Bio
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. 

Title
Medical Optimization of the Oral and Maxillofacial Surgery Patient: A Surgeon’s Perspective

Abstract
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.

Learning Objectives
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.

Bio
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.

Titles
1) The Role of the Osteocyte in Mechanotransduction
2) Muscle and Bone: Partners for Life

The Role of the Osteocyte in Mechanotransduction
Abstract
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.

Learning Objectives
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
Abstract
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.

Learning Objectives
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.

Bio
Senior scientist, Calif. Pacific Medical Center Research Institute; emeritus Prof. of Medicine & Epidemiology, UCSF. Led pivotal trials of alendronate, denosumab and zoledronate for osteoporosis. He has received awards from all major osteoporosis societies for his research on prevention of fractures. He was elected to the National Academy of Medicine.

Title
Common Drug Treatments for Osteoporosis

Abstract
The most commonly used initial treatments for prevention of fracture, alendronate (a bisphosphonate) and denosumab, inhibit bone resorption. Bisphosphonates bind to the surface of bone and their effects gradually wane after discontinuation. Denosumab is a more potent antiresorptive that inhibits the development and action of bone resorbing osteoclasts. Bone resorption rebounds with bone loss and increased risk of vertebral fracture when it is discontinued after ≥ 3 years. They reduce the risk of all types of fractures. Bone forming drugs, such as romosozumab, are more effective and are warranted in patients at very high risk by a bone density (BMD) T-score < -3 or a recent fracture. Romosozumab is given for 12 months and must be followed by treatment with an anti-resorptive to maintain the BMD.

Learning Objectives:
Understand:
1). Comparative efficacy of these 3 common drugs for osteoporosis.
2). The adverse effects of those treatments. 
3). ) The different consequences of stopping treatments.

Bio
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.

Title
The Intersection of Immune Biology, Mechanobiology, and Bone Regeneration

Abstract
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.   

Learning Objectives
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

Bio
Kent Leach is the Lawrence J. Ellison Endowed Professor of Musculoskeletal Research and Vice Chair of Research in the Department of Orthopaedic Surgery and Professor of Biomedical Engineering at the University of California, Davis. His research interests are focused on developing cell-instructive biomaterials for the repair or replacement of damaged bone, cartilage, and muscle, understanding the role of innate immune cells and inflammation on bone healing and cancer, and translation from the bench to the clinic. He is the Editor-in-Chief of the Journal of Biomedical Materials Research Part A, the official journal of the Society for Biomaterials (SFB). He is also the Program Director of one of eight NIH-funded training grants focused on training predoctoral students in musculoskeletal health research.

Title
Engineering Approaches For Stem Cell-Mediated Musculoskeletal Tissue Repair

Abstract
Advances in early detection of disease and increases in lifespan necessitate new strategies to repair or replace damaged organs and tissues. While stem cells hold immense promise for tissue repair, their successful translation to the clinic has been underwhelming due to challenges in maintaining viability and properly instructing their behavior. My research is directed toward incorporating cues from the native environment and natural extracellular matrix (ECM) into the design of cell culture platforms and musculoskeletal tissue engineered constructs. We are developing materials-based strategies to prolong cell survival, direct the behavior of transplanted or host cells within bone defects, and interrogate the behavior of various cell populations in more physiologically relevant conditions. This talk will feature examples of our recent work in designing biomaterials to instruct cell fate and enhance tissue formation and function for musculoskeletal tissue regeneration and repair.    

Learning Objectives
1). Understand current limitations of cell-based approaches to musculoskeletal repair
2). Learn how biomaterials can guide stem cell fate
3). Appreciate the translational potential of materials for cell transplantation and bone regeneration

Bio
Robert E. Marx, DDS, FACS, 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.

Title
Oral and Maxillofacial Surgery Bone Grafting; Past, Present and Future

Abstract
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.

Learning Objectives
1). For the attendees to learn the various indications for in-situ tissue engineering of bone in the maxillofacial area.
2). For the attendees to understand the combinations of cells-signal-matrix using allogeneic bone of the correct particle size, rhBMP-2/ACS, and the stem cells/progenitor cells in bone marrow.
3). For the attendees to know of the best dosages of stem/progenitor cells from bone marrow and how to obtain them as well as the best dosages of rhBMP-2/ACS for bone regeneration with reduction in post operative edema.

Bio
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.

Title
Biomaterials for Biomolecule and Cell Delivery in Tissue Engineering Applications

Abstract
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.

Learning Objectives
1). Discuss injectable and 3D-printable biomaterials for use as tissue engineering scaffolds.
2). Discuss drug delivery systems for bioactive molecules in tissue engineering.
3). Discuss biomaterials-enabled cell therapies in tissue engineering.

Bio
Dr. Vicki Rosen arrived at Harvard School of Dental Medicine (HSDM) by way of industry, having spent the early part of her career as a scientist at Genetics Institute, a biotechnology company, where she was a member of the research team that identified the bone morphogenetic protein (BMP) genes in 1988. She became a professor in the Faculty of Medicine in 2001, and chair of the Department of Developmental Biology at HSDM in 2005.

