Biomaterials pp 283-300 | Cite as

Microparticulate Release Systems Based on Natural Origin Materials

  • Gabriela A. Silva
  • Filipa J. Costa
  • Nuno M. Neves
  • Rui L. Reis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 553)

Abstract

It has been a long path for particulate systems in biomedical applications. Since long time ago that these micron and nanosize systems synthesised from the most varied materials find application in the biomaterials field, mainly as drug delivery carrier systems. The aim of drug delivery systems is to facilitate the dosage and duration of the drug effect, causing the minimal harm to the patient and improving human health1,2. Typically, they allow for the reduction of the dosage frequency3 and are non-toxic4. Back in time, these systems designed for the controlled delivery of drugs were found extremely promising for several applications, such as the delivery of insulin5–8, contraceptives9–12, cancer therapeutics13–16 among others17.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Langer, R., 1991, Drug Delivery Systems. Mrs Bulletin 16:47–49Google Scholar
  2. 2.
    Pillai, O., Dhanikula, A. B. and Panchagnula, R., 2001, Drug delivery: an odyssey of 100 years. Current Opinion in Chemical Biology 5:439–446CrossRefGoogle Scholar
  3. 3.
    Pillai, O. and Panchagnula, R., 2001, Polymers in drug delivery. Current Opinion in Chemical Biology 5:447–451CrossRefGoogle Scholar
  4. 4.
    Kumar, M., 2000, Nano and microparticles as controlled drug delivery devices. Journal of Pharmacy and Pharmaceutical Sciences 3:234–258Google Scholar
  5. 5.
    Belmin, J. and Valensi, P., 2003, Novel drug delivery systems for insulin — Clinical potential for use in the elderly. Drugs & Aging 20:303–312CrossRefGoogle Scholar
  6. 6.
    Victor, S. P. and Sharma, C. P., 2002, Stimuli sensitive polymethacrylic acid microparticles (PMAA) — Oral insulin delivery. Journal of Biomaterials Applications 17:125–134CrossRefGoogle Scholar
  7. 7.
    Ramadas, M., Paul, W., Dileep, K. J., Anitha, Y. and Sharma, C. P., 2000, Lipoinsulin encapsulated alginate-chitosan capsules: intestinal delivery in diabetic rats. Journal of Microencapsulation 17:405–411CrossRefGoogle Scholar
  8. 8.
    Carino, G. P., Jacob, J. S. and Mathiowitz, E., 2000, Nanosphere based oral insulin delivery. Journal of Controlled Release 65:261–269CrossRefGoogle Scholar
  9. 9.
    Kost, J., Liu, L. S., Gabelnick, H. and Langer, R., 1994, Ultrasound as a Potential Trigger to Terminate the Activity of Contraceptive Delivery Implants. Journal of Controlled Release 30:77–81CrossRefGoogle Scholar
  10. 10.
    Dasaratha Dhanaraju, M., Vema, K., Jayakumar, R. and Vamsadhara, C., 2003, Preparation and characterization of injectable microspheres of contraceptive hormones. International Journal of Pharmaceutics 268:23–29CrossRefGoogle Scholar
  11. 11.
    Janes K. A., F. M. P., Marazuela A., Fabra A., Alonso M. J., 2001, Chitosan nanoparticles as delivery systems for doxorubicin. Journal of Controlled Release 73:255–267CrossRefGoogle Scholar
  12. 12.
    Dhanaraju, M. D., Vema, K., Jayakumar, R. and Vamsadhara, C., 2003, Preparation and characterization of injectable microspheres of contraceptive hormones. International Journal of Pharmaceutics 268:23–29CrossRefGoogle Scholar
  13. 13.
    Ehrhart, N., Dernell, W. S., Ehrhart, E. J., Hutchison, J. M., Douple, E. B., Brekke, J. H., Straw, R. C. and Withrow, S. J., 1999, Effects of a controlled-release cisplatin delivery system used after resection of mammary carcinoma in mice. American Journal of Veterinary Research 60:1347–1351Google Scholar
  14. 14.
    Yapp, D. T. T., Lloyd, D. K., Zhu, J. and Lehnert, S. M., 1998, Cisplatin delivery by biodegradable polymer implant is superior to systemic delivery by osmotic pump or ip injection in tumor–bearing mice. Anti-Cancer Drugs 9:791–796CrossRefGoogle Scholar
  15. 15.
