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Dr. Tara Aghaloo is Professor in Oral and Maxillofacial Surgery at UCLA. She completed her DDS at UMKC, and OMFS residency, MD, and PhD at UCLA. She is a diplomate of the American Board of Oral and Maxillofacial Surgery, and her clinical practice focuses on bone and soft tissue regeneration, and dental implant surgery. She is a board member of the OsteoScience Foundation, Past President of the AO, and Associate Editor of the JOMS.
Medical Optimization of the Oral and Maxillofacial Surgery Patient: A Surgeon’s Perspective
Although surgeons train to become technical experts who manage intraoperative and postoperative challenges, our patients are becoming significantly more complex. Whether we perform elective surgery on patients at extremes of age or patients present with more chronic diseases than we can count, we must be able to deliver predictable outcomes and surgical success. But, how do we get there? Gone are the days of only operating on young, healthy patients. Now, as oral and maxillofacial surgeons (OMSs), our patients often have several medical providers, take a plethora of prescription and herbal supplements (not to mention an occasional illicit substance), and fail to maintain a healthy diet and fitness regimen. Favorable surgical outcomes depend greatly on an optimized patient who can handle anesthetic medications, quickly resume normal daily activities, heal hard and soft tissues without undue sequelae, and take in adequate nutrition. Post-surgical recovery is clearly coupled with maximized systemic health, where patients may need a preoperative “tuned-up”. This presentation will identify important risk factors, state-of-the-art diagnostics, and the latest regenerative strategies to help practicing OMS optimize our aged, osteoporotic, and compromised patients before surgical intervention.
1). This presentation will discuss medically compromised patients and risk factors associated with poor surgical outcomes.
2). This presentation will discuss optimizing aged and compromised patients prior to surgical intervention.
3). This presentation will familiarize the participant with growth factors and cellular therapies to enhance hard and soft regeneration.
Dr. Bonewald is the Founding Director of the Indiana Center for Musculoskeletal Health, ICMH, with over 100 members from 27 schools and four campuses. She received her Ph.D. in Immunology/Microbiology from the Medical University of South Carolina, was promoted from Assistant to Full Professor at the Univ. of Texas Health Science Center at San Antonio and served as director of the Bone Biology Research Program and as Vice Chancellor for Research at the University of Missouri-Kansas City. She is a Past-President of the American Society for Bone and Mineral Research and the Association of Biomolecular Resource Facilities. She has served as Chair of the Board of Scientific Councilors for the NIH NIDCR and served on Council for NIH NIAMS. She received the IADR “Basic Research in Biological Mineralization Award”, the Sun Valley “RIB Award”, the prestigious ASBMR William F. Neuman award and is a UM Curators Professor Emeritas, an IU Distinguished Professor and an AAAS Fellow. She has been continually funded by NIH for over thirty years and is best known for her work in the study ofosteocytes and is responsible for tools used by researchers globally to determine osteocyte biology and function. She is currently studying bone and muscle crosstalk with aging.
1) The Role of the Osteocyte in Mechanotransduction
2) Muscle and Bone: Partners for Life
The Role of the Osteocyte in Mechanotransduction
The osteocyte is a mechanosensory, multifunctional cell regulating calcium and phosphate mineral homeostasis and regulating osteoblast and osteoclast function. Whereas mechanosensation and mechanotransduction does not appear to affect the osteocyte’s ability to regulate mineral metabolism, it does play a critical role in the expression of factors that target osteoblasts and osteoclasts. For example, mechanical loading stimulates the production of factors such as PGE2 and Wnts that have positive effects on osteoblastic bone formation. Conversely, unloading results in an increase in molecules such as sclerostin which inhibits bone formation and RANKL that promotes osteoclastic bone resorption. Osteocytes form a highly connected intricate network within the bone matrix that can communicate with cells on the bone surface through their dendritic processes, extracellular vesicles and soluble factors. Loading of bone is transmitted though the bone fluid which applies fluid flow shear stress to the cell body and dendrites, but the dendrites have the greatest sensitivity. Osteocytes can live for decades in the bone matrix, however, with age, they osteocyte become susceptible to several states, thought to negatively affect the capacity of the cell to sense mechanical load. Aged cells are exposed to increased reactive oxygen species making the cell more susceptible to apoptosis while at the same time some cells become senescent. A portion of the cells develop a hypermineralized perilacunar matrix, a portion die resulting in empty lacunae that fill in with mineral, called micropetrosis, but the majority develop a senescence-associated secretory phenotype, SASP. This results in a highly compromised osteocyte lacunocanalicular network with fewer cells, fewer dendrites per cell, and less connectivity. This reduced connectivity may be responsible for the loss of bone response to loading. In contrast to the young animal where loading induces new bone formation, in the aged skeleton, there is either little or no response to exercise. Exercise can delay the negative effects of aging and we have found that contracted muscle secreted factors can synergize with suboptimal loading of bone to promote new bone formation. Understanding osteocyte mechanosensation and transduction provides key insights into the beneficial effects of exercise.
