Abstract
The term “tissue engineering” refers to methods and techniques used to improve the regeneration of human cells and tissues, including the manipulation of natural and synthetic materials which provide both the structural integrity and the biochemical information to young cells when they are growing into a specific kind of tissue. This chapter deals with the application of tissue engineering to bone tissue regeneration and is focused to the polymer structures studied and used as temporary templates to promote bone reconstruction. After a brief introduction about the general principle of regenerative medicine, the scaffold design criteria and their applications, attention will be focused to scaffold for bones. A scaffold classification is reported based on the type of constituent polymers and a detailed discussion is provided about these materials highlighting advantages and drawbacks for each of them. Moreover, polymer scaffold preparation and characterization techniques are described and discussed with some examples. Finally clinical aspects and criticisms are also presented to show the state of art of the topic.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Amidi, M., Romeijn, S.G., Verhoef, J.C., Junginger, H.E., Bungener, L., Huckriede, A., Crommelin, D.J.A., Jiskoot, W.: N-Trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination: biological properties, immunogenicity in a mouse model. Vaccine 25, 144–155 (2007)
Asti, A., Visai, L., Dorati, R., Conti, B., Saino, E., Sbarra, S., Gastaldi, G., Benazzo, F.: Improved cell growth by Bio-Oss/PLA scaffolds for use as a bone substitute. Technol. Health Care 16, 401–413 (2008)
Asti, A., Gastaldi, G., Dorati, R., Saino, E., Conti B., Visai, L., Benazzo, F.: Human adipose-derived stem cells (hASCs) grown on PLGA, PLGA/HAP and titanium scaffolds for surgical applications. Bioinorg. Chem. Appl. Article ID 831031,12 (2010)
Badylak, S.F.: Modification of natural polymers: collagen. In: Atala, A., Lanza, R. P. (eds.) Methods of Tissue Engineering. pp. 505–514. Academic Press, San Diego (2002)
Bartolo, P.J.S., Almeida, H., Laoui, T.: Rapid prototyping and manufacturing for tissue engineering scaffolds. Int. J. Comput. Appl. Technol. 36(1), 1–9 (2009)
Benedetti, L., Cortivo, R., Berti, T., Berti, A., Pea, F., Mazzo, M., Moras, M., Abatangelo, G.: Biocompatibility and biodegradation of different hyaluronan derivatives (Hyaff) implanted in rats. Biomaterials 14, 1154–1160 (1994)
Cai, X., Tong, H., Shen, X., Chen, W., Yan, J., Hu, J.: Preparation and characterization of homogeneous chitosan–polylactic acid/hydroxyapatite nanocomposite for bone tissue engineering and evaluation of its mechanical properties. Acta Biomater. 5(7), 2693–2703 (2009)
Campoccia, D., Hunt, J.A., Doherty, P.J., Zhong, S.P., O’Regan, M., Benedetti, L.: Quantitative assessment of the tissue response to films of hyaluronan derivatives. Biomaterials 17, 963–975 (1996)
Cao, H., Kuboyama, N.: A biodegradable porous composite scaffold of PGA/β-TCP for bone tissue engineering. Bone 46, 386–395 (2010)
Chang, Y., Bender, J.D., Phelps, M.V.B., Allcock, H.R.: Synthesis and self-association behavior of biodegradable amphiphilic poly[bis(ethyl glycinat-N-y)phosphazene]-PEO block copolymers. Biomacromolecules 3, 1364–1369 (2002)
Chesnutt, B.M., Yuan, Y., Buddington, K., Haggard, W.O., Bumgardner, J.D.: Composite chitosan/nano-hydroxyapatite scaffolds induce osteocalcin production by osteoblasts in vitro and support bone formation in vivo. Tissue Eng. Part A 15(9), 2571–2579 (2009)
