The MIDAS touch: Frameworks for procedural model innovation and validation.

Background: Simulation-based procedural practice is crucial to emergency medicine skills training and maintenance. However, many commercial procedural models are either nonexistent or lacking in key elements. Simulationists often create their own novel models with minimal framework for designing, building, and validation. We propose two interlinked frameworks with the goal to systematically build and validate models for the desired educational outcomes. Methods: Simulation Academy Research Committee and members with novel model development expertise assembled as the MIDAS (Model Innovation, Development and Assessment for Simulation) working group. This working group focused on improving novel model creation and validation beginning with a preconference workshop at 2023 Society for Academic Emergency Medicine Annual Meeting. The MIDAS group sought to (1) assess the current state of novel model validation and (2) develop frameworks for the broader simulation community to create, improve, and validate procedural models. Findings: Workshop participants completed 17 surveys for a response rate of 100%. Many simulationists have created models but few have validated them. The most common barriers to validation were lack of standardized guidelines and familiarity with the validation process.We have combined principles from education and engineering fields into two interlinked frameworks. The first is centered on steps involved with model creation and refinement. The second is a framework for novel model validation processes. Implications: These frameworks emphasize development of models through a deliberate, form-follows-function methodology, aimed at ensuring training quality through novel models. Following a blueprint of how to create, test, and improve models can save innovators time and energy, which in turn can yield greater and more plentiful innovation at lower time and financial cost. This guideline allows for more standardized approaches to model creation, thus improving future scholarship on novel models.

Distance simulation in the health professions: a scoping review.

BACKGROUND: Distance simulation is defined as simulation experiences in which participants and/or facilitators are separated from each other by geographic distance and/or time. The use of distance simulation as an education technique expanded rapidly with the recent COVID-19 pandemic, with a concomitant increase in scholarly work. METHODS: A scoping review was performed to review and characterize the distance simulation literature. With the assistance of an informationist, the literature was systematically searched. Each abstract was reviewed by two researchers and disagreements were addressed by consensus. Risk of bias of the included studies was evaluated using the Risk of Bias 2 (RoB 2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tools. RESULTS: Six thousand nine hundred sixty-nine abstracts were screened, ultimately leading to 124 papers in the final dataset for extraction. A variety of simulation modalities, contexts, and distance simulation technologies were identified, with activities covering a range of content areas. Only 72 papers presented outcomes and sufficient detail to be analyzed for risk of bias. Most studies had moderate to high risk of bias, most commonly related to confounding factors, intervention classification, or measurement of outcomes. CONCLUSIONS: Most of the papers reviewed during the more than 20-year time period captured in this study presented early work or low-level outcomes. More standardization around reporting is needed to facilitate a clear and shared understanding of future distance simulation research. As the broader simulation community gains more experience with distance simulation, more studies are needed to inform when and how it should be used.

Workshop in Simulation Debriefing for Educators in Medicine: Creation, implementation, and evaluation of a debriefing curriculum for novice simulation educators.

Objectives: Debriefing is an integral component of simulation education, and effective debriefing education is required to maintain effective simulation programs. However, many educators report financial and logistical barriers to accessing formal debriefing training. Due to limited educator development opportunities, simulation program leaders are often compelled to utilize educators with insufficient debriefing training, which can limit the impact of simulation-based education. To address these concerns, the SAEM Simulation Academy Debriefing Workgroup authored the Workshop in Simulation Debriefing for Educators in Medicine (WiSDEM), a freely available, concise, and ready-to-deploy debriefing curriculum with a target audience of novice educators without formal debriefing training. In this study, we describe the development, initial implementation, and evaluation of the WiSDEM curriculum. Methods: The Debriefing Workgroup iteratively developed the WiSDEM curriculum by expert consensus. The targeted level of content expertise was introductory. The curriculum's educational impact was assessed by surveying participants on their impressions of the curriculum and their confidence and self-efficacy in mastery of the material. Additionally, facilitators of the WiSDEM curriculum were surveyed on its content, usefulness, and future applicability. Results: The WiSDEM curriculum was deployed during the SAEM 2022 Annual Meeting as a didactic presentation. Thirty-nine of 44 participants completed the participant survey, and four of four facilitators completed the facilitator survey. Participant and facilitator feedback on the curriculum content was positive. Additionally, participants agreed that the WiSDEM curriculum improved their confidence and self-efficacy in future debriefing. All surveyed facilitators agreed that they would recommend the curriculum to others. Conclusions: The WiSDEM curriculum was effective at introducing basic debriefing principles to novice educators without formal debriefing training. Facilitators felt that the educational materials would be useful for providing debriefing training at other institutions. Consensus-driven, ready-to-deploy debriefing training materials such as the WiSDEM curriculum can address common barriers to developing basic debriefing proficiency in educators.

