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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-ß1 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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