*4.1.5 Palladium-based nanomaterials (PdNPs)*

The major biomedical applications of PdNPs include targeted drug delivery [53, 54], anti-cancer therapy [55, 56], anti-microbial activities [57], biosensors and intracellular analysis-hydrogen sensors [58, 59], biocatalysts [60], and catalysis [61]. Graphene oxide (GO) has treated to create an anchoring OH site on the surface of GO. The subsequent GO-g-PLA was synthesized by the polymerization reaction in the presence of GO-MDI-OH and PLA. Finally, GO-g-PLA-Pd NPs was used for the electrochemical detection of serotonin [62].

### **4.2 Metal oxides-based nanomaterials**

Biodegradation and biocompatibility of metal oxide nanoparticles (MONPs) are investigated medical applications. It is vital that the surface modification of MOPs must be adequate stable to resist against the salts and proteins in vivo and also become water soluble. It is elucidated that super paramagnetic iron oxides nanoparticles (SPIONPs) are significantly biocompatible. The behavior of SPIONPs for drug delivery applications based on their surface structure and conjugated targeting ligands/proteins [63–66].

The most important application of SPIONPs are include targeting of drug by engineered delivering system [67, 68], for cancer therapeutic [69, 70], diagnosis of many kinds of cancers [67], contrasting agents for bioimaging [71], ultrasensitive in vivo molecular imaging [72], anti-microbial activities [73, 74], biosensing and inter cellular analysis [75], and cancer therapy using photo thermal technique [76, 77]. The distinctive properties of iron oxide MNPs are appropriate for biocatalysis [78, 79].

ZnO NPs are used as anti-microbial, anti-biotic, and anti-fungal (fungicide) agents by incorporating them in coatings, bandages, nanofiber, nanowire, plastics, alloy, and textiles. They possess suitable electrical, dielectric, magnetic, optical, imaging, catalytic, biomedical, and bioscience properties. ZnO is a white powder that insoluble in water. ZnO is applicable in many kinds of ointments that used to treat skin irritations. Also, ZnO has many industrial applications such as in semiconductors, ceramics, and glass compositions [80, 81]. The well-known biomedical applications of ZnO NPs are found as targeted drug delivery destruction of tumor cells [82, 83], biomedical imaging and drug delivery systems [84], tumor characterization [85, 86], anti-cancer therapy [87], contrast agent in medical imaging [88], anti-microbial activities [89], biomarkers [90], and biosensors [91–94].

A suitable food packaging can increase the shelf life of food products in addition to save their initial quality. The biodegradable polymer has various limitations such as fragility due to their low mechanical properties. Due to high aspect ratio of nanoparticles, their properties have significant differences from conventional size particles. ZnO nanostructured materials have presented valuable properties which have led to variety of applications such as food packaging applications.

Combination of ZnO nanoparticles and polyvinyl alcohol results a more effective and environmentally friendly material for food stuff packaging [95].

Titanum oxide (TiO2) nanoparticles can enhance cell attachment and proliferation on its composite surfaces. The polymer/TiO2 composite films exhibit enhanced cell adhesion and a tendency to increased Ca-containing mineral deposition. Also, TiO2 nanoparticles might act as interfacial bonding to tissue by means of the formation of a biologically active hydroxyapatite layer on implant surface. Boccaccini fabricated PDLLA films contain TiO2 nanoparticles. Thus, if TiO2 NPs are introduced in PLLA matrix, some disadvantages are anticipated to be improved. However, one of the most problems in master batch production of TiO2 is the agglomeration in the PLLA matrix. The aggregated TiO2 NPs in the composite reduce the mechanical properties and hence is necessary more researches to solve the TiO2 agglomeration [96].