Adaptation of a Simulation Model and Checklist to Assess Pediatric Emergency Care Performance by Prehospital Teams.

INTRODUCTION: Simulation tools to assess prehospital team performance and identify patient safety events are lacking. We adapted a simulation model and checklist tool of individual paramedic performance to assess prehospital team performance and tested interrater reliability. METHODS: We used a modified Delphi process to adapt 3 simulation cases (cardiopulmonary arrest, seizure, asthma) and checklist to add remote physician direction, target infants, and evaluate teams of 2 paramedics and 1 physician. Team performance was assessed with a checklist of steps scored as complete/incomplete by raters using direct observation or video review. The composite performance score was the percentage of completed steps. Interrater percent agreement was compared with the original tool. The tool was modified, and raters trained in iterative rounds until composite performance scoring agreement was 0.80 or greater (scale <0.20 = poor; 0.21-0.39 = fair, 0.40-0.59 = moderate; 0.60-0.79 = good; 0.80-1.00 = very good). RESULTS: We achieved very good interrater agreement for scoring composite performance in 2 rounds using 6 prehospital teams and 4 raters. The original 175 step tool was modified to 171 steps. Interrater percent agreement for the final modified tool approximated the original tool for the composite checklist (0.80 vs. 0.85), cardiopulmonary arrest (0.82 vs. 0.86), and asthma cases (0.80 vs. 0.77) but was lower for the seizure case (0.76 vs. 0.91). Most checklist items (137/171, 80%) had good-very good agreement. Among 34 items with fair-moderate agreement, 15 (44%) related to patient assessment, 9 (26%) equipment use, 6 (18%) medication delivery, and 4 (12%) cardiopulmonary resuscitation quality. CONCLUSIONS: The modified checklist has very good agreement for assessing composite prehospital team performance and can be used to test effects of patient safety interventions.

Characterizing preferred terms for geographically distant simulations: distance, remote and telesimulation.

Background: Simulationists lack standard terms to describe new practices accommodating pandemic restrictions. A standard language around these new simulation practices allows ease of communication among simulationists in various settings. Methods: We explored consensus terminology for simulation accommodating geographic separation of participants, facilitators or equipment. We used an iterative process with participants of two simulation conferences, with small groups and survey ranking. Results: Small groups (n = 121) and survey ranking (n = 54) were used with distance, remote, and telesimulation as leading terms. Each was favored by a third of the participants without consensus. Conclusion: This research has deepened our understanding of how simulationists interpret this terminology, including the derived themes: (1) physical distance/separation, (2) overarching nature of the term and (3) implications from existing terms. We further deepen the conceptual discussion on healthcare simulation aligned with the search of the terminologies. We propose there are nuances that prevent an early consensus recommendation. A taxonomy of descriptors specifying the conduct of distance, remote and telesimulation is preferred.

Procedural task trainer gaps in emergency medicine: A rift in the simulation universe.

