**7. Acknowledgment**

This study was supported by Grants-in-Aid for Young Scientists (B) (20700393) from the Ministry of Education, Science, and Culture, Japan.

Mechanical and Biological Properties of

2004;98:40-7.

Mater Med. 2008;19:3473-9.

Mater Med. 2010;21:1891-8.

Bio-Inspired Nano-Fibrous Elastic Materials from Collagen 273

[20] Shen X, Nagai N, Murata M, Nishimura D, Sugi M, Munekata M. Development of

[21] Nagai N, Kumasaka N, Kawashima T, Kaji H, Nishizawa M, Abe T. Preparation and

[22] Glattauer V, White JF, Tsai WB, Tsai CC, Tebb TA, Danon SJ, et al. Preparation of

[23] Srinivasan A, Sehgal PK. Characterization of biocompatible collagen fibers--a promising candidate for cardiac patch. Tissue Eng Part C Methods. 2010;16:895-903. [24] Yunoki S, Mori K, Suzuki T, Nagai N, Munekata M. Novel elastic material from collagen for tissue engineering. J Mater Sci Mater Med. 2007;18:1369-75. [25] Yunoki S, Matsuda T. Simultaneous processing of fibril formation and cross-linking improves mechanical properties of collagen. Biomacromolecules. 2008;9:879-85. [26] Yunoki S, Nagai N, Suzuki T, Munekata M. Novel biomaterial from reinforced salmon

[27] Nagai N, Kobayashi H, Katayama S, Munekata M. Preparation and characterization of

[28] Lee CR, Grodzinsky AJ, Spector M. The effects of cross-linking of collagen-

contraction, proliferation and biosynthesis. Biomaterials. 2001;22:3145-54. [29] Olde Damink LH, Dijkstra PJ, van Luyn MJ, van Wachem PB, Nieuwenhuis P, Feijen J.

[30] Goissis G, Marcantonio E, Jr., Marcantonio RA, Lia RC, Cancian DC, de Carvalho WM.

[31] Koide T, Daito M. Effects of various collagen crosslinking techniques on mechanical

[32] Suh H, Lee WK, Park JC, Cho BK. Evaluation of the degree of cross-linking in UV

[33] Weadock KS, Miller EJ, Bellincampi LD, Zawadsky JP, Dunn MG. Physical crosslinking

[34] Toba T, Nakamura T, Matsumoto K, Fukuda S, Yoshitani M, Ueda H, et al. Influence of

[35] Nakajima N, Ikada Y. Mechanism of amide formation by carbodiimide for

[36] Olde Damink LH, Dijkstra PJ, Van Luyn MJ, Van Wachem PB, Nieuwenhuis P, Feijen J.

bioconjugation in aqueous media. Bioconjug Chem. 1995;6:123-30.

therapy applications. J Biomed Mater Res A. 2010;92:1301-9.

applications. J Biomater Sci Polym Ed. 2009;20:567-76.

glutaraldehyde cross-linking. Biomaterials. 1999;20:27-34.

properties of collagen film. Dent Mater J. 1997;16:1-9.

treatment. J Biomed Mater Res. 1995;29:1373-9.

degradation. J Biomed Mater Res. 1995;29:139-47.

coated collagen. ASAIO J. 2002;48:17-20.

irradiated porcine valves. Yonsei Med J. 1999;40:159-65.

carbodiimide. Biomaterials. 1996;17:679-84.

salmon milt DNA/salmon collagen composite for wound dressing. J Mater Sci

characterization of collagen microspheres for sustained release of VEGF. J Mater Sci

resorbable collagen-based beads for direct use in tissue engineering and cell

collagen gel prepared by fibril formation and cross-linking. J Biosci Bioeng.

collagen from soft-shelled turtle (Pelodiscus sinensis) skin for biomaterial

glycosaminoglycan scaffolds on compressive stiffness, chondrocyte-mediated

In vitro degradation of dermal sheep collagen cross-linked using a water-soluble

Biocompatibility studies of anionic collagen membranes with different degree of

of collagen fibers: comparison of ultraviolet irradiation and dehydrothermal

dehydrothermal crosslinking on the growth of PC-12 cells cultured on laminin

Changes in the mechanical properties of dermal sheep collagen during in vitro

#### **8. References**


[1] Lee CH, Singla A, Lee Y. Biomedical applications of collagen. Int J Pharm. 2001;221:1-22. [2] Friess W. Collagen--biomaterial for drug delivery. Eur J Pharm Biopharm. 1998;45:113-36. [3] Na GC, Phillips LJ, Freire EI. In vitro collagen fibril assembly: thermodynamic studies.

[4] Williams BR, Gelman RA, Poppke DC, Piez KA. Collagen fibril formation. Optimal in vitro conditions and preliminary kinetic results. J Biol Chem. 1978;253:6578-85. [5] Kadler KE, Holmes DF, Trotter JA, Chapman JA. Collagen fibril formation. Biochem J.

[6] Cen L, Liu W, Cui L, Zhang W, Cao Y. Collagen tissue engineering: development of

[7] Glowacki J, Mizuno S. Collagen scaffolds for tissue engineering. Biopolymers.

