In recent years, nano-biocomposites from biodegradable biocompatible polymers have gained significant attention for a wide range of biomedical applications owing to their U.S. Food and Drug Administration (FDA) approval for most of polymers. Nano-biocomposites obtained by adding biopolymers or nanofillers often result in improved material properties without having any toxic products (Bordes et al. 2009; Alok et al. 2011). Such eco-friendly biodegradable polymers are mainly destined to biomedical applications, drug/protein delivery tuning, and formulating biomedical devices. Biopolymers can be either chemically synthesized or biosynthesized from microorganisms. Figure 1 gives a classification with four different categories of biopolymers, depending on the synthesis method employed (Averous and Boquillon 2004). Biopolymers obtained from microorganisms, agro resources, and biotechnology are from renewable resources.

Biodegradable Polyester Biocomposites

Many types of polyester have been the predominant choice for materials in biocompatible and biodegradable drug delivery systems. Polyesters such as PLGA, PGA, PLA, PCL, etc., are polymers that have gained significant attention for a wide range of applications in the biomaterial field. Owing to their biodegradability and biocompatibility, polyesters have been widely used as carriers for drug, protein, and gene delivery. Fine-tuning of the drug release from polyesters has been extensively studied for many years (Agarwal 2012).
Homopolymers and copolymers derived from glycolic acid or glycolide, lactic acid or lactide, and ε-caprolactone are studied extensively for more than a decade for vast biomedical applications. Among all polyesters, aliphatic polyesters are the most investigated degradable polymer for biomedical applications and have been used in sutures, drug delivery devices, and tissue engineering scaffolds. Polyesters are of utmost interest in biomedical applications because these biomaterials can be broken down and resorbed without removal or surgical revision (Fong et al. 2011). Polyesters are susceptible to acid, base-catalyzed hydrolysis, or enzymes present in the body. Fine-tuning of mechanical and drug delivering properties makes polyesters a natural choice towards tissue fixation and controlled drug delivery applications (Vert et al. 1992).
Poly(L-lactic acid) (PLLA) is the most prevalent in this category, and though reports of the use of PLLA can be found in the 1960s, exceptional amount of work has been performed and published recently. PLLA is the product resulting from polymerization of L,L-lactide (also known as L-lactide). Being able to degrade into innocuous lactic acid, PLLA has widespread applications in sutures, drug delivery devices, prosthetics, scaffolds, vascular grafts, bone screws, pins, and rods or as plates. Strong mechanical properties and degradation into innocuous end product are the main reasons for such variety of applications (Shikinami et al. 2005). PLLA is U.S. Food and Drug Administration-approved for a variety of applications and is available commercially in a variety of grades. Some of the commercially available products are NatureWorks (Cargill, USA), Lacty (Shimadzu, Japan), PDLA (Purac, the Netherlands), PLA (Galactic/Total, Belgium), and Ecoloju (Mitsubishi, Japan) (Bordes et al. 2009). Some studies suggest the potential use of PLLA as a bone reinforcement material. The mechanical properties of neat PLLA might not be enough for high load-bearing applications. This explains the need to incorporate different elements like oriented fibers, HAP, or clays to form nanocomposites. This result in an increase in the flexural modulus and strength, which corresponds with bone replacement implants (Shikinami et al. 2005).
Poly(glycolic acid) (PGA) is another aliphatic biodegradable polyester with applicability in the field of biomaterials. However, unlike PLLA, high water solubility of PGA and fast hydrolysis on exposure to aqueous conditions affect the mechanical properties adversely. Thus, water solubility and its high melting point limit the use of PGA in bionanocomposites.
Another biodegradable biocompatible FDA-approved polyester commonly known as poly DL-lactide/glycolide or poly(lactide-co-glycolide) (PLGA), which degrades by hydrolysis of its ester linkages in the presence of water into lactic acid and glycolic acid (Fig. 2; Steele et al. 2012).