Chua, C.K., Feng, C., Lee, C.W., Ang, G.Q.: Rapid investment casting: direct and indirect approaches via model maker II. Int. J. Adv. Manuf. Technol. 25(1), 26–32 (2005)
Colonna, C., Conti, B., Perugini, P., Pavanetto, F., Modena, T., Dorati, R., Iadarola, P., Genta, I.: Ex vivo evaluation of prolidase loaded chitosan nanoparticles for the enzyme replacement therapy. Eur. J. Pharm. Biopharm. 70, 58–65 (2008)
Day, R.M., Boccaccini, A.R., Shurey, S., Roether, J.A., Forbes, A., Hench, L.L.: Assessment of polyglycolic acid mesh and bioactive glass for soft tissue engineering scaffolds. Biomaterials 25, 5857–5866 (2004)
Dorati, R., Colonna, C., Genta, I., Modena, T., Conti, B.: Effect of porogen on the physico-chemical properties and degradation performance of PLGA scaffolds. Polym. Degrad. Stab. 94, 694–701 (2010)
Ghosh, S., Viana, J.C., Reis, R.L., Mano, J.F.: The double porogen approach as a new technique for the fabrication of interconnected poly(l-lactic acid) and starch based biodegradable scaffolds. J. Mater. Sci. Mater. Med. 18, 185–193 (2007)
Gianolio, D.A., Philbrook, M., Avila, L.Z., Young, L.E., Plate, L., Santos, M.R., Bernasconi, R., Liu, H., Ahn, S., Sun, W., Jarrett, P.K., Miller, R.J.: Hyaluronan-tethered opioid depots: synthetic strategies and release kinetics in vitro and in vivo. Bioconjugate Chem. 19(9), 1767–1774 (2008)
Ginty, P.J., Barry, J.J.A., White, L.J., Howdle, S.M., Shakesheff, K.M.: Controlling protein release from scaffold using polymer blends and composites. Eur. J. Pharm. Biopharm. 68, 82–89 (2008)
Gopferich, A., Tessmar, J.: Polyanhydrides degradation and erosion. Adv. Drug Deliv. Rev. 54, 911 (2002)
Guarino, V., Ambrosio, L.: The synergic effect of polylactide fiber and calcium phosphate particle reinforcement in poly-epsilon-caprolactone based composite scaffolds. Acta Biomater. 4, 1778–1787 (2008)
Guarino, V., Taddei, D., DiFoggia, M.: The influence of hydroxyapatite particles on in vitro degradation behaviour of poly epsilon caprolactone based composite scaffolds. Tissue Eng. Part A 15, 3655–3668 (2009)
Gupta, D., Tator, C.H., Shoichet, M.S.: Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials 27(11), 2370–2379 (2006)
Gupta, D., Venugopal, J., Mitra, S., GiriDev, V.R., Ramakrishna, S.: Nanostructured biocomposite substrates by electrospinning and electrospraying for the mineralization of osteoblasts. Biomaterials 30(11), 2085–2094 (2009)
Hadjidakis, D.J., Androulakis, I.I.: Bone remodeling. Ann. N. Y. Acad. Sci. 1092, 385–396 (2006)
Hassenkam, T., Fantner, G.E., Cutroni, J.A., Weaver, J.C., Morse, D.E., Hansma, P.K.: High resolution AFM imaging of intact and fractured trabecular bone. Bone 35(1), 4–10 (2004)
Hench, L.L.: Bioceramics: from concept to clinic. J. Am. Ceram. Soc. 74, 1487–1510 (1991)
Hench, L.L.: Bioceramics. J. Am. Ceram. Soc 81(7), 1705–1728 (1998)
Hoeman, C.D., Sun, J., Legare, A., McKee, M.D., Buschmann, M.D.: Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthritis Cartilage 13(4), 318–329 (2005)
Homma, A., Sato, H., Okamachi, A., Emura, T., Ishizawa, T., Kato, T., Matsuura, T., Sato, S., Tamura, T., Higuchi, Y., Watanabe, T., Kitamura, H., Asanuma, K., Yamazaki, T., Ikemi, M., Kitagawa, H., Morikawa, T., Ikeya, H., Maeda, K., Takahashi, K., Nohmi, K., Izutani, N., Huang, M., Khor, E., Lim, L.Y.: Uptake and cytotoxicity of chitosan molecules, nanoparticles: effects of molecular weight, degree odf deacetylation. Pharm. Res. 21(2), 344–353 (2004)
