本篇研究中利用臭氧改質聚乳酸薄膜(Poly( L-lactic acid))，利用臭氧在薄膜產生過氧化物，以進行介質單體(intermediate regent) ASI (acryl-N -succinimide)的接枝，並進一步將 P-15-EEEE胺基酸序列固定在聚乳酸薄膜上。
藉由碘離子法，確定利用臭氧處理可成功產生過氧化物於聚乳酸表面，並進一步找出了最佳化之臭氧處理時間、臭氧流率及臭氧處理溫度。接著透過紅外線光譜儀(FTIR-Microscopy )、元素分析 (Elemental Analyzer，EA )及胺基酸分析 (Amino acid assay)可確定ASI及p-15-EEEE已成功的接在聚乳酸基材上。
在生物測試(bio-test)部份，以改質前後的聚乳酸進行ROS細胞培養，對細胞密度、ALP活性及鈣鹽沉積進行分析，結果顯示P-15改質的確有效提高了聚乳酸的細胞親和性與成骨促進性。在體內實驗部份(in vivo study)，透過H＆E染色得知，材料接上ASI與P-15並未造成嚴重的發炎或異物反應(foreign body reaction)，且可促進周圍組織膠原蛋白的分泌。由生物測試結推斷聚乳酸骨誘導（osteoinduction）影響可藉由此改質法加以提升，使聚乳酸基材(PLLA substrate)更有效的應用於硬骨再生的領域中。

In this study, ozone treatment was applied to modify PLLA (Poly( L-lactic acid)) with the intermediate regent, ASI (acryl-N -succinimide). Then, the further immobilizations of P15, the peptide related to the attachment, proliferation and mineralization of osteoblastic cells, was carried out by the reaction with ASI. Ozone activation was proved to successfully create peroxides on the PLLA surface from the iodide method. By changing activation time, activation temperature, reaction bath or oxygen flow rate, the amount of peroxides can be controlled. The immobilizations of ASI and P15 were confirmed and quantitative analyzed by FTIR spectrum, elementary analysis and amino acid analyzer.

From in vitro and in vivo experiments, the cultured rat osteosarcoma 17/2.8 (ROS) cells expressed significantly higher ALPase activity and more calcium deposition with P15 immobilization. The in vivo experiments revealed that no irritation and foreign body reaction were induced due to the modification of ASI and peptides. The osteoinduction effect of PLLA can be enhanced with the modification in this research. With this modification process, the PLLA substrate can be successfully and efficiently modified and become much more effective and specific to bone regeneration.

參考文獻

Aharoni S.M., Prevorsek D.C., Schmitt G.J., Eur. Pat. 012316(1979).

Akhouayri O., Lafage-Proust M.H., Rattner A., Laroche N., Caillot-Augusseau A., Alexandre C., Vico L., "Effects of static or dynamic mechanical stresses on osteoblast phenotype expression in three-dimensional contractile collagen gels," Journal of cellular biochemistry, vol. 76 (2), pp.217-230(2000).

Allen A.O., Hochanadel C.J., Ghormley J.A., Davis T. W., "decomposition of water and aqueous solutions under mixed fast neutron and gamma-radiation," J. Phys. Chem., vol. 56, pp.575(1952).

Anderson J.M., "Inflammatory Response to Implants," ASAIO Journal, vol. 34, pp.101-107(1988).

Bhatnagar R.S., Qian J.J., Gough C.A., "The role in cell binding of a beta-bend within the triple helical region in collagen alpha 1 (I) chain : Strectural and biological evidence for conformational tautomerism on fiber surface," J. Biomed Struct Dyn, vol. 14, pp.547-560(1997).

Bhantnagar R.S., Qian J.J., Wedrychowska A., Sadeghi M., Wu Y.M., Smith N., "Design of biomimetic habitats for tissue engineering with P-15, a synthetic peptide analogue of collagen," Tissue Eng., vol. 5 , pp.53-65(1999).

Bhaskar S.N., Brady J.M., Getter L., Grower M.F., Driskell T., "Biodegradable ceramic implants in bone. Electron and light microscopic analysis," Oral Surgery, Oral Medicine, Oral Pathology, vol. 32, pp.336-346(1971).

Boss J.H., Biocompatibility: Review of the Concept and Its Relevance to Clinical Practice. Biomaterials and Bioengineering Handbook, edited by Wise DL et al., (2000).

