BRIGHAM AND WOMEN´S HOSPITAL
Thomas S. Thornhill, MD
JOHN B. AND BUCKMINSTER BROWN PROFESSOR OF ORTHOPAEDIC SURGERY, HARVARD MEDICAL SCHOOL
CHAIRMAN, DEPARTMENT OF ORTHOPAEDICS, BRIGHAM AND WOMEN´S HOSPITAL, BOSTON MASSACHUSETTS








Introduction

We are well along fiscal year 2009 and, like most of you, are feeling the affects of the recession. While healthcare is a bit immune and we have not seen any significant decrease in volume, there clearly have been significant reductions in our unrealized gains. Moreover, our overall development base has been challenged by the economy and the Madoff scandal. At any rate, the bulk of the news from the Department of Orthopedics is favorable. One of the greatest boosts to the department has been a 7-figure gift from Ed and Gretchen Fish. This has been an unbelievable savior for our department in both its research and educational arenas. Ed and Gretchen have been great friends to the BWH and to the Department of Orthopedics.

We are juggling a multi-campus strategy that has both challenges and opportunities. Our main campus at the Brigham has shown an increase in our outpatient volume and an increase in the acuity and overall operative volume. Our new operating rooms are wonderful. We have up-to-date imaging and for those of you who remember the Brigham, we no longer use ultraviolet light. The up-to-date laminar flow and the space suites used for most joint replacements have kept our infection rate extremely low. It is amazing to go back to the old operating rooms for a visit and wonder how we were able to do the cases that even fill our much larger rooms. We, like most of you, are now fully digital and have digital templating systems that work, for the most part, throughout our clinics and ORs.

Our Faulkner campus represents our greatest growth and our greatest capacity to grow. With Michael Wilson as Chief of Orthopedics at the Faulkner and with his orthopedic advisory group, we have established a stronger orthopedic identity in the operating room. There are many initiatives underway which include a service specific OR team and consolidation of the orthopedic equipment. We are on track to beat budget by 40% in fiscal year 09 as compared to 35% in fiscal year 08.

We see patients at several different campuses including BWH, 850 Boylston Street, Faulkner, Braintree, and now Foxboro. The opening of Foxboro’s Patriot Place includes a surgery center and is adjacent to the Patriots Gillette Stadium. While this is predominantly a BWH facility, the orthopedics is done in combination with our colleagues at Massachusetts General Hospital.

Another 3-year initiative that we are still working on is improving our outpatient facilities and patient satisfaction. This was originally started by a grant from the Hatch Foundation and organized through the IHI group. We started at our Faulkner Foot and Ankle Clinic and developed some very interesting metrics that have allowed us to improve all facets of our outpatient care. This has certainly benefited both our Faulkner and 850 programs and we have now concentrated on our main campus. We have hired a concierge to troubleshoot some of the problems and it has been a tremendous success.

Dr. John Wright has led our improvement of inpatient services and both quality, cost effectiveness and efficiency in the operating room. As you know, academic medical centers face significant challenges in OR efficiency for many reasons including the important task of teaching. I have been through multiple attempts over 25+ years, but I am encouraged that this latest effort is very promising.

BWPO DEPARTMENT OF ORTHOPEDICS ADMINISTRATION

Our department administrator Mr. Tom Gakis left to be the administrative head of the 300-member Department of Medicine at UMass, Worcester. This took his commute from over an hour to under 15 minutes. Tom has remained helpful in the transition. We have had the benefit of Colleen Burns Hernandez acting as the interim manager and had just hired a new administrator who will begin June 1st. I think that during Tom Gakis’ tenure, we have put together an administrative structure that works on all fronts. Just to make things more confusing, we also went through a billing transition, which as you know can be troublesome. We are encouraged by our initial experience and have some wonderful individuals who have made tremendous differences. I was going to name some of the many individuals involved, but I will not, as I am sure I would omit a few and I do not want any headhunters calling.

RESIDENCY UPDATES

As you know, Jim Herndon has retired from his job as Residency Program Director and Dr. Dempsey Springfield was selected as the new Director. We are fortunate in that Dempsey comes with a large experience as both a program director, Department Chair and member of the RRC. There clearly is a paradigm shift in the training of orthopedic residents. This will be driven through by the ACGME and it forces us to re-engineer our thinking. The HCORP Executive Committee has two outstanding PGY-5 residents who attend the meetings and the resident council has been and is very involved with the changes. I am sure that many of these will be covered in the program director’s report so I will not reiterate them at this point. I heard a great line the other day after a chiefs committee where someone said, “everything has been said but not everyone has had a chance to say it.”

