Effects of Mechanical and Biochemical Stimulation of Bone Marrow on Bone Formation and Ingrowth

Abstract

Nearly 500,000 joint replacement procedures are performed annually with the intention to remove damaged tissue and restore normal joint activity to patients suffering from osteoarthritis. Current methods of joint fixation are limited to two methods: the use of bone cement to stabilize the orthopaedic implant in the bone and the use of osseointegration to encourage bone to integrate into the implant surface. Osseointegrative surfaces have lower rates of revision surgery, making it an ideal fixation method for younger patients. However, current osseointegrative technologies have yet to replace bone cement as a fixation method in total knee arthroplasty, highlighting the need for improved surface designs to compensate for the unique mechanics in the knee. Additive manufacturing is a highly tunable method of design that can be applied to orthopaedic implants. However the current timeline for exploring new scaffolds is resource intensive and alternative methods of evaluating design iterations needs to be addressed.

Here an in situ bioreactor was used for modeling bone formation into porous, additively manufactured scaffolds. Scaffolds were inserted into cancellous bone both normal and orthogonal to loading to provide different levels of contact between the two surfaces. Initially, an in situ bioreactor model previously used in bone marrow mechanobiology studies was used for evaluating the impact of a WNT agonist and its impact on bone formation. Additionally circulating chemokines within the media and the importance of maintaining them within the media was shown to retain normal bone remodeling behavior. Osseointegration due to mechanical stimulation of bone marrow alone was also explored. Stimulation of bone marrow resulted in bone formation within scaffold pores. When the same orientation was subjected to compressive loading, bone formation did not increase, supporting the need for increased mechanical strain in the bone.

Finally, a transverse loading model was designed. Three different magnitudes of compressive loading were applied to bones with scaffolds inserted orthogonal to loading. Strains in the bone were higher and fell within the normal physiological range and resulted in the highest areas of bone measured. Interestingly, location along the scaffold surface did not impact overall bone ingrowth into the pores. While overall ingrowth was less than values measured in vivo, depth penetration aligns with current in vivo reports.

This is the first time that bone formation has been modeled in situ and provides a unique evaluation method of new orthopaedic scaffold designs. These studies highlight the potential for an in situ method for evaluating everchanging scaffold designs prior to in vivo testing. Beyond preclinical testing, this system could further the understanding of osseointegration at a local level, resulting from both mechanical and biochemical interactions, ultimately influencing new implant designs.