Broad ClassificationTypes of Biomaterials

Polymers, synthetic and natural Metals Composites Ceramics

Composites
Composite materials, are engineered or naturally occurring materials made from two or more constituent materials with significantly different physical or chemical properties which remain separate and distinct at the macroscopic or microscopic scale within the finished meterial

Wood is a commonly encountered composite material of cellulose fibers in a matrix of lignin

Composites
Examples: reinforced plastics such as fiberglass, resins and glue natural materials such as bone, dentin, skin, foams are composites in which one phase is empty space (porous structure)

Application in biomaterials:
dental filling composites (resisns or polymer matrix + ceramics) reinforced methyl methacrylate bone cement and ultrahigh molecular weight polyethylene orthopedic implants (collagen matrix + hydroxyapatite or metals)

Composites - Structure
Composites differ from homogeneous materials The properties of a composite material depend upon:

shape of the heterogeneities volume fraction occupied by them Interface among the two components of the matrix
The shape of the heterogeneities is classified as follows.

a) the particle, with no long dimension b) the fiber, with one long dimension c) the platelet or lamina.

Morphology of basic composite inclusions. (a) particle, (b) fiber, (c) platelet

Composites Mechanical properties

The physical properties of composite materials are generally not isotropic (independent of direction of applied force) in nature, but rather are typically: anysotropic (different depending on the direction of the applied force or load) orthotropic (different depending on the rotation axes) For instance, the stiffness of a composite panel will often depend upon the orientation of the applied forces and/or moments. In contrast, isotropic materials (for example, aluminium or steel), in standard wrought forms, typically have the same stiffness regardless of the directional orientation of the applied forces and/or moments.

NanoComposites
A nanocomposite is as a multiphase solid material where one of the phases has one, two or three dimensions of less than 100 nanometers (nm), or structures having nano-scale repeat distances between the different phases that make up the material

NanoComposites
In mechanical terms, nanocomposites differ from conventional composite materials due to the exceptionally high surface to volume ratio of the reinforcing phase and/or its exceptionally high aspect ratio.

Scanning Electron Microscope (SEM) images of nanocomposites

NanoComposites
Reinforcing material can be made up: particles (e.g. minerals) sheets (e.g. exfoliated clay stacks) fibres (e.g. carbon nanotubes or electrospun fibres). The area of the interface between the matrix and reinforcement phase(s) is typically an order of magnitude greater than for conventional composite materials. The properties are related to local chemistry, degree of thermoset cure, polymer chain mobility, polymer chain conformation, degree of polymer chain ordering or crystallinity can all vary significantly and continuously from the interface with the reinforcement into the bulk of the matrix. This large amount of reinforcement surface area means that a relatively small amount of nanoscale reinforcement can have an observable effect on the macroscale properties of the composite. For example, adding carbon nanotubes improves the electrical and thermal conductivity. Other kinds of nanoparticulates may result in enhanced optical properties, dielectric properties, heat resistance or mechanical properties such as stiffness, strength and resistance to wear and damage. In general, the nano reinforcement is dispersed into the matrix during processing.

Types of Nanocomposites
Ceramic-matrix nanocomposites In this group of composites the main part of the volume is occupied by a ceramic, i.e. a chemical compound from the group of oxides, nitrides, borides, silicides etc. The other component can be: a metal (improving optical, electrical and magnetic properties as well as tribological, corrosion-resistance and other protective properties) Carbon nanotubes example (a material made with nanophase alumina particles as the matrix and dispersions of both single and double walled carbon nanotubes as fillers exhibited a 25% increase in fracture toughness)g

Types of Nanocomposites
Polymer-matrix nanocomposites (PNC) is a polymer or copolymer having dispersed in its nanoparticles. These may be of different shape (e.g., platelets, fibers, spheroids), but at least one dimension must be in the range of 1 to 100 nm

Nanocomposites biomaterials
Bone tissue = natural nanocomposite

Collagen matrix Hydroxyapatite (HA) Bone cells

Bone tissue is a mineralized connective tissue. It is formed by cells, called osteoblasts, that deposit a matrix of Type-I collagen and also release calcium, magnesium, and phosphate ions that ultimately combine chemically within the collagenous matrix into a crystalline mineral, known as bone mineral, in the form of hydroxyapatite.

