Thomas M. Best

Tissue Engineering and Cell-Based Therapies for Fractures and Bone Defects

Bone fractures and segmental bone defects are a significant source of patient morbidity and place a staggering economic burden on the healthcare system. The annual cost of treating bone defects in the US has been estimated to be

Not missing the future: A call to action for investigating the role of regenerative medicine therapies in pediatric/adolescent sports injuries

5 billion, while enormous costs are spent on bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. Autologous bone grafts represent the gold standard for the treatment of bone defects. However, they are associated with variable clinical outcomes, postsurgical morbidity, especially at the donor site, and increased surgical costs. In an effort to circumvent these limitations, tissue engineering and cell-based therapies have been proposed as alternatives to induce and promote bone repair. This review focuses on the recent advances in bone tissue engineering (BTE), specifically looking at its role in treating delayed fracture healing (non-unions) and the resulting segmental bone defects. Herein we discuss: (1) the processes of endochondral and intramembranous bone formation; (2) the role of stem cells, looking specifically at mesenchymal (MSC), embryonic (ESC), and induced pluripotent (iPSC) stem cells as viable building blocks to engineer bone implants; (3) the biomaterials used to direct tissue growth, with a focus on ceramic, biodegradable polymers, and composite materials; (4) the growth factors and molecular signals used to induce differentiation of stem cells into the osteoblastic lineage, which ultimately leads to active bone formation; and (5) the mechanical stimulation protocols used to maintain the integrity of the bone repair and their role in successful cell engraftment. Finally, a couple clinical scenarios are presented (non-unions and avascular necrosis—AVN), to illustrate how novel cell-based therapy approaches can be used. A thorough understanding of tissue engineering and cell-based therapies may allow for better incorporation of these potential therapeutic approaches in bone defects allowing for proper bone repair and regeneration.

Development of a lumbar EMG-based coactivation index for the assessment of complex dynamic tasks

In August 2016, a group including sport medicine clinicians, researchers, and a bioethicist met in Vail, Colorado to discuss regenerative medicine and its potential role in youth sports injuries. There was consensus that a call to action is urgently needed to understand the current evidence base, the risks and rewards, and future directions of research and clinical practice for regenerative medicine therapies in youth sports. We present here a summary of our meeting, which was supported by the National Youth Sports Health and Safety Institute (NYSHSI), a partnership between the American College of Sports Medicine (ACSM) and Sanford Health. The group’s goal is to educate practitioners and the public, and to pioneer a means of accumulating meaningful clinical data on regenerative medicine therapies in pediatric and adolescent athletes.

Massage and postexercise recovery: the science is emerging

Abstract The objective of this study was to develop and test an EMG-based coactivation index and compare it to a coactivation index defined by a biologically assisted lumbar spine model to differentiate between tasks. The purpose was to provide a universal approach to assess coactivation of a multi-muscle system when a computational model is not accessible. The EMG-based index developed utilised anthropometric-defined muscle characteristics driven by torso kinematics and EMG. Muscles were classified as agonists/antagonists based upon ‘simulated’ moments of the muscles relative to the total ‘simulated’ moment. Different tasks were used to test the range of the index including lifting, pushing and Valsalva. Results showed that the EMG-based index was comparable to the index defined by a biologically assisted model (r2 = 0.78). Overall, the EMG-based index provides a universal, usable method to assess the neuromuscular effort associated with coactivation for complex dynamic tasks when the benefit of a biomechanical model is not available. Practitioner Summary: A universal coactivation index for the lumbar spine was developed to assess complex dynamic tasks. This method was validated relative to a model-based index for use when a high-end computational model is not available. Its simplicity allows for fewer inputs and usability for assessment of task ergonomics and rehabilitation.

Applying physical science principles to mid-substance Achilles tendinopathy and the relationship to eccentric lengthening exercises

Athletes use a variety of postexercise recovery techniques with the belief that they are effective at enhancing return to competition and training. Common modalities include massage, cold water immersion, compression, electrical stimulation, vibration therapy and a combination of one or more of these strategies. Other approaches include diet and hydration protocols, active recovery and sleep. Despite their popularity, the evidence for the effectiveness of most of these modalities is rather limited, although recent efforts are advancing their science which should help in the recommendation of optimal indications and protocols. The scientific literature on postexercise massage has accelerated in the last decade. A number of clinical and animal studies have addressed biological plausibility. Clinical studies have investigated the long-held claims that massage mediates leucocyte migration and attenuates the inflammatory response to exercise,1 as well as decreases pain, muscle tone and hyperactivity.2 These reports suggest that massage mediates molecular processes linked to inflammation, specifically by …

An Exploratory Electromyography-Based Coactivation Index for the Cervical Spine:

Mid‐substance Achilles tendinopathy is common in the active population. Eccentric (lengthening) exercises are known to be effective in alleviating the clinical condition. To better understand mid‐substance Achilles tendinopathy and the response to lengthening exercises physical science principles of elasticity are applied. We apply elastic motion laws to the spring‐like tendon as well as the normal and pathological adaptation seen with this common injury. We will validate important assumptions of the spring‐like behavior of the tendon and then apply these findings to the injured and rehabilitating states. Our analysis considers that the tendon can be viewed as being spring‐like with elasticity principles being applicable and the force exerted on the tendon during lengthening is primarily in a uniaxial direction. This applied lengthening force results in tendon mechanical and structural adaptation. Injury, and ultimately the clinical condition, occurs when the applied force exceeds the ability of the tendon to normally adapt. Morphological changes of the injured tendon are an attempt by the body to make the tendon more compliant. Lengthening exercises can be assessed as achieving this task with an improvement of tendon compliance. Physical science analysis proposes that the preferred rehabilitation tendon pathway is to try and decrease tendon stiffness to allow for more tendon lengthening. The bodys morphological alterations of the pathological tendon are also consistent with this approach. For mid‐substance Achilles tendinopathy, this adaptation of decreased stiffness ultimately increases the tendons ability to withstand applied force during lengthening.