I have asked each of our division chiefs and each of our principal investigators to write a brief synopsis of their activities. The extent to which it is included reflects the response from the individuals. I will try to fill in the gaps as best I can.

MUSCULOSKELETAL CLINICAL DIVISIONS

Hand/Upper Extremity Service

Barry Simmons reports: The Hand and Upper Extremity Service, directed by Barry P. Simmons, MD and including Philip E. Blazer, MD and Brandon E. Earp, MD, welcomed an addition to the faculty. We are fortunate to be joined by George S.M. Dyer, MD. George completed his Orthopaedic residency in the Harvard Combined program in 2007 and was our Hand Fellow, 2007-2008. After obtaining his undergraduate degree from Harvard, George was a member of the US Air Force for 7 years. While in the Air Force he dealt with casualty evacuation and treatment and decided he would prefer to be on the receiving end, so he attended Harvard Medical School before starting our Orthopaedic program. Although interested in treating all disorders of the Upper Extremity, he has a special interest in Veterans and those injured in the recent conflicts, partly due to his own military service. He is director of the Hand and Upper Extremity service at the Veterans Administration Hospital and has revitalized the division. He is especially interested in upper extremity joint replacement. A recent publication evaluated acute carpal tunnel syndrome in patients with fractures of the distal radius.

Philip E. Blazar continues to be extremely active clinically and academically. In charge of the educational programs for our division, he has organized weekly conferences both for the fellows as well as the residents rotating through our service. As well, he was awarded the best poster award at the national meeting of the American Society for Surgery of the Hand, co-authored by Brandon Earp and Tamara Rozental, one of our former fellows. Other academic pursuits are osteoarthritis of the carpometacarpal joint, evaluation of the triangular fibrocartilage complex by MRI, collengenase injections for the treatment of Dupuytren’s disease, surgical and non-surgical treatment of distal radius fractures and long-term evaluation of patients who underwent total elbow replacements.

Brandon E. Earp has an extremely busy clinical service. She has also co-authored a paper on arthroscopic treatment of osteoarthritis of the carpometacarpal joint.

Barry P. Simmons has been an invited lecturer to Hand Societies in Georgia and Texas, speaking on his main area of concentration, arthritis of the hand and wrist. Along, with the rest of the faculty he has contributed to two chapters for Arthritis texts. The administrative challenges continue, especially in the area of funding for fellowship education and evaluation of fellow performance.

The Harvard Combined Orthopaedic Fellowship, which includes the Hand and Upper Extremity service at Children’s Hospital, continues to attract a large number of talented applicants. Now in its 27th year, and planning for our second alumni/ ae reunion in 2009, we continue to train 3 fellows a year. The cross-rotation with the fellowship at the MGH, started in 2000, remains enormously beneficial and has allowed us to participate in educating over 70 fellows. Our current fellows, Michael Garcia, Ross Richer and Farnaz Yassaee joined us after completing residencies in Chicago and New York respectively.

Foot and Ankle Service

Chris Chiodo reports on the Foot and Ankle service as follows: The Foot and Ankle division has enjoyed another productive year, both clinically and academically.

On the clinical front, the Foot and Ankle Center renovations are complete. Patients are also seen at the main campus and Foxboro. The new operating rooms at the Faulkner, developed under the direction of Mike Wilson, are now also finished.

Academically, the Division’s research into autologous bone graft, performed in collaboration with Dr. Julie Glowacki, was presented at the American Orthopedic Foot and Ankle Society (AOFAS) Summer Meeting in Toronto. At the same meeting, the Division presented its results for a new technique for peroneal groove deepening. New research into complications associated with Achilles tendon repair has just been accepted for presentation at the upcoming AOFAS Summer Meeting in Vancouver. In addition original research, numerous invited reviews and chapters have been completed this year.

Drs. Chiodo and Wilson recently hosted the AOFAS Complete Foot Course here in Boston. This is a national meeting for orthopedic surgeons and other allied health professionals who treat patients with foot and ankle disorders. There were over 100 attendees and the course was very well received. In addition to the national faculty, local speakers included Dr. Rich DeAsla from the MGH and Dr. Mark Slovenkai from the New England Baptist Hospital.

Dr. Wilson remains busy in his role as Chairman of the Orthopedics Department at Faulkner Hospital. In this role he continues to grow Orthopedics at the Faulkner. This year he will also be inducted into the American Orthopaedic Association.

Dr. Chiodo has finished his second consecutive term as the President of the Massachusetts Orthopedic Association. He also completed his term as Chair of the Young Physicians Society of the AOFAS. Looking forward, he has been elected to the Board of Councilors of the AAOS and asked to chair the AAOS Achilles Tendon Clinical Guideline Committee.