Nanocomposites biomaterials
Hydroxyapatite (HA) Naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities Bone Dental
400 nm

TEM of HA crystals

An ideal bone substitute should maintain its mechanical properties as it degrades until the newly regenerating bone can adequately support the loading, however, such biodegradable and biocompatible polymeric composites/nanocomposites are yet to be developed.

Nanocomposites for bone tissue regeneration Polymer + nano-HA

Biodegradability of the organic matrix (PLA/PGLA hydrogels polysaccharides ) Biocompatibility Injectability

Nanocomposites of resorbable polymers

Good mechanical properties Bioactive properties Enhance deposition of calcium phosphate forming an apatite layer improving the adhesion of bone cells
. Polymer nanocomposites containing hydroxyapatite (HAp): collagen/HAp, PLA/collagen/HAp, alginates/collagen/HAp, chitozan/Hap, gelatine/HAp, PCL/HAp, PLA/HAp
one implant scaffolds made of these materials contain pores of the size allowing the osteoblasts to penetrate inside the implant. During the next stage, the in-growth of blood vessels and neurons occurs inside the defect filled by the implant. After fulfilling the role of a scaffold, the polymer resorbable matrix undergoes a self-decay process, and the implant is replaced by patient's own new bone tissue.

Example of polymer nanocomposite

Scanning Electron Microscope (SEM) Polymer (PCL)+ HA after simulation body fluid (SBF)

Polymer (PCL)+ HA

Deposition of apatite crystals

Nanocomposites for ristorative dentistry

Dental filling materials are crosslinked resins with high abrasion resistance. Inorganic micro and recently nanofillers are introduced to improve their properties. However, the shrinkage of the resin component during the polymerization reaction is still a critical limitation of dental composite resins. polymerization shrinkage of composite resin: curing methods (chemical or light-curing), placement techniques (incremental or bulk), cavity configuration size of the restoration

Nanocomposites for ristorative dentistry

it is not obvious how nano-sized particles can enhance the fracture resistance of dental nanocomposites since fracture toughness usually scales with the power of the characteristic microstructural length scale controlling the fracture process. To be an effective toughening agent, the nanosized particles must increase the process zone size at the onset of critical fracture either through an increase in the fracture strength due to their small size scale or the inducement of one or more new toughening mechanisms by virtue of their size scale or the large surface areas to volume ratio

Ceramics for composites

Alumina, Zirconium, Calcium phosphate, Silica, pyrrolytic carbon, hydroxyapatite are common; Porous ceramic materials exhibit much lower strengths but have been found extremely useful as coatings for metallic implants; The coating aids in tissue fixation of the implant by providing a porous surface for the surrounding tissue to grow into and mechanically interlock; and, Certain ceramics are considered bioactive ceramics if they establish bonds with bone tissue.

Ceramics for composites

Bioceramics Three different classes : 1) Bioinerts (Al2O3, carbonio vetroso) they do not induce reactions with the physiological fluids 2) Bioreasorbable (hydroxyapatite, or Ca-P) filler materials which can degradate in the tissue 3) Bioactive (e.g. bioglass) improve fouling phenomena increasing the bone formation

Ceramics Ca-P Interesting properties: not toxic not interactions with fibrous tissues possibility to form a direct bond with bone tissue promote bone tissue growth

Binding with bone tissue

Dental prostheses
95% of fixed prostheses are made by a metal structure with ceramics component (metal-ceramics implant). The system has good stability despite of the high number of sollecitation of the oral cavity. Other protheses: composites made of glass fibers or PE instead of the metal which are strong enough and stable and guarantee a good adhesion with the ceramic component.

