Biomedical Engineering Reference
In-Depth Information
the aim of this chapter is to describe the process of bone repair and
regeneration under the new insights provided by cellular and molecular
biology tools. First, the temporal and spatial sequence of events leading to
bone healing is reported, based on histological findings from experimental
implants and retrievals. in the second part, the role of stem cells, from the
host or delivered using tissue engineering approaches, in the process of bone
regeneration is described. the third part is an elucidation of the molecular
events that determine precursor cells that form specific connective tissue, that
is bone. the last part is focused on the complex system of different growth
factors and cytokines which act as autocrine and/or paracrine effectors to
regulate osteogenesis.
ongoing research and further understanding of the bone healing process
will aid the strategies for bone regenerative therapies.
3.2 Bone healing
the complex series of integrated cellular events that ultimately lead to bone
healing has been extensively elucidated in experimental models.
3
primary
fracture healing is an artificial situation that occurs when rigid fixation devices
(that is, screws and plates) are surgically applied so that the fracture surfaces
are rigidly held in contact. in this process, there is little if any participation
from the periosteum or external soft tissues, but a direct involvement of the
cortex, the endosteum and the bone marrow. osteoclasts on each side of the
fracture undergo a tunnelling resorptive response whereby they re-establish
new haversian systems, therefore providing pathways for the penetration
of blood vessels.
4
Most fractures, however, heal by conservative treatment
(i.e. cast immobilization) or by elastic stabilization through external or
intramedullary fixation devices, so that micromotion occurs between fracture
surfaces. in secondary fracture healing, a large amount of reparative tissue
(so called fracture callus) is generated by a combination of intramembranous
and endochondral bone formation by the periosteum and the surrounding
tissues, with a less important role for the bone marrow.
5
the histological phases of bone healing can be summarized as: (1) an
early inflammation phase (haematoma formation, inflammation, angiogenesis)
with granulation tissue formation; (2) a reparative phase, with cartilaginous
callus formation and replacement of callus by lamellar bone; and (3) a late
bone remodelling phase in which the original bone shape is obtained.
3.2.1 Inflammation
Fracture trauma involves not only an interruption of skeletal integrity but
also a disruption of normal vascular structures and nutrient flow at the
fracture site, leading to a reduced oxygen tension and a disruption of marrow