1). Osteocytes are the key mechanosensory cells in the skeleton.
2). Mechanically loaded osteocytes produce factors that promote bone formation, whereas unloading induces osteocytes to make factors that promote bone resorption.
3). Aging compromises the osteocyte and its network making the skeleton less responsive to loading.
Muscle and Bone: Partners for Life
Originally, it was assumed that only a mechanical interaction existed between bone and muscle where the muscle pulled on the bone to allow movement. Now we know that each organ secretes factors, myokines and osteokines, that have effects on the opposing tissue. Bone and muscle are tightly intertwined throughout life, from development through aging. Genetic disease with mutations in muscle can have effects on bone and vice versa. With trauma, muscle accelerates bone healing. With aging, frequently osteoporosis and sarcopenia occur simultaneously. Loaded bone produces factors that have positive effects on muscle generation and function such as prostaglandin E2, and Wnts, while resorbing bone produces factors such as Receptor activator of nuclear factor kappa-Β ligand, RANKL and Transforming Growth factor beta that have negative effects on muscle. Conversely, static, resting muscle produces factors such as myostatin, which has not only negative autocrine effects but also has negative effects on bone. Contracted or exercised muscle produces factors such as irisin and beta-aminoisobutyric acid, BAIBA, which have positive effects on bone but through very different receptors and signaling mechanisms. The combination of these biochemical signals with mechanical loading can synergize to increase bone or muscle mass. This synergy emphasizes the importance of exercise where not only is muscle contracted but in addition bone is loaded to maintain a healthy musculoskeletal system and whole body health.
1). Though both are mechanical organs, they also produce factors that have effects on the opposing organ.
2). Contraction of muscle and loading of bone induces anabolic factors, whereas static muscle and unloaded bone produce catabolic factors.
3). Muscle factors interact with suboptimal loading to induce bone formation.
Dr. John P. Fisher is the MPower Professor, Distinguished-Scholar Teacher, Fischell Family Distinguished Professor, and Department Chair in the Fischell Department of Bioengineering at the University of Maryland. Dr. Fisher is also the Director of the Center for Engineering Complex Tissue (CECT), that aims to create a broad community focusing on 3D printing and bioprinting for regenerative medicine applications. Dr. Fisher’s group investigates biomaterials, stem cells, bioprinting, and bioreactors for regenerating lost tissues, particularly bone, cartilage, and soft tissues. Dr. Fisher’s laboratory has published over 200 articles, book chapters, editorials, and proceedings (14,500+ citations / 69 h-index) and delivered over 350 invited and contributed presentations, with support from NIH, NSF, FDA, NIST, DoD, and other institutions.
3D Printing Strategies for Bone Engineering
Generating complex tissues has been an increasing focus in tissue engineering and regenerative medicine. With recent advances in bioprinting technology, our laboratory has focused on developing platforms for treating and understanding clinically relevant problems, with a particular focus on bone and cartilage. We utilize digital light processing-based and extrusion-based additive manufacturing to generate biomaterial implants, cell-laden constructs, and bioreactors to expand critical populations. This presentation will cover the diverse range of materials and processes developed in our laboratory and their application to relevant, emerging problems in orthopedic tissue engineering.
1). Identify key bioprinting strategies particularly useful in bone engineering, including extrusion bioprinting and digital light processing printing
2). Explain the utility of computational assisted design (CAD) and associated modeling in the design and assessment of osteochondral implants
3). Describe the fabrication of cell-biomaterial constructs in bone engineering.
Robert E. Guldberg is the DeArmond Executive Director of the Phil and Penny Knight Campus for Accelerating Scientific Impact and Vice President of the University of Oregon. His research focuses on musculoskeletal mechanobiology, regenerative medicine, and orthopaedic medical devices. Dr. Guldberg has produced over 280 peer-reviewed publications and co-founded six start-ups. He is past Chair of the Americas Chapter of the Tissue Engineering and Regenerative Medicine International Society (TERMIS) and serves on the Leadership Council of the Wu Tsai Human Performance Alliance, a $220 million global initiative to promote wellness and peak performance through scientific discovery and innovation.
