420 9.4  Personalizing Healthcare

normal process of endocytosis by which eukaryotic cells internalize extracellular material

(see Chapter 2). Other emerging targeted delivery tools involve synthetic biological 3D

nanostructures, for example, made from DNA, to act as molecular cages to enable the effi­

cient delivery of a variety of drugs deep into a cell while protecting it from normal cellular

degradation processes before it is released to exert its pharmacological effect.

Exciting nanomedicine developments also include bionanoelectric devices to interface

with nerve and muscle tissue, such as in the brain and the heart. Devices used in cellular

repair are sometimes referred to as nanoscale robots, or nanobots. Much recent media

coverage concerning nanobots has involved speculation over the terrifying implications were

they to go wrong. Such as consuming the entire Earth or at the very least turning it into a

gray goo. However, the realistic state of the art in nanobot technology is still at a technically

challenging stage; to get even natural nanoscale machines to work unmodified outside of

their original biological function, let alone to generate de novo molecular machines that can

be programmed by the user to perform cellular tasks, is hard enough, as any veteran student

in this area of biophysics will attest!

The most promising emerging area of nanomedicine currently involves methods to facili­

tate tissue regeneration. This can be achieved through the use of biomimetic materials and

the application of stem cells. Stem cells in multicellular eukaryotic organisms are cells that

have not yet differentiated. Differentiation is not to be confused with the mathematical term

in calculus, but here is a biological process in which cells undergo morphological and bio­

chemical changes in their life cycle to commit to being a specific cell type, for example, a

nerve cell and a muscle cell. However, prior to this stage, cells are described as stem cells and

can in principle differentiate into any cell type depending on external triggers involving both

the external chemical environment and mechanical signals detected by the cell from the out­

side world. Thus, if stem cells are transplanted from an appropriate donor source, they can

in principle replace damaged tissue. In some countries, including the United States, there are

still some levels of ongoing ethical debate as to the use of stem cells as a therapeutic aid to

alleviate human suffering.

The development of biomimetic structures as replacements for damaged/​diseased tissues

has experienced many successes, such as materials either directly replace the damaged tissue

and/​or act as a growth template to permit stem cells to assemble in highly specific regions

of space to facilitate the generation of new tissues. Biomimetic tissue replacement materials

focus largely on being mimics for the structural properties of the healthy native tissue, for

example, hard structural tissues such as bone and teeth and also softer structural extracel­

lular matrix material such as collagen mimics.

Biocompatible inorganic biomimetics has focused on using materials that can be

synthesized in aqueous environments under physiological conditions that exhibit chemical

and structural stability. These particularly include noble metals such as gold, platinum, and

palladium, as well as metal oxide semiconductors such as zinc oxide and copper(I) oxide,

but also chemically inert plastics such as polyethylene, which benefit from having a low

frictional drag while being relatively nonimmunogenic, and also some ceramics, and so all

have applications in joint replacements. Inorganic surfaces are often precoated with short

sequence peptides to encourage binding of cells from surrounding tissue.

Collagen is a key target for biomimetization. It provides a structural framework for the

connective tissues in the extracellular matrix (see Chapter 2) as well as plays a key role in the

formation of new bone tissue from bone producing cells (called osteoblasts) embedded in

the extracellular matrix. Chemically modifying collagen, for example, by generating multiple

copies of a cell binding domain, can increase the rate at which new bone growth occurs. This

effect can be characterized using a range of biophysical techniques such as confocal micros­

copy and SEM in vitro. Thus, modified collagen replacement injected into the connective

tissue of a patient suffering from a bone depletion disease into local regions of bone deple­

tion, detected and quantified using x-​ray and CT imaging in vivo, can act as a biomimetic

microenvironment for osteoblasts to stimulate the regeneration of new bone tissue.

Mimicking the naturally porous and fibrous morphology of the extracellular matrix can

also be utilized in biomimetization of tissues and organs. Some biomimetic tissues can be