Title

開發多孔性聚乳酸微粒作為軟組織填補劑之應用

Translated Titles

Development of porous polylactic acid for the soft tissue filling applications

DOI

10.6841/NTUT.2013.00095

Authors

黃曼婷

Key Words

聚乳酸 ; 生物可分解性 ; 生物相容性 ; 填充劑 ; 脂肪幹細胞 ; Polylactic acid ; Biodegradable ; Biocompatible ; Filler ; Adipose-Derived Stem Cell

PublicationName

臺北科技大學化學工程研究所學位論文

Volume or Term/Year and Month of Publication

2013年

Academic Degree Category

碩士

Advisor

方旭偉

Content Language

繁體中文

Chinese Abstract

本實驗研究內容為開發多孔性聚乳酸作為真皮刺激物,主要機制是藉由注入的生醫材料觸發發炎反應,使纖維母細胞靠近,進而分泌膠原蛋白,達到真皮增生之目的。除了可以達到填補效果,並可以延長填補時效。 因為其生物可分解性、生物可吸收性及生物相容性的性質,已經被廣泛的運用在生物醫學上。利用聚乳酸,開發具有多孔性微粒之生醫材料,同時建立多孔性聚乳酸微粒製程,完成性質測定及找出最佳條件、材料對細胞毒性檢測等。聚乳酸搭配凝膠形成注射型軟組織填補劑注入所需人體填補部位,如凹陷部位。 目前市面上之真皮刺激分子,常見的有氫氧基磷灰石及聚乳酸等,現行缺點問題在於材料製程方面,則是顆粒大小不一致,表面形貌不規則且材料於填補劑內分散性不佳,因而導致真皮刺激反應不均勻,局部有過量反應,臨床現象 像是丘疹及肉芽組織腫大。為提升應用性,透過本製程所得到多孔性聚乳酸微粒開發作成填補劑與已上市的品牌-Sculptra做比較,例如:外觀、黏彈性、分散性等。最後,將脂肪幹細胞和所選定多孔性聚乳酸填補劑相混,檢測生物相容性。 因此本實驗目的是,開發大小形貌均勻之多孔性聚乳酸微粒改善現行真皮刺激不均填補效果,並且優化填補劑配方,達自然柔軟效果。

English Abstract

The experimental research for the development of porous polylactic acid as a dermal stimulant, the main mechanism is implanted biomaterials by inducing inflammation, so that fibroblasts close, and then secrete collagen, reaching the dermis proliferation purposes. In addition to filling effect can be achieved, and can be extended to fill the prescription.Because of its biodegradable, bioabsorbable and biocompatible nature, has been widely used in biomaterial applications. Use of polylactic acid, the development of porous particles, while establishing a porous polylactic acid particle processes, complete determination of the nature and identify the best conditions, the material on cytotoxicity detection. Polylactic acid with a gel-forming injectable soft tissue filling agent is injected into the body to fill the necessary parts, such as fold part. Currently on the market, often with hydroxyapatite and polylactic acid, etc. The problem is that the existing shortcomings material fabrication process, it is different particle size, surface morphology and the material in the filling material irregularities within the dispersion is not well, resulting in uneven dermal irritation, locally excessive reaction, clinical phenomena such as pimples and granulation tissue swelling. To enhance the application, obtained through the process of polylactic acid particles porous filling material made with the development of the brand-Sculptra listed for comparison, for example: the appearance, viscoelasticity, dispersion and so on. Finally, the selected adipose stem cells and polylactide porous filling material mixed, testing biocompatibility. Therefore, the purpose of the experiment is to develop a uniform size of the porous morphology of polylactic acid particles to improve the existing dermal stimulation uneven fill effects, and optimizing fill formulations, the effect of the natural softness.

