• 沒有找到結果。

5-2-1 建立系統性參數

未來可針對基材建立系統性之參數,研究分析出不同之參數,所 製作出電紡絲之纖維形態之差異,在統整之後,便可以製造出一致性 高、不同直徑大小之奈米電紡絲,會更有利於實驗數據之比較與分析。

5-2-2 收集器之改良

本研究所製作出之奈米電紡絲纖維走向皆為亂數分佈不纖布形 態,這是由於電紡平台之收集器的部分並無進行改裝,所以並無法控 制奈米纖維落在收集器上時之方向性,在過去的一些研究中指出,可 以利用不同的纖維收集方式以控制奈米纖維之方向性。第一種設置是 將靜態的金屬收集器置換成一可轉動之金屬滾筒收集器,由於滾筒轉 動的力量使得纖維得以平行排列(圖 5 - 1a),以此方式可製做出平行 排列纖維的薄膜(Chew et al., 2005; Matthews et al., 2002)。第二種設置 是將滾筒的長度縮小或是在滾筒上纏繞金屬線(圖 5 - 1bc),由於電紡 絲收集的範圍變小了,所以可以製作出線狀的電紡絲,但長度只有滾 筒的周徑長(Bhattarai et al., 2005; Xu et al., 2004)。第三種設置方式則 可製作出平行排列之連續電紡絲線,電紡絲先噴在置有金屬收集器的

收集(圖 5 - 2) (Khil et al., 2005; Smit et al., 2005)

(a) (b) (c)

圖 5 - 1:(a)滾輪式電紡裝置;(b)金屬線圈式電紡裝置;(c)圓盤式電 紡裝置。

圖 5 - 2:平行排列連續電紡絲線之電紡裝置(Smit et al., 2005)。

5-2-3 材料選擇

未來研究可以選擇具有生物可降解性的材料來製作奈米電紡 絲,如:聚乳酸-甘醇酸(PLGA)、左旋型聚乳酸(PLLA)、聚己內酯 (PCL)、膠原蛋白…等。依據不同的需求而使用不同的材料來製作奈

米纖維細胞支架,將可以增加未來組織工程可應用之範圍。

5-2-4 加強基材強度及力學評估

加強基材之強度,可以增加基材之耐用性,將會是可否進行進一 步體內動物實驗之重要因素,而加強強度之方式有許多種,如交聯、

編織等。因此,未來可以研究不同加強基材強度的方式對於強度增加 及細胞反應之影響,以找出最合適之加強基材強度方式。

5-2-5 生物反應器

當基材與細胞相容性之研究達到不錯的效果時,可以著手開發生 物反應器,以模擬出體內之環境,藉由生物反應器之研究,可以了解 在模擬體內環境之後,對於細胞之生長反應、細胞外基質之分泌是否 能達到更好的效果,甚至可以減少人工組織植入體內後,與植體與體 內整合之時間。

5-2-6 幹細胞培養

雖然纖維母細胞擁有不錯的合成膠原蛋白之能力,但其分化能力 是受到限制的,若使用此一種類之細胞,將會縮小組織工程可應用之 領域。因此,使用幹細胞培養將會是不錯的選擇,由於幹細胞有非常 好的分化能力及自我更新的表現。除此之外,幹細胞也有非常穩定的

織培養,應該會有更好的成效。

5-2-7 動物試驗

以目前的科技發展,以人工的方式畢竟還是無法完全模擬出體內 之環境,因此,最後的願景當然還是能夠進行動物試驗,對於臨床之 應用才有足夠之意義。

參考文獻

Altman, G. H., Horan, R. L., Lu, H. H., Moreau, J., Martin, I., Richmond, J. C., et al. (2002). Silk matrix for tissue engineered anterior

cruciate ligaments. Biomaterials, 23(20), 4131-4141.

Anselme, K. (2000). Osteoblast adhesion on biomaterials. Biomaterials, 21(7), 667-681.

Balto, H. A. (2004). Attachment and morphological behavior of human periodontal ligament fibroblasts to mineral trioxide aggregate: a scanning electron microscope study. J Endod, 30(1), 25-29.

Barnes, C. P., Sell, S. A., Boland, E. D., Simpson, D. G., & Bowlin, G. L.