Bostman O.M., "Absorbable implants for the fixation of fractures," J. Bone and Joint Surgery, vol. 73A, pp.148-153(1991).

Boutevin B., Robin J. J., Serdani A., "Synthesis and applications of graft-copolymers from ozonized poly(vinylidene fluoride) .2. ," Eur. Polym. J, vol. 28, pp.1507(1992).

Buddy D., Ratner, Stephanie J. B., "Biomaterials: Where we have been and where we are going," Annu. Rev. Biomed. Eng., vol. 6, pp.41–75(2004).

Cam D., Hyon S. H., Ikada Y., "Degradation of high molecular weight poly(L-lactide) in Alkaline Medium," Biomaterials, vol. 16 ,
pp.833-843(1885).

Cardin A.D., Weintraub HJR "Molecular modeling of protein-glycosaminoglycan interactions," Arteriosclerosis, vol. 9(1), pp.21-32(1989).

Catoire B., Verney V., Hagege R., mICHEL "A study of polypropylene peroxidation by ozonization using electron-spin-resonance and transmission electron-microscopy," polymer, vol. 33 (11), pp.2307-2311(1992).

Chan C.M., Polymer surface modification and characterization. Munich, Germany: Hanser; (1994).

Chen P.P., Zhang S.M., Cheng L., Huang S.L., Liu J., Zhou W., Gong H., Luo Q.M., "Adhesion and proliferation of chondrocytes on nano- HA/PDLLA scaffolds for bone tissue engineering," Bioceramics 18, pts 1 and 2 key engineering materials, 309-311: 919-922, Part 1-2(2006).

Choi S.H., Nho Y.C., "Radiation-induced graft copolymerization of mixture of acrylic acid and acrylonitrile onto polypropylene film," korea polymer journal, vol. 6, (4), pp.287-294(1998).

Cook A.D., Hrkach J.S., Gao N.N., Johnson I.M., Pajvani U.B., Cannizzaro S.M., Langer R., "Characterization and development of RGD-peptide-modified poly(lactic acid-co-lysine) as an interactive, resorbable biomaterial," Journal of biomedical materials research, vol. 35 (4), pp.513-523(1997).

Cui Y.L., Di Qi A., Liu W.G., Wang X.H., Wang H., Ma D.M., De Yao K, "Biomimetic surface modification of poly(L-lactic acid) with chitosan and its effects on articular chondrocytes in vitro," Biomaterials, vol. 24 (21), pp.3859-3868(2003).

Cutright D.E., Hunsuck E.E., "Tissue reaction to the biodegradable polylactic acid suture," Oral Surgery, vol. 31, pp.134-139(1971).

Dalton B.A., Mcfarland C.D., Underwood P.A., Steele J.G., "Role of the heparin-binding domain of fibronectin in attachment and spreading of human bone-derived cells," Journal of cell science, vol. 108, pp.2083-2092(1995).

Dasgupta S., "Surface modification of polyolefins for hydrophilicity and bondability: Ozonization and grafting hydrophilic monomers on ozonized polyolefins," J. Appl. Polym. Sci. , vol. 41(1-2),
pp.233-248(1990).

Dee K.C., Andersen T.T., Bizios R., "Design and function of novel osteoblast-adhesive peptides for chemical modification of biomaterials," Journal of biomedical materials research, vol. 40 (3), pp.371-377(1998).

Evan G., Brandt K., Widmer M.S., Lu L., Meszlenyi R.K., Gupta P.K., Mikos A.G., Hodges J., Williams J., Gurlek A., Nabawi A., Lohman R., Patrick C.W., "In Vivo Evaluation of Poly(L-lactic acid)Porous Conduits for Peripheral Nerve Regeneration," Biomaterials, vol. 20, pp.1109-1115(1999).

Filmon R., Basle MF, Atmani H., Chappard D., "Adherence of osteoblast-like cells on calcospherites developed on a biomaterial combining poly(2-hydroxyethyl) methacrylate and alkaline phosphatase, " BONE., vol. 30 (1), pp.152-158(2002).

Filmon R., Grizon F., Basle M.F., Chappard D., "Effects of negatively charged groups (carboxymethyl) on the calcification of poly(2-hydroxyethyl methacrylate)," Biomaterials, vol. 23 (14), pp.3053-3059(2002).