Deterioration of fresh fruits and vegetables during storage treat microorganisms breeding such as *Aspergillus niger* (*A. niger*) and *Bacillus subtilis* (*B. subtilis*), which can be a seriously danger for human health. For antibacterial and preservative properties, a self-assembled film of graphene oxide (GO) and chitosan (CS) with titanium dioxide (TiO2) nanoparticles are introduced. These non-cytotoxic nanometer-scale films, with the ratio of 1:20:4 for graphene oxide, chitosan, and titanium dioxide nanoparticles, respectively, exhibited valuable antibacterial activity against the biofilm forming strains *A. niger* and *B. subtilis*. Also, the nanocomposites did not show any cytotoxicity against mammalian somatic cells and plant cells. Nanocomposites disrupted microbial film formation while avoiding internalization by animal and plant cells. Due to their selectivity and safety, these nanocomposites demonstrate potential as antimicrobial coatings for food preservation [97].

#### **4.3 Silica nanoparticles (SNPs)**

The performance of SNPs as nanofillers in polymer nanocomposite has significant attention, because of increased in demand for new materials with enhancement in thermal, mechanical, physical, and chemical properties of various kinds of composites (**Figure 8**). Synthesis of SNPs using sol-gel treatment has significant improvement in the development of SNPs/polymer nanocomposites [98].

Gardella et al. developed a novel catalytic system, consisting of palladium nanoclusters homogenously dispersed on the surface of nanostructured polymer fibers based on poly(L-lactide) (PLLA) and polyhedral oligomeric silsesquioxanes (POSS). In fact, PLLA nanofibers that contain amino silsesquioxane molecules (POSS-NH2) have capability to interact with metal precursor prepared by electrospinning. The prepared system proves a relevant catalytic activity toward the hydrogenation of stilbene under heterogeneous conditions [99].

#### **4.4 Carbon-based nanomaterials**

### *4.4.1 Carbon nanotubes*

The carbon nanotubes (CNTs) have been investigated for a variety of applications based on their unique electrical, optical, and mechanical properties. The exceptional mechanical properties of CNTs have led to their use as effective reinforcing filler for polymer composites. It was expected that CNTs would display superlative mechanical properties by analogy with graphite. The inside of CNTs can be filled with some elements or compounds, such as C60, to produce hybrid nanomaterials which possess unique intrinsic properties. The properties of the CNTs/

**93**

*Poly(L-Lactide) Bionanocomposites*

*DOI: http://dx.doi.org/10.5772/intechopen.85035*

type, diameter, and length of the nanotubes.

matrices (**Figure 9**).

**Figure 8.**

*Chemical scheme of silica.*

*4.4.2 Functionalization of CNTs*

*4.4.3 Functionalization in chemical base*

1.Covalent functionalization.

developed [117, 118].

2.Noncovalent functionalization.

polymer composites will vary significantly depending on the distribution of the

In CNTs, only few concentrated acids are capable of breaking the bonds between carbon atoms. Consequently, when CNTs reinforce a composite, the mentioned stability becomes a problem at the interaction between the matrix and CNTs. Uncontrolled agglomeration is another noticeable difficulty that can interfere on CNTs due to its nanometer size. To increase the interaction between matrix and reinforcement is submitting CNTs to a process called functionalization. Functionalization of CNTs is a mix of physical and chemical processes that inserts functional groups on the sidewall of CNTs. The introduction of this procedure can also be helpful to obtain better dispersion of carbon nanotubes into relevant

Functionalization is one of the most effective methods in improving the surface

properties of CNTs so that the application potentials can be fully realized. The methods of functionalization for CNTs range from chemical modification to physi-

In chemical base, there are two methods for functionalization of CNTs:

The carbon nanotubes (CNTs) are another important and novel category of NPs that has been investigated extensively in medicine and drug delivery systems. The CNTs can interact with various bio-macromolecules such as DNA and proteins by physical adsorption. Additionally, in order to conjugate covalently targeting moieties or therapeutic molecules to CNTs, numerous chemical modifications were

In the field of research on medical application of CNTs, Zheng et al. elucidated the interactions between DNA molecules and CNTs [119]. In the case of singlestranded DNA, CNTs could disperse effectively in aqueous media. Up to date, the improvement of mechanical properties of CNTs might be counted primarily for

Each method has some advantages and some disadvantages.

cal interaction, and mechanical manipulations (**Figure 10**).