(2007). Nanofiber technology: Designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev, 59(14),

1413-1433.

Bellincampi, L. D., Closkey, R. F., Prasad, R., Zawadsky, J. P., & Dunn, M. G. (1998). Viability of fibroblast-seeded ligament analogs after autogenous implantation. J Orthop Res, 16(4), 414-420.

Bhattarai, N., Edmondson, D., Veiseh, O., Matsen, F. A., & Zhang, M. Q.

(2005). Electrospun chitosan-based nanofibers and their cellular compatibility. Biomaterials, 26(31), 6176-6184.

Castner, D. G., & Ratner, B. D. (2002). Biomedical surface science:

Foundations to frontiers. Surf Sci, 500, 28-60.

Chen, M., Patra, P. K., Warner, S. B., & Bhowmick, S. (2007). Role of fiber diameter in adhesion and proliferation of NIH 3T3 fibroblast on electrospun polycaprolactone scaffolds. Tissue Eng, 13(3),

Chew, S. Y., Wen, J., Yim, E. K. F., & Leong, K. W. (2005). Sustained release of proteins from electrospun biodegradable fibers.

Biomacromolecules, 6(4), 2017-2024.

Cooper, J. A., Jr., Bailey, L. O., Carter, J. N., Castiglioni, C. E., Kofron, M. D., Ko, F. K., et al. (2006). Evaluation of the anterior cruciate ligament, medial collateral ligament, achilles tendon and patellar tendon as cell sources for tissue-engineered ligament. Biomaterials, 27(13), 2747-2754.

Cooper, J. A., Lu, H. H., Ko, F. K., Freeman, J. W., & Laurencin, C. T.

(2005). Fiber-based tissue-engineered scaffold for ligament replacement: design considerations and in vitro evaluation.

Biomaterials, 26(13), 1523-1532.

Curtis, A., & Wilkinson, C. (1997). Topographical control of cells.

Biomaterials, 18(24), 1573-1583.

Dunn, M. G., Liesch, J. B., Tiku, M. L., & Zawadsky, J. P. (1995).

Development of Fibroblast-Seeded Ligament Analogs for Acl Reconstruction. J Biomed Mater Res, 29(11), 1363-1371.

Elisseeff, J., Puleo, C., Yang, F., & Sharma, B. (2005). Advances in skeletal tissue engineering with hydrogels. Orthod Craniofac Res, 8(3), 150-161.

Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006). Matrix elasticity directs stem cell lineage specification. Cell, 126(4), 677-689.

Formhals, A. (1934). US Patent 1975504. US Patent 1975504.

Gaudet, C., Marganski, W. A., Kim, S., Brown, C. T., Gunderia, V., Dembo, M., et al. (2003). Influence of type I collagen surface

density on fibroblast spreading, motility, and contractility. Biophys J, 85(5), 3329-3335.

Ge, Z., Yang, F., Goh, J. C., Ramakrishna, S., & Lee, E. H. (2006).

Biomaterials and scaffolds for ligament tissue engineering. J Biomed Mater Res A, 77(3), 639-652.

Gu, Z. Q., Xiao, J. M., & Zhang, X. H. (1998). The development of artificial articular cartilage--PVA-hydrogel. Biomed Mater Eng, 8(2), 75-81.

He, W., Ma, Z. W., Yong, T., Teo, W. E., & Ramakrishna, S. (2005).

Fabrication of collagen-coated biodegradable polymer nanofiber mesh and its potential for endothelial cells growth. Biomaterials, 26(36), 7606-7615.

He, W., Yong, T., Teo, W. E., Ma, Z. W., & Ramakrishna, S. (2005).

Fabrication and endothelialization of collagen-blended

biodegradable polymer nanofibers: Potential vascular graft for blood vessel tissue engineering. Tissue Eng, 11(9-10), 1574-1588.

Hou, H., Jun, Z., Reuning, A., Schaper, A., Wendorff, J. H., & Greiner, A.

(2002). Poly(<i>p</i>-xylylene) Nanotubes by Coating and Removal of Ultrathin Polymer Template Fibers. Macromolecules, 35(7), 2429-2431.