Fujimura K., Bessho K., Kusumoto K., Ogawa Y., Iizuka T., "Experimental studies on bone inducing activity of composites of atelopeptide type I collagen as a carrier for ectopic osteoinduction by rhBMP-2," Biochemical and biophysical research communication, vol. 208, pp.316-322(1995).

Fujimoto K., Takebayashi Y., Inoue H., Ikada Y., "Ozone-induced graft-polymerization onto polymer surface," Journal of polymer science part a-polymer chemistry, vol. 31 (4), pp.1035-1043(1993).

Garbassi F., Morra M., Occhiello E., Polymer surfaces. Chichester: Wiley; (1994).

Gatenholm P., Ashida T., Hoffman A.S., "Hybrid biomaterials prepared by ozone-induced polymerization .1. Ozonation of microporous polypropylene," Journal of polymer science part a-polymer chemistry, vol. 35, (8), pp.1461-1467(1997).

Gogolewski S., Jvanovic M., Perren S.M., Dillon J.G., Highes M.K., "Tissue Response and in Vivo Degradation of Selected Polyhydroxyacidsa:Polyactides(PLA), poly(3-hydroxybutyrate)(PHB) and Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHB/VA)," Journal of biomedical materials research, vol. 27, pp.1135-1148(1993).

Haddadiasl V., Burford R.P., garnett j.l., "Radiation graft modification of ethylene-propylene rubber .2. effect of additives," Radiation physics and chemistry, vol. 45 (2), pp.191-198(1995).

Hollinger J.O., Leong K.,: Poly(α-hydroxy acids): "Carrier for bone morphogenetic proteins," Biomaterials, vol. 17, pp.187-194(1996).

Hou L.T., Liu C.M., Lei J.Y., Wong M.Y., Chen J.K., "Biological effects of cementum and bone extracts on human periodontal fibroblasts," Journal of periodontology, vol. 71 (7), pp.1100-1109(2000).

Hou X., Zhang B.L., She F., Cui Y.L., Shi K.Y., Yao K.D., "Surface of gelatin modified poly(L-lactic acid) film," Chinese journal of polymer science , vol. 21 (3), pp.277-283(2003).

Hyon S.H., "Biodegradable poly(lactic acid) microspheres for drug delievery system," Yonsei medical journal, vol. 41, pp.720-734(2000).

Ijiri S., Nakamura T., Fujisawa Y., Hazama M., Komatsudani S., "Ectopic bone induction in porous apatite-wollastonite-contaning glass ceramic combined with bone morphogenetic protein," Journal of biomedical materials research, vol. 35, pp.421-432(1997).

Ishaug S.L., Jaszemski M.J., Bizios R., Mikos A.G., "Osteoblast function of synthetic biodegradable polymers," Journal of biomedical materials research, vol. 28, pp.1445-1453(1994).

Jacro M., "Calcium phosphate ceramics as hard tissue prosthetics(Review)," Clinical orthopaedics and related research, vol. 157, pp.259-278(1981).

Karlsson J.O., Gatenholm P., "Solid-supported wettable hydrogels preparted by ozone induce grafting," Polymer, vol. 19, pp.4251-4256(1996).

Kefeli A.A., Razumovskii S.D., Markin V.S., and Zaikov G.Y., polym. Sci. USSR, vol. 14 :2812

Kneser U., Schaefer D.J., Munder B., Klemt C., Andree C., Stark G.B., "Tissue engineering of bone," Minimally invasive therapy & allied technologies, vol. 11, pp.107-116(2002).

Kojima H., Fujio R., Yukita T., Oonishi A., Bridgestone Tire Co Ltd Jpn. Pat 47,036,273; (1972).

Ko Y.G., Kim Y.H., Park K.D., Lee H.J., Lee W.K., Park H.D., Kim S.H., Lee G.S., Ahn D.J., "Immobilization of poly(ethylene glycol) or its sulfonate onto polymer surfaces by ozone oxidation," Biomaterials, vol. 22 (15), pp.2115(2001).

Lallier T.E., Yukna R., St. Marie S., Moses R., "The putative collagen binding peptide hastens periodontal ligament cell attachment to bone replacement graft materials," J. periodontol, vol. 72, pp.990(2001).

Lam K.H., Schakeneraad J.M., Esselbrugge H., Feijen J., Nieuwenhuis P., "The effect of phagocytosis of poly(l-lactic acid)fragments on cellular morphology and viability," Journal of biomedical materials research, vol. 27, pp.1569-1577(1993).