    Ike, O., Shimizu, Y., Wada, R., Hyon, S. H. and Ikada, Y., 1992, Controlled Cisplatin Delivery System Using Poly(D,L-Lactic Acid). Biomaterials 13:230–235CrossRefGoogle Scholar
  16. 16.
    Arica, B., Calis, S., Kas, H. S., Sargon, M. F. and Hincal, A. A., 2002, 5-Fluorouracil encapsulated alginate beads for the treatment of breast cancer. International Journal of Pharmaceutics 242:267–269CrossRefGoogle Scholar
  17. 17.
    Schlapp, M. and Friess, W., 2003, Collagen/PLGA microparticle controlled composites for local delivery of gentamicin. Journal of Pharmaceutical Sciences 92:2145–2151CrossRefGoogle Scholar
  18. 18.
    Mateo, C., Fernandez-Lorente, G., Pessela, B. C. C., Vian, A., Carrascosa, A. V., Garcia, J. L., Fernandez-Lafuente, R. and Guisan, J. M., 2001, Affinity chromatography of polyhistidine tagged enzymes — New dextran-coated immobilized metal ion affinity chromatography matrices for prevention of undesired multipoint adsorptions. Journal of Chromatography A 915:97–106CrossRefGoogle Scholar
  19. 19.
    Mao, Q. M., Johnston, A., Prince, I. G. and Hearm, M. T. 1991, High-Performance Liquid-Chromatography of Amino-Acids, Peptides and Proteins.113. Predicting the Performance of Nonporous Particles in Affinity-Chromatography of Proteins. Journal of Chromatography 548:147–163CrossRefGoogle Scholar
  20. 20.
    An, X. N., Su, Z. X. and Zeng, H. M., 2003, Preparation of highly magnetic chitosan particles and their use for affinity purification of enzymes. Journal of Chemical Technology and Biotechnology 78:596–600CrossRefGoogle Scholar
  21. 21.
    Sun, Y. M., Yu, C. W., Liang, H. C. and Chen, J. P., 1999, Temperature-sensitive latex particles for immobilization of alpha-amylase. Journal of Dispersion Science and Technology 20:907–920CrossRefGoogle Scholar
  22. 22.
    Dasilva, M. A., Burrows, H. D., Formosinho, S. J., Gil, M. H., Lourenco, A. R., Paula, F. J. A. and Piedade, A. P., 1991, Photopolymerization of Acrylamide onto Magnetite Particles — Preparation of Magnetic Supports for Enzyme Immobilization. Materials Letters 11:96–100CrossRefGoogle Scholar
  23. 23.
    Safarikova, M., Roy, I., Gupta, M. N. and Safarik, I., 2003, Magnetic alginate microparticles for purification of alpha-amylases. Journal of Biotechnology 105:255–260CrossRefGoogle Scholar
  24. 24.
    Lee, T. H., Wang, J. and Wang, C.-H., 2002, Double-walled microspheres for the sustained release of a highly water soluble drug: characterization and irradiation studies. Journal of Controlled Release 83:437–452CrossRefGoogle Scholar
  25. 25.
    Mi F.-L., S. S.-S., Lin Y.-M., Wu Y.-B., Peng C.-K. and Tsai Y.-H., 2003, Chitin/PLGA blend microspheres as a biodegradable drug delivery system: a new delivery system for protein. Biomaterials 24:5023–5036CrossRefGoogle Scholar
  26. 26.
    Rongved, P., Klaveness, J. and Strande, P., 1997, Starch microspheres as carriers for X-ray imaging contrast agents: Synthesis and stability of new amino-acid linker derivatives. Carbohydrate Research 297:325–331CrossRefGoogle Scholar
  27. 27.
    Sahin, S., Selek, H., Ponchel, G., Ercan, M. T., Sargon, M., Hincal, A. A. and Kas, H. S., 2002, Preparation, characterization and in vivo distribution of terbutaline sulfate loaded albumin microspheres. Journal of Controlled Release 82:345–358CrossRefGoogle Scholar
  28. 28.
    Silva G. A., D. A. C. P., Coutinho O. P., Reis R. L., 2004, Evaluation of the encapsulation ability and release profile of starch-based particles using glucocorticoids as model drugs. in final stage of preparationGoogle Scholar
  29. 29.
    Sinha, V. R. and Trehan, A., 2003, Biodegradable microspheres for protein delivery. Journal of Controlled Release 90:261–280CrossRefGoogle Scholar
  30. 30.