Dr. James Ioli, who leads our Podiatry division, has completed his term as President of the Massachusetts Podiatric Society. He continues to head up Podiatry at the Brigham and has brought on Kim Thurmond, DPM, to help see patients there. Kim has had a productive first year and is an appreciated member of our team. In addition to the main campus, Dr. Ioli sees patients both at Braintree and 850 Boylston.

Spine Service

The spine service has been a great success story with Chris Bono, Mitch Harris and Greg Brick. Their collaboration with colleagues at Dana Farber, MGH and with the non- operative spine centers physicians is the way an AMC should run.

Chris Bono reports: The combined BWH-MGH orthopaedic spine fellowship continues to flourish and prosper. We recently had interviews and are attracting a very high caliber of candidates from prestigious residencies such as Columbia, Stanford, Yale, NYU-Hospital for Joint Disease, Brown, and Dartmouth. Our three current fellows, Gregory Deblasi, MD, Richard Lee, MD, and Andrew Schoenfeld, MD, have been extremely productive both academically and clinically, each having already completed at least one publishable project. We are very proud that one of our fellows, Andrew Schoenfeld, will be pursuing an academic career in a military position in Texas. He has taken on innumerable research and publishing projects since starting his fellowship in August. We are certain that Andrew will be a major academic leader in the future.

The spine research division has also been extremely productive. Under the direction of Natalie Warholic, the spine research coordinator, we have initiated, are actively running, or have completed approximately seven IRB protocols. Our work has been presented at the annual meetings of the International Society of the Study of the Lumbar Spine, North American Spine Society, Scoliosis Research Society, and Orthopaedic Research Society. Moreover, our research has resulted in many high-quality publications, seven of which have been published or accepted within the past twelve months. In addition, the spine division has approximately six studies that have been submitted for publication. On a personal level, the faculty members of the spine division continue to achieve many great accomplishments on the regional, national, and international level. Dr. Harris continues to lead the Instructional Course Lecture about thoracolumbar fracture management at the AAOS annual meeting, serving as the course coordinator this year.. Recently, he accepted an invitation from the AAOS Technology Overview Committee to participate on its committee evaluating the efficacy and safety of cervical disc replacements. He has also accepted a position on the AAOS Leadership Development Committee. During the 2008-09 year, Mitch had five spine papers published or accepted for future publication.

Dr. Bono has been appointed a position on the Board of Directors of the North American Spine Society as well as the Chair of the Evidence-Based Guideline Committee for that society. Furthermore, Chris has been appointed the Orthopaedic Surgery Deputy Editor of The Spine Journal and the Chair of the Adult Spine Education Subcommittee for the American Academy of Orthopaedic Surgeons. Both from his work with his peers at BWH and in collaboration with colleagues in national and international work groups, Chris has published 14 peer-reviewed articles in the 2008-09 year and is in the midst of editing a novel text about spine surgery entitled, Prove It! Evidence-Based Analysis of Common Spine Problems, published by Lippincott, Williams & Wilkins.

Sports Medicine and Shoulder Service

This service continues to be very productive. Tom Minas, Scott Martin and Larry Higgins truly bridge the gap between sports and arthroplasty. Andreas Gomoll recently traveled to Asia as an AOSSM Traveling fellow.

Larry Higgins reports; Dr. Laurence Higgins serves as the Chief of the Sports Medicine and Shoulder Service and serves as the Fellowship Director of the Harvard Shoulder Service with Dr. Jon JP Warner (Chief at the Massachusetts General Hospital). The service is comprised of Dr. Tom Minas, Director of the Cartilage Repair Center with Dr. Andreas Gomoll. Dr. Scott Martin serves as the Fellowship Director of the Sports Section.

This year, the Sports and Shoulder Service has had many academic, research and education breakthroughs. Clinical growth remains extremely strong, attracting referrals both regionally, nationally and internationally for management of complex sports and shoulder problems. The combined service accounts for well over 1600 surgical cases, and is robustly represented at all three Brigham campuses (BWH, Faulkner Hospital and Patriot Place).

Academic highlights include eighteen peer reviewed publications (LDH 7, AG 6, TM 5), four instructional video submissions, seven chapters in textbooks and over fifty presentations at national and international meetings. The Sports Medicine and Shoulder Service was faculty for six instructional courses this year at the AAOS. Within the last year, Dr. Gomoll was selected to be a Traveling Fellow for the AOSSM, a prestigious honor highlighting his accomplishments.