*Poly(L-Lactide) Bionanocomposites DOI: http://dx.doi.org/10.5772/intechopen.85035*

**Figure 8.** *Chemical scheme of silica.*

*Peptide Synthesis*

solve the TiO2 agglomeration [96].

**4.3 Silica nanoparticles (SNPs)**

**4.4 Carbon-based nanomaterials**

*4.4.1 Carbon nanotubes*

Combination of ZnO nanoparticles and polyvinyl alcohol results a more effective

Titanum oxide (TiO2) nanoparticles can enhance cell attachment and proliferation on its composite surfaces. The polymer/TiO2 composite films exhibit enhanced cell adhesion and a tendency to increased Ca-containing mineral deposition. Also, TiO2 nanoparticles might act as interfacial bonding to tissue by means of the formation of a biologically active hydroxyapatite layer on implant surface. Boccaccini fabricated PDLLA films contain TiO2 nanoparticles. Thus, if TiO2 NPs are introduced in PLLA matrix, some disadvantages are anticipated to be improved. However, one of the most problems in master batch production of TiO2 is the agglomeration in the PLLA matrix. The aggregated TiO2 NPs in the composite reduce the mechanical properties and hence is necessary more researches to

Deterioration of fresh fruits and vegetables during storage treat microorganisms breeding such as *Aspergillus niger* (*A. niger*) and *Bacillus subtilis* (*B. subtilis*), which can be a seriously danger for human health. For antibacterial and preservative properties, a self-assembled film of graphene oxide (GO) and chitosan (CS) with titanium dioxide (TiO2) nanoparticles are introduced. These non-cytotoxic nanometer-scale films, with the ratio of 1:20:4 for graphene oxide, chitosan, and titanium dioxide nanoparticles, respectively, exhibited valuable antibacterial activity against the biofilm forming strains *A. niger* and *B. subtilis*. Also, the nanocomposites did not show any cytotoxicity against mammalian somatic cells and plant cells. Nanocomposites disrupted microbial film formation while avoiding internalization by animal and plant cells. Due to their selectivity and safety, these nanocomposites

demonstrate potential as antimicrobial coatings for food preservation [97].

improvement in the development of SNPs/polymer nanocomposites [98]. Gardella et al. developed a novel catalytic system, consisting of palladium nanoclusters homogenously dispersed on the surface of nanostructured polymer fibers based on poly(L-lactide) (PLLA) and polyhedral oligomeric silsesquioxanes (POSS). In fact, PLLA nanofibers that contain amino silsesquioxane molecules (POSS-NH2) have capability to interact with metal precursor prepared by electrospinning. The prepared system proves a relevant catalytic activity toward the

hydrogenation of stilbene under heterogeneous conditions [99].

The performance of SNPs as nanofillers in polymer nanocomposite has significant attention, because of increased in demand for new materials with enhancement in thermal, mechanical, physical, and chemical properties of various kinds of composites (**Figure 8**). Synthesis of SNPs using sol-gel treatment has significant

The carbon nanotubes (CNTs) have been investigated for a variety of applications based on their unique electrical, optical, and mechanical properties. The exceptional mechanical properties of CNTs have led to their use as effective reinforcing filler for polymer composites. It was expected that CNTs would display superlative mechanical properties by analogy with graphite. The inside of CNTs can be filled with some elements or compounds, such as C60, to produce hybrid nanomaterials which possess unique intrinsic properties. The properties of the CNTs/

and environmentally friendly material for food stuff packaging [95].

**92**

polymer composites will vary significantly depending on the distribution of the type, diameter, and length of the nanotubes.

In CNTs, only few concentrated acids are capable of breaking the bonds between carbon atoms. Consequently, when CNTs reinforce a composite, the mentioned stability becomes a problem at the interaction between the matrix and CNTs. Uncontrolled agglomeration is another noticeable difficulty that can interfere on CNTs due to its nanometer size. To increase the interaction between matrix and reinforcement is submitting CNTs to a process called functionalization. Functionalization of CNTs is a mix of physical and chemical processes that inserts functional groups on the sidewall of CNTs. The introduction of this procedure can also be helpful to obtain better dispersion of carbon nanotubes into relevant matrices (**Figure 9**).