Objectives: We identified and quantified the gap between emergency medicine (EM) procedures currently taught using simulation versus those that educators would teach if they had better procedural task trainers. Additionally, we endeavored to describe which procedures were taught using homemade models and the barriers to creation and use of additional homemade models. Methods: Using a modified Delphi process, we developed a survey and distributed it to a convenience sample of EM simulationists via the Society for Academic Emergency Medicine Simulation Academy listserv. Survey items asked participants to identify procedures they thought should be taught using simulation ("most important"), do teach using simulation ("most frequent"), would teach if a simulator or model were available ("most needed"), and do teach using simulation with "homemade" models ("most frequent homemade"). Results: Thirty-seven surveys were completed. The majority of respondents worked at academic medical centers and were involved in simulation-based education for at least 6 years. Three procedures ranked highly in overall teaching importance and currently taught categories. We identified four procedures that ranked highly as both important techniques to teach and would teach via simulation. Two procedures were selected as the most important procedures that the participants do teach via simulation but would like to teach in an improved way. We found 14 procedures that simulationists would teach if an adequate model was available, four of which are of high importance. Conclusions: This study captured data to illuminate the procedural model gap and inform future interventions that may address it and meet the overarching objective to create better and more readily available procedure models for EM simulation educators in the future. It offers an informed way of prioritizing procedures for which additional homemade models should be created and disseminated as well as barriers to be aware of and to work to overcome. Our work has implications for learners, educators, administrators, and industry.

Technology Literacy in Undergraduate Medical Education: Review and Survey of the US Medical School Innovation and Technology Programs.

BACKGROUND: Modern innovations, like machine learning, genomics, and digital health, are being integrated into medical practice at a rapid pace. Physicians in training receive little exposure to the implications, drawbacks, and methodologies of upcoming technologies prior to their deployment. As a result, there is an increasing need for the incorporation of innovation and technology (I&T) training, starting in medical school. OBJECTIVE: We aimed to identify and describe curricular and extracurricular opportunities for innovation in medical technology in US undergraduate medical education to highlight challenges and develop insights for future directions of program development. METHODS: A review of publicly available I&T program information on the official websites of US allopathic medical schools was conducted in June 2020. Programs were categorized by structure and implementation. The geographic distribution of these categories across US regions was analyzed. A survey was administered to school-affiliated student organizations with a focus on I&T and publicly available contact information. The data collected included the founding year, thematic focus, target audience, activities offered, and participant turnout rate. RESULTS: A total of 103 I&T opportunities at 69 distinct Liaison Committee on Medical Education-accredited medical schools were identified and characterized into the following six categories: (1) integrative 4-year curricula, (2) facilitated doctor of medicine/master of science dual degree programs in a related field, (3) interdisciplinary collaborations, (4) areas of concentration, (5) preclinical electives, and (6) student-run clubs. The presence of interdisciplinary collaboration is significantly associated with the presence of student-led initiatives (P=.001). "Starting and running a business in healthcare" and "medical devices" were the most popular thematic focuses of student-led I&T groups, representing 87% (13/15) and 80% (12/15) of respondents, respectively. "Career pathways exploration for students" was the only type of activity that was significantly associated with a high event turnout rate of >26 students per event (P=.03). CONCLUSIONS: Existing school-led and student-driven opportunities in medical I&T indicate growing national interest and reflect challenges in implementation. The greater visibility of opportunities, collaboration among schools, and development of a centralized network can be considered to better prepare students for the changing landscape of medical practice.

Emergency Tracheal Intubation in Patients with COVID-19: A Single-center, Retrospective Cohort Study.

