SYNTHESIS AND IN VITRO/IN VIVO RESPONSE TO PEPTIDEPOLYMER CONJUGATES - Biologically-Responsive Hybrid Biomaterials - page 112

foreign body from the rest of the host. Host tolerance of the material will result in
matrix remodeling processes as fibroblasts and endothelial cells that infiltrate the
site produce extracellular matrix (ECM) components such as collagen,
fibronectin and hyaluronic acid and form the new ECM, scar tissue. While the
matrix bed is laid down, matrix degrading agents such as matrix metalloproteases
and collagenases help rearrange and organize a structured ECM.
These delicately orchestrated complex events described above comprise the
host response that is often determined by the chemistry of the material's surface.
Controlling each host response event and achieving complete restoration of
normal tissue structure and function is a difficult task given our currently limited
mechanistic understanding of host response. However, rather than a relatively
passive approach of implanting a material and monitoring the host response, an
active approach of tailoring host response through the presentation of
biofunctional peptides may prove to be one significant stride toward avoiding
host rejection of the material.
2.2. In vitro response to biomaterials
In vitro assays allow the assessment of material cytotoxicity on cells and are
invaluable in screening biomaterials to gain insight into material degradation,
mechanical strength over time and whether the materials leach toxic substances
that affect the viability of cells. Three major assays for testing material
biocompatibility and toxicity in vitro include agar diffusion, extraction, and
direct cell-biomaterial contact method. Material toxicity can be investigated
through the agar diffusion method by covering a confluent layer of cells with
agar containing a viability stain, then placing the biomaterial on the agar surface
and examining the extent of the viable cells under and around the material after
an incubation period. Thus agar diffusion assays are useful in evaluating material
toxicity, and the method is often applied to highly dense materials [1,2].
Extraction studies (i.e., elution, extract dilution) are also employed to observe
any linear relationship between cell cytotoxicity and the concentration of
extracted biomaterial. The threshold concentration of the material extract on
minimal and maximal cytotoxicity can be investigated with a confluent layer of
cells being exposed to serially diluted material extract and assessing cell viability
after the incubation period. Usually, the cells in the targeted implant area are
candidates for the extract dilution test and how much of the material extract is
absorbed by these cells can also be determined [3].