Tissue responses to implanted materials - Biomaterials and Devices for the Circulatory System - page 14

release of antibiotics from the biomaterial itself as with surface coating, and
local irrigation with catheters even after wound closure. All these measures
are targeted to the intra- and initial post-implantation period. Infections
are more likely to appear after a latent period. Two energy source modali-
ties that have been studied and appear to potentiate local antimicrobial
effect are ultrasonic energy (Nelson et al. , 2002) and very low current densi-
ties (Costerton et al. , 1994). Even more appealing is published work utilising
molecular-based therapy targeting genes regulating biofi lm formation
(Balaban et al. , 2007).

1.7 Carcinogenesis

Early experimental work with small animal models has recognised foreign
body-induced carcinogenesis as a reproducible process (Oppenheimer et
al. , 1955). Implantation of foreign prosthetic material of certain shapes such
as large non-perforated polymer fi lms is well known to induce sarcomatous
lesions in rodents while perforated or minced fi lms are non-carcinogenic or
only weakly carcinogenic (Moizhess and Vasiliev, 1989). As already dis-
cussed, implantation of prosthetic material within host tissue initiates a
cascade of cellular as well as humoral events that mostly take place at the
interface between host tissue and foreign body. The adhesion of cellular
components derived from the blood pool in an attempt to 'rid' the host of
this readily recognised foreign material initiated an acute in the fi rst instance
immune response with a predominance of macrophages and multinucleated
giant cells. Interestingly the profi le of adsorbed serum proteins plays a
pivotal role in human macrophage behaviour (Jenney and Anderson, 2000).
As it is practically impossible for the host defensive mechanisms to remove
the immune stimulus the ongoing infl ammatory process gradually tran-
scends into a chronic infl ammatory response. Macrophages and giant cells
maintain the propagation of this local infl ammatory response that macro-
scopically leads to the formation of a surrounding capsule. The degree of
thickness, neoangiogenesis, and fi brosis ensuing capsule formation may
vary.
Cellular interactions within the interface microenvironment may poten-
tially lead to the appearance of a wide variety of poorly differentiated
sarcomas or fi brosarcomas (Oppenheimer et al. , 1955). It is highly likely
that by-products of an ongoing infl ammatory response including free
oxygen radicals provide the mutagenic stimuli for any malignant transfor-
mation observed. A range of polymers has been shown to possess carcino-
genic potential (Oppenheimer et al. , 1955) as have various metals
(Oppenheimer et al. , 1956).
Data have been published by the International Agency for Research
regarding the evaluation of carcinogenic risks to humans based on com-

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