INTRODUCTION: The objective of this study was to compare airway management technique, performance, and peri-intubation complications during the novel coronavirus pandemic (COVID-19) using a single-center cohort of patients requiring emergent intubation. METHODS: We retrospectively collected data on non-operating room (OR) intubations from February 1-April 23, 2020. All patients undergoing emergency intubation outside the OR were eligible for inclusion. Data were entered using an airway procedure note integrated within the electronic health record. Variables included level of training and specialty of the laryngoscopist, the patient's indication for intubation, methods of intubation, induction and paralytic agents, grade of view, use of video laryngoscopy, number of attempts, and adverse events. We performed a descriptive analysis comparing intubations with an available positive COVID-19 test result with cases that had either a negative or unavailable test result. RESULTS: We obtained 406 independent procedure notes filed between February 1-April 23, 2020, and of these, 123 cases had a positive COVID-19 test result. Residents performed fewer tracheal intubations in COVID-19 cases when compared to nurse anesthetists (26.0% vs 37.4%). Video laryngoscopy was used significantly more in COVID-19 cases (91.1% vs 56.8%). No difference in first-pass success was observed between COVID-19 positive cases and controls (89.4% vs. 89.0%, p = 1.0). An increased rate of oxygen desaturation was observed in COVID-19 cases (20.3% vs. 9.9%) while there was no difference in the rate of other recorded complications and first-pass success. DISCUSSION: An average twofold increase in the rate of tracheal intubation was observed after March 24, 2020, corresponding with an influx of COVID-19 positive cases. We observed adherence to society guidelines regarding performance of tracheal intubation by an expert laryngoscopist and the use of video laryngoscopy.

Handoffs and Nurse Calls: Overnight Call Simulation for Fourth-Year Medical Students.

Introduction: Interns must be able to give and receive handoffs and use handoff information to respond to calls from nursing staff regarding patient concerns. Medical students may not receive adequate instruction in these tasks and often feel unprepared in this aspect of transitioning to residency. This program simulated an overnight call experience for fourth-year medical students emphasizing handoffs, nurse calls, and medical emergency response. Methods: The program utilized a combination of traditional didactics and simulated handoffs, nurse calls, and patient scenarios to allow groups of fourth-year medical students to independently manage a simulated overnight call. The program was designed for students as part of a larger Transition to Residency capstone course. Results: We ran four sessions over 3 years, with a total of 105 medical student participants. All students reported increased confidence or comfort in their ability to manage handoffs and respond to nurse calls. Students reported that the sessions were helpful and realistic. Discussion: This program provided fourth-year medical students with a realistic and useful opportunity to simulate handoffs and response to nurse calls, which increased their confidence and comfort. Minor changes were made between iterations of the course with continued positive feedback from medical students. The course is generalizable and can be adapted to the needs and resources of different institutions.

Benchmark Performance of Emergency Medicine Residents in Pediatric Resuscitation: Are We Optimizing Pediatric Education for Emergency Medicine Trainees?

BACKGROUND: The majority of children in the United States seek emergency care at community-based general emergency departments (GEDs); however, the quality of GED pediatric emergency care varies widely. This may be explained by a number of factors, including residency training environments and postgraduate knowledge decay. Emergency medicine (EM) residents train in academic pediatric EDs, but didactic and clinical experience vary widely between programs, and little is known about the pediatric skills of these EM residents. This study aimed to assess the performance of senior EM residents in treating simulated pediatric patients at the end of their training. METHODS: This was a prospective, cross-sectional, simulation-based cohort study assessing the simulated performance of senior EM resident physicians from two Massachusetts programs leading medical teams caring for three critically ill patients. Sessions were video recorded and scored separately by three reviewers using a previously published simulation assessment tool. Self-efficacy surveys were completed prior to each session. The primary outcome was a median total performance score (TPS), calculated by the mean of individualized domain scores (IDS) for each case. Each IDS was calculated as a percentage of items performed on a checklist-based instrument. RESULTS: A total of 18 EM resident physicians participated (PGY-3 = 8, PGY-4 = 10). Median TPS for the cohort was 61% (IQR = 56%-70%). Median IDSs by case were as follows: sepsis 67% (IQR = 50%-67%), seizure 67% (IQR = 50%-83%), and cardiac arrest 67% (IQR = 43%-70%). The overall cohort self-efficacy for pediatric EM (PEM) was 64% (IQR = 60%-70%). CONCLUSIONS: This study has begun the process of benchmarking clinical performance of graduating EM resident physicians. Overall, the EM resident cohort in this study performed similar to prior GED teams. Self-efficacy related to PEM correlated well with performance, with the exception of knowledge relative to intravenous fluid and vasopressor administration in pediatric septic shock. A significant area of discrepancy and missed checklist items were those related to cardiopulmonary resuscitation and basic life support maneuvers.

