Figure 1. (A) Basic concept of
surface engineering of biomaterials to control the interaction between
living matter and biomaterials. (B) Surface engineering includes
modification on original surface and additional layer coating to control
over surface properties. By altering surface characteristics, various
purposes can be fulfilled including enhanced biocompatibility,
antibacterial ability, cells regulation and delivery of bioactive agents
for specific applications.
When extracorporeal devices such as orthopedic implants, drug-eluting
stents, tissue engineering scaffolds and microfluidics first contact
with the living matter of human body, the body would elicit a foreign
body response involving inflammation, blood coagulation, fibrous
encapsulation, and rejection in extreme cases[1].
Protein adsorption is the first major event in the interaction between
the living matter and implanted devices. Subsequent events such as
cellular activities and signaling pathways initiation are largely
dependent on their interactions with the deposited protein layer. For
example, the complement system can be activated by protein adsorption.
Blood-coagulation process will be initiated for wound healing.
Neutrophils are responsible for the acute inflammatory response; they
will migrate to the interface and degrade the foreign objective.
Monocytes will be recruited to the biomaterials-tissue interface and
differentiated into macrophages attempting to eliminate foreign objects,
which marks the chronic inflammatory response. Macrophages uptake the
debris as well as injured tissue and clear them through phagocytosis.
However, with a large mass of foreign objective, a “frustrated
phagocytosis” occurs resulting in aggregation of macrophages to form
multinucleated foreign body giant cells. Fibroblasts will be activated
and secrets collagen fibers aligned parallel to the surface of
biomaterials that forms a fibrous capsule. Fibrous encapsulation is
always formed around the implant to screen it from the body. Those
undesirable reactions result in destruction of local tissue as well as
implants failure. Such non-specific protein adsorption is governed by
protein properties such as protein structure, polarity and charge
distribution, and features of biomaterial surface including chemistry
and topography as well as environmental conditions including pH and
temperature[2]. Engineering biomaterials with an
anti-fouling surface will create a protein-resistance layer to improve
their performance. Herein, we first described surface engineering
methods to construct anti-fouling surface by underscoring the use of PEG
in both macroscopic surface and nanoparticle system.
The adsorption of plasma protein will benefit the bacterial adhesion as
well. Upon binding to the surface, bacteria will proliferate rapidly and
secrete extracellular matrix leading to biofilm formation (Figure 2).
The biofilm is a colony of immobilized bacteria on the surface of
biomaterial that exhibits a robust structure. Bacterial biofilms are
much harder to eradicate by antibiotics than circulating
bacteria[3]. The biofilm formation results in
device-related infections limiting the success of implant and medical
interventions. Anti-biofouling surface formation is known as the
“passive” strategy to address the problems of bacterial adhesion.
“Active” strategy by construction of anti-bacterial surface is
discussed as well. Various bactericidal substances are incorporated in
surface modifications including silver ions, antimicrobial peptides,
antibiotics and antibacterial polymers.