On the research front, Dr. Higgins received the Prospective Clinical Grant from the OREF, a funded three year grant evaluating the role of Vitamin D on the pathogenesis of Rotator Cuff Arthropathy. This grant has allowed the Sports Medicine and Shoulder Service to grow the basic science research for the Division, and will serve as the substrate for the next round of NIH R03 funding. Additionally, a prospective patient database is officially capturing all surgical cases from the Shoulder Service, markedly facilitating future prospective and retrospective studies. Plans are underway to expand this to capture all arthroscopic knee surgeries as well.

The notable highlight in our Educational mission is the recent ACGME accreditation of the Sports Medicine Fellowship. This rigorous accreditation process acknowledges the growth of the Sports Fellowship at the BWH and allows the graduating fellows the opportunity to sit for the CAQ in Sports Medicine. Additionally, the BWH Sports Fellowship is now part of the AOSSM national match, which will greatly expand our applicant pool.

This year, Dr. Higgins is serving as Chairman for the combined ASES/AAOS Orthopedic Learning Center Course on Advance Shoulder Surgery. This honor is bestowed after serving as faculty for over eleven OLC courses, and represents our Divisions commitment to education of our residents, fellows and colleagues.

Trauma

Mitchel B. Harris continues to serve as the BWH trauma Chief with Mark Vrahas as the Chief of the Partners Trauma Service. The Trauma Service has had another very productive year. The report with their updates and activities is within the “Partners Trauma Service” article in the Journal.

Arthroplasty Service

The Arthroplasty Service, traditionally the heart and soul of first the Robert Breck Brigham and then the Brigham and Women’s Hospital, has remained strong and its volume has increased. With the addition of Jeff Katz and Elena Losina to the Orthopedic and Arthritis Center for Outcomes Research (OrACORe), we now have a much more robust outcomes program. Our major limitation in arthroplasty reporting has been the fact that any corporate association precludes the surgeon from being involved in a clinical study of a project or there is a conflict. Hopefully, the new method of fellowship sponsorship through an independent organization will resolve some of these conflicts. At any rate, our primary and revision programs have both grown. We have elected to concentrate certain techniques (service replacement, patient specific implants, computer navigation, etc., in the hands of one surgeon). This hopefully will reduce the learning curve, allow for evidence based outcomes and enable us to understand the efficacy of new technologies. Moreover, many of the principal investigators in the laboratory are working in areas of materials technology (Anuj Bellare) and bone cell biology (Julie Glowacki). There was participation from the Arthroplasty team both at the Hip Society and the Knee Society at the recent AAOS.

Orthopedic Oncology

Dr John Ready reports: The Orthopedic Oncology Service at Brigham and Women’s Hospital provides care to patients with bone and soft tissue sarcoma as well as metastatic disease of the skeleton. These patients are cared for at both the Dana-Farber Cancer Institute and Brigham and Women’s Hospital. Both Dr. John E. Ready and Dr. John A. Abraham have clinics to assess and treat patients with oncological concerns at the Center for Sarcoma and Bone Oncology at Dana-Farber Cancer Institute and in the clinic space in the BWH Orthopedic and Arthritis Center. The service consists of Dr. Ready and Dr. Abraham, as well as ancillary staff. There are two physician extenders, Susanna Santos, physician assistant and Shannah Young, nurse practitioner. There are also two residents assigned to the Orthopedic Oncology Service. One is a PGY-5 and the other is a PGY-3. The service schedule is set up such that one resident is assigned to each attending. The residents switch at the midpoint of their 8-week rotation, so they spend equal time with each attending on the service. The service is set up such that one of the attendings is usually in the clinic each day and the other attending is in the operating room. Floor consults are handled by each of the attendings and cases that need to go to the operating room are done based on the availability of operating room time.

The research in the department is largely based on the clinical review of the Orthopedic oncology experience. Dr. Michael Weaver (PGY-5) presented a paper this year at the American Academy of Orthopedic Surgeons on a group of patients with cementless stems utilized in oncological reconstructions with a megaprosthesis. This paper was coauthored by the Orthopedic Oncology Department here at Brigham and Women’s Hospital and our partners at Massachusetts General Hospital.

Several submissions have been made for major meetings over the next year. Dr. Abraham is presently working on a project utilizing computer navigation as a means of resecting large pelvic bone and soft tissue sarcomas. He has done the cadaver work and is now ready to transition this to the operating room. He has submitted this to the ISOLS meeting for presentation here in Boston in September.

Dr. Michael Banffy (PGY-3) has reviewed our experience with stress fractures in patients with bisphosphonates. This also includes our colleagues from the Partners Trauma Service.