Virtual Mentoring: Two Adaptive Models for Supporting Early-career Simulation Investigators in the Era of Social Distancing.

BACKGROUND: Early-career simulation investigators identify limited mentorship as a common barrier to disseminating scholarship and launching a successful academic career in emergency medicine (EM). Conferences often bridge this gap, but the COVID-19 pandemic has forced their indefinite delay. Virtual solutions are needed to capitalize on the breadth of national simulation research experts and grow mentorship in a postpandemic world. METHODS: We developed two complementary innovations to facilitate scholarship development and minimize COVID-associated career challenges resulting from social distancing requirements. The e-fellows forum (FF) provides a capstone experience for works-in-progress and the e-consultation service (CS) supports simulation research during the earlier project stages of design and development. In conjunction with the Society for Academic Medicine's Simulation Academy, we applied videoconferencing technology for both of these novel, virtual innovations. We analyzed corresponding chat transcripts and detailed field notes for emerging themes. In addition, we collected quantitative data via participant surveys regarding their experiences and impact on their projects. RESULTS: Nine simulation fellows presented at the FF and seven junior simulation investigators participated in the CS sessions. Most preferred the virtual format (56% FF, 66% CS) and found the sessions to be helpful in project advancement (66% FF, 100% CS). COVID-19 affected most projects (89% FF, 67% CS). We identified three themes via qualitative analysis: design concerns and inquiries, validation or support shown by mentors and peers, and professional cohesion. CONCLUSIONS: Participants felt that both virtual mentorship innovations advanced their simulation research projects and fostered a sense of professional cohesion within a greater community of practice. These benefits can be powerful at a time where simulation researchers in EM feel disconnected in an era of social distancing. Our future work will include adaptations to a hybrid model with both virtual and in-person modalities as well as creation of more e-mentorship opportunities, thus broadening the early-career simulation research community of practice.

Closing the gap: a call for a common blueprint for remote distance telesimulation.

The physical requirements mandated by the COVID-19 pandemic have presented a challenge and an opportunity for simulation educators. Although there were already examples of simulation being delivered at a distance, the pandemic forced this technique into the mainstream. With any new discipline, it is important for the community to agree on vocabulary, methods and reporting guidelines. This editorial is a call to action for the simulation community to start this process so that we can best describe and use this technique.

Practice Makes Perfect: Simulation in Emergency Medicine Risk Management.

Simulation has been steadily changing the safety culture in the healthcare industry and allowing individual clinicians and interdisciplinary teams to be proactive in the culture of risk reduction and improved patient safety. Literature has demonstrated improved patient outcomes, improved team based skills, systems testing and mitigation of latent safety threats. Simulation may be incorporated into practice via different modalities. The simulation lab is helpful for individual procedures, in situ simulation (ISS) for system testing and teamwork, community outreach ISS for sharing of best practices and content resource experts. Serious medical gaming is developing into a useful training adjunct for the future.

Barriers and Solutions to Advancing Emergency Medicine Simulation-based Research: A Call to Action.

