Biomedical Engineering Reference
In-Depth Information
C HAPTER 3
Bone Morphogenetic Proteins
and Tissue Engineering of Bone
A. Hari Reddi
Abstract
Tissue engineering is the emerging science of design and manufacture of tissues including
bones and joints. The three key ingredients for both tissue engineering and
morphogenesis are inductive morphogenetic signals responding stem cells and the
assembly of extracellular matrix. The long-term goal of our research is to produce spare parts
for the human musculoskeletal tissues. Regeneration of musculoskeletal tissues recapitulates
embryonic development and morphogenesis. Morphogenesis is the developmental cascade of
pattern formation, body plan establishment leading to adult form and function. Therefore,
signals involved in morphogenesis will be of utility in tissue engineering of bones and joints.
Although bone and articular cartilage are adjacent tissues, there is marked difference in their
regenerative potential. Bones has maximal regenerative potential; on the other hand cartilage is
feeble. BMPs have pleiotropic roles in initial pattern formation, cell differentiation and main-
tenance of bone and articular cartilage. The regenerative potency of bone is due to bone mor-
phogenetic proteins (BMPs) in the bone matrix. BMPs act via BMP receptors and Smads 1, 5
and 8 to initiate lineage of cartilage and bone. The homeostasis of tissue engineered bone and
cartilage is dependent on the interface of tissue extracellular matrix and biomechanics. The use
of BMPs in gene therapy and isolation of stem cells and their microenvironmental niche of
extracellular matrix results in functional bone and cartilage. In conclusion, these are exciting
times in functional tissue engineering of bone.
Introduction
One of the challenges confronted by an orthopaedic surgeon is the repair and restoration of
large segment skeletal defects resulting from resection of a malignant bone neoplasms. Al-
though large segment bone allografts have gained increasing acceptance it has the drawbacks of
potential fractures. 3,38 The problem of bone fractures in patients with postmenopausal os-
teoporosis, metastases due to breast and prostate cancer and metabolic diseases such as diabetes
requires the application of principles of tissue engineering to bone. 8,13,16,27,28
Tissue engineering is the science of design and fabrication of new tissues for functional
restoration of impaired organs and replacement of lost parts due to cancer, disease and
trauma. 26,27 Among the many tissues in the body, bone has the highest potential for regenera-
tion and therefore is a prototype paradigm for the enunciation of principles of tissue engineer-
ing in general. The accumulating knowledge in tissue engineering will lead to the design of
bone with predetermined shapes for orthopaedic surgery applications.
The three key ingredients for tissue engineering and tissue regeneration are signals, stem
cells and scaffolding. The specificity of signals is dependent on tissue morphogenesis and in-
ductive cues in the embryo and they are generally recapitulated during regeneration. 30 Bone
 
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