## *4.4.2 Functionalization of CNTs*

Functionalization is one of the most effective methods in improving the surface properties of CNTs so that the application potentials can be fully realized. The methods of functionalization for CNTs range from chemical modification to physical interaction, and mechanical manipulations (**Figure 10**).

## *4.4.3 Functionalization in chemical base*

In chemical base, there are two methods for functionalization of CNTs:


Each method has some advantages and some disadvantages.

The carbon nanotubes (CNTs) are another important and novel category of NPs that has been investigated extensively in medicine and drug delivery systems. The CNTs can interact with various bio-macromolecules such as DNA and proteins by physical adsorption. Additionally, in order to conjugate covalently targeting moieties or therapeutic molecules to CNTs, numerous chemical modifications were developed [117, 118].

In the field of research on medical application of CNTs, Zheng et al. elucidated the interactions between DNA molecules and CNTs [119]. In the case of singlestranded DNA, CNTs could disperse effectively in aqueous media. Up to date, the improvement of mechanical properties of CNTs might be counted primarily for

#### **Figure 9.**

*TEM micrograph of pristine MWCNTs (a), MWCNT-COOHs (b), MWCNT-OHs (c, d), and MWCNT-OH-*graft*-PLACL(e, f) [100].*

their using as composite reinforcements for tissue engineering and preparation of artificial scaffolds [120]. More recently, researchers have considered their attention to utilizing the multi-functional nature of CNTs in engineering tissue scaffolds. Most particularly, the CNTs were incorporated to fabricate electrically conductive artificial scaffolds.

### *4.4.4 Graphene nanoparticles*

Due to the similarity between graphene and CNTs, several medical applications such as drug delivery systems, scaffold reinforcements, and injectable cellular labeling agents have been committed using graphene and graphene oxide (GO) [121]. For reinforcement of biodegradable polymers by graphene, in one case, the PLLA/GO nanocomposites were prepared by solution mixing. The results show that the crystallization of PLLA enhanced and the spherulite morphology change were insignificant when the content of GO exceeded 0.5 wt%, because the extreme GO increased the number of nucleation sites while restricting the PLA crystal growth. Thus, the arrangement of nanopores did not mimic the spherulites because of imperfect crystal morphology [122].

#### **4.5 Nano hydroxyapatite (HANs)**

Owing to its biocompatibility and osteoconductive properties, nano hydroxyapatite (nHA) is widely used bioceramic for bone graft substitute. nHA with

**95**

engineering [124].

**Figure 10.**

**4.6 Magnetic nanoparticles (MNs)**

*Poly(L-Lactide) Bionanocomposites*

*DOI: http://dx.doi.org/10.5772/intechopen.85035*

biodegradable and biocompatible polymer-based composite scaffolds have been explored for bone grafting. Hence, the nHA/biopolymer nanocomposites proved to be promising for bone tissue engineering [123]. Composite fibers composed of PLA-g-HANs and PLA matrix was prepared by electro-spinning for tissue

*Scheme of possible addition reactions for the functionalization of CNTs [101–116].*

The MNs are a class of nanomaterials which can be performed using adequate magnetic field. The MNs can be conjugated with any protein, drug and gene, and by that MNs serve as contrast agent for magnetic resonance imaging (MRI) by changing the MRI signal. Additionally, MNs serve as a therapeutic tool by improving drug delivery to the target organ. Drug controlled releasing using nanostructured functional materials are attracting increasing attention in some diseases such as cancer therapy and other ailments. The potential of MNs stems from the intrinsic properties of their magnetic cores combined with their drug loading capability and the biochemical properties [125]. Therapeutic compounds are attached to MNs and magnetic fields generated outside the body are focused on specific targets [126]. In the field of biopolymer nanocomposites, iron oxide MNs with sizes less than 10 nm have been successfully deposited on multi-walled CNTs (MWCNTs) by in situ high temperature decomposition of iron(III) acetylacetonate and MWCNTs in polyol solution [127]. The PLLA has been covalently grafted onto the surface of mMWCNTs. The mMWCNTs/PLLA nanocomposite possess significant mechanical, electronic, super paramagnetic, and biocompatible properties, which means that the mMWCNTs/PLLA will have great potential applications in the fields of nanobiomaterials and nanotechnology, and the addition of mMWCNTs/PLLA can treat novel properties to PLLA and other biodegradable polymers [128] (**Figure 11**).

