**20. Smart biomaterials**

Materials which respond to environmental changes are attractive particularly in vivo as these can be utilized to control drug release, cell adhesiveness, mechanical properties, or permeability. These environmental changes can be brought about by stimulants like pH [98], temperature [99], and light [100]. The body employs changes in pH to facilitate a range of different processes. For example, along the gastrointestinal track, food is broken down into nutritive substances in the stomach under acidic pH ∼ 2 and subsequently absorbed in the small intestine (pH ∼ 7). Patient often prefers the oral drug delivery requiring routine, periodic delivery of drugs and for effectiveness, the drug must resist the stomach acidic pH. The pH-sensitive materials that are mindful of gastrointestinal tract pH variation have been developed to transport drugs successfully through the stomach to the small intestine. Such successful materials include pH responsive hydrogels prepared from poly(methacrylic acid) grafted with poly(ethylene glycol) (PMAA-g-PEG) that swells in response to pH. For instance, the gel shrinks by trapping the drug cargo pH ∼ 2 as interpolymer complexes are formed, but at physiological pH ∼ 7, the gel can swell 3–25 times based on its composition as it releases its cargo in the target site [101]. Insulin-loaded PMAA-g-PEG gels have been orally delivered to diabetic mice with a significant decrease in glucose levels as protein function is protected in acidic and digestive enzymes environments [102].

#### **20.1 Self-assembled biomaterials**

Self-organization or self-assembly is based on the formation of weak noncovalent bonds, like hydrogen, ionic, or Van der Waals bonds or hydrophobic interactions [103]. In amphiphilic molecules, there are hydrophobic and hydrophilic segments that self-assemble to form nanometer 3D structures like micelles, vesicles, and tubules, which depend on the molecule's length and composition [104–107]. When any of these are dispersed in aqueous solvent, the hydrophobic segments agglomerate and water is expelled to produce a well-ordered structure useful in biomedical applications. Phospholipid a naturally occurring amphiphilic molecule that is largely compose of cell membrane is one such amphiphilic molecules while an oligomer, a polymer of amino acids, can be synthesized to have hydrophobic, hydrophilic, charged, etc., regions that can self-assemble into a macroscopic hydrogel [108]. The self-assembled biomaterials can be engineered for use in nanotechnology, tissue engineering for drug and cell carriers.