    Soriano, I., Llabres, M. and Evora, C., 1995, Release control of albumin from polylactic acid microspheres. International Journal of Pharrnaceutics 125:223–230CrossRefGoogle Scholar
  31. 31.
    Takagi, M., Hayashi, H. and Yoshida, T., 1999, Starch particles modified with gelatin as novel small carriers for mammalian cells. Journal of Bioscience and Bioengineering 88:693–695CrossRefGoogle Scholar
  32. 32.
    Tuncel, A. and Piskin, E., 1996, Nonswellable and swellable poly(EGDMA) microspheres. Journal of Applied Polymer Science 62:789–798CrossRefGoogle Scholar
  33. 33.
    Czejka, M. J., Jager, W. and Schuller, J., 1989, Mitomycin-C Determination Using LoopColumn Extraction — a Rapid and Sensitive High-Performance Liquid-Chromatographic Assay for Pharmacokinetic Studies with Spherex Starch Particles. Journal of Chromatography-Biomedical Applications 497:336–341CrossRefGoogle Scholar
  34. 34.
    Erdogan, S., Ozer, A. Y., Volkan, B., Caner, B. and Bilgili, H., 2003, Particulate drug delivery systems in diagnosis of venous thrombosis. Journal of Controlled Release 87:238–240Google Scholar
  35. 35.
    Genc, O., Arpa, C., Bayramoglu, G., Arica, M. Y. and Bektas, S., 2002, Selective recovery of mercury by Procion Brown MX 5BR immobilized poly(hydroxyethylmethacrylate/chitosan) composite membranes. Hydrometallurgy 67:53–62CrossRefGoogle Scholar
  36. 36.
    Silva G.A., C. F. J., Coutinho O. P., Radin S., Ducheyne P., Reis R. L., 2003, Synthesis and evaluation of novel bioactive starch/Bioactive Glass microparticles. Journal of Biomedical Materials Research: Part AGoogle Scholar
  37. 37.
    Yenice, I., Calis, S., Atilla, B., Kas, H. S., Ozalp, M., Ekizoglu, M., Bilgili, H. and Hincal, A. A., 2003, In vitro/in vivo evaluation of the efficiency of teicoplanin-loaded biodegradable microparticles formulated for implantation to infected bone defects. Journal of Microencapsulation 20:705–717CrossRefGoogle Scholar
  38. 38.
    Qu, Q. Q., Ducheyne, P. and Ayyaswamy, P. S., 2002, Bioactive, degradable composite microspheres — Effect of filler material on surface reactivity. In Microgravity Transport Processes in Fluid, Thermal, Biological, and Materials Sciences pp. 556–564Google Scholar
  39. 39.
    Schepers, E., Barbier, L., van Steenberghe, D. and Ducheyne, P., 2001, Guided tissue regeneration versus two types of bioactive glass particles in the treatment of furcation type II defects in the beagle dog. Journal of Dental Research 80:1215–1215Google Scholar
  40. 40.
    Qiu, Q. Q., Ducheyne, P. and Ayyaswamy, P. S., 2001, 3D Bone tissue engineered with bioactive microspheres in simulated microgravity. In Vitro Cellular & Developmental Biology-Animal 37:157–165CrossRefGoogle Scholar
  41. 41.
    Qiu, Q. Q., Ducheyne, P. and Ayyaswamy, P. S., 2000, New bioactive, degradable composite microspheres as tissue engineering substrates. Journal of Biomedical Materials Research 52:66–76CrossRefGoogle Scholar
  42. 42.
    Qiu, Q. Q., Ducheyne, P. and Ayyaswamy, P. S., 1999, Fabrication, characterization and evaluation of bioceramic hollow microspheres used as microcarriers for 3-D bone tissue formation in rotating bioreactors. Biomaterials 20:989–1001CrossRefGoogle Scholar
  43. 43.
    Hutmacher, D. W., 2000, Scaffolds in tissue engineering bone and cartilage. Biomaterials 21:2529–2543CrossRefGoogle Scholar
  44. 44.
    Santavirta, S., Konttinen, Y. T., Saito, T., Gronblad, M., Partio, E., Kemppinen, P. and Rokkanen, P., 1990, Immune-Response to Polyglycolic Acid Implants. Journal of Bone and Joint Surgery-British Volume 72:597–600Google Scholar
  45. 45.
