Biomedical Engineering Reference
In-Depth Information
the restoration of oxygen supply and nutrients, fibroblasts produce collagen fibers
that span wound, epithelium regenerates and proliferates beneath the clot. Wound
contraction occurs to pull closer together ends of damaged tissue, and temporary
healing is acheived. Upon initial healing, the wound remodels over an extended
period of time where matrix elements are broken down and resynthesized with
precise orientation and mechanical properties. This leads to a complete regenera-
tion of the tissue.
If the framework is destroyed or large number of cells is damaged, acute in-
flammation may
resolve
or
heal by scarring
and may progress to chronic inflamma-
tion. Sometimes, it is common for a mixed acute and chronic response to coexist.
Acute inflammation itself can damage otherwise healthy cells, which could then
further stimulate inflammation. A number of local or systemic signaling molecules
are released to which the immune system responds by recruiting more cellular com-
ponents. These cellular components release cytotoxic or degradative molecules to
destroy the material. Persistent activation of the immune system is deleterious: the
released products can destroy the neighboring healthy tissue and chronic macro-
phage activation culminates in the fibrotic scar tissue formation, where increased
amounts of fibers are present. Scar tissue is not as vascularized as original tissue
and it is not as flexible, elastic, or strong as the original tissue. Scar tissue formed
in a muscular organ such as the heart or bladder may inhibit function. Scar tissue
may adhere to adjacent organs, which could lead to loss of function of ligaments
and tendons. Formation of scar tissue near a joint compromises the joint mobility.
Consider the case of total hip replacement prosthetic devices. Debris created
by the wear of implant-articulating surfaces is attacked by macrophages. Macro-
phages can respond directly to wear particles released from the surface. Phagocy-
tosis of wear particles by macrophage induces signaling mechanisms, which release
inflammatory mediators [Figure 6.6(b)]; integration of signaling events triggers a
dynamic process of cytoskeletal rearrangement accompanied by membrane remod-
eling at the cell surface that leads to engulfment. The time scale for these interac-
tions begins within seconds of implantation and can continue through many years.
Some fibroblasts may also phagocytose wear debris. The mechanism of uptake and
dealing with wear debris is identical to the way that phagocytic cells ingest and kill
bacteria.
Macrophages gather and ingest foreign substances and introduce these sub-
stances (antigens) to T cells and B cells of the immune system for appropriate
action. However, the immune response is not effective against the plastic parti-
cles and cells may continue to respond. Chronic activation of macrophages occurs
through the components of
adaptive immune response
(i.e., T cells and B cells).
For example, activated T cells produce stimulatory molecules, which influence a
number of immune compartments including the activation of more innate immune
cells. However, T cells are normally quiescent and cannot directly recognize intact
foreign materials; their activation and subsequent clonal expansion is dependent on
proper presentation by antigen presenting cells (APCs that includes macrophages
and dendritic cells). This continuous response is deleterious as the released cel-
lular mediators affect cells present in the surrounding tissue including bone such
as fibrobalsts, osteoblasts, and osteoclasts. Activation of osteoclasts in the bone
may lead to bone resorption, which eventually leads to bone loss (osteolysis) next
