30. Marolt, D., Campos, I. M., Bhumiratana, S., Koren, A., Petridis, P., Zhang, G., ... & Vunjak-Novakovic, G., “Engineering bone tissue from human embryonic stem cells. ”Proceedings of the National Academy of Sciences, 2012. 109(22): p. 8705-8709.
    31. Mohan, S. and D.J. Baylink, “Bone growth factors.” Clinical orthopaedics and related research, 1991(263): p. 30-48.
    32. 張至宏 and 林峰輝, “源源不絕的骨骼銀行─ 談硬骨組織工程.” 科學發展, 356:, 2002: p. 18-21.
    33. 葉麗仙, “LED 光照刺激對人類牙齦纖維母細胞的影響.” 2009.
    34. Eichler, J., P. Hutzschenreuter, and I. Rosenbladt, “The behavior of biological parameters in experimental hyperthermia.” Der Anaesthesist, 1969. 18(7): p. 210-215.
    35. Bauer, T.W. and G.F. Muschler, “Bone graft materials: an overview of the basic science. ”Clinical Orthopaedics and Related Research®, 2000. 371: p. 10-27.
    36. Boccaccini, A. R., Chen, Q., Lefebvre, L., “Gremillard, L., & Chevalier, J., Sintering, crystallisation and biodegradation behaviour of Bioglass®-derived glass–ceramics.” Faraday discussions, 2007. 136: p. 27-44.
    37. Benaqqa, C., Chevalier, J., Saädaoui, M., & Fantozzi, G., “Slow crack growth behaviour of hydroxyapatite ceramics. ”Biomaterials, 2005. 26(31): p. 6106-6112.
    38. 鳳君曾, “Individualized Design and Developement to The Physically Disabilities of 3D Printing Ankle-Foot Orthosis for Functional Performances.” National Taiwan Normal University (Taiwan), 2018.
    39. Paris, J. L., Román, J., Manzano, M., Cabañas, M. V., & Vallet-Regí, M., “Tuning dual-drug release from composite scaffolds for bone regeneration.” International journal of pharmaceutics, 2015. 486(1-2): p. 30-37.
    40. Lee, D.C. and L.W. Jang, “Preparation and characterization of PMMA–clay hybrid composite by emulsion polymerization. ”Journal of Applied Polymer Science, 1996. 61(7): p. 1117-1122.
    41. Ligon, S. C., Liska, R., Stampfl, J., Gurr, M., & Mülhaupt, R., “Polymers for 3D printing and customized additive manufacturing.” Chemical reviews, 2017. 117(15): p. 10212-10290.
    42. McMenamin, P. G., Quayle, M. R., McHenry, C. R., & Adams, J. W., “The production of anatomical teaching resources using three‐dimensional (3D) printing technology. ”Anatomical sciences education, 2014. 7(6): p. 479-486.
    43. Hung, C. C., Li, Y. T., Chou, Y. C., Chen, J. E., Wu, C. C., Shen, H. C., & Yeh, T. T., “Conventional plate fixation method versus pre-operative virtual simulation and three-dimensional printing-assisted contoured plate fixation method in the treatment of anterior pelvic ring fracture.” International orthopaedics, 2019. 43(2): p. 425-431.
    44. Roseti, L., Parisi, V., Petretta, M., Cavallo, C., Desando, G., Bartolotti, I., & Grigolo, B., “Scaffolds for bone tissue engineering: state of the art and new perspectives.” Materials Science and Engineering: C, 2017. 78: p. 1246-1262.
    45. Jiang, Y. and Q. Wang, “Highly-stretchable 3D-architected mechanical metamaterials.” Scientific reports, 2016. 6(1): p. 1-11.
    46. Schuster, M., Turecek, C., Kaiser, B., Stampfl, J., Liska, R., & Varga, F., “Evaluation of biocompatible photopolymers I: Photoreactivity and mechanical properties of reactive diluents. ”Journal of Macromolecular Science, Part A, 2007. 44(5): p. 547-557.
    47. Athanasiou, K.A., G.G. Niederauer, and C.M. Agrawal, “Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers.” Biomaterials, 1996. 17(2): p. 93-102.
    48. Anderson, J.M. and M.S. Shive, “Biodegradation and biocompatibility of PLA and PLGA microspheres.” Advanced drug delivery reviews, 1997. 28(1): p. 5-24.
    49. Lam, C. X., Hutmacher, D. W., Schantz, J. T., Woodruff, M. A., & Teoh, S. H., “Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo.” Journal of Biomedical Materials Research Part A, 2009. 90(3): p. 906-919.
    50. Morrison, R. J., Hollister, S. J., Niedner, M. F., Mahani, M. G., Park, A. H., Mehta, D. K., ... & Green, G. E., “Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients.” Science translational medicine, 2015. 7(285): p. 285ra64-285ra64.
    51. Paun, I. A., Popescu, R. C., Mustaciosu, C. C., Zamfirescu, M., Calin, B. S., Mihailescu, M., ... & Luculescu, C. R., “Laser-direct writing by two-photon polymerization of 3D honeycomb-like structures for bone regeneration.” Biofabrication, 2018. 10(2): p. 025009.