    Paivarinta, U., Bostman, O., Majola, A., Toivonen, T., Tormala, P. and Rokkanen, P., 1993, Intraosseous Cellular-Response to Biodegradable Fracture Fixation Screws Made of Polyglycolide or Polylactide. Archives of Orthopaedic and Trauma Surgery 112:71–74CrossRefGoogle Scholar
  46. 46.
    Ignatius, A. A., Betz, O., Augat, P. and Claes, L. E., 2001, In vivo investigations on composites made of resorbable ceramics and poly(lactide) used as bone graft substitutes. Journal of Biomedical Materials Research 58:701–709CrossRefGoogle Scholar
  47. 47.
    Toth, J. M., Wang, M., Scifert, J. L., Cornwall, G. B., Estes, B. T., Seim, H. B. and Turner, A. S., 2002, Evaluation of 70/30 D,L-PLa for use as a resorbable interbody fusion cage. Orthopedics 25:S1131–S1140Google Scholar
  48. 48.
    Filipovic-Grcic J. V. D., Moneghini M., Becirevic-Lacan M., Magarotto L., Jalsenjak I., 2000, Chitosan microspheres with hydrocortisone and hydrocortisone-hydroxypropyl-B-cyclodextrin inclusion complex. European Journal of Pharmaceutical Sciences 9:373–379CrossRefGoogle Scholar
  49. 49.
    Hata H. O. H., Machida Y., 2000, Preparation of CM-chitin microspheres by complexation with iron(II) in w/o emulsion and their biodisposition characteristics in mice. Biomaterials 21:1779–1788CrossRefGoogle Scholar
  50. 50.
    Lim S. T., M. G. P., Berry D. J., and Brown M. B., 2000, Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. Journal of Controlled Release 66:281–292CrossRefGoogle Scholar
  51. 51.
    Mao H-Q. R. K., Troung-Le V. L., Janes K. A., Lin K. Y., Wang Y., August J. T., Leong K. W., 2001, Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. Journal of Controlled Release 70:399–421CrossRefGoogle Scholar
  52. 52.
    Cui Z. M. R. J., 2001, Chitosan-based nanoparticles for topical genetic immunization. Journal of Controlled Release 75:409–419CrossRefGoogle Scholar
  53. 53.
    Aiedeh K. and Taha, M. O., 2001, Synthesis of iron-crosslinked succinate and ironcrosslinked hydroxamated chitosan succinate and their in vitro evaluation as potential matrix materials for oral theophylline sustained-release beads. European Journal of Pharmaceutical Sciences 13:159–168CrossRefGoogle Scholar
  54. 54.
    Vaz, C. M., Fossen, M., van Tuil, R. F., de Graaf, L. A., Reis, R. L. and Cunha, A. M., 2003, Casein and soybean protein-based thermoplastics and composites as alternative biodegradable polymers for biomedical applications. Journal of Biomedical Materials Research Part A 65A:60–70CrossRefGoogle Scholar
  55. 55.
    Vaz, C. M., van Doeveren, P., Reis, R. L. and Cunha, A. M., 2003, Soy matrix drug delivery systems obtained by melt-processing techniques. Biomacromolecules 4:1520–1529CrossRefGoogle Scholar
  56. 56.
    Vaz, C. M., van Doeveren, P., Reis, R. L. and Cunha, A. M., 2003, Development and design of double-layer co-injection moulded soy protein based drug delivery devices. Polymer 44:5983–5992CrossRefGoogle Scholar
  57. 57.
    Vaz, C. M., De Graaf, L. A., Reis, R. L. and Cunha, A. M., 2003, Effect of crosslinking, thermal treatment and UV irradiation on the mechanical properties and in vitro degradation behavior of several natural proteins aimed to be used in the biomedical field. Journal of Materials Science-Materials in Medicine 14:789–796CrossRefGoogle Scholar
  58. 58.
    Vaz, C. M., de Graaf, L. A., Reis, R. L. and Cunha, A. M., 2003, In vitro degradation behaviour of biodegradable soy plastics: effects of crosslinking with glyoxal and thermal treatment. Polymer Degradation and Stability 81:65–74CrossRefGoogle Scholar
  59. 59.
    Silva, G. A., Vaz, C. M., Coutinho, O. P., Cunha, A. M. and Reis, R. L., 2003, In vitro degradation and cytocompatibility evaluation of novel soy and sodium caseinate-based membrane biomaterials. Journal of Materials Science Materials in Medicine 14:1055–1066CrossRefGoogle Scholar
  60. 60.