Title
Studying Skeletal Development to Enhance Bone Repair

Abstract
Our knowledge of skeletal development has increased exponentially over the last 20 years due in part to the widespread adoption of new experimental techniques focused on regulating gene expression. Information now available on the signaling pathways and skeletal stem and progenitor cells that interact to form the skeleton has led to new strategies for enhancing bone formation in a variety of clinical settings. During my talk I will discuss osteobiologics currently approved by the FDA or in clinical trials for enhancing bone repair and how we might predict which osteobiologic(s) might be most efficacious in specific clinical settings based on our understanding of skeletal development.

Learning Objectives
1). Multiple signaling pathways interact in precise spatial and temporal patterns during skeletal development.
2). All skeletal stem/progenitor cells are not the same so will not be activated by the same signaling cascades.
3). The local extracellular matrix and resident cells form a niche that influences bone formation and the capacity for regeneration.

Bio
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. 

Title
The Role of Periosteal Cell Mechanotrans- duction in Load-Induced Bone Formation

Abstract
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.  

Learning Objectives
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?

Bio
Dr. Genevieve Romanowicz is a post-doctoral scholar and Portland Oral Health Fellow working with Dr. Robert Guldberg at the Knight Campus for Accelerating Scientific Impact, University of Oregon. Her research focuses on translating cutting-edge regenerative engineering strategies to clinically relevant maxillofacial problems. She obtained her DDS and PhD from the University of Michigan in 2021, studying bone composition and biomechanics. Dr. Romanowicz was selected as a rising leader in the fields of oral, dental, and craniofacial research as part of the NIDCR MIND-the-Future program. Her current work encompasses bone tissue engineering, bone-like organoids, and biomarkers to predict fracture healing.

Title
Advancing Tissue Engineering Therapies via Testing in a Clinically Relevant Craniofacial Defect Model

Abstract
Oro-antral communication (OAC) defects (unnatural openings created between the mouth and the sinus) frequently occur in dentistry and oral maxillofacial surgery as an adverse consequence of complicated extractions, malignancies, or trauma. While alternative surgical or regenerative approaches are of interest to improve functional patient outcomes, there are no widely accepted preclinical models of OAC defects to rigorously test new therapies. Therefore, we have created a new pre-clinical model of OAC which mimics the human condition with failed bone healing at 8 weeks. With this model, we are testing therapeutic delivery systems and regenerative strategies to promote bone and soft tissue regeneration in OAC defects. I will review our ongoing efforts to promote bone regeneration in this challenging craniofacial defect model.

Learning Objectives
1). Understand the current limitations for development of regenerative strategies in craniofacial defect models
2). Learn what new biomaterials are available for testing in the pre-clinical setting
3). Appreciate how focusing on clinically relevant craniofacial defect models can infuse new regenerative strategies into pre-clinical development

Bios
Dr. Varanasi is an Associate Professor at UT Arlington whose research focuses on the development of novel nanocomposite scaffolds and nano-scale implant coatings to improve musculoskeletal tissue regeneration in large volumetric defects. Dr. Witek is an Assistant Professor at NYU College of Dentistry with research interests in the evaluation of a range of (bio)materials as well as 3D printing for regenerative medicine applications.

Title
Novel Approaches for Bone Grafting the Compromised Wound Healing Environment

Abstract
The reconstruction of large, morphologically complex maxillofacial bone defects continues to be a challenge for surgeons. Treatment is further complicated in compromised wound healing environments. We present two novel materials for bone regeneration in these clinically challenging scenarios: 1) Bioactive, 3D-printed ceramic scaffolds, and 2) Plasma Enhanced Chemical Vapor Deposition (PECVD) of semiconductor-based coatings. Promising preclinical data shows these strategies have the capacity to regenerate bone in irradiated critical-size defects and have strong potential for clinical translation.

Learning Objectives
1). Discuss biomaterial concepts for tissue replacement and tissue-material interactions.
2). Learn how direct inkjet written 3D-printed bioceramic scaffolds can be used to create patient-specific bone grafting materials.
3). Understand how semiconductor-based coatings can drive osteoinductive and angiogenic responses in bone healing.

Bio
Dr. Young completed an integrated OMS/MD/PhD program at Rice University and UTHealth Houston in 2013. He subsequently was awarded an NIH K99/R00 Pathway to Independence Award and spent two years as a post-doc research fellow at Harvard University before returning to the Katz Department of OMS at UTHealth Houston in 2015. Dr. Young’s primary role is as an NIH-funded surgeon-scientist studying translational applications of biomaterials in craniomaxillofacial tissue regeneration and cancer immunotherapy.

Title
Developing a Challenging Preclinical Model of Compromised Wound Healing

Abstract
The craniomaxillofacial (CMF) region is highly complex, composed of morphologically intricate skeletal elements, extensive neural and vascular networks, special sense organs, lining tissues, and the dentition. The loss of tissue owing to traumatic, developmental, and pathological etiologies in a relatively small region presents a considerable reconstructive challenge. Treatment is further complicated in compromised wound healing environments. We will discuss the development of a clinically relevant, reproducible model of compromised wound healing, and how it can be used to inform future strategies aimed at improving bone regeneration in these situations.

Learning Objectives
1). Provide an overview of the complexities and challenges of treating patients with complex craniofacial bone defects.
2).Learn about multiple preclinical models used to evaluate bone regeneration in the maxillofacial complex.
3). Under stand how a new preclinical model of compromised wound healing was developed, characterized, and can be used to test bone grafting strategies.