We also have a comprehensive review of Leiomyosarcoma from BWH/DFCI which has been presented at the annual MSTS meeting by Dr. Michael Weaver and is now ready for submission for publication.

MUSCULOSKELETAL RESEARCH

Musculoskeletal Service Line: One of the major hallmarks of the Robert Breck Brigham Hospital was the working relationship between Rheumatology and Orthopedics. My first interest in orthopedics came as a medical resident on the Rheumatology Service. This is a unique relationship that we have continued to foster into the present time. The BWH Rheumatology Service is one of if not the largest in the United States. Their research budget is about 20 million dollars and we have many projects together in areas of immunology, bone biology, proteomics, and stem cell research. To report on the individual programs and associations with our Rheumatology colleagues in the laboratory would be beyond the scope of this report. I will, therefore, in the next section, list the highlights of the BWH Orthopedic principal investigators. I have asked each group to submit a brief report and I have included all of those that were submitted.

Orthopedic and Arthritis Center for Outcom es Research (OrAC ORe)
Jeffrey N. Katz, MD, MSc

Jeffrey N. Katz, MD, MSc, is Associate Professor of Medicine and Orthopedic Surgery at HMS and Associate Professor of Epidemiology at Harvard School of Public Health. He is the Director of the Orthopedic and Arthritis Center for Outcomes Research (OrACORe), a multidisciplinary research group in the Department of Orthopedic Surgery at BWH. OrACORe is comprised of fifteen individuals including faculty and staff with backgrounds ranging from rheumatology and medicine to epidemiology, biostatistics, nursing, physical medicine and rehabilitation. OrACORe faculty is engaged in cutting edge grant supported research. Dr. Katz, for example, is Principal Investigator of the MeTeOR Trial (Meniscal Tear in Osteoarthritis Research), a NIAMS funded five center ran domized clinical trial of arthroscopic partial meniscectomy in patients with osteoarthritis. He is also Principal Investigator of the BWH Multidisciplinary Clinical Research Center, a P60 Center grant funded by NIAMS. He is PI and Director of the a NIAMS funded T32 training grant for musculoskeletal clinical research. Dr. Katz has published over 250 peer reviewed papers on diverse musculoskeletal and orthopedics problems. He is also Deputy Editor for Methodology of the Journal of Bone and Joint Surgery and Deputy Editor of Spine.

Skeletal Biology Research Laboratory
Julie Glowacki, PhD

Professor Julie Glowacki is Director of the Skeletal Biology Research Laboratory, which studies basic, clinical, and translational aspects of skeletal pathophysiology, skeletal cell differentiation, effects of age and vitamin D status on bone physiology, mechanisms of chondro/osteoinduction, and tissue engineering approaches for skeletal regeneration. In the past year, achievements in basic research include the surprising discoveries that human marrow stromal cells activate vitamin D substrate with hydroxylating enzymes and that the level of expression of the hydroxylases is related to vitamin D status of the subject from whom the cells were obtained. These observations suggest that vitamin D metabolism in bone marrow may be part of paracrine regulation of bone metabolism. Another startling discovery made with discarded marrow cells is that cells from subjects receiving bisphosphonates at the time of orthopedic surgery show a marked suppression of in vitro differentiation of osteoclasts, compared with cells from age and gender matched subjects. That lack of osteoclast differentiation was attributable to significant suppression of RANKL, a factor that stimulates osteoclast differentiation, and upregulation of OPG, a factor that inhibits it. It is remarkable that those effects of in vivo administration of bisphosphonates are sustained in the marrow, even when removed from the patient and studied in cell cultures. These observations suggest two things: first, that bisphosphonates inhibit generation of new osteoclasts in addition to their known anti-resorptive effects on mature osteoclasts, and second that the inhibition endures even after discontinuation of the bisphosphonate. In a recent editorial in the New England Journal of Medicine, Dr. Glowacki commented on new information about accumulation of apoptotic osteoclasts in biopsies from some patients treated with bisphosphonates.