Langer R., Vacanti J.P., "Tissue engineering," Science, vol. 260, pp.920-926(1993).

Lin Y.M., Boccaccini A.R., Polak J.M., Bishop A.E., "Biocompatibility of poly-DL-lactic acid (PDLLA) for lung tissue engineering," Journal of biomaterials applications, vol. 21 (2), pp.109-118(2005).

Mayhan K.G., Janssen R.A., Bertrand W.J., US. Patent 4, 311, 573, (1982).

Majeska R.J., Rodan S.B., Rodan G.A., "Parathyroid hormone-responsive clonal cell-lines from rat osteo-sarcoma," Endocrinology, vol. 107 (5), pp.1494-1503(1980).

Ma Z.W., Gao C.Y., Juan J., Ji J., Gong Y.H., Shen J.C., "Surface modification of poly-L-lactide by photografting of hydrophilic polymers towards improving its hydrophilicity," Journal of applied polymer science, vol. 85 (10), pp.2163-2171(2002).

Ma Z.W., Gao C.Y., Shen J.C., "Surface modification of poly-L-lactic acid (PLLA) membrane by grafting acrylamide: An effective way to improve cytocompatibility for chondrocytes," Journal of biomaterials science-polymer edition, vol. 14 (1), pp.13-25(2003).

Ma Z.W., Gao C.Y., Gong Y.H., Shen J.C., "Cartilage tissue engineering PLLA scaffold with surface immobilized collagen and basic fibroblast growth factor," Biomaterials, vol. 26 (11), pp.1253-1259(2005).

Michel A., Castaneda E., Guyot A., "Peroxide in poly(vinyl-chloride) ozonization," Journal of macromolecular science-chemistry A12, vol. 2, pp.227-247(1978).

Moad G., Solomon D.H., "The chemistry of free radical polymerization, " Pergamon, (1995).

Nakamura T., Yamamuro T., Higashi S., Kokubo T., Ito S: "A new glass-ceramic for bone replacement: Evaluation of its bonding to bone tissue," Journal of biomedical materials research, vol. 19 pp.685-698(1985).
Nguyen H., Qian J.J., Bhatnagar R.S., Li S., "Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix in hydrogels," biochemical and biophysical research communications, vol. 311 (1), pp.179-186(2003).

Oneill T., "Grafting of acrylic acid onto radiation-peroxidized polypropylene film in presence of ferrous ion," Journal of polymer science part a-1-polymer chemistry, vol. 10 (2), pp.569-80(1972).

Park H., Park K., "Biocompatibility issues of implantable drug delivery systems," Pharmaceutical research, vol. 13, pp.1770-1776(1996).

Park J.C., Hwang Y.S., Lee J.E., Park K.D., Matsumura K., Hyon S.H., Suh H., "Type I atelocollagen grafting onto ozone-treated polyurethane films: Cell attachment, proliferation, and collagen synthesis," Journal of biomedical materials research, vol. 52 (4), pp.669-677(2000).

Peeling J., Jazzar M.S., Clark D.T., "An ESCA study of the surface ozonization of polystyrene film," J. Polym. Sci., vol. 20, pp.1797-1805(1982).

Peeling J., Clark D.T., "Surface ozonation and photo-oxidation of polyethylene film," Journal of polymer science part a-polymer chemistry, vol. 21 (7), pp.2047-2055(1983).

Priest D.J., "Fold surface of polyethylene single crystals as assessed by selective degradation .1. ozone degradation method," Journal of polymer science part a-2-polymer physics, vol. 9 (10), pp.1777-80(1971).

Qian J.J., Bhatnagar R.S., "Enhance cell attachment to anorganic bone mineral in the presence of a synthetic peptide related to collagen," J. biomed. Mater. Res., vol. 31, pp.545-554(1996).

Quirk R.A., Chan W.C., Davies M.C., Tendler SJB, Shakesheff K.M., "Poly(L-lysine)-GRGDS as a biomimetic surface modifier for poly(lactic acid)," Biomaterials, vol. 22 (8), pp.865-872(2001).

Radder A.M., Davies J.E., Leenders H., Van Blitterswijk C.A., "Interfical behavior of PEO/PBT copolymers(polyactive) in a calavarial system. An in vitro study," Journal of biomedical Materials Research, vol. 28, pp.269-277(1994).