Simulation technology has successfully improved patient safety and care quality through training and assessment of individuals, teams, and health care systems. Emergency medicine (EM) continues to be a leader and pioneer of simulation, including administration of simulation-based fellowships and training programs. However, EM simulation-based research has been limited by low rates of publication and poor methodologic rigor. The Society for Academic Emergency Medicine (SAEM) Simulation Academy is leading efforts to improve the quality of scholarship generated by the EM simulation community and to foster successful research careers for future generations of EM simulationists. Through a needs assessment survey of our membership and a year-long consensus-based approach, we identified two main clusters of barriers to simulation-based research: lack of protected time and dedicated resources and limited training and mentorship. As a result, we generated four position statements with implications for education, training, and research in EM simulation and as a call to action for the academic EM community. Recommendations include expansion of funding opportunities for simulation-based research, creation of multi-institutional simulation collaboratives, and development of mentorship and training pathways that promote rigor in design and methodology within EM simulation scholarship.

A Call for a Reconsideration of the Use of Fecal Occult Blood Testing in Emergency Medicine.

BACKGROUND: Fecal occult blood testing (FOBT) was developed to detect microscopic bleeding caused by colorectal neoplasms. The role of FOBT in the emergency department (ED) is typically used for 5 different clinical workups: trauma, anemia, syncope, hypotension, and before the administration of systemic anticoagulants or thrombolytics. OBJECTIVE: We scrutinized the literature to assess the utility of FOBT for its 5 most common applications in the emergent setting. DISCUSSION: Logic and clinical evidence advocating for FOBT usage in the aforementioned situations are lacking. The test itself requires specific drug and dietary restrictions that are often violated or never met when patients present to the ED with acute pathologies. In addition, the poor sensitivity and specificity of the test in these scenarios dictate that neither a negative nor positive FOBT should change the subsequent clinical workup of patients presenting to the ED. CONCLUSION: Clinical decision making should seldom be predicated on the results of a FOBT in the ED setting.

Qualitative analysis of cocaine and heroin users' main partner sex-risk behavior: is safety in love safety in health?

BACKGROUND: In 2009, 27% of the 48,100 estimated new cases of HIV were attributed to heterosexual contact with an infected or at-risk person. Sexually active adults are less likely to use condoms in relationships with main partners than with non-regular partners, despite general knowledge that condom use reduces HIV transmission. METHODS: The purpose of this secondary qualitative analysis was to explore and contextualize perceptions of main partnerships, HIV risk, and attitudes toward condom use within main partner relationships among a subsample of intervention-arm cocaine- and/or heroin-using patients enrolled in a negative trial of brief motivational intervention to reduce the incidence of sexually transmitted disease and unsafe sexual behaviors. The open-ended portion of these interview audiotapes consisted of questions about perceptions of risk and attitudes about condom use with main partners. Enrollees were aged 18-54, English or Spanish speaking, and included in this analysis only if they reported having a main partner. We identified codes and elaborated important themes through a standard inductive three step coding process, using HyperRESEARCH™ software. RESULTS: Among 48 interviewees, 65% were male, half were non-Hispanic white, over 60% were 20-39 years of age, 58% had intravenous drug use (IDU), and 8% were HIV-positive. Participants defined respect, support, trust, and shared child-rearing responsibility as the most valued components of main partner relationships. Condom use was viewed occasionally as a positive means of showing respect with main partners but more often as a sign of disrespect and a barrier to intimacy and affection. Enrollees appraised their partners' HIV risk in terms of perceptions of physical health, cleanliness, and sexual and HIV testing history. They based decisions regarding condom use mainly on perceived faithfulness, length of involvement, availability of condoms, and pregnancy desirability. CONCLUSIONS: Risk appraisal was commonly based on appearance and subjective factors, and condom use with main sexual partners was described most often as a demonstration of lack of trust and intimacy. TRIAL REGISTRATION: NCT01379599.

Bone formation during distraction osteogenesis is dependent on both VEGFR1 and VEGFR2 signaling.