Drs. Chris Bono, Chris Chiodo, Mitch Harris, Larry Higgins, Tom Thornhill, Mike Wilson, and John Wright are active surgeon members of the Skeletal Biology Research Laboratory. Current research is funded by NIH grants, BWH Biospecimens Pilot Awards, and the OREF. A new grant was awarded from the HHS Assistant Secretary for Preparedness and Response for the development of new therapeutics for the treatment of exposure to ionizing radiation. Collaborating with Dr. Joel Greenberger, Chairman of Radiation Oncology at the University of Pittsburgh, Dr. Glowacki is evaluating the effect of novel mitochondrial-targeted anti-oxidants to mitigate the irradiation- induced impairment of bone healing. Ongoing basic science work concerns the mechanisms of skeletal aging, effects of age on cell signaling pathways, effects of vitamin D status on marrow cell differentiation, and vitamin D metabolism by human marrow cells. Tissue engineering research involves the regulation of chondrocyte and osteoblast differentiation, optimization of the Mizuno tissue bioreactor, and mechanisms of actions with differentiation agents to enhance histogenesis. Dr. Shuichi Mizuno’s latest work concerns the effects of hydrostatic pressure on chondrocytogenesis of human adiposederived stem cells and a novel method of chondrocyte culture with a semipermeable membrane pouch and hydrostatic pressure. Translational and clinical research continues our multidisciplinary program to improve follow-up management of osteoporosis in fragility fracture patients, expand fracture pathways with other in-hospital caregivers, the effect of fracture on circulating pre-osteoblasts, regional differences in quality of bone grafts, the natural history of osteoporosis in patients with osteoarthritis, the pathophysiology of rotator cuff arthropathy, importance of vitamin D status for skeletal health, and the impact of medications in vivo on marrow biology in vitro.

Dr. Glowacki continues to serve the department as Co-Chair of the BWH Musculoskeletal Research Center of Excellence, representative to the BWH Biomedical Research Institute’s Research Oversight Committee and the Partners Steering Committee for the Biospecimens Enterprise for Translational Research (BETR), and as Professional Standards Officer for BWH Research Staff. She is a member of the NIH review panel for Musculoskeletal Tissue Engineering, and advises NASA and the FDA. Julie was honored last year with a Mentor Recognition Award from the American Medical Association.

Orthopedic Nanotechnology Laboratory
Anuj Bellare, PhD

In 2008, the research of the Orthopedic Nanotechnology Laboratory focused on the improvement in the mechanical properties of radiation crosslinked polyethylene for use in total joint replacement prostheses for high-stress applications. The first approach was to increase the modulus of radiation crosslinked and remelted polyethylene via high-pressure crystallization. Unlike conventional compression molding and ram extrusion, which apply pressure on polyethylene in a 0.1-20 MPa pressure range, high-pressure crystallization utilizes pressures in a range of 50-500MPa. Our studies demonstrated that the modulus of crosslinked polyethylene can be increased to values higher than uncrosslinked polyethylene using this technique, providing a wear resistant, oxidation resistant crosslinked polyethylene with a higher resistance to creep deformation and a higher fatigue strength than the 1st generation remelted, radiation crosslinked polyethylenes.

A second study, which we used to improve the mechanical properties of crosslinked polyethylene, was to incorporate Vitamin E (alpha-tocopherol) antioxidant into the interior regions of polyethylene while maintaining the surface regions free of antioxidant, prior to irradiation. It is known that antioxidants suppress crosslinking so it is beneficial to have antioxidants in the bulk regions where crosslinking is undesirable due to its deleterious effect on mechanical properties. The lack of antioxidants in the surface regions prior to radiation ensures that they become highly crosslinked during radiation. Postradiation annealing was shown to diffuse the Vitamin E into those surface regions from the Vitamin E-rich, interior regions thereby providing an oxidation resistant component. Using this technique, crosslinks were highest in the surface regions where they were needed most for high wear resistance. This technique is currently being optimized for implant applications.

A third polyethylene study, conducted in our laboratory by Michele Boffano, an orthopedic resident from the University of Turin, was to examine the deformation behavior of polyethylene. It was shown that there is a gradual decrease in the crystallinity of polyethylene with compressive strain. It is advantageous to decrease the crystallinity of polyethylene prior to radiation because lower crystallinity means that less free radicals are trapped in the crystalline lamellae of polyethylene and more crosslinks form in the amorphous regions in between lamellae due its higher content. A decrease in free radicals occurs when this irradiated polyethylene is annealed, which simultaneously decreases the undesirable anisotropy induced by compression, providing a crosslinked polyethylene with a low but detectable level of free radicals. The free radicals are not a concern when the polyethylene contains antioxidants, which do not greatly affect its deformation behavior since they are present in very low concentrations of about 500-1000ppm. Thus, this project increased the level of crosslinking for a given radiation dose by making more amorphous content available due to a reduction in crystallinity via compression.