PLGA has been used to deliver chemotherapeutics, proteins, vaccines, antibiotics, analgesics, anti-inflammatory drugs, and siRNA. Most often PLGA is fabricated into microspheres, microcapsules, nanospheres, or nanofibers to facilitate controlled delivery of drugs. PLGA offers several advantages as delivery devices, for example, site-specific/localized drug delivery through surface functionalization and control of drug release from the matrix by changing its monomer’s ratio, molecular weight, and terminal end groups (Huang et al. 2013). Surface functionalization has been done for various purposes such as PEG to evade secondary immune response, folic acid for tumor targeting, and acrylates for bioadhesion (Tables 1 and 2).

Poly(ε-caprolactone) (PCL) is a biodegradable and nontoxic aliphatic polyester exhaustively studied as the biomedical nanocomposite. PCL is obtained by the ringopening polymerization of ε-caprolactone in the presence of metal alkoxides (aluminum isopropoxide, tin octoate, etc.). PCL shows a very low Tg (61 C) and a low melting point (65 C), which limits some applications. Therefore, PCL is generally blended or modified (e.g., copolymerization, cross-linking). The copolymerization is commonly done with other lactones such as glycolide, lactide, and poly(ethylene oxide) (PEO) or by nanofiller incorporation in order to wide range of properties as per application. The rubbery state because of low Tg permits the diffusion of this polymer species at body temperature, thus making it a promising candidate for controlled release and soft tissue engineering (Vert et al. 1992). This is important for the preparation of long-term implantable devices, as its degradation is even slower than that of polylactide.

Polypeptide-Based Nanocomposites

A wide range of possibilities in materials design and application are provided by polypeptide nanocomposites as ability to adopt specific secondary, tertiary, and quaternary structures, a drawback of synthetic polymers (Hule and Pochan 2007). Specific sites of the polypeptide backbone can be modified by incorporating specific amino acid functionality with desired activity. The increased mechanical properties and thermal properties of nanocomposites with addition of fillers are comparable to other widely explored biomedical devices and biomaterials. The secondary conformation of the nanocomposite matrix can be affected by the molecular weight of the polypeptide. Polylysine (ε-poly-L-lysine, PLL) is a small natural homopolymer of the essential amino acid L-lysine that is produced by bacterial fermentation (Chaurasia et al. 2012; Gao et al. 2003; Ramanathan et al. 2004; Tasis et al. 2006; Iijima 1991; Ajayan et al. 1994). L-lysine residues generally constitute homopolypeptide ε-polylysine, in which epsilon (ε) refers to the linkage of the lysine molecules. α-Polylysine improves cell adhesion, hence commonly used to coat tissue cultureware. Several secondary structures of PLL are the random coil, α-helix, or β-sheet in aqueous solution, and transitions can be easily achieved using pH, temperature, salt concentration, or use of cosolvent. These different conformations and transitions can be studied using circular dichroism (CD), FTIR, and Raman spectroscopy. PLL preferentially forms β-sheet structure irrelevant to nanocomposite film formation method at high concentrations (Hule and Pochan 2007). These secondary structures of polypeptides aid the design of new nanomaterials for specific desired applications in the biomedical arena. Such nanocomposites with addition of fillers give strength to matrix, and potential applications include drug delivery matrices, tissue engineering scaffolds, and bioengineering materials (Fong et al. 2011).