Topic Category 工程學院 > 化學工程研究所
工程學 > 化學工業
Reference
  1. 1. Dastoor, S.F., C.E. Misch, and H.-L. Wang, "Dermal Fillers for Facial Soft Tissue Augmentation," Journal of Oral Implantology, vol. 33, no. 4, 2007, pp.191-204.
    連結:
  2. 2. Klein, A.W. and M.L. Elson, "The History of Substances for Soft Tissue Augmentation," Dermatologic Surgery, vol. 26, no.12, 2000, pp. 1096-1105.
    連結:
  3. 3. Griffey, S., N.D. Schwade, and C.G. "Wright, Particulate dermal matrix as an injectable soft tissue replacement material," Journal of Biomedical Materials Research, vol. 58, no.1, 2001, pp. 10-15.
    連結:
  4. 4. Bergeret-Galley, C., "Comparison of resorbable soft tissue fillers," Aesthetic Surgery Journal, vol. 24, no. 1, 2004 ,pp. 33-46.
    連結:
  5. 6. Hyon, S.-H., et al., "Poly (vinyl alcohol) hydrogels as soft contact lens material," Journal of Biomaterials Science, vol. 5, no. 5, 1994, pp. 397-406.
    連結:
  6. 7. Kobayashi, M., Y.-S. Chang, and M. Oka," A two year in vivo study of polyvinyl alcohol-hydrogel (PVA-H) artificial meniscus," Biomaterials, vol. 26,no. 16, 2005 , pp. 3243-3248.
    連結:
  7. 8. Peppas, N.A. and R.E. Berner Jr," Proposed method of intracopdal injection and gelation of poly (vinyl alcohol) solution in vocal cords: polymer considerations," Biomaterials, vol. 1, no. 3, 1980 , pp. 158-162.
    連結:
  8. 9. 吳益豪,以浸鍍法於鈦金屬表面架構抗菌藥物之控制釋放機制,碩士論文, 國立台北科技大學生物科技研究所,臺北,2010。
    連結:
  9. 10. Nelson, D.L. and M.M. Cox, Lehninger principles of biochemistry, New York: Wh Freeman, 2010.
    連結:
  10. 12. Burgess, C.M. and R.M. Quiroga, "Assessment of the safety and efficacy of poly-L-lactic acid for the treatment of HIV-associated facial lipoatrophy," J Am Acad Dermatol, vol. 52, no. 2, 2005, pp. 233-239.
    連結:
  11. 13. Cutright, D.E. and E.E. Hunsuck, "Tissue reaction to the biodegradable polylactic acid suture," Oral Surgery, Oral Medicine, Oral Pathology, vol. 31, no. 1, 1971, pp. 134-139.
    連結:
  12. 14. 蘇尹翎,雙乳化法製備生物可分解聚酯奈米微粒之藥物釋放研究,碩士論文, 淡江大學化學工程與材料工程研究所,臺北,2007。
    連結:
  13. 15. Garti, N., "Double emulsions—scope, limitations and new achievements. Colloids and Surfaces A," Physicochemical and Engineering Aspects, vol. 123, 1997, pp. 233-246.
    連結:
  14. 16. Schramm, L.L., Emulsions, Foams, and Suspensions, Canada: Wiley-Vch, 2006 .
    連結:
  15. 17. Wang, H., et al., "Influence of formulation methods on the in vitro controlled release of protein from poly (ester) microspheres." Journal of controlled release, vol. 17, no. 1, 1991, pp. 23-31.
    連結:
  16. 18. Chang, C.-M. and R. Bodmeier, "Organic solvent-free polymeric microspheres prepared from aqueous colloidal polymer dispersions by aw/o-emulsion technique," International journal of pharmaceutics, vol. 130, no. 2, 1996 , pp. 187-194.
    連結:
  17. 23. T. Florence, J.A.R., "Emulsion stabilization by non-ionic surfactants: experiment and theory," Pharmacy and Pharmacology, vol. 23, 1971 , pp.233-251.
    連結:
  18. 24. Zuk, P.A., et al., "Human adipose tissue is a source of multipotent stem cells. Molecular biology of the cell," vol. 13, no. 12, 2002 , pp. 4279-4295.
    連結:
  19. 26. Bunnell, B.A., et al., "Adipose-derived stem cells: isolation, expansion and differentiation," Methods, vol. 45, no. 2, 2008 , pp. 115-120.
    連結:
  20. 27. Cui, L., et al., "Repair of articular cartilage defect in non-weight bearing areas using adipose derived stem cells loaded polyglycolic acid mesh," Biomaterials, vol. 30, no. 14, 2009, pp. 2683-2693.
    連結:
  21. 28. Conrad, C., et al., "Multipotent mesenchymal stem cells acquire a lymphendothelial phenotype and enhance lymphatic regeneration in vivo," Circulation, vol. 119, no. 2, 2009, pp. 281-289.