A fourth project we undertook was to develop a soft, wearresistant, bearing material, which can be potentially used to develop meniscus bearings and also for application in intervertebral disks. This technology uses a blend of polyethylene with a polyethylene-like copolymer which is elastomeric in nature, i.e. its crystallinity is less than 5% compared to the 45-70% crystallinity of orthopedic grade polyethylene. Our laboratory acquired a compounder equipped with screw-extruders to blend these two components into various relative weight fractions. Our mechanical tests revealed that the modulus of the polymerblend was dominated by the elastomer, providing a soft bearing material. Gamma radiation and melting of these blends crosslinks the two macromolecules together is expected to increase their wear resistance. We are currently in the process of fabricating more blends to measure the friction and wear resistance after radiation crosslinking.

The first of these studies has been accepted as a full paper by the Journal of Biomedical Materials Research: Applied Biomaterials. The latter three studies were presented as posters at the Annual Meeting of the Orthopedic Research Society, Las Vegas in 2009. Manuscripts are being prepared to submit a more comprehensive version of these studies in various peerreviewed journals.

Center for Molecular Orthopedics
Keith Crawford

The research focus of the Center for Molecular Orthopedics is in the area of stem cell biology and regenerative medicine. The Director of this Department is a MD-PhD and is investigating the regulatory networks of newly discovered adult stem cells with pluripotent capability. CMO research is roughly 2,000 sq-ft and there is a collaborative relationship with the Laboratory of Innovative Technology. Residents interested in research with the Center would have access to flow cytometry, automated fluorescence light microscopy, Light Cycler (QPCR), Mass Spectrometer, Biotrove and Geniome gene expression platforms. CMO has a working collaboration with the Laboratory of Innovative Technology at the Harvard Catalyst.

Tissue Engineering
Myron Spector, PhD

We have added several novel tools to our technology toolbox for an array of applications of musculoskeletal and neural tissue engineering. In addition, in the course of investigation of the composition and structure of select musculoskeletal tissues, including the rotator cuff and intervertebral disc, we have discovered the presence of the principal joint lubricating molecule, the glycoprotein, lubricin.

Our recent studies have shown that the formation of cartilage in vitro by chondrocytes growing in collagen scaffolds is enhanced if the scaffold permits cell-mediated contraction of the construct, and a increase in the cell number density. This process recapitulates the condensation of chondroprogenitor cells identified in vivo decades ago as the initiating event in chondrogenesis. We have shown how the contracture of the collagen scaffolds can be controlled by cross-link density.

In anticipating the benefits of physical and chemical regulators of cell function in musculoskeletal and neural tissue engineering we have developed methodology to employ: 1) extracorporeal shock waves to enhance proliferation of osteoprogenitor cells, and 2) nanoparticle non-viral vectors for transfer of genes to cells, including mesenchymal stem cells. The genes which have recently been employed to date include: OP-1, endostatin, and glial cell line-derived neurotrophic factor.

A notable finding of our recent studies is the demonstration of the distribution of lubricin in the rotator cuff and intervertebral disc. Our journal articles are the first reports of this critically important lubricating molecule in these musculoskeletal tissues. This work provides a basis for understanding the tribology of these tissues, and the mechanisms underlying various disorders.

Grants Since the Last Chairman’s Report

M. Spector was awarded a competing continuation of his VA Research Career Scientist Award in Musculoskeletal Tissue Engineering for the period 2008-2013 (~$750,000 total direct costs).

Tissue Engineering Publications Since the Last Chairman’s Report

Zhang D, Johnson LJ, Hsu H-P, and Spector M. Cartilaginous deposits in subchondral bone in regions of exposed bone in osteoarthritis of the human knee: A histomorphometric study of PRG4 distribution in OA cartilage. J. Orthop. Res. 2007;25:873-883.

Tang S and Spector M. Incorporation of hyaluronic acid into collagen scaffolds for the control of chondrocyte-mediated contraction and chondrogenesis. Biomed. Mater. 2007;2:S135-S141.

Steinert A, Palmer GD, Capito R, Hofstaetter JG, Pilapil C, Ghivizzani SC, Spector M, and Evans CH. Genetically enhanced engineering of meniscus tissue by ex vivo delivery of a TGF-1 cDNA. Tiss. Engr. 2007;13:2227-2237.

Tang S, Vickers SM, Hsu H-P, and Spector M. Fabrication and characterization of porous hyaluronic acid-collagen composite scaffolds. J. Biomed. Mater. Res. 2007;82:323-335.

Ma J, Tian W-M, Hou S-P, Xu Q-Y, Spector M, and Cui F-Z. An experimental test of stroke recovery by implanting a hyaluronic acid hydrogel carrying a Nogo receptor antibody in a rat model. Biomed. Mater.: Mater. in Tissue Engr. and Regen. Med. 2007;2:233-240.