Karageorgiou, V., & Kaplan, D. (2005). Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 26(27), 5474-5491.

Karp, G. (2005). Cell and Moledular Biology: John Wiley & Sons, Inc.

Khil, M. S., Bhattarai, S. R., Kim, H. Y., Kim, S. Z., & Lee, K. H. (2005).

Novel fabricated matrix via electrospinning for tissue engineering.

Khor, E., & Lim, L. Y. (2003). Implantable applications of chitin and chitosan. Biomaterials, 24(13), 2339-2349.

Kim, I. Y., Seo, S. J., Moon, H. S., Yoo, M. K., Park, I. Y., Kim, B. C., et al. (2008). Chitosan and its derivatives for tissue engineering applications. Biotechnol Adv, 26(1), 1-21.

Lee, C. H., Shin, H. J., Cho, I. H., Kang, Y. M., Kim, I. A., Park, K. D., et al. (2005). Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast. Biomaterials, 26(11), 1261-1270.

Li, M. Y., Mondrinos, M. J., Gandhi, M. R., Ko, F. K., Weiss, A. S., &

Lelkes, P. I. (2005). Electrospun protein fibers as matrices for tissue engineering. Biomaterials, 26(30), 5999-6008.

Li, W. J., Laurencin, C. T., Caterson, E. J., Tuan, R. S., & Ko, F. K.

(2002). Electrospun nanofibrous structure: A novel scaffold for tissue engineering. J Biomed Mater Res, 60(4), 613-621.

Lin, V. S., Lee, M. C., O'Neal, S., McKean, J., & Sung, K. L. P. (1999).

Ligament tissue engineering using synthetic biodegradable fiber scaffolds. Tissue Eng, 5(5), 443-451.

Lu, H. H., Cooper, J. A., Manuel, S., Freeman, J. W., Attawia, M. A., Ko, F. K., et al. (2005). Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies.

Biomaterials, 26(23), 4805-4816.

Ma, Z. W., He, W., Yong, T., & Ramakrishna, S. (2005). Grafting of gelatin on electrospun poly(caprolactone) nanofibers to improve endothelial cell spreading and proliferation and to control cell orientation. Tissue Eng, 11(7-8), 1149-1158.

Malette, W. G., Quigley, H. J. (1985). US Patent 4,532,134.

Matthews, J. A., Wnek, G. E., Simpson, D. G., & Bowlin, G. L. (2002).

Electrospinning of collagen nanofibers. Biomacromolecules, 3(2), 232-238.

Middleton, J. C., & Tipton, A. J. (2000). Synthetic biodegradable

polymers as orthopedic devices. Biomaterials, 21(23), 2335-2346.

Miyashita, H., Shimmura, S., Kobayashi, H., Taguchi, T., Asano-Kato, N., Uchino, Y., et al. (2006). Collagen-immobilized poly(vinyl alcohol) as an artificial cornea scaffold that supports a stratified corneal epithelium. J Biomed Mater Res B Appl Biomater, 76(1), 56-63.

Murphy, P. G., Loitz, B. J., Frank, C. B., & Hart, D. A. (1994). Influence of exogenous growth factors on the synthesis and secretion of collagen types I and III by explants of normal and healing rabbit ligaments. Biochem Cell Biol, 72(9-10), 403-409.

No, H. K., Young Park, N., Ho Lee, S., & Meyers, S. P. (2002).

Antibacterial activity of chitosans and chitosan oligomers with different molecular weights. Int J Food Microbiol, 74(1-2), 65-72.

Noth, U., Schupp, K., Heymer, A., Kall, S., Jakob, F., Schutze, N., et al.

(2005). Anterior cruciate ligament constructs fabricated from human mesenchymal stem cells in a collagen type I hydrogel.

Cytotherapy, 7(5), 447-455.

Ratner, B. D., Hoffman, A. S., Schoen, F. J., & Lemons, J. E. (2004).

Biomaterials Science (2nd ed.): Elsevier Inc.

Rho, K. S., Jeong, L., Lee, G., Seo, B. M., Park, Y. J., Hong, S. D., et al.

(2006). Electrospinning of collagen nanofibers: effects on the

healing. Biomaterials, 27(8), 1452-1461.

