The Role of Growth-Generated Strains and Pressures in Cranial Development

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Abstract

Development is regulated by intrinsic factors within cells and by inductive signals. This thesis introduces the concept that connected tissues growing at different rates necessarily generate complicated distributions of physical deformations (strains) and pressures. The hypothesis that these growth-generated strains and pressures act as inductive signals throughout development is presented, and the role of growth-generated strains and pressures in cranial development and in skeletal condensation growth is investigated.

In the first study, general theoretical techniques for estimating sutural bone deposition rate and strain magnitude during mammalian cranial development are developed. These techniques are then applied to human development. The results indicate that human sutural strain is small (approximately 0.0021 to 0.041% at 1 month of age) and decreases with increasing age.

In the second study, morphological measurements and tensile tests are performed on sagittal sutures from rats, and the strain present in the suture in vivo are estimated. The results show that sutural strains in rats (average of 0.027 ± 0.019% for postnatal days two to sixty) are similar in magnitude to the estimate of sutural strains in young humans. In the third study, surgical experiments and finite element modeling are used to calculate the residual tensile strains present in vivo in the dura mater of rats. The results show that large residual tensile strains are present in vivo and are age dependent (average of 4.76 ± 1.51 for immature rats vs. 0.36 ± 0.12% for mature rats).

In the final study, growth-generated strains and pressures are correlated with in vivo gene expression during growth of a skeletal condensation. The results show that areas of tensile strain correlate with expression of osteogenic or fibrogenic genes, and areas of pressure correlate with genes associated with chondrocyte differentiation and maturation.

The findings presented in this thesis illustrate the existence and potential importance of growth-generated strains and pressures in cranial development and in skeletal condensation growth. In addition, the concepts and findings presented in this thesis suggest that a richer appreciation of the events that control early skeletal patterning and development can be gained by understanding the relationships between growth-generated strain/pressure and local tissue, cell, and molecular biology.

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