Rezania A., Healy K.E., "Integrin subunits responsible for adhesion of human osteoblast-like cells to biomimetic peptide surfaces," Journal of orthopaedic research, vol. 17 (4), pp.615-623(1999).

Rezania A., Healy K.E., "Biomimetic peptide surfaces that regulate adhesion, spreading, cytoskeletal organization, and mineralization of the matrix deposited by osteoblast-like cells," Biotechnology progress, vol. 15 (1), pp.19-32(1999).

Rezania A., Johnson R., Lefkow A.R., Healy K.E., "Bioactivation of metal oxide surfaces. 1. Surface characterization and cell response," Langmuir, vol. 15 (20), pp.6931-6939(1999).

Reddi A.H., Gay S., Miller E.J., "Transitions in collagen types during matrix-induced cartilage, bone and bone marrow development," Proceedings of national academy of science of the United States of Americal, vol. 18, pp.207-212(1987).

Rokkanen P., Bostman O., Hirvensalo E., "Absorable implants in the fization of fractures, osteomies, arthrodeses and ligaments," Acta orthopaedica scandinavica suppl, vol. 260, pp.19-20(1994).

Ronda G.A., Majeska R.J., "Phenotypic maturation of osteoblastic soteosarcoma cells in culture," Prog. clin. boil. res., vol. 110, pp.249-259(1982).

Rucci N., Migliaccio S., Zani B.M., Taranta A., Teti A., "Characterization of the osteoblast-like cell phenotype under microgravity conditions in the NASA-approved Rotating Wall Vessel bioreactor (RWV)," Journal of cellular biochemistry, vol. 85 (1), pp.167-179(2002).

Saitoh H., Takata T., Nikai H., Shintan H., Hyon S.S., Ikada Y., "Tissue compatibility of polylactic acid in skeletal site," Journal of material science: Material me, vol. 5, pp.194-199(1994) .

Sandhu H.S., Kanim L., Kabo J.M., Toth J.M., Zeegen E.N., Liu D., Delamarter R.B., Dawson E.G., "Effective doses of recombinant human bone morphogenetic protein-2 in experimental spinal fusion," Spine, vol. 21, pp.211-2122(1996).

Shyter A., Gazit D., Passi-Even L., Majeska R., Gronwicz G., Rodan G.A., "Formation of calcifying by osteosarcoma cells in diffusion chamber in vivo," Calcif. tissue int,, vol. 39, pp.49-54(1986).

Sinha V.R., Khosla L., "Bioabsorable polymers for implantable Therapeutic System," Drug Development and Industrial Pharmacy, vol. 24, pp.112-1139(1998).

Socrates G., Infrared characteristic group frequencies tables and charts, 2nded., Wiley, New York, pp.74-79 (1998).

Spector M：Basic principles of Tissue engineering. Tissue engineering applications in maxillofacial surgery and periodontics(Edit by Lynch SE, Genco RJ, Marx RE), pp.3-16(1999).

Steinmann B.U., Reddi A.H., "Changes in synthesis of type I- and III- collagen during matrix induced endochondral bone differentiation in rat," Biochemical journal, vol. 186, pp.919-924 (1980).

Suh H., Hwang Y.S., Lee J.E., Han C.D., Park J.C., "Behavior of osteoblasts on a type I atelocollagen grafted ozone oxidized poly L-lactic acid membrane," Biomaterials, vol. 22 (3), pp.219-230(2001).

Suh H.: Tissue restoration, "Tissue engineering, and regenerative medicine," Yonsei medical journal, vol. 41, pp.681-684(2000).

Tamada Y., Ikada Y., "Fibroblast growth on polymer surfaces and biosynthesis of collagen," J. biomed. Mater. Res., vol. 28, pp.783-789(1994).

Tanaka Y., Sato H., Mita K., Shimizu M., Kuraray Co Ltd Jpn Pat 61,136,507; (1986).
Teraoka F., Nakagawa M., Hara M., "Surface modification of poly(L-lactide) by atmospheric pressure plasma treatment and cell response," Dental materials journal, vol. 25 (3), pp.560-565(2006).

Thiede M.A., Yoon K., Golub E.E., Noda M., Rodan G.A., "Structure and expression of rat osteosarcoma(ROS-17/2.8)alkaline phosphatase: product of a signal copy gene," Nat. acad. Sci., vol. 85, pp.319-323(1985).

