Biomedical Engineering Reference
In-Depth Information
pushing a finger into an inflated balloon. The point of invagination is the endoderm, which
eventually forms the gut. After gastrulation, the ectoderm is brought into position relative
to the endoderm and a third germ layer is formed between the two: the mesoderm. This
middle layer is formed via cell-cell interactions and soluble growth factor action. Several
determined stem cells originate from the mesoderm, including hematopoietic tissue, mesen-
chymal tissue, muscle, kidney, and notochord. Blood cells originate from the ventral meso-
derm. Some hematopoietic cells migrate into the yolk sac to form blood islands consisting
mainly of erythroid cells (“primitive” hematopoiesis). Intraembryonic hematopoiesis origi-
nates from the aortic region in the embryo and leads to “definitive” hematopoiesis. It
appears that the embryonic origin of hematopoietic cells is from bipotent cells that give rise
to both the vasculature (the endothelium) and hematopoietic cells. Hematopoietic stem cells
are then found in the liver in the fetus. Around birth, the hematopoietic stem cells migrate
from the liver into the bone marrow, where they reside during postnatal life. Interestingly,
the umbilical cord blood contains hematopoietic stem cells capable of engrafting pediatric,
juvenile, and small adult patients. This developmental process illustrates the asymmetric
nature of stem cell division during development and increasing restriction in developmental
potential. Furthermore, the migration of stem cells during development is important. Under-
standing the regulatory and dynamic characteristics of the stem cell fate processes is very
important to tissue engineering.
Tissue Repair
When tissue is injured, a healing response is induced. The wound healing process is
comprised of a coordinated series of cellular events. These events vary with ontological
age. Fetal wound healing proceeds rapidly and leads to the restoration of scarless tissue.
In contrast, postnatal healing is slower and often leads to scarring, which generally permits
satisfactory tissue restoration, while not always fully restoring normal tissue structure. Some
pathological states resemble wound healing. A variety of fibrotic diseases involve similar
processes to tissue repair and subsequent scarring. The increasing appreciation of stem cell
compartments and their descendant maturational lineages and the changes that occur in them
with age are likely to provide an improved understanding of wound healing phenomena.
THE SEQUENCE OF EVENTS IN WOUND HEALING
Immediately following injury, control of bleeding starts with the rapid adhesion of circu-
lating platelets to the site of damage. Within seconds, the platelets are activated, secrete
contents from their storage granules, spread, and recruit more platelets to the thrombus that
has started to develop. Within minutes of injury, the extent of hemorrhaging is contained
through the constriction of surrounding blood vessels.
Thenextphaseofthewoundhealingprocessinvolves the release of agents from the
platelets at the injured site that cause vasodilatation and increased permeability of neigh-
boring blood vessels. The clotting cascade is initiated and results in the cleavage of fibrin-
ogen by thrombin to form a fibrin plug. The fibrin plug, along with fibronectin, holds the
tissue together and forms a provisional matrix. This matrix plays a role in the early
recruitment of inflammatory cells and later in the migration of fibroblasts and other
accessory cells.
Inflammatory cells now migrate into the injured site. Neutrophils migrate from circulating
blood and arrive early on the scene. As the neutrophils degranulate and die, the abundance