The Intersection of Immune Biology, Mechanobiology, and Bone Regeneration
Complex musculoskeletal trauma with injury to bone and soft tissue is associated with high complication rates and poor functional recovery. Advances in biomaterials-mediated delivery strategies have shown promise for promoting functional regeneration. However, the response to advanced treatments remains variable with nonresponding patients suffering prolonged pain and disability. There is increasing recognition that patient-specific immune responses and the local mechanical environment can potently affect the efficacy of advanced regenerative therapies. Our lab has identified systemic immune response biomarkers to predict patient outcomes as well as time-dependent windows of local mechanical signals that promote vascular bone regeneration. This presentation will review our recent work, including efforts to apply our findings to develop new therapeutic intervention strategies.
1). Understand the effects of local mechanical loading on bone healing
2). Learn how immune responses correlate with bone healing outcomes
3). Appreciate how the interactions of immune biology, mechanobiology, and bone regeneration can suggest new therapeutic strategies
Robert E. Marx, DDS, is Professor of Surgery and Chief of the Division of Oral and Maxillofacial Surgery at the University of Miami Miller School of Medicine as well as Chief of Surgery at Jackson South Community Hospital in Miami, He is well known as an educator, researcher,
and innovative surgeon. He has pioneered new concepts and treatments for pathologies of the oral and maxillofacial area as well as new techniques in reconstructive surgery including stem cell therapies.
His many prestigious awards, including the Harry S. Archer Award, the William J. Giles Award, the Paul Bert Award, the Donald B. Osbon Award, and the Daniel Laskin Award, attest to his accomplishments and commitment to the field of oral and maxillofacial surgery.
His textbook “Oral and Maxillofacial Pathology: A Rationale for Diagnosis and Treatment” has also won the American Medical Writers Associations Prestigious Book of the year Award and his other textbooks “Platelet Rich Plasma: Dental and Craniofacial Applications”, “Tissue Engineering”, “Oral and Intravenous Bisphosphonates Induced Osteonecrosis”, and an “Atlas of Bone Harvesting” have been best sellers. He is also a writer of fiction medical mystery novels. His first publication “Deadly Prescription” is currently a “Best Seller” on Amazon.
Oral and Maxillofacial Surgery Bone Grafting; Past, Present and Future
Bone grafting has been an inherent part of our specialty since its inception. From the past, nonvascularized block grafts gave way to cancellous marrow grafts and now to today’s free vascular osteocutaneous grafts and
in-situ tissue engineered grafts. Numerous innovations and discoveries have paved the way. An incomplete list would include rigid fixation, microvascular techniques with vein couplers, platelet rich plasma,
recombinant human bone morphogenetic protein, and bone marrow stem cell aspirates among others. The result has been more predictable bone regeneration and a better quality of bone with reduced morbidity and in many cases reduced cost.
As oral and maxillofacial surgery proceeds into the future, the vision includes growth factor loaded scaffolds, exosomes, adipose derived stem cells, cartilage together with bone regeneration, more recombinant growth factors, among others. Although oral and maxillofacial surgery will share the bone regeneration advances with our orthopedic colleagues, we will continue to lead the way forward as we have done in the past.
Antonio Mikos, Dipl. Eng, PhD
Louis Calder professor of bioengineering and chemical and biomolecular engineering, Director of the Center for Engineering Complex Tissues; center for excellence in tissue engineering and J.W. Cox laboratory for biomedical engineering, Rice University
Antonios G. Mikos is the Louis Calder Professor of Bioengineering and Chemical and Biomolecular Engineering at Rice University. His research focuses on the synthesis, processing, and evaluation of new biomaterials for use as scaffolds for tissue engineering, as carriers for controlled drug delivery, as non-viral vectors for gene therapy, and as platforms for disease modeling.
He is the author of over 690 publications and the inventor of 32 patents. Mikos is a Member of the National Academy of Engineering, the National Academy of Medicine, the National Academy of Inventors, the Chinese Academy of Engineering, the Academia Europaea, and the Academy of Athens. He is a Founding Editor and Editor-in-Chief of the journal Tissue Engineering.
