Large Section Cortical Bone Repair and Regeneration
Goals and Objectives
Bone is a highly dynamic tissue that constantly remodels itself in response to changes in biophysical stress. One of the challenges of tissue
engineering with respect to bone is that as dynamic as bone is, it cannot regenerate the major tissue loss due to surgery or trauma. This is largely
due to the nature of endochondral bone development, where long bones arise from a cartilage model through a process of calcification, vascularization,
and ossification. Without the model or scaffold, proper replacement of bone lost to surgery or disease does not normally take place. Current therapies
include the use of permanent implants that are while sufficiently strong, actually weaken adjacent bone due to stress shielding. Recent attention has
turned toward the development of implants that will both serve as a scaffold akin to the cartilage model and are biodegradable, thus negating the need
for surgery to remove the implant. The goal of this collective effort is to design and fabricate an osteoinductive and osteogenic fiber-reinforced
composite scaffold as an orthopedic implant for the regeneration of extensive, segmental, compact-bone defects. The lines of experimentation that form
the Specific Aims of our program will include: (1) the design and fabrication of a biocompatible and biodegradable fiber-reinforced porous polymeric
composite scaffold; and (2) examining the ability of the fabricated scaffolds to support the growth and differentiation of osteoblasts and endothelial
cells in vitro, testing combinations of growth factors in augmenting the colonization of these matrices, and assessing the capacity of osteoblasts to
remodel the scaffold into bone; (3) three dimensional scaffolds will be tested in an animal model. In this proposal application we will focus on the
first item of the above-mentioned list. It is anticipated that these studies will generate an experimental foundation for future applications where
funding will be solicited from other funding sources.
Potential Impact and Intellectual Merit
We envision that our strategy will enable the formation of new natural cortical bones with no permanent foreign scaffolds left in the human body that
would otherwise elicit inflammatory responses. It also requires no post healing operation to remove the scaffolds and thus avoids additional cost and
unnecessary suffering. If successful, the impact of this research work on the human health will be significant. Fractured cortical bone with large
defect can then be repaired with the formation of new natural cortical bone at the fracture site and restoring the condition of the original cortical
bone. This method is critically needed for both peacetime and wartime injuries. In addition, people with abnormal unequal length in their limbs can
also benefit from this method of repair and regeneration of cortical bones.