    Osth, K., Strindelius, L., Larhed, A., Ahlander, A., Roomans, G. M., Sjoholm, I. and Bjork, E., 2003, Uptake of ovalbumin-conjugated starch microparticles by pig respiratory nasal mucosa in vitro. Journal of Drug Targeting 11:75–82CrossRefGoogle Scholar
  61. 61.
    Sousa, R. A., Mano, J. F., Reis, R. L., Cunha, A. M. and Bevis, M. J., 2002, Mechanical Performance of Starch Based Bioactive Composite Biomaterials Molded with Preferred Orientation for Potential Medical Applications. Polym Eng & Sci 42:1032–1045CrossRefGoogle Scholar
  62. 62.
    Reis, R. L. and Cunha, A. M., 1995, Characterization of two biodegradable polymers of potential application within the biomaterials field. Journal of Materials Science-Materials in Medicine 6:786–792CrossRefGoogle Scholar
  63. 63.
    Reis, R. L., Mendes, S. C., Cunha, A. M. and Bevis, M. J., 1997, Processing and in vitro degradation of starch/EVOH thermoplastic blends. Polymer International 43:347–352CrossRefGoogle Scholar
  64. 64.
    Vaz, C. M., Reis, R. L. and Cunha, A. M., 2001, Degradation model of starch-EVOH plus HA composites. Materials Research Innovations 4:375–380CrossRefGoogle Scholar
  65. 65.
    Borissova, R., Lammek, B., Stjarkvist, P. and Sjoholm, I., 1995, Biodegradable Microspheres.16. Synthesis of Primaquine-Peptide Spacers for Lysosomal Release from Starch Microparticles. Journal of Pharmaceutical Sciences 84:249–255CrossRefGoogle Scholar
  66. 66.
    Laakso, T., 1987, Preparation and Properties of Polyacryl Starch Microparticles Potential-Drug Carriers in the Treatment of Lysosomal Parasitic Diseases. Acta Pharmaceutica Suecica 24:208–208Google Scholar
  67. 67.
    Baillie, A. J., Coombs, G. H., Dolan, T. F., Hunter, C. A., Laakso, T., Sjoholm, I. and Stjamkvist, P., 1987, Biodegradable Microspheres.9. Polyacryl Starch Microparticles as a Delivery System for the Antileishmanial Drug, Sodium Stibogluconate. Journal of Pharmacy and Pharmacology 39:832–835CrossRefGoogle Scholar
  68. 68.
    Artursson, P., Edman, P., Laakso, T. and Sjoholm, I., 1984, Characterization of Polyacryl Starch Microparticles as Carriers for Proteins and Drugs. Journal of Pharmaceutical Sciences 73:1507–1513CrossRefGoogle Scholar
  69. 69.
    Chellat, F., Tabrizian, M., Dumitriu, S., Chomet, E., Rivard, C. H. and Yahia, L., 2000, Study of biodegradation behavior of chitosan-xanthan microspheres in simulated physiological media. JBiomed Mater Res 53:592–599CrossRefGoogle Scholar
  70. 70.
    Chellat, F., Tabrizian, M., Dumitriu, S., Chomet, E., Magny, P., Rivard, C. H. and Yahia, L., 2000, In vitro and in vivo biocompatibility of chitosan-xanthan polyionic complex. J Biomed Mater Res 51:107–116CrossRefGoogle Scholar
  71. 71.
    Sivakumar, M., Manjubala, I. and Panduranga Rao, K., 2002, Preparation, characterization and in-vitro release of gentamicin from coralline hydroxyapatite-chitosan composite microspheres. Carbohydrate Polymers 49:281–288CrossRefGoogle Scholar
  72. 72.
    Wu, T.-J., Huang, H.-H., Lan, C.-W., Lin, C.-H., Hsu, F.-Y. and Wang, Y.-J., 2004, Studies on the microspheres comprised of reconstituted collagen and hydroxyapatite. Biomaterials 25:651–658CrossRefGoogle Scholar
  73. 73.
    Borden, M., Attawia, M., Khan, Y. and Laurencin, C. T., 2002, Tissue engineered microsphere-based matrices for bone repair:: design and evaluation. Biomaterials 23:551–559CrossRefGoogle Scholar
  74. 74.
    Wilson, J. and Low, S. B., 1992, Bioactive Ceramics for periodontal treatment: comparative studies in the patus monkey. JApplied Biomaterials 3:123–129CrossRefGoogle Scholar
  75. 75.