*Poly(L-Lactide) Bionanocomposites DOI: http://dx.doi.org/10.5772/intechopen.85035*

*Peptide Synthesis*

their using as composite reinforcements for tissue engineering and preparation of artificial scaffolds [120]. More recently, researchers have considered their attention to utilizing the multi-functional nature of CNTs in engineering tissue scaffolds. Most particularly, the CNTs were incorporated to fabricate electrically conductive

*TEM micrograph of pristine MWCNTs (a), MWCNT-COOHs (b), MWCNT-OHs (c, d), and MWCNT-*

Due to the similarity between graphene and CNTs, several medical applications

Owing to its biocompatibility and osteoconductive properties, nano hydroxyapatite (nHA) is widely used bioceramic for bone graft substitute. nHA with

such as drug delivery systems, scaffold reinforcements, and injectable cellular labeling agents have been committed using graphene and graphene oxide (GO) [121]. For reinforcement of biodegradable polymers by graphene, in one case, the PLLA/GO nanocomposites were prepared by solution mixing. The results show that the crystallization of PLLA enhanced and the spherulite morphology change were insignificant when the content of GO exceeded 0.5 wt%, because the extreme GO increased the number of nucleation sites while restricting the PLA crystal growth. Thus, the arrangement of nanopores did not mimic the spherulites because of

**94**

artificial scaffolds.

*OH-*graft*-PLACL(e, f) [100].*

**Figure 9.**

*4.4.4 Graphene nanoparticles*

imperfect crystal morphology [122].

**4.5 Nano hydroxyapatite (HANs)**

**Figure 10.** *Scheme of possible addition reactions for the functionalization of CNTs [101–116].*

biodegradable and biocompatible polymer-based composite scaffolds have been explored for bone grafting. Hence, the nHA/biopolymer nanocomposites proved to be promising for bone tissue engineering [123]. Composite fibers composed of PLA-g-HANs and PLA matrix was prepared by electro-spinning for tissue engineering [124].

## **4.6 Magnetic nanoparticles (MNs)**

The MNs are a class of nanomaterials which can be performed using adequate magnetic field. The MNs can be conjugated with any protein, drug and gene, and by that MNs serve as contrast agent for magnetic resonance imaging (MRI) by changing the MRI signal. Additionally, MNs serve as a therapeutic tool by improving drug delivery to the target organ. Drug controlled releasing using nanostructured functional materials are attracting increasing attention in some diseases such as cancer therapy and other ailments. The potential of MNs stems from the intrinsic properties of their magnetic cores combined with their drug loading capability and the biochemical properties [125]. Therapeutic compounds are attached to MNs and magnetic fields generated outside the body are focused on specific targets [126].

In the field of biopolymer nanocomposites, iron oxide MNs with sizes less than 10 nm have been successfully deposited on multi-walled CNTs (MWCNTs) by in situ high temperature decomposition of iron(III) acetylacetonate and MWCNTs in polyol solution [127]. The PLLA has been covalently grafted onto the surface of mMWCNTs. The mMWCNTs/PLLA nanocomposite possess significant mechanical, electronic, super paramagnetic, and biocompatible properties, which means that the mMWCNTs/PLLA will have great potential applications in the fields of nanobiomaterials and nanotechnology, and the addition of mMWCNTs/PLLA can treat novel properties to PLLA and other biodegradable polymers [128] (**Figure 11**).

#### **Figure 11.**

*SEM images of m-MWCNTs-g-PLLA in the absence (a) and presence (b) of an external magnetic field [128].*