INTRODUCTION: Distraction osteogenesis (DO) is characterized by the induction of highly vascularized new bone formation through an intramembranous process largely devoid of the formation of cartilage. MATERIALS AND METHODS: To test the hypothesis that DO is strictly dependent on vascualrization, we inhibited vascular endothelial growth factor (VEGF) activity by antibody blockade of both receptors VEGFR1 (Flt-1) and VEGFR2 (Flk-1) or only VEGFR2 (Flk-1) in a previously developed murine tibia DO model. During normal DO, VEGFR1 (Flt-1), VEGFR2 (Flk-1), VEGFR3 (Flt4) and all four VEGF ligand (A, B, C, and D) mRNAs are induced. RESULTS: The expression of mRNA for the receptors generally paralleled those of the ligands during the period of active distraction. Bone formation, as assessed by muCT, showed a significant decrease with the double antibody treatment and a smaller decrease with single antibody treatment. Vessel volume, number, and connectivity showed progressive and significant inhibition in all of these of parameters between the single and double antibody blockade. Molecular analysis showed significant inhibition in skeletal cell development with the single and double antibody blockade of both VEGFR1 and 2. Interestingly, the single antibody treatment led to selective early development of chondrogenesis, whereas the double antibody treatment led to a failure of both osteogenesis and chondrogenesis. CONCLUSIONS: Both VEGFR1 and VEGFR2 are functionally essential in blood vessel and bone formation during DO and are needed to promote osteogenic over chondrogenic lineage progression.

Genetic variation in the patterns of skeletal progenitor cell differentiation and progression during endochondral bone formation affects the rate of fracture healing.

These studies examined how genetic differences that regulate architectural and bone material properties would be expressed during fracture healing and determine whether any of these features would affect rates of healing as defined by regain of strength. Controlled fractures were generated in three inbred strains of mice: A/J, C57Bl/6J (B6), and C3H/HeJ (C3H). Both the A/J and B6 strains showed faster healing than the C3H strain based on regains in strength and stiffness. Strain-specific architectural features such as moment of inertia, cross-sectional area, and cortical thickness were all recapitulated during the development of the callus tissues. None of these traits were directly relatable to rates of fracture healing. However, rates of healing were related to variations in the temporal patterns of chondrogenic and osteogenic lineage development. The B6 strain expressed the highest percentage of cartilage gene products and had the longest period of chondrocyte maturation and hypertrophy. The slowest healing strain (C3H) had the shortest period of chondrogenic development and earliest initiation of osteogenic development. Although the A/J strain showed an almost identical pattern of chondrogenic development as the C3H strain, A/J initiated osteogenic development several days later than C3H during fracture healing. Long bone growth plates at 28 days after birth showed similar strain-specific variation in cartilage tissue development as seen in fracture healing. Thus, the B6 strain had the largest growth plate heights, cell numbers per column, and the largest cell size, whereas the C3H columns were the shortest, had the smallest number of cells per column, and showed the smallest cell sizes. These results show that (1) different strains of mice express variations of skeletal stem cell lineage differentiation and (2) that these variations affect the rate of fracture healing.

Three-dimensional reconstruction of fracture callus morphogenesis.

Rat and mouse femur and tibia fracture calluses were collected over various time increments of healing. Serial sections were produced at spatial segments across the fracture callus. Standard histological methods and in situ hybridization to col1a1 and col2a1 mRNAs were used to define areas of cartilage and bone formation as well as tissue areas undergoing remodeling. Computer-assisted reconstructions of histological sections were used to generate three-dimensional images of the spatial morphogenesis of the fracture calluses. Endochondral bone formation occurred in an asymmetrical manner in both the femur and tibia, with cartilage tissues seen primarily proximal or distal to the fractures in the respective calluses of these bones. Remodeling of the calcified cartilage proceeded from the edges of the callus inward toward the fracture producing an inner-supporting trabecular structure over which a thin outer cortical shell forms. These data suggest that the specific developmental mechanisms that control the asymmetrical pattern of endochondral bone formation in fracture healing recapitulated the original asymmetry of development of a given bone because femur and tibia grow predominantly from their respective distal and proximal physis. These data further show that remodeling of the calcified cartilage produces a trabecular bone structure unique to fracture healing that provides the rapid regain in weight-bearing capacity to the injured bone.