Time for a paradigm shift in the classification of muscle injuries

Objective Develop a coactivation index for the neck and test its effectiveness with complex dynamic head motions. Background Studies describing coactivation for the cervical spine are sparse in the literature. Of those in existence, they were either limited to a priori definitions of agonist/antagonist activity that limited the testing to sagittal and lateral planes or consisted of isometric exertions. Multiplanar movements would allow for a more realistic understanding of naturalistic movements in the cervical spine and propensity for neck pain. However, a gap in the literature exists in which a method to describe coactivation during complex dynamic motions does not exist for the cervical spine. Methods An electromyography-based coactivation index was developed for the cervical spine based on previously tested methodology used on the lumbar spine without a high-end model and tested using a series of different postures and speeds. Results Complex motions involving twisting (i.e., flexion and twisting) and higher speed had higher magnitudes of coactivation than uniplanar motions in the sagittal or lateral plane, which was expected. The coupled motion of flexion and twisting showed four to five times higher coactivation than uniplanar (sagittal or lateral) movements. Conclusion The coactivation index developed accommodates multiplanar, naturalistic movements. Testing of the index showed that motions requiring higher degrees of head control had higher effort due to coactivation, which was expected. Application Overall, this coactivation index may be utilized to understand the neuromuscular effort of various tasks in the cervical spine.

Transcriptomic analysis of synovial extracellular RNA following knee trauma: A pilot study

Muscle injuries remain one of the most common injuries in sport, yet despite this, there is little consensus on how to either effectively describe or determine the prognosis of a specific muscle injury. Numerous approaches to muscle classification and grading of medicine have been applied over the last century, but over the last decade the limitations of historic approaches have been recognized. As a consequence, in the past 10 years, clinical research groups have begun to question the historic approaches and reconsider the way muscle injuries are classified and described. Using a narrative approach, this manuscript describes several of the most recent attempts to classify and grade muscle injuries and highlights the relative strengths and weaknesses of each system. While each of the new classification and grading systems have strengths, there remains little consensus on a system that is both comprehensive and evidence based. Few of the currently identified features within the grading systems have relevance to accurately determining prognosis.

Forces Generated by Vastus Lateralis and Vastus Medialis Decrease with Increasing Stair Descent Speed

Traumatic knee injuries often result in damage to articular cartilage and other joint structures. Such trauma is a strong risk factor for the future development and progression of osteoarthritis (OA). The molecular mechanisms and signaling pathways modulating response to knee joint trauma remain unclear. Moreover, investigations of biomarkers influencing responses have been targeted rather than broad, unbiased discovery studies. Herein, we characterize the complete complement of extracellular RNA (exRNA) in the synovial fluid of 14 subjects following knee injury. Fluid was collected during surgery from the injured knees, and from the contralateral knee in a subset, undergoing surgical repair of the ACL and/or meniscal repair/debridement. Arthroscopic grading of chondral damage in four knee compartments was performed using the Outerbridge classification. exRNA was extracted and subjected to massively parallel total RNA sequencing. Differential abundance of RNA was calculated between the subject cohorts of injured and non‐injured knee, average Outerbridge score ≥0.5 and less, and chronic and acute injury duration defined as ≤4 months till surgery or longer. Overall, expression of several thousand genes was identified in the synovial fluid. Furthermore, differential expression analysis suggests a role of exRNA fragments of matrix metalloproteinases and skeletal muscle fiber genes in the response to traumatic injury. Together, these data suggest that high‐throughput approaches can indicate exRNA molecular signatures following knee trauma. Future studies are required to more fully characterize the biological roles of these exRNA and the cadence of their respective release that may lead to translational treatment options for post‐traumatic OA.

Spinal Loading and Immune Responses to Personality and Mental Load During Repetitive Lifting

Stair descent (SD) is a common, difficult task for populations who are elderly or have orthopaedic pathologies. Joint torques of young, healthy populations during SD increase at the hip and ankle with increasing speed but not at the knee, contrasting torque patterns during gait. To better understand the sources of the knee torque pattern, we used dynamic simulations to estimate knee muscle forces and how they modulate center of mass (COM) acceleration across SD speeds (slow, self-selected, and fast) in young, healthy adults. The vastus lateralis and vastus medialis forces decreased from slow to self-selected speeds as the individual lowered to the next step. Since the vasti are primary contributors to vertical support during SD, they produced lower forces at faster speeds due to the lower need for vertical COM support observed at faster speeds. In contrast, the semimembranosus and rectus femoris forces increased across successive speeds, allowing the semimembranosus to increase acceleration downward and forward and the rectus femoris to provide more vertical support and resistance to forward progression as SD speed increased. These results demonstrate the utility of dynamic simulations to extend beyond traditional inverse dynamics analyses to gain further insight into muscle mechanisms during tasks like SD.