Nano-composite biomaterials that respond to light

Producing clay nanocomposites based on in-situ photopolymerization combines the unique advantages of UV curing technology with potential enhanced performance upon addition of nanostructured materials. Polymerizable surfactants that are required to modify clay surface can react with monomers and incorporate into polymer matrices during the UV curing process. Increased interaction between clay surfaces and polymer networks can also facilitate the further exfoliation of clay platelets during the polymerization process, which could allow further property improvement with the same amount of clay.

Characterization of nanocomposites
X-ray diffraction (XRD) analysis Data are an average of all the sample

TEM analysis morphological information

 Use of Nanotechnology in Regenerative Medicine

Polysaccharide based hydrogels show poor mechanical properties and their application is limited for soft tissues The addition of an inorganic phase with dimensions at the nanoscale : Improves the mechanical properties at macroscale level Creates chemically different domains with different mechanical properties inside the hydrogel.

Synthesis of new scaffolds made of a hard component such as nanophase metal oxide, nanoparticles of HA or carbon nanotubes mixed with a soft component of a polymer matrix
Reference: L.Zhang et al.; Nano Today 2009,4 4,66-80

Physical Entrapment of metal oxide NPs

Synthesis Strategy
CMC hydrogel
Absorbance
0.09 0.08 0.07 0.06 0.05 0.04 0.03

UV-visible spectrum
UV-Vis spectra of purged water

CMC hydrogel + TiO2 NPs

0.02 0.01 200 250 300 350 400

Wavelenghts nm

Release of NPs under a mechanical stress TiO2 NPs dispersion

Chemical Entrapment of metal oxide NPs

Silanization of TiO2 NPs
(3-Aminopropyl)trimethoxysilane (APTMS)

H3C O H3C O Si NH2

OH

H3CO

TiO2 TiO 2

HO HO HO

APTMS
OH

H3C

O O O Si NH2

TiO H3C TiO 2

OH

EtOH /H2O pH = 5 CH3COOH

H3C

Chemical Entrapment of metal oxide NPs

Synthesis Strategy of Hybrid Hydrogel
O OR
O

CMC polymer
HO
O HO O O HO OH O O OH HO O O OH n O

O OH O O O
O

NH

OR O HO OH O n NH

O OR

TiO2 2

EDC, NHS
O RO

NH

O O NH

HN

+ Silanized TiO2 NPs

H3C O

pH 4.75,
stirring overnight

NH

TiO2

O O O O HO O OH O
n

HN O

HO

OH

TiO H3C TiO 2

H3C
2

O O

Si

NH2
HO

O O OH

OH HO O O O OR O n

Chemical Entrapment of TiO2 NPs

0.40 0.35 0.30 0.25

FT-IR Analysis
CMC polymer CMC-TiO2 hydrogel
COO-

1060

Absorbance

am. C=O

1598

TiO2
1421 1323

0.20 0.15 0.10 0.05 0.00 2000 1800 1724

1640

Evidence of amidic bond formation between polymer and functionalized NPs. The hydrogels has been cross-linked

1600

1400

1200
-1

1000

800

w a v e n u m b e rs (c m )

SEM/EDS
The Si and Ti are almost overlapped and uniformly distributed Si Ti

Chemical Entrapment of TiO2 NPs

Morphological Analysis
SEM AFM Surface roughness Ra 1.0 0.1nm

CMC hydrogel

Surface roughness Ra 50-100nm

CMC-TiO2 NPs hydrogel

Chemical Entrapment of TiO2 NPs

Mechanical Properties
Rheological measurements

G CMC-DAP hydrogel CMC-TiO2 hydrogel 409 285

G 30 26 116
The hydrogel crosslinked with TiO2 NPs and DAP showed ENHANCED mechanical properties than CMC native ones The hydrogel crosslinked only with TiO2 NPs showed POOR mechanical properties

CMC-TiO2-DAP 1021 hydrogel (TiO2 1%)

The further addition of a chemical cross-linker increase the mechanical behaviour