    Stanley, H. R., Hall, M. B., Colaizzi, F. and Clark, A. E., 1987, Residual alveolar rige maintenance with a new endosseous implant material. JProsthetic Dentristy 58:607–613CrossRefGoogle Scholar
  76. 76.
    Wilson, J. and Merwin, G. E., 1988, Biomaterials for facial bone augmentation: comparative studies. JApplied Biomaterials 22:159–177Google Scholar
  77. 77.
    Reis, R. L., Cunha, A. M., Allan, P. S. and Bevis, M. J., 1996, Mechanical behavior of injection-molded starch-based polymers. Polymers for Advanced Technologies 7:784–790CrossRefGoogle Scholar
  78. 78.
    Reis, R. L., Cunha, A. M., Fernandes, M. H. and Correia, R. N., 1997, Treatments to induce the nucleation and growth of apatite-like layers on polymeric surfaces and foams. Journal of Materials Science-Materials in Medicine 8:897–905CrossRefGoogle Scholar
  79. 79.
    Reis, R. L., Cunha, A. M., Allan, P. S. and Bevis, M. J., 1997, Structure development and control of injection-molded hydroxylapatite-reinforced starch/EVOH composites. Advances in Polymer Technology 16:263–277CrossRefGoogle Scholar
  80. 80.
    Reis, R. L., Cunha, A. M. and Bevis, M. J., 1999, Oriented composites meet tough orthopedic demands. Modern Plastics 76:73–75Google Scholar
  81. 81.
    Sousa, R. A., Kalay, G., Reis, R. L., Cunha, A. M. and Bevis, M. J., 2000, Injection molding of a starch/EVOH blend aimed as an alternative biomaterial for temporary applications. Journal of Applied Polymer Science 77:1303–1315CrossRefGoogle Scholar
  82. 82.
    Reis, R. L., Cunha, A. M., Allan, P. S. and Bevis, M. J., 1996, Mechanical Behaviour of Injection Moulded Starch Based Polymers. JPolym Adv Tech 7:784–790CrossRefGoogle Scholar
  83. 83.
    Gomes, M. E., Ribeiro, A. S., Malafaya, P. B., Reis, R. L. and Cunha, A. M., 2001, A new approach based on injection moulding to produce biodegradable starch-based polymeric scaffolds: morphology, mechanical and degradation behaviour. Biomaterials 22:883–889CrossRefGoogle Scholar
  84. 84.
    Gomes, M. E., Godinho, J. S., Tchalamov, D., Cunha, A. M. and Reis, R. L., 2002, Alternative tissue engineering scaffolds based on starch: processing methodologies, morphology, degradation, mechanical properties and biological response. Materials Science and Engineering: C 20:19–26CrossRefGoogle Scholar
  85. 85.
    Malafaya, P. B., Elvira, C., Gallardo, A., San Roman, J. and Reis, R. L., 2001, Porous starch-based drug delivery systems processed by a microwave route. J Biomater Sci Polym Ed 12:1227–1241CrossRefGoogle Scholar
  86. 86.
    Boesel, L. F., Mano, J. F., Elvira, C. and Reis, R. L., 2003, Hydrogels and hydrophilic partially degradable bone cements based on biodegradable blends incorporating starch. In Biodegradable polymers and plastics (E., C.).Kluwer Academic, Drodrecht, pp.Google Scholar
  87. 87.
    Mendes, S. C., Reis, R. L., Bovell, Y. P., Cunha, A. M., van Blitterswijk, C. A. and de Bruijn, J. D., 2001, Biocompatibility testing of novel starch-based materials with potential application in orthopaedic surgery: a preliminary study. Biomaterials 22:2057–2064CrossRefGoogle Scholar
  88. 88.
    Mendes, S. C., Bezemer, J., Claase, M. B., Grijpma, D. W., Bellia, G., Degli-Innocenti, F., Reis, R. L., De Groot, K., Van Blitterswijk, C. A. and De Bruijn, J. D., 2003, Evaluation of two biodegradable polymeric systems as substrates for bone tissue engineering. Tissue Engineering 9:S91–S101CrossRefGoogle Scholar
  89. 89.
    Gomes, M. E., Reis, R. L., Cunha, A. M., Blitterswijk, C. A. and de Bruijn, J. D., 2001, Cytocompatibility and response of osteoblastic-like cells to starch-based polymers: effect of several additives and processing conditions. Biomaterials 22:1911–1917CrossRefGoogle Scholar
  90. 90.