    連結:
  22. 29. Vieira, N.M., et al., "Human multipotent adipose‐derived stem cells restore dystrophin expression of Duchenne skeletal‐muscle cells in vitro," Biology of the Cell, vol. 100, no. 4, 2008 , pp. 231-241.
    連結:
  23. 30. Fraser, J.K., et al., "Fat tissue: an underappreciated source of stem cells for biotechnology," Trends in biotechnology, vol. 24, no. 4, 2006 , pp. 150-154.
    連結:
  24. 32. Mischen, B.T., et al., "Metabolic and functional characterization of human adipose-derived stem cells in tissue engineering," Plastic and reconstructive surgery, vol. 122, no. 3, 2008 , pp. 725-738.
    連結:
  25. 33. Schipper, B.M., et al., "Regional anatomic and age effects on cell function of human adipose-derived stem cells," Annals of plastic surgery, vol. 60, no. 5, 2008 , pp. 538-544.
    連結:
  26. 34. Hanson, A.D., et al., "Osteogenic effects of rest inserted and continuous cyclic tensile strain on hASC lines with disparate osteodifferentiation capabilities," Annals of biomedical engineering, vol. 37, no. 5, 2009 , pp. 955-965.
    連結:
  27. 35. Mitchell, J.B., et al., " Immunophenotype of Human Adipose‐Derived Cells: Temporal Changes in Stromal‐Associated and Stem Cell–Associated Markers," Stem cells, vol. 24, no. 2, 2006 , pp. 376-385.
    連結:
  28. 37. Sun, N., et al., "Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells," Proceedings of the National Academy of Sciences, vol. 106, no. 37 , 2009 , pp. 15720-15725.
    連結:
  29. 38. Oh, Y.J., et al.," Preparation of budesonide-loaded porous PLGA microparticles and their therapeutic efficacy in a murine asthma model," Journal of Controlled Release, vol. 150, no. 1, 2011 , pp. 56-62.
    連結:
  30. 39. Jain, R.A., "The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices," Biomaterials, vol. 21, no. 23, 2000, pp. 2475-2490.
    連結:
  31. 41. Yoshimura, K., et al., "Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates," Journal of cellular physiology, vol. 208, no. 1 , 2006 , pp. 64-76.
    連結:
  32. 42. Miranville, A., et al., "Improvement of postnatal neovascularization by human adipose tissue-derived stem cells," Circulation, vol. 110, no. 3 , 2004 , pp. 349-355.
    連結:
  33. 43. Boquest, A.C., et al., "Isolation and transcription profiling of purified uncultured human stromal stem cells: alteration of gene expression after in vitro cell culture," Molecular biology of the cell, vol. 16, no. 3, 2005, pp. 1131-1141.
    連結:
  34. 44. Leong, D.T., et al.," The osteogenic differentiation of adipose tissue-derived precursor cells in a 3D scaffold/matrix environment," Current Drug Discovery Technologies, vol. 5, no. 4, 2008 , pp. 319-327.
    連結:
  35. 5. Sculptra http://www.sculptraaesthetic.com/faq/sculptra-cost.aspx.
  36. 11. Danny Vleggaar, M.," Facial enhancement and the European experience with Sculptra™(poly-l-lactic acid)," Journal of Drugs in Dermatology, vol.3, no. 5, 2004, pp. 542-547.
  37. 19. 歐靜枝,應用化工 乳化溶化技術實務,臺南: 復漢出版社有限公司,2000。
  38. 20. 鍾瑞芬,聚酯微粒之水解和藥物釋放研究,碩士論文,國立台北科技大學有機高分子研究所,臺北,2002。
  39. 21. 孫一明、許紹菁,「微粒包覆技術及其在藥物制放上之應用」,化工技術,第七卷,第五期,1999,第166-173頁。
  40. 22. Davis、陳志良, 陳建海,「聚羥基丁酸酯-羥基戊酸酯共聚物/明膠微粒的構造型態與性能」,高分子材料科學與工程,第十六卷,第五期,2000。
  41. 25. 聶續強,「脂肪源性幹細胞研究及其應用進展」,中國修復重建外科雜誌, 第二十五卷,第七期,2011,第854-858頁。
  42. 31. Qiang, W., "The application of chitosan in cartilage tissue engineering[J]," Foreign Medical Sciences Biomedical Engineering, vol.2 , 2002 , pp. 004.
  43. 36. 趙春華,幹細胞原理、技術與臨床,北京: 化學工業出版社,2006。
  44. 40. 科以侃,儀器分析(最新修訂版),臺北: 文京圖書有限公司,1996,第191-193頁。
Times Cited
  1. 吳書璇(2014)。製備多孔性聚乳酸微粒於軟組織填補劑之開發。臺北科技大學生物科技研究所學位論文。2014。1-57。