    52. Stayton, P. S., Drobny, G. P., Shaw, W. J., Long, J. R., & Gilbert, M., “Molecular recognition at the protein-hydroxyapatite interface. ”Critical Reviews in Oral Biology & Medicine, 2003. 14(5): p. 370-376.
    53. Kim, S. S., Park, M. S., Jeon, O., Choi, C. Y., & Kim, B. S., “Poly (lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering.” Biomaterials, 2006. 27(8): p. 1399-1409.
    54. Zhang, R. and P.X. Ma, “Poly (α‐hydroxyl acids)/hydroxyapatite porous composites for bone‐tissue engineering. I. Preparation and morphology.” Journal of Biomedical Materials Research, 1999. 44(4): p. 446-455.
    55. Hong, Z., Zhang, P., He, C., Qiu, X., Liu, A., Chen, L., ... & Jing, X., “Nano-composite of poly (L-lactide) and surface grafted hydroxyapatite: mechanical properties and biocompatibility.” Biomaterials, 2005. 26(32): p. 6296-6304.
    56. Hong, Z., Zhang, P., Liu, A., Chen, L., Chen, X., & Jing, X., “Composites of poly (lactide‐co‐glycolide) and the surface modified carbonated hydroxyapatite nanoparticles. ”Journal of Biomedical Materials Research Part A, 2007. 81(3): p. 515-522.
    57. Arcos, D., C. Ragel, and M. Vallet-Regı, “Bioactivity in glass/PMMA composites used as drug delivery system.” Biomaterials, 2001. 22(7): p. 701-708.
    58. Ge, H., Hu, Y., Jiang, X., Cheng, D., Yuan, Y., Bi, H., & Yang, C., “Preparation, characterization, and drug release behaviors of drug nimodipine‐loaded poly (ε‐caprolactone)‐poly (ethylene oxide)‐poly (ε‐caprolactone) amphiphilic triblock copolymer micelles. ”Journal of pharmaceutical sciences, 2002. 91(6): p. 1463-1473.
    59. Cidonio, G., Alcala-Orozco, C. R., Lim, K. S., Glinka, M., Mutreja, I., Kim, Y. H., ... & Oreffo, R. O., “Osteogenic and angiogenic tissue formation in high fidelity nanocomposite Laponite-gelatin bioinks. ”Biofabrication, 2019. 11(3): p. 035027.
    60. Wang, Y., Miao, Y., Zhang, J., Wu, J. P., Kirk, T. B., Xu, J., ... & Xue, W., “Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery.” Materials Science and Engineering: C, 2018. 84: p. 44-51.
    61. Yan, J., Wang, Y., Zhang, X., Zhao, X., Ma, J., Pu, X., ... & Zhang, W., “Snakegourd root/Astragalus polysaccharide hydrogel preparation and application in 3D printing.” International journal of biological macromolecules, 2019. 121: p. 309-316.
    62. 楊牧君, “孔洞結構力分析於積層製造人工髖關節之應用”. 2018.
    63. Sung, H. W., Chang, Y., Liang, I. L., Chang, W. H., & Chen, Y. C., “Fixation of biological tissues with a naturally occurring crosslinking agent: fixation rate and effects of pH, temperature, and initial fixative concentration.” Journal of biomedical materials research, 2000. 52(1): p. 77-87.
    64. Huang, L. L., Sung, H. W., Tsai, C. C., & Huang, D. M., “Biocompatibility study of a biological tissue fixed with a naturally occurring crosslinking reagent.” Journal of Biomedical Materials Research, 1998. 42(4): p. 568-576.
    65. Lai, J.-Y., Y.-T. Li, and T.-P. Wang, “In vitro response of retinal pigment epithelial cells exposed to chitosan materials prepared with different cross-linkers. ”International journal of molecular sciences, 2010. 11(12): p. 5256-5272.
    66. Rodriguez, P. G., Felix, F. N., Woodley, D. T., & Shim, E. K.,“ The role of oxygen in wound healing: a review of the literature.” Dermatologic surgery, 2008. 34(9): p. 1159-1169.
    67. 連彩妏, “幾丁聚醣, 核醣, 梔子素與台灣鯛魚鱗粉末混和膜交聯之生醫材料特性研究”. 2011.
    68. Sung, H. W., Huang, R. N., Huang, L. L., Tsai, C. C., & Chiu, C. T.,“ Feasibility study of a natural crosslinking reagent for biological tissue fixation.”Journal of Biomedical Materials Research, 1998. 42(4): p. 560-567.
    69. Rastogi, P. and B. Kandasubramanian, “Review of alginate-based hydrogel bioprinting for application in tissue engineering.” Biofabrication, 2019. 11(4): p. 042001.
    70. Jiang, Z., Y. Yu, and H. Wu, “Preparation of CS/GPTMS hybrid molecularly imprinted membrane for efficient chiral resolution of phenylalanine isomers. ”Journal of membrane science, 2006. 280(1-2): p. 876-882.

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