About

Daniel Howe is a member of The Alliance for Inclusive Design at NC State University, which focuses on advancing inclusive design through collaborative research and industry practice. The Alliance aims to influence research, industry standards, and practical applications of inclusive design, working with colleagues across NC State University, partner universities, governmental agencies, non-profit organizations, and professional design firms. While specific details about Daniel Howe's individual research focus or contributions are not provided in the available page text, his association with the Alliance indicates a commitment to promoting inclusive design practices within the built environment.

Research topics

• Anatomy
• Medicine
• Surgery
• Pathology
• Radiology

Selected publications

• An Exploratory Assessment of Associations Between Serum Estrogen to Progesterone Ratio and Anterior Cruciate Ligament Size, Biomechanics, and T2* Relaxation Time in the Porcine Model

  Journal of Biomechanical Engineering · 2026-03-12

  article

  Adolescent females are at a higher risk of anterior cruciate ligament (ACL) injury than males. While prior studies have associated injury timing and menstrual cycle phase, these data are limited by indirect cycle tracking and lack of analysis on ACL structure, mechanics, or composition. Additionally, little is known about how female sex hormones influence the distinct ACL bundles. This exploratory study investigated associations between serum sex hormone concentrations and size, mechanics, and composition of the ACL and its bundles in a female adolescent pig model. Serum from nine adolescent female Yorkshire crossbreed pigs was collected pre-euthanasia and analyzed for levels of estradiol, progesterone, and testosterone. The ACL and its bundles were assessed for size via magnetic resonance imaging (MRI), mechanics via robotic testing, and composition via biochemical and histological analyses. While individual hormone levels and the estradiol-to-progesterone (E/P) ratio had no association with most metrics, the E/P ratio was significantly associated with ACL size and T2* relaxation time. Higher E/P ratios were negatively associated with anteromedial (AM) bundle cross-sectional area (CSA) (R2 = 0.44) and overall ACL volume (R2 = 0.49) and positively associated with posterolateral (PL) bundle T2* relaxation time (R2 = 0.69, p < 0.05). Serum E/P ratio was also positively associated with normalized ACL stiffness, but there were no associations observed for tissue composition. The results of this exploratory study indicate that the ACL may be responsive to exposure to the relative concentration of female sex hormone in a bundle-specific manner.

  PublisherDOI

• Early degenerative changes are different between partial and complete anterior cruciate ligament injury and associate with joint instability in a skeletally immature porcine model

  UNC Libraries · 2025-11-09

  articleOpen access
  PublisherDOI

• Early degenerative changes are different between partial and complete anterior cruciate ligament injury and associate with joint instability in a skeletally immature porcine model

  Osteoarthritis and Cartilage · 2024-11-08 · 2 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Poster 151: Femoral Cartilage T2* Relaxation Times Correlate With Inflammatory Biomarker MCP-1 Levels In Serum, But Not Synovial Fluid, After ACL Injury In A Skeletally Immature Porcine Model