    Marques, A. P., Reis, R. L. and Hunt, J. A., 2002, The biocompatibility of novel starchbased polymers and composites: in vitro studies. Biomaterials 23:1471–1478CrossRefGoogle Scholar
  91. 91.
    Salgado, A. J., Gomes, M. E., Chou, A., Coutinho, O. P., Reis, R. L. and Hutmacher, D. W., 2002, Preliminary study on the adhesion and proliferation of human osteoblasts on starch-based scaffolds. Materials Science & Engineering C-Biomimetic and Supramolecular Systems 20:27–33CrossRefGoogle Scholar
  92. 92.
    Elvira, C., Mano, J. F., San Roman, J. and Reis, R. L., 2002, Starch-based biodegradable hydrogels with potential biomedical applications as drug delivery systems. Biomaterials 23:1955–1966CrossRefGoogle Scholar
  93. 93.
    Azevedo, H. S., Gama, F. M. and Reis, R. L., 2003, In vitro assessment of the enzymatic degradation of several starch based biomaterials. Biomacromolecules 4:1703–1712CrossRefGoogle Scholar
  94. 94.
    Elvira, C., Mano, J. F., San Roman, J. and Reis, R. L., 2002, Starch-based biodegradable hydrogels with potential biomedical applications as drug delivery systems. Biomaterials 23:1955–1966CrossRefGoogle Scholar
  95. 95.
    Pereira, C. S., Cunha, A. M., Reis, R. L., Vazquez, B. and San Roman, J., 1998, New starch-based thermoplastic hydrogels for use as bone cements or drug-delivery carriers. Journal of Materials Science-Materials in Medicine 9:825–833CrossRefGoogle Scholar
  96. 96.
    Leonor, I. B. and Reis, R. L., 2003, An innovative auto-catalytic deposition route to produce calcium-phosphate coatings on polymeric biomaterials. Journal of Materials Science-Materials in Medicine 14:435–441CrossRefGoogle Scholar
  97. 97.
    Oliveira, A. L., Elvira, C., Reis, R. L., Vazquez, B. and San Roman, J., 1999, Surface modification tailors the characteristics of biomimetic coatings nucleated on starch-based polymers. Journal of Materials Science-Materials in Medicine 10:827–835CrossRefGoogle Scholar
  98. 98.
    Demirgoz, D., Elvira, C., Mano, J. F., Cunha, A. M., Piskin, E. and Reis, R. L., 2000, Chemical modification of starch based biodegradable polymeric blends: effects on water uptake, degradation behaviour and mechanical properties. Polymer Degradation and Stability 70:161–170CrossRefGoogle Scholar
  99. 99.
    Gomes, M. E., Sikavitsas, V. I., Behravesh, E., Reis, R. L. and Mikos, A. G., 2003, Effect of flow perfusion on the osteogenic differentiation of bone marrow stromal cells cultured on starch-based three-dimensional scaffolds. Journal of Biomedical Materials Research Part A 67A:87–95CrossRefGoogle Scholar
  100. 100.
    Marques, A. P., Reis, R. L. and Hunt, J. A., 2002, The biocompatibility of novel starchbased polymers and composites: in vitro studies. Biomaterials 23:1471–1478CrossRefGoogle Scholar
  101. 101.
    Mendes, S. C., Reis, R. L., Bovell, Y. P., Cunha, A. M., van Blitterswijk, C. A. and de Bruijn, J. D., 2001, Biocompatibility testing of novel starch-based materials with potential application in orthopaedic surgery: a preliminary study. Biomaterials 22:2057–2064CrossRefGoogle Scholar
  102. 102.
    Silva, G. A., Costa, F. J., Pedro, A., Coutinho, O. P., Neves, N. M. and Reis, R. L., 2004, The response of starch-based particles to in vitro bioactivity and biocompatibility testing. in preparation Google Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Gabriela A. Silva
    • 1
    • 2
  • Filipa J. Costa
    • 1
  • Nuno M. Neves
    • 1
    • 2
  • Rui L. Reis
    • 1
    • 2
  1. 1.3B’s Research Group-Biomaterials, Biodegradables, BiomimeticsUniversity of MinhoBragaPortugal
  2. 2.Department of Polymer EngineeringUniversity of MinhoGuimarãesPortugal

Personalised recommendations