Xu X, Capito RM, and Spector M. , Plasmid size determines chitosan nanoparticle mediated gene transfer to chondrocytes. J. Biomed. Mater. Res. 2008;84A:1038-1048.

Xu X, Capito RM, and Spector M. ,Delivery of plasmid IGF-1 to chondrocytes via cationized gelatin nanoparticles. J. Biomed. Mater. Res. 2008;84A:73-83.

Funakoshi T, Schmid T, Hsu H-P, and Spector M. Lubricin distribution in the goat infraspinatus tendon: A basis for interfascicular lubrication. J. Bone and Joint Surg. 2008;90A:803-814.

Madaghiele M, Sannino A, Yannas I.V. and Spector M. Collagen-based matrices with axially oriented pores. J. Biomed. Mater. Res. 2008;85A:757-767.

Pfeiffer E, Vickers SM, Frank E, Grodzinsky AJ, and Spector M. The effects of glycosaminoglycan content on the compressive modulus of cartilage engineered in type II collagen scaffolds. Osteoarth. and Cart. 2008;16:1237-1244.

Bolliet C, Bohn MC, and Spector M. Non-viral delivery of the gene for glial cell line-derived neurotrophic factor to mesenchymal stem cells in vitro via a collagen scaffold. Tissue Engr. 2008;14:207-214.

Spector M. Editorial: Ideas and inspiration: A remembrance of Philip J Boyne, DMD, MS, DSc. Biomed. Mater. 2008;3:1-2.

Cui F-Z, Lee I, and Spector M. Editorial: The scope of a journal. Biomed. Mater. 2008;3:1-2.

Sun X-D, Jeng L, Bolliet C, Olsen BR, and Spector M. Nonviral endostatin plasmid transfection of mesenchymal stem cells via collagen scaffolds. Biomaterials 2009;30:1222–1231.

Shine KM and Spector M. The presence and distribution of lubricin in the caprine intervertebral disc. J. Orthop. Res. (In press).

OPERATION WALK BOSTON

As many of you know, Dr. Larry Dorr from Los Angeles started Operation Walk several years ago and it has grown to several independent organizations based on his model. Two years ago, I took a small group and joined Doug Dennis and Operation Walk Denver in Panama. In 2008 we combined efforts with Operation Walk Denver to do our second trip, this time to Santo Domingo in the Dominican Republic. We have just returned from our 2009 trip to Santo Domingo and I am pleased to report that we performed 55 total hip and total knees on 40 patients in four days. This was a team of five surgeons including Dick Scott and myself from the BWH, David Mattingly from the NEBH, John Siliski from the MGH and Dr. Lowry Barnes from Arkansas. Lowry was one of our former fellows. We had five anesthesiologists led by Dr. Mercedes Concepcion and we took a team of about 50 nurses, physical therapists, OR personnel, and equipment managers. Dr. Coleen Sabatini, a PGY-5, served as our medical coordinator and did an outstanding job. Dr. Jeremy Smith, one of our PGY-3s, also came and was superb. Our plan is to return next year to Santo Domingo and we hope to further integrate resident participation in Operation Walk Boston. The funding for this has been through contributions made to our 501(c) (3) which is imbedded in Partners in Health. We also had tremendous support from the BWH and from DePuy Orthopaedics.

In addition to the many surgeries we performed, we had an academic program arranged by Dick Scott and had many of the orthopedic surgeons from the Dominican Republic in attendance. Moreover, we had nursing, physical therapy and medical school student educational programs that were based around quality, efficiency, and practical issues such as sterilization and adoption of the WHO surgical safety pause protocol.

ALUMNI AFFAIRS

Our colleague, Dr. Mark Koris suffered a stroke in December 2007 and was hospitalized for many months. After his acute hospitalization, he was transferred to Spaulding Rehabilitation and then to the Hebrew Senior Life Facility. Mark has been home for many months and I am pleased to report that he is making steady progress. He was in the office the other day. He gets out on a daily basis to do both his physical therapy and occupational therapy. He has attended most of his son’s baseball games and both Mark and Francine are working hard and are optimistic. He plans to be in attendance at Smith Day this year. I am sure that he would love to hear from you and we all wish him well.

Last November, we had a reunion of the old Robert Breck Brigham; it coincided with the November birthdays of Clement Sledge, Ed Nalebuff and me. Many of the old RBBH employees were there. It was great to see Bob Poss, Fred Ewald, Clement Sledge, Bill Thomas, Dick Scott and some of the rheumatologists. Unfortunately, it coincided with the major Rheumatology meeting, so we were missing a significant part of our medical team.

It was nice to see so many of you at the AAOS and we extend best wishes to all.





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