[8] Sano A, Maeda M, Nagahara S, Ochiya T, Honma K, Itoh H, et al. Atelocollagen for

[9] Ramshaw JA, Peng YY, Glattauer V, Werkmeister JA. Collagens as biomaterials. J Mater

[10] Schlegel AK, Mohler H, Busch F, Mehl A. Preclinical and clinical studies of a collagen

[11] Tiller JC, Bonner G, Pan LC, Klibanov AM. Improving biomaterial properties of collagen films by chemical modification. Biotechnol Bioeng. 2001;73:246-52. [12] Hao W, Hu YY, Wei YY, Pang L, Lv R, Bai JP, et al. Collagen I gel can facilitate

[13] Kanayama T, Nagai N, Mori K, Munekata M. Application of elastic salmon collagen gel

[14] Nagai N, Kubota R, Okahashi R, Munekata M. Blood compatibility evaluation of elastic

[15] Nagai N, Mori K, Munekata M. Biological properties of crosslinked salmon collagen

[16] Nagai N, Nakayama Y, Zhou YM, Takamizawa K, Mori K, Munekata M. Development

[17] Nagai N, Mori K, Satoh Y, Takahashi N, Yunoki S, Tajima K, et al. In vitro growth and

[18] Hosseinkhani H, Hosseinkhani M, Tian F, Kobayashi H, Tabata Y. Bone regeneration on

[19] Nagai N, Yunoki S, Suzuki T, Sakata M, Tajima K, Munekata M. Application of cross-

gelatin gel from salmon collagen. J Biosci Bioeng. 2008;106:412-5.

salmon collagen gel. J Biomed Mater Res A. 2007;82:395-402.

homogenous bone formation of adipose-derived stem cells in PLGA-beta-TCP

to uniaxial stretching culture of human umbilical vein endothelial cells. J Biosci

fibrillar gel as a scaffold for human umbilical vein endothelial cells. J Biomater

of salmon collagen vascular graft: mechanical and biological properties and preliminary implantation study. J Biomed Mater Res B Appl Biomater. 2008;87:432-

differentiated activities of human periodontal ligament fibroblasts cultured on

a collagen sponge self-assembled peptide-amphiphile nanofiber hybrid scaffold.

linked salmon atelocollagen to the scaffold of human periodontal ligament cells. J

novel biomaterials and applications. Pediatr Res. 2008;63:492-6.

protein and gene delivery. Adv Drug Deliv Rev. 2003;55:1651-77.

**8. References** 

Biochemistry-Us. 1989;28:7153-61.

Sci Mater Med. 2009;20 Suppl 1:S3-8.

membrane (Bio-Gide). Biomaterials. 1997;18:535-8.

scaffold. Cells Tissues Organs. 2008;187:89-102.

1996;316 ( Pt 1):1-11.

Bioeng. 2008;105:554-7.

Appl. 2008;23:275-87.

Tissue Eng. 2007;13:11-9.

Biosci Bioeng. 2004;97:389-94.

9.

2008;89:338-44.


**14** 

*Italy* 

*In Silico* **Study of Hydroxyapatite and** 

**Sheds Light on Biomaterials** 

**Bioglass®: How Computational Science** 

Marta Corno, Fabio Chiatti, Alfonso Pedone and Piero Ugliengo *Dipartimento di Chimica I.F.M. and NIS, Università di Torino, Torino Dipartimento di Chimica, Università di Modena & Reggio Emilia, Modena* 

Hydroxyapatite and Bioglass® are two well-known biomaterials, belonging to the vast class of ceramic supplies, both highly biocompatible and widely applied in the biomedical field. In spite of a huge research regarding engineering applications of both inorganic materials, still many aspects of their tissue integration mechanism have not been completely cleared at a molecular level. Thus, *in silico* studies play a fundamental role in the prediction and analysis of the main interactions occurring at the surface of these biomaterials in contact with the biological fluid when incorporated in the living tissue (prevalently bones or teeth). Hydroxyapatite [HA, Ca10(PO4)6(OH)2] owes its relevance and use as a biomaterial since it constitutes the majority of the mineral phase of bones and tooth enamel in mammalians (Young & Brown, 1982). For sake of completeness, we mention that hydroxyapatite is also studied as an environmental adsorbent of metals and a catalyst (Matsumura & Moffat, 1996; Toulhat et al., 1996). One of the first applications of HA in biomedicine dates back to 1969, when Levitt *et al.* hot-pressed it in powders for biological experimentations (Levitt et al., 1969). From then on, several commercial forms of HA have appeared on the market. The material has also been utilized for preparing apatitic bioceramic, due to its bioresorbability which can be modulated changing the degree of cristallinity. There are so many examples of applications, from Mg2+-substituted hydroxyapatite (Roveri & Palazzo, 2006) to the synthesis of porous hydroxyapatite materials by colloidal processing (Tadic et al., 2004), starch consolidation (Rodriguez-Lorenzo et al., 2002), gel casting (Padilla et al., 2002) and more. Furthermore, recent applications follow a biologically inspired criterion to combine HA to a collagen matrix aiming at the improvement of mechanical properties and bioactivity (Wahl et al., 2007). However, a complete review of all the practical as well as

hypothetical uses of HA in the biomaterial area is outside the scope of this Chapter.

Inside the bone, a highly hierarchical collagen-mineral composite, hydroxyapatite is in the form of nano-sized mineral platelets (Currey, 1998; Fratzl et al., 2004; Weiner & Wagner, 1998) and contains carbonate ions for the 4-8 weight % (Roveri & Palazzo, 2006). In section 2.1 of this Chapter, two aspects of defects which can be encountered in a synthetic or natural HA sample will be presented. The first aspect deals with non-stoichiometric surfaces and

**1. Introduction** 

