Guided Tissue Regeneration of the Anterior Cruciate Ligament

Martha Murray, MD
Advisor: Myron Spector, MD
Discussor: Joseph Vacanti, MD

Dr. Martha Murray presented her continuing work on ligament regeneration for the treatment of anterior cruciate ligament (ACL) ruptures. Based on histologic evaluation of intact ACL’s harvested during total knee arthroplasty as well as ruptured ACL’s retrieved during reconstructive procedures, Dr. Murray characterized three distinct morphologic cell types –fusiform, ovoid, and spheroid— which are non-uniformly distributed throughout the length of the ACL. She defined three phases of tissue response to ACL rupture –inflammation, epi-ligamentous regeneration, and proliferation—and observed that blood supply to the ACL remnant is indeed preserved or augmented after rupture. Finally, Dr. Murray was able to promote the migration of remnant ACL cells through a collagen-glycosaminoglycan scaffold with near normal cell density in vitro. She hopes that these and future studies will aid in designing a biological solu-tion to the repair of ruptured ACL

Dr. Joseph Vacanti, in his discussion of Dr. Murray’s work, commended her sound scientific approach to this common orthopaedic disorder, emphasizing the need for biologic solutions to ligamentous repair. He challenged Dr. Murray and her advisor, Dr. Myron Spector, to further define the histologic organization and differentiation of these migrating cells in hopes of better defining the process of guided tissue regeneration.

The Active Elderly Patient: Outcome after Operative Treatment of Distal Radius Fractures

Paul Weitzel, MD
Advisor: Jesse Jupiter, MD
Discussor: Mark Koris, MD

Noting the increasing number of active persons over the age of 60 years in the United States, Dr. Paul Weitzel presented his thesis. In this project, he and his advisor, Dr. Jesse Jupiter, studied 25 patients over the age of 60 years who failed closed reduction and cast immobilization of their distal radius fractures and went on to open reduction and internal fixation. After an average follow-up of three years, all patients went on to heal their fractures, with 95% excellent or good radiographic results. Using the Patient Rated Wrist Evaluation and Physical Activity Survey of Elderly scores, these patients were found to have clinical and functional results comparable to patients of all ages with similar injuries. Only 10% had any decrease in their pre-injury activity, and there were no cases of implant failure or loss of fixation, despite concerns of osteoporotic bone. Dr. Weitzel concluded that age should not influence the decision to surgically fix distal radius fractures, and that good functional results can be achieved in patients older than 60 years. 

Dr. Mark Koris led the discussion of this presentation, noting the improved mechanical constructs currently available for the fixation of distal radius fractures in patients with osteoporotic bone. He called for a prospective randomized control study to assess the results of closed reduction and casting versus open reduction-internal fixation in this patient population.

The Influence of CBFA1 and Osteocalcin on the Osteotropism of Metastatic Breast Cancer

Andrew Hecht, MD
Advisor: Peter Hauschka, MD
Discussor: Henry Mankin, MD

Intrigued by the observations that beast cancer cells commonly metastasize to bone and often express osteoblastic proteins, Dr. Andrew Hecht addressed the issue of osteotropism in breast cancer. Through Northern and Western blot analysis of cells metastatic to bone, Dr. Hecht and his advisor, Dr. Peter Hauschka, discovered high levels of core binding factor A1 (CBFA1), a transcription factor that serves as a "master switch" in osteoblast differentiation, and osteocalcin, a protein produced by osteoblasts, in breast cancer cells metastatic to bone. He hypothesized that this mimicry of the osteoblas-tic phenotype contributes to the ability of breast cancer cells to metastasize to bone, either through the avoidance of immunosurveillance or through a yet uncharacterized osteoblast-osteoclast interaction. Future studies will be directed at understanding the mechanism by which this may occur. Andrew Hecht Henry Mankin 

In the discussion of Hecht’s thesis, Dr. Henry Mankin called for intensive investigation into this aspect of cancer biology, speculating that inhibitors of CBFA1 and other osteoblast proteins may aid in the future prevention and treatment of skeletal metastasis.