Hou, Q.P., Walsh, M.C., Freeman, J.J.A., Barry, S.M., Howdle, K.M.: Incorporation of protein within fibre-based scaffolds using a post-fabrication entrapment method. J. Pharm. Pharmacol. 58, 895–902 (2006)
Ifkovits, J.L., Burdick, J.A.: Photopolymerizable and degradable biomaterials for tissue engineering applications. Tissue Eng. 13(10), 2369–2385 (2007)
Jacobs, C.R.: The mechanobiology of cancellous bone structural adaptation. J. Rehabil. Res. Dev. 37, 209–216 (2000)
Kanda, M., Suzuki, R.: Novel hyaluronic acid-methotrexate conjugates for osteoarthritis treatment. Bioorg. Med. Chem. 17(13), 4647–4656 (2009)
Katayama, Y., Montenegro, R., Freier, T., Midha, R., Belkas, J.S., Shoichet, M.S.: Coil-reinforced hydrogel tubes promote nerve regeneration equivalent to that of nerve autografts. Biomaterials 27(3), 505–518 (2006)
Khan, Y., Yaszemski, M.J., Mikos, A.G., Laurencin, C.T.: Tissue engineering of bone: material and matrix considerations. J. Bone Joint Surg. 90, 36–42 (2008)
Kim, H.D., Valentini, R.F.: Retention and activity of BMP-2 in hyaluronic acid-based scaffolds in vitro. J. Biomed. Mater. Res. Part A 59(3), 573–584 (2002)
Kim, T.K., Yoon J.J., Lee, D.S., Park, T.G.: Gas foamed open porous biodegradable polymeric microspheres. Biomaterials 27(2), 152–159 (2006)
Kim, I.Y., Seo, S.J., Moon, H.S., Yoo, M.K., Park, I.Y., Kim, B.C., Cho, C.S.: Chitosan and its derivatives for tissue engineering applications. Biotechnol. Adv. 26(1), 1–21 (2008)
Kisiday, J.D., Jim, M., DiMicco, M.A., Kurz, B., Grodzinsky, A.J.: Effects of dynamic compressive loading on chondrocyte biosynthesis in self assembling peptide scaffolds. J. Biomech. 37(5), 595–604 (2004)
Klein, A.W.: Collagen substances. Facial Plast. Surg. Clin. North. Am. 9(2), 205–218 (2001)
Klok, H.-A., Hwang, J.J., Hartgerink, J.D., Stupp, S.I.: Self assembling biomaterials: l-lysine-dendron-substitute cholesterylg(l-lactic acid). Macromolecules 35(16), 6101–6111 (2002)
Krauland, A.H., Alonso, M.J.: Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system. Int. J. Pharm. 340, 134–142 (2007)
Lakshmi, N.S., Laurencin, C.T.: Polymers as biomaterials for tissue engineering and controlled drug delivery. Adv. Biochem. Eng./Biotechnol. 102, 47–90 (2006)
Lakshmi, S., Katti, D.S., Laurencin, C.T.: Biodegradable polyphosphazenes for drug delivery applications. Adv. Drug Deliv. Rev. 25;55(4), 467–482 (2003)
Lakshmi, S., Lee, D., Bender, J.D., Barrett, E.W., Greish, Y.E., Brown, P.W., Allcock, H.R., Laurencin, C.T.: Synthesis, characterization and in vitro osteocompatibility evaluation of novel biodegradable [poly(ethylalanato)(alkyloxybenzoate)phosphazenes]. J. Biomater. Res. 76A, 206–213 (2006)
Li, M., Mondrinos, M.J., Chen, X., Gandhi, M.R., Ko, F.K., Lelkes, P.I.: Co-electrospun poly(lactide-co-glycolide), gelatin, and elastin blends for tissue engineering scaffolds. J. Biomed. Mater. Res. A 79(4), 963 (2006)
Li, J., Du, Y., Liang, H.: Influence of molecular parameters on the degradation of chitosan by a commercial enzyme. Polym. Degrad. Stab. 92(3), 515–524 (2007)
Lim, Y.M., Gwon, H.J., Shin, J., Jeun, J.P., Nho, Y.C.: Preparation of porous poly (ε-caprolactone) scaffolds by gas foaming process and in vitro/in vivo degradation behavior using γ-ray irradiation. J. Ind. Eng. Chem. 14(4), 436–441 (2008)