Other Types of Nano-Biocomposites

Polyhydroxyalkanoates (PHAs) are linear polyesters produced in nature by bacterial fermentation of sugar or lipids (Aldor and Keasling 2003; Li et al. 2007a). They can be either thermoplastic or elastomeric material with wide melting range from 40 C to 180 C. Polyhydroxyalkanoates (PHA)-based nano-biocomposites are useful in making bioplastic because of their biodegradability but possess some drawbacks, such as brittleness and poor thermal stability (Aldor and Keasling 2003). This limits their application, and hence, often they are intercalated with clay. PHA/clay nano-biocomposites are prepared by solvent intercalation and/or melt intercalation processes. PHA-based nano-biocomposites have a wide range of applications in sutures, cardiovascular patches, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, and in wound dressings and as hemostats (Park et al. 2005; Reddy et al. 2003).
Poly(urethane urea) (PUU) block copolymers are used in ventricular assist devices and total artificial hearts as blood sacs. Polyurethane ureas (PUUs) are prepared with the same conditions as polyurethanes, with the difference that diamines are used instead of diols as chain extenders, which constitute the hard segments with improved mechanical and thermal properties. The higher cohesion of urea linkages develops stronger, three-dimensional hydrogen bonding in PUU (Oprea et al. 2013). One of the main disadvantages of PUUs in medical devices is their relatively high permeability to air and water vapor. The majority of the component of copolymer is the soft segment called the poly(tetramethylene oxide), which is responsible for the permeability and diffusive properties of the polymer. Addition of organically modified layered silicates overcomes the permeability and diffusive drawbacks while still maintaining the desired biocompatibility and mechanical properties of the nanobiocomposites (Xu et al. 2000). This additional silicate imparts increase in barrier properties because of intercalated clay layers in the polymer matrix with increases in the modulus and strength of the nanocomposite.
More recently polymer-based nanocapsules are being used to design drug delivery system with improved solubility, bioavailability, and controlled release for a specific target. Polymer-based nanocapsules provided stability of drug molecules from degradation by external factors such as light or by enzymatic attack in their transit through the digestive tract (Mosqueira et al. 2001; Ourique et al. 2008).
Polymer modification has been done in order to obtain more hydrophilic surfaces or polymer coatings to attain favorable behavior regarding active substance stability in the case of encapsulation (Mora-Huertas et al. 2010).
In Fig. 3 micelles, formed from amphiphilic block copolymers (ABCs), with cores and coronas have been demonstrated as a powerful tool for cell imaging, disease diagnosis, and delivery of various water-insoluble materials (including quantum dots, magnetic nanoparticles, and drugs).

For example, PEG–PCL and PEG–PLA, are some of the block copolymers, used for nano-encapsulation. This type of polymers are used to encapsulate hydrophobic/hydrophilic drug or active ingredients depends on application and process.
The tri-block copolymers, PCl–PEG–PCl [poly(e-caprolactone)–poly(ethylene glycol)–poly(e-caprolactone)], were used to encapsulate and deliver ibuprofen. The release profile of ibuprofen was significantly affected by the block length of the copolymer composition and the extent of loading. The in vitro profile shows a sustained release of 10 % loading ibuprofen from 3 to 15 days. Release profile depends on the ratio of e-caprolactone to ethylene glycol-derived subunits in copolymer chains. With 5 to 20 wt% ibuprofen loading, release was continued for 2–24 days for copolymer whose e-caprolactone molar ratio to ethylene glycolderived subunits was 2.49 (Yu and Liu 2005).
Another example of the effect of nano-encapsulation was reported on reverse multidrug resistance in tumor cells when PEG–PCL was used. This study shows a novel drug delivery system, where an anticancer drug, doxorubicin, was encapsulated by polyethyleneglycol–polycaprolactone (PEG–PCL) using solvent evaporation method. The size of doxorubicin-loaded polymer nanocomposite was about a diameter of 36 nm and a zeta potential of +13.8 mV. The encapsulation efficiency of doxorubicin was 48.6 %  2.3 %. This drug/polymer nanocomposite showed sustained release profile, increased uptake, and cellular cytotoxicity, as well as decreased efflux of doxorubicin in adriamycin-resistant K562 tumor cells (Diao et al. 2011).
Block copolymer nanocomposites are used for bioimaging. One of the primary conditions applicable in bioimaging is micelle-encapsulated superparamagnetic nanocomposites, which should be dispersible and stable in aqueous medium besides other criteria.
It was reported that amphiphilic poly(e-carpolactone)-block-poly(ethylene glycol) copolymers were linked to a fluorophore, 2,1,3-benzothiadiazole (BTD). This resulted in new type of bioimaging agent. The polymers form micelles in aqueous solutions with average diameters of 45 nm and 78 nm depending on the polymer structures. So, neutral and hydrophobic biocompatible emitters can be made by using the block copolymer in a rational way (Tian et al. 2010).