Sahoo, S., Ouyang, H., Goh, J. C. H., Tay, T. E., & Toh, S. L. (2006).

Characterization of a novel polymeric scaffold for potential application in tendon/ligament tissue engineering. Tissue Eng, 12(1), 91-99.

Serrano, M. C., Pagani, R., Vallet-Regi, M., Pena, J., Ramila, A.,

Izquierdo, I., et al. (2004). In vitro biocompatibility assessment of poly(epsilon-caprolactone) films using L929 mouse fibroblasts.

Biomaterials, 25(25), 5603-5611.

Shields, K. J., Beckman, M. J., Bowlin, G. L., & Wayne, J. S. (2004).

Mechanical properties and cellular proliferation of electrospun collagen type II. Tissue Eng, 10(9-10), 1510-1517.

Smit, E., Buttner, U., & Sanderson, R. D. (2005). Continuous yarns from electrospun fibers. Polymer, 46(8), 2419-2423.

Subbiah, T., Bhat, G. S., Tock, R. W., Parameswaran, S., & Ramkumar, S.

S. (2005). Electrospinning of nanofibers. J Appl Polym Sci, 96(2), 557-569.

Sun, T., Mai, S. M., Norton, D., Haycock, J. W., Ryan, A. J., & MacNeil, S. (2005). Self-organization of skin cells in three-dimensional electrospun polystyrene scaffolds. Tissue Eng, 11(7-8), 1023-1033.

Tan, S. H., Inai, R., Kotaki, M., & Ramakrishna, S. (2005). Systematic parameter study for ultra-fine fiber fabrication via electrospinning process. Polymer, 46(16), 6128-6134.

Taylor, G. (1969). Electrically Driven Jets. P Roy Soc Lond A Mat, 313(1515), 453-&.

Teo, W. E., & Ramakrishna, S. (2006). A review on electrospinning

design and nanofibre assemblies. Nanotechnology, 17(14), R89-R106.

Tuzlakoglu, K., Bolgen, N., Salgado, A. J., Gomes, M. E., Piskin, E., &

Reis, R. L. (2005). Nano- and micro-fiber combined scaffolds: A new architecture for bone tissue engineering. J Mater Sci-Mater M, 16(12), 1099-1104.

Ueno, H., Mori, T., & Fujinaga, T. (2001). Topical formulations and

wound healing applications of chitosan. Adv Drug Deliv Rev, 52(2), 105-115.

Venugopal, J., Ma, L. L., Yong, T., & Ramakrishna, S. (2005). In vitro study of smooth muscle cells on polycaprolactone and collagen nanofibrous matrices. Cell Biol Int, 29(10), 861-867.

Woo, S. L., Hildebrand, K., Watanabe, N., Fenwick, J. A., Papageorgiou, C. D., & Wang, J. H. (1999). Tissue engineering of ligament and tendon healing. Clin Orthop Relat Res(367 Suppl), S312-323.

Xu, C. Y., Inai, R., Kotaki, M., & Ramakrishna, S. (2004). Aligned biodegradable nanotibrous structure: a potential scaffold for blood vessel engineering. Biomaterials, 25(5), 877-886.

Yang, F., Murugan, R., Wang, S., & Ramakrishna, S. (2005).

Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials, 26(15), 2603-2610.

Yang, F., Xu, C. Y., Kotaki, M., Wang, S., & Ramakrishna, S. (2004).

Characterization of neural stem cells on electrospun poly(L-lactic acid) nanofibrous scaffold. J Biomat Sci-Polym E, 15(12),

Yarin, A. L., Koombhongse, S., & Reneker, D. H. (2001). Bending instability in electrospinning of nanofibers. J Appl Phys, 89(5), 3018-3026.

Yoshimoto, H., Shin, Y. M., Terai, H., & Vacanti, J. P. (2003). A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials, 24(12), 2077-2082.

Zhang, Y. Z., Venugopal, J., Huang, Z. M., Lim, C. T., & Ramakrishna, S.

(2005). Characterization of the surface biocompatibility of the electrospun PCL-collagen nanofibers using fibroblasts.

Biomacromolecules, 6(5), 2583-2589.

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