Repair and Rehabilitation of Skeletal Tissues by Mechanical Loading

Principal Investigators: Dennis R. Carter, PhD and Gary S. Beaupré, PhD

Project Staff: Angelie Agarwal, PhD; R. Lane Smith, PhD; Eric E. Sabelman, PhD; Stuart B. Goodman, MD, PhD; Nicholas J. Giori, MD, PhD; and Derek P. Lindsey, MS

Project Category: Other

The proposed project will consist of a series of complementary experimental and computational studies that examine the role of mechanical stimuli in the repair and regeneration of bone, cartilage, and tendon defects. The goal of this work is to develop tissue-specific loading protocols to guide and enhance the tissue repair and regeneration process. The founding hypothesis for our study is that differentiation of mesenchymal stem cells can be directed in a predictable way by the local mechanical environment to achieve tissue and organ-specific specialization. The results of the proposed study will provide an important link between cell-based studies and clinical rehabilitation techniques. Guided regeneration will unquestionably become an important component of future treatments for skeletal diseases such as osteoporosis and osteoarthritis.

A primary function of skeletal tissues is a mechanical one related to locomotion, manipulation, and structural support. The sensitivity of skeletal tissues to mechanical stimuli is in large part responsible for the exquisite relationship between function and morphology that all skeletal tissues attain. Sensitivity to mechanical stimuli also plays a central role in tissue repair and regeneration that occurs during physical rehabilitation, with fracture healing as an example of a prototypical regeneration process.

In this study we will develop experimental protocols and computational models that examine the mechanical influence on repair and regeneration of skeletal tissues. These models will be used to identify the limitations of current tissue regeneration techniques and to develop guidelines for improving the long-term success of bone, cartilage and tendon regeneration. The ultimate clinical goal is to develop protocols for repairing skeletal defects using autologous marrow-derived mesenchymal stem cells in patients.

Milestones

• The culture and expansion of human bone marrow-derived MSCs has been established
• A protocol for seeding the MSCs inside a porous collagen scaffold has been implemented
• The design of a prototype tensile strain device is complete
• The design of a combined pressure-stretching device is in progress

Funding Source: VA RR&D Merit Review

Funding Status: Funded