Bone Healing and Failure - Engineered Bone: Tissue Engineering Intelligence Unit - page 45

C HAPTER 5

Bone Healing and Failure

Ashley R. Poynton and Joseph M. Lane

Introduction

Facture healing is a complex process resulting from the interaction of cellular elements

that are activated and controlled by an array of proinflammatory cytokines and signaling
proteins. This process is both temporal and spatial in nature and results in the formation
of new bone that has properties very similar to the original prefracture structure. In children,
the repair process simulates regeneration and results in bone that is both structurally and me-
chanically identical to native bone. This is a unique healing process compared to elsewhere in
the body where healing results in scar formation. The ability of the skeleton to repair itself in
this manner is a vital survival mechanism. Despite this ability, the repair process may fail. There
are many reasons why this may occur, some are obvious and well understood while little is
known about others, particularly at a cellular level.
To understand the mechanisms of failure of fracture healing one must have a comprehen-
sive knowledge of the fracture repair process. To achieve this, animal models have been devel-
oped that allow the repair process to be studied in a detailed and reproducible manner. 1,2 The
series of biological events, and their physical and chemical controlling factors, that lead to
successful fracture healing have become more defined. However, many questions remain con-
cerning the precise mechanisms of intercellular signaling and related issues.
The purpose of this chapter is to outline the current available knowledge on fracture repair
and discuss the factors leading to its failure.

Overview of the Bone Repair Process
Prior to any discussion of fracture healing it is important to make the distinction between
primary and secondary healing as most of the data on fracture healing pertains to the latter.
Primary fracture healing can be defined as primary cortical healing which involves a direct
attempt by the cortex to reestablish itself. This type of healing occurs when there is precise
anatomical reduction of the fracture followed by rigid internal fixation. The key component
here is very low inter-fragmentary strain. 3-5 When these conditions exist the formation of dis-
crete remodeling units known as cutting cones occurs. 3,4 Osteoclasts on one side of the fracture
begin to resorb bone and form tunnels that cut across the fracture line. This establishes a new
Haversian system and allows blood vessel penetration. Endothelial and perivascular mesenchy-
mal cells follow and become the osteoprogenitor cells for osteoblasts. In this method of bone
repair endochondral ossification is absent and there is little or no callus formation callus. It is
seen only with open reduction and rigid internal plate and screw fixation, and naturally for
stress fractures. 3,4
Secondary fracture healing is a far more common process of bone repair and has been
studied in great detail in animal fracture models. 1-3
The key tissue in secondary bone repair is the periosteum which contains committed
osteoprogenitor cells and uncommitted undifferentiated mesenchymal cells both of which con-
tribute to the process. 3 The response of the periosteum to injury is a fundamental one that