Trindade M.C., smith R.L., Jacobs J., Goodman S.B., : New insights in the biological effects of wear debris from total joint replacements. Biomaterials and bioengineering handbook, edit by Wise DL pp.407-432, (2000).

Vacanti J.P., Morse M.A., Saltzman W.M., Domb A.J., Perez-Atayde A., Langer R., "Selective cell transplantation using bioabsorable artificial polymers as materice," Journal of pediatric surgery, vol. 23, pp.3-9(1988).
Van Wachem P.B., Hogt A.H., Beugeling T., Feijen J., Bantjes A., Detmers J.P., Van Aken W.G., "Adhesion of cultured human endothelial cells onto methacrylate polymers with varying surface wettability and charge," Biomaterials, vol. 8, pp.323-328(1987).

Wang S., Cui W., Bei J., "Bulk and surface modification of polylactide," Anal. Bioanal. Chem., vol. 381, pp.547-556(2005).

Wang S.G., Hou J.W., Bei J.Z., Zhao Y.Q., "Tissue engineering and peripheral nerve regeneration (III) - Sciatic nerve regeneration with PDLLA nerve guide," Science in china series b-chemistry, vol. 44 (4), pp.419-426(2001).

Weider R., Koehler B., Ebert W., Scholl T., Klauss H., Bayer AG., Eur. Pat 0,751,167; (1997).

Weiss R.E., Reddi A.H., "Synthesis and localization of fibronectin during collagenous matrix-mesenchymal cell interaction and differentiation of cartilage and bone in vitro," Proceedings of national academy of sciences of the United States of America, vol. 77, pp.2074-2078(1980).

Yang X., Bhatnagar R.S., Li S., "Biomimetic collagen scaffolds for human bone cell growth and differentiation," Tissue engineering, vol. 10 (7-8), pp.1148-1159(2004).

Yang F., Murugan R., Ramakrishna S., Wang X., Ma Y.X., Wang S., "Fabrication of nano-structured porous PLLA scaffold intended for nerve tissue engineering," Biomaterial, vol. 25 (10), pp.1891-1900(2004).

Yuan Y.L., Zhang J., Ai F., Yuan J., Zhou J., Shen J., Lin S.C., "Surface modification of SPEU films by ozone induced graft copolymerization to improve hemocompatibility," Colloids and surfaces b-biointerfaces, vol. 29 (4), pp.247-256(2003).

Yukna R.A., Callan D.P., Krauser J.T., Evans G.H., Aichelmann-Reidy M.E., Moore K., Cruze R., Scott J.B., "Multi-center clinical evaluation of combiniation anorganic bovine-derived hydroxyapatite matrix (ABM)/cell binding peptide(P-15) as a bone replacement graft material in human periodontal osseous defect : 6-month results," J. Periodontol, vol. 69, pp.655-663(1998).

Yukna R.A., Krauser J.T., Callan D.P., Evans G.H., Cruz R., Martin M., "Multi-center clinical comparison of combination anorganic bovine-derived hydroxyapatite matrix (ABM)/cell binding peptide (P-15) and ABM in human periodontal osseous defects. 6-month results," Journal of periodontology, vol. 71 (11), pp.1671-1679(2000).

Yukuta T., Ohhashi T., Taniguchi Y., Arai K., Bridgestone tire Co Ltd pn Pat 49,034,592; (1974).

Zegzula H.D., Buck D.C., Brekke J., Wozney J.M., Hollinger J.O., "Bone formation with use of rhBMP-2(recombinant human bone morphogenetic protein-2)," Journal of bone and joint surgery, vol. 79A, pp.1778-1790(1997).

Zhang P.B., Wu H., Deng C., Hong Z.K., Wang X., Chen X.S., Jing X.B., "Blend of PLGA, RGD grafted copolymer and nanocomposite of PLLA grafted hydroxyapatite for bone tissue engineering," Tissue engineering , vol. 12 (4), pp.1074-1075(2006).

Zhao B., Brittain W., J. Polymer brushes: "Surface-immobilized macromolecules," Progress in polymer science, vol. 25 (5), pp.677-710(2000).

張博均,自製多乳聚合物之生物相容性及做為骨成形蛋白載體之研究,國立台灣大學醫學院臨床牙醫研究所2002