Lu, H.H., Tang, A., Oh, S.C., Spalazzi, J.P., Dionisio, K.: Compositional effects on the formation of a calcium phosphate layer and the response of osteoblast-like cells on polymer-bioactivecomposites. Biomaterials 26, 2281–2288 (2005)
Ma, P.X.: Biomimetic materials for tissue engineering. Adv. Drug Del. Rev. 60, 184–198 (2008)
Mackie, E.J.: Osteoblasts: novel roles in orchestration of skeletal architecture. Int. J. Biochem. Cell Biol. 35, 1301–1305 (2003)
Mäenpää, K., Ellä, V., Mauno, J., Kellomäki, M., Suuronen, R., Ylikomi, T., Miettinen, S.: Use of adipose stem cells and polylactide discs for tissue engineering of the temporomandibular joint disc. J. R. Soc. Interface (2009). doi:10.1098/rsif.2009.0117
Mason, C., Dunnill, P.: A brief definition of regenerative medicine. Regen. Med. 3(1), 1–5 (2008)
Matsuno, T., Hashimoto, Y., Adachi, S., Omata, K., Yoshitaka, Y., Ozeki, Y., Umezu, Y., Tabata, Y., Nakamura, M., Satoh, T.: Preparation of injectable 3D-formed beta-tricalcium phosphate bead/alginate composite for bone tissue engineering. Dent Mater J27 (6), 827–834 (2008).
Mironov, V., Boland, T., Trusk, T., Forgacs, G., Markwald, R.R.: Organ printing: computer-aided jet-based 3D tissue engineering. Trends Biotech. 21(4), 157–161 (2003)
Nie, H., Wang, C.-H.: Fabrication and characterization of PLGA/HAP composite scaffolds for delivery of BMP-2 plasmid DNA. J Control Release. 120(1–2), 111–121 (2007)
Patterson, J., Siew, R., Herring, S.W., Lin, A.S.P., Guldberg, R., Stayton, P.S.: Hyaluronic acid hydrogels with controlled degradation properties for oriented bone regeneration. Biomaterials 31(26), 6772–6781 (2010)
Place, E.S., George, J.H., Williams, C.K., Stevens, M.M.: Synthetic polymer scaffolds for tissue engineering. Chem. Soc. Rev. 38, 1139–1151 (2009)
Porpiglia, F., Renard, J., Billia, M., Morra, I., Terone, C., Scarpa, R.M.: Biological glues and collagen fleece for hemostasis during laparoscopic partial nephrectomy: technique and results of perspective study. J. Endourol. 21(4), 423–428 (2007)
Porter, J.R., Ruckh, T.T., Popat, K.C.: Bone tissue engineering: a review in bone biomimetics and drug delivery strategies. Biotechnol. Prog. 25, 1539–1560 (2009)
Portero, A., Remunan-Lopez, C., Criado, M.T., Alonso, M.J.: Reacetylated chitosan microspheres for controlled delivery of antimicrobial agents to the gastric mucosa. J. Microencapsul. 19(6), 797–809 (2002)
Reichert, J.C., Heymer, A., Berner, A., Eulert, J., Nöth, U.: Fabrication of polycaprolactone collagen hydrogel constructs seeded with mesenchymal stem cells for bone regeneration. Biomed. Mater. 4(6), 5001 (2009)
Rezwan, K., Chen, Q.Z., Blaker, J.J., Boccaccini, A.R.: Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 27, 3413–3431 (2006)
Safadi, F.F., Xu, J., Smock, S.L., Kanaan, R.A., Selim, A.H., Odgren, P.R., Marks Jr, S.C., Owen, T.A., Popoff, S.N.: Expression of connective tissue growth factor in bone: its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo. J. Cell. Physiol. 196, 51–62 (2003)
Salerno, A., Di Maio, E., Iannace, S., Netti, P.A.: Engineering of foamed structures for biomedical application. J. Cell. Plast. 45, 103–117 (2009)
Sayin, B., Somavarapu, S., Li, X.W., Thanou, M., Sesardic, D., Alpar, H.O., Senel, S.: Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. Int. J.Pharm. 363, 139–148 (2008)