Biomaterials for Biomolecule and Cell Delivery in Tissue Engineering Applications
Advances in biology, materials science, chemical engineering, computer science, and other fields have allowed for the development of tissue engineering, an interdisciplinary convergence science. Our laboratory has focused on the development and characterization of biomaterials-based strategies for the regeneration of human tissues with the goal of improving healthcare outcomes. In a collaborative effort with physicians, surgeons, and other scientists, we have produced new material compositions and three-dimensional scaffolds, and investigated combinations of biomaterials with cell populations and bioactive agents for their ability to induce tissue formation and regeneration. We have examined the effects of material characteristics, such as mechanical properties, topographical features, and functional groups, on cell behavior and tissue guidance, and leveraged biomaterials as drug delivery vehicles to release growth factors and other signals with spatial and temporal specificity. This presentation will review recent examples of diverse biomaterials-based approaches for regenerative medicine applications and highlight emerging areas of growth.
Dr. Muschler is a Professor of Orthopaedic Surgery and Biomedical Engineering at the Cleveland Clinic, with a clinical practice that integrates joint replacement, and joint preservation.
Dr. Muschler’s Regenerative Medicine Laboratory has earned continuous federal funding for over 26 years, focusing on stem and progenitor cell biology, tissue engineering and regenerative medicine. He has served as Vice Chair of Bioengineering (2004-2013); Director of the Orthopaedic Research Center (2005-2013), Vice Chair of the Orthopaedic and Rheumatologic Institute (2007-2013) and has served as Director of the Cleveland Clinic Joint Preservation Center since 2017.
Dr. Muschler led the development of several multi-institutional collaborative translational networks. He founded and led the Ohio-based Clinical Tissue Engineering Center (2005-2012), and served as the founding Co-Director of the Armed Forces Institute of Regenerative Medicine (AFIRM) (2008-2011), dedicated to the accelerated development of therapies to serve wounded warriors. He was inducted as a Fellow in the American Association for the Advancement of Science in 2023.
Stem Cell Science: Asking Questions, Solving Problems, Creating Opportunities
This presentation will explore options for cell sourcing connective tissue progenitor cells (CTPs) and generation of CTP-derived cells for use in cellular therapies musculoskeletal disease, from perspectives of optimal harvest, intraoperative processing options for concentration and selection, as well as methods for in vitro cell selection and expansion, and quality assessment.
1). Understand the composition and heterogeneity of clinical sources of connective tissue progenitors.
2). Understand the strengths and weaknesses of intraoperative methods for cell processing.
3). Understand the tools and processes becoming available for in vitro selection and expansion of cells for therapeutic purposes.
Studying Skeletal Development to Enhance Bone Repair
Abstract Coming Soon
Medical Management of the Geriatric and Osteoperotic Patient: Therapies to Improve Surgical Outcomes
Abstract Coming Soon
Dr. Emily Moore completed her BS/MS in Biomedical Engineering (BME) at Case Western Reserve University with a focus on orthopaedic biomaterials and osseointegration. She received a PhD in BME at Columbia University studying primary cilia in osteocyte and periosteal cell mechanotransduction and load-induced bone formation in Christopher Jacobs’s lab. Emily is currently a postdoc in Vicki Rosen’s lab investigating the role of BMP signaling in appositional bone growth and periosteal cell mechanotransduction.
The Role of Periosteal Cell Mechanotrans- duction in Load-Induced Bone Formation
The periosteum is a thin tissue surrounding bone that contains stem/progenitor cells involved in bone development, growth, repair, and load-induced bone formation. BMP signaling is critical for these biological processes. Here, we investigate the role of BMP signaling in appositional growth and mechanically induced osteogenic differentiation of periosteal cells. We designed an ex vivo appositional growth model and generated a periosteum-derived cell line to interrogate BMP2-mediated BMP signaling. Using these tools, we found that Bmp2 expression is upregulated in mechanically stimulated periosteal cells. When BMP2 is removed from periosteal lineage cells, BMP signaling is lost and appositional growth is severely attenuated. This work will enhance our understanding of periosteal activity and the role of BMP2 in load-induced bone formation.
1). How does BMP2 and associated BMP signaling regulate periosteal activity?
2). What is the role of BMP signaling in periosteal cell mechanotransduction?
3). Is the primary cilium important for periosteal cell BMP signaling?
Advancing Tissue Engineering Therapies via Testing in a Clinically Relevant Craniofacial Defect Model
Abstract Coming Soon
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