Biomedical Engineering Reference
In-Depth Information
While antibiotics can be effective against freely floating bacteria, microorganisms grow-
ing in biofilms are significantly less susceptible to antibiotics and host defenses than their
counterparts not growing in a biofilm. Antimicrobial resistance, however, is on the rise,
even for freely floating bacteria. Whereas resistant bacteria were previously common only
in intensive care units, more recently such organisms (e.g.,
) are
found in extended-care facilities and home health care sites. The primary defense the body
has against infection from bacteria is the innate immunity provided by immune cells such
as neutrophils, macrophages, and dendritic cells. However, the biofilm, which in biomate-
rials terms is a polysaccharide alginate matrix, protects the entry of the toxic molecules that
the immune cells secrete. For example
Staphylococcus epidermidis
biofilm protects the bacteria
from interferon gamma-mediated leukocyte killing. Bacteria such as
Pseudomonas aeruginosa
Staphylococcus aureus
have developed an ability to thwart neutrophils and macrophages by chemically blocking
their migration and making it difficult for the immune cells to phagocytose (swallow) them.
Biomaterials' researchers have attempted to produce anti-infective devices or implants
by (1) mechanical design alternatives for indwelling catheters (liquid:air breaks, skin cuffs,
antibiotic fills); (2) tethered, covalently attached anti-infective agents, bound directly to the
surface of the material (silver coatings, tethered quaternary ammonium, synthetic antibi-
otics); or (3) the release of soluble toxic agents (chlorhexidine, antibiotics) into the adjacent
surroundings. These current approaches have done little to stop the epidemic rise in bacte-
rial infections and may have contributed to the rise of antibiotic-resistant bacteria.
Mechanical design alternatives have had only marginal success. Tethered anti-infective
agents are only toxic to the initial wave of incoming bacteria and provide little residual effects
once layers of dead cells accumulate. Regardless of the type of drug-release method used,
release of a toxic agent from a biomaterial of a soluble anti-infective agent will inevitably stop
once the entrapped agent is depleted. Further, delivery of sublethal dosages of antibiotics can
lead to accelerated biofilm formation and induced virulence factor expression.
Increasing scientific research in biofilm formation has led to the possibility of several
new approaches, including enhancing the phagocytosis of the bacteria by the immune cells
by delivering artificial molecules that accelerate and increase the binding of the neutrophils
to the bacteria; using antibody therapy, which causes the biofilm to detach; and increasing
the ability of the dendritic immune cells to attack bacteria by applying a vaccine to the
implanted biomaterial.
5.4.5 Biomaterial Degradation and Resorption
Biomaterials may be permanent or degradable. The degradation process may be chemi-
cally driven or accomplished by cells. Bioresorbable implants are designed to degrade grad-
ually over time in the biological environment and be replaced with natural tissues. The goal
is to meet the requirements of strength and cell support while the regeneration of tissues is
occurring. Small changes in biomaterial chemistry and structure may greatly alter the
resorption rate, allowing for materials to be tailored for various applications or leading to
unexpected product failure. Collagen and the lactic acid and/or glycolic acid polymers
(PLLA and PGA or copolymer PLGA) are the most commonly used for resorbable applica-
tions. PLLA and PGA degrade through a process of hydrolytic degradation of the polyester
bond. At low molecular weights, the implant can disintegrate and produce small fragments