Sell, S.A., Francis, M.P., Garg, K., McClure, M.J., Simpson, D.G., Bowlin, G.L.: Cross-linking methods of electrospun fibrinogen scaffolds for tissue engineering applications. Biomed. Mater. 3(4), 450–501 (2008)
Shen, Y.H., Shoichet, M.S., Radisic, M.: Vascular endothelial growth factor immobilized in collagen scaffold promotes penetration and proliferation of endothelial cells. Acta Biomater. 4(3), 477–489 (2008)
Singh, I., Kumar, V., Ratner, B.D.: Generation of porous microcellular 85/15 poly(dl)-lactide-co-glycolide foams for biomedical applications. Biomaterials 25(3), 2611–2617 (2004)
Smith, I.O., Liu, X.H., Smith, L.A., Ma, P.X.: Nanostructured polymer scaffolds for tissue engineering and regenerative medicine. Adav. Rev. 1, 226–236 (2009)
Stella, J.A., D’Amore, A., Wagner, W.R., Sacks, M.S.: On the biomechanical function of scaffolds for scaffolds for engineering load-bearing soft tissues. Acta Biomater. 6(7), 2365–2381 (2010)
Tabata, Y.: Tissue regeneration based on growth factor release. Tissue Eng. 9(S1), 5–15 (2004)
Tabata, Y.: Biomaterial technology for tissue engineering aplications. J. R. Soc. Interface 6, S311–S324 (2009)
Tessmar, J.K., Gopferich, A.M.: Matrices and scaffolds for protein delivery in tissue engineering. Adv. Drug Del. Rev. 59, 274–291 (2007)
Thushari, H.M., Herath, U., DiSilvio, L., Evans, J.R.G.: Biological evaluation of solid freeformed, hard tissue scaffold for orthopedic applications. J. Appl. Biomater. Biomech. 8(2), 89–96 (2010)
Tran, N., Webster, T.J.: Nanotechnology for bone materials. WIREs Nanomed. Nanobiotechnol. 1, 336–351 (2009)
Van Tomme, S.R., Hennink, W.E.: Biodegradable dextran hydrogels for protein delivery applications. Expert Res. Med. Dev. 4, 147–164 (2007)
Wan, L.S., Xu, Z.K.: Polymer surfaces structured with random or aligned electrospun nanofibers to promote the adhesion of blood platelets. J. Biomed. Mater. Res. Part A 89(1), 168–175 (2009)
Wang, S., Lu, L., Yaszemski, M.J.: Bone tissue-engineering material poly(propylene fumarate): correlation between molecular weight, chain dimensions, and physical properties. Biomacromolecules 7(6), 1976–1982 (2006)
Weigel, T., Schinkel, G., Lendlein, A.: Design and preparation of polymeric scaffolds for tissue engineering. Future Drugs 6, 835–851 (2006)
Williams, D.F.: On the mechanisms of biocompatibility. Biomaterials 29(20), 2941–2953 (2008)
Williams, J.M., Adewunmib, A., Scheka, R.M., Flanagan, C.L., Krebsbacha, P.H., Feinberg, S.E., Hollister, S.J., Das, S.: Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials 26, 4817–4827 (2005)
Xynos, I.D., Edgar, A.J., Buttery, L.D.K., Hench, L.L., Polak, M.: Gene expression profiling of human osteoblests following treatment with the ionic production of Bioglass 45S5 dissolution. J. Biomed. Mater. Res. 55, 151–157 (2001)
Yuan, Y., Chesnutt, B.M., Utturkar, G., Haggard, W.O., Yang, Y., Ong, J.L., Bumgardner, J.D.: The effect of cross-linking of chitosan microspheres with genipin on protein release. Carbohydr. Polym. 68(3), 561–567 (2007)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Dorati, R., Colonna, C., Genta, I., Conti, B. (2011). Polymer Scaffolds for Bone Tissue Regeneration. In: Zilberman, M. (eds) Active Implants and Scaffolds for Tissue Regeneration. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8415_2010_59
Download citation
DOI: https://doi.org/10.1007/8415_2010_59
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-18064-4
Online ISBN: 978-3-642-18065-1
eBook Packages: EngineeringEngineering (R0)