  Orthopaedic Journal of Sports Medicine · 2023-07-01

  articleOpen access

  Objectives: Pediatric anterior cruciate ligament (ACL) injuries are on the rise and result in high rates of post-traumatic osteoarthritis (PTOA). The pro-inflammatory biomarker monocyte chemoattractant protein-1 (MCP-1) is elevated in serum and synovial fluid (SF) in skeletally mature ACL injured patients as well as patients with OA, making it a potential target for treatments to prevent PTOA. Understanding the time course of MCP-1 after ACL injury and how it relates to cartilage health in skeletally immature subjects is important for identifying OA risk and developing novel treatment targets for OA prevention. Therefore, the objective of this study was to evaluate the time course of MCP-1 levels in serum and synovial fluid (SF) after ACL injury in a skeletally immature porcine model and assess how MCP-1 levels relate to T2* magnetic resonance imaging (MRI) measurements, indicative of cartilage matrix organization. We hypothesized that higher levels of MCP-1 in serum and synovial fluid post-injury would correspond to higher cartilage T2* values 12 weeks after ACL injury. Methods: All experimental protocols were approved by the NC State IACUC. Juvenile (3 month old) female Yorkshire cross-breed pigs (n=7) underwent unilateral arthroscopic ACL transection (ACLT) and a sham operation in the contralateral joint (Fig. 1A). Prior to surgery and at 2, 4, and 12 weeks post- operatively, injured stifle SF and serum samples were collected (pre-op synovial fluid only obtained from 4 animals). MRI scans were performed prior to surgery and at 12 weeks post-operatively. MCP-1 levels in serum and SF samples were evaluated longitudinally using a commercial enzyme-linked immunosorbent assay. Cartilage matrix organization was evaluated longitudinally using T2* MRI. Specifically, both knee joints were imaged using a 3T Siemens MAGNETOM Skyra MRI system (T2 SWI sequence, FA=15°, TR=50ms, TE: 3.4, 7, 13.47, 21, 29, 37.07ms, voxel size: 0.5x0.5x0.8mm). T2* relaxation maps were created in MATLAB by fitting mono-exponential curves on a voxel-by-voxel basis. Weight-bearing cartilage was segmented from the medial and lateral compartments of the femur, and the median T2* value of each compartment was calculated. Paired MCP-1 levels in the serum and injured stifle SF across all time points were compared using linear regression. Multiple paired t-tests with Holm-Sidak correction were performed to compare cartilage T2* values between ACLT and sham- operated joints at each time point. The interlimb percent difference in femoral cartilage T2* at 12 weeks was calculated and compared to MCP-1 levels in serum and SF using linear regressions and several methods to assess MCP-1 levels (Fig. 2). Statistical significance was set at α=0.05 overall for each analysis. Results: Generally, MCP-1 levels in serum and ACLT stifle SF were elevated after ACLT (Fig. 1). The serum MCP-1 response over time differed between animals. Specifically, serum MCP-1 levels peaked at 2 weeks in 2 animals, peaked at 4 weeks in 3 animals, and decreased after ACLT in 2 animals (Fig 1A). Contrastingly, ACLT stifle SF MCP-1 responses were more consistent between animals; six peaked at 2 week and returned near baseline levels by 12 weeks (Fig 1B). The linear regression between paired measurements of MCP-1 concentrations in the serum and ACLT stifle SF were associated (p=0.053), yet had high variability (r 2 =0.15, Fig. 1C). Interlimb differences in cartilage matrix organization were largest and most consistent at 12 weeks in the medial femoral cartilage compartment, where median T2* times were 8% longer in the medial femoral cartilage compartment of the ACLT limb compared to sham limb, yet this was not statistically significant due to variability between animals (p&gt;0.05, Fig. 2). In the lateral femoral cartilage, the median T2* times were 3-4% longer at 12 weeks (p&gt;0.05) and were more variable between subjects compared to the medial femoral cartilage. Associations between the interlimb percent difference in medial femoral cartilage T2* and serum MCP-1 fit well (r 2 =0.25-0.69), with Methods 2, 3, and 5 achieving statistical significance (p=0.02, p=0.03, p=0.03), but resulted in poor fits for associations with SF MCP-1 (r 2 =0.07-0.45) using a variety of MCP-1 measurement methods (Fig 2C). Similar associations between lateral femoral cartilage T2* and serum MCP- resulted in poor fits (r 2 =0.01-0.24), and associations with SF MCP-1 resulted in negative slopes (Methods 2-5, r 2 =0.00-0.58). Conclusions: This preliminary study showed that inflammatory biomarker MCP-1 levels in serum displayed a subject-dependent response, which correlated with later femoral cartilage compositional changes after ACLT in the skeletally immature porcine model. This partially supported our hypothesis. The poor correlation between serum and SF MCP-1 indicate different local and systemic responses to ACLT. The stronger correlations between serum MCP-1 and cartilage T2* values could point to the importance of the systemic inflammatory response to OA progression. The increases in cartilage T2* values and serum MCP-1 levels after ACL injury in this study are consistent with those reported in adult humans. This study includes several limitations, including the use of an animal model to study human disease, the small sample size, and the relatively short time-course. However, the results demonstrate feasibility of using a large animal porcine model to longitudinally study the link between early MCP-1 serum levels and long-term cartilage health after ACL injury. Establishing the pig as a preclinical model to study longitudinal inflammation and OA progression after ACL injury will enable development of effective treatments before translating to humans.

  PublisherOA PDFDOI

• Neo-Natal Castration Leads to Subtle Differences in Porcine Anterior Cruciate Ligament Morphology and Function in Adolescence

  Journal of Biomechanical Engineering · 2023-10-13 · 1 citations

  articleOpen access

  Female adolescent athletes are at a higher risk of tearing their anterior cruciate ligament (ACL) than male counterparts. While most work related to hormones has focused on the effects of estrogen to understand the increased risk of ACL injury, there are other understudied factors, including testosterone. The purpose of this study was to determine how surgical castration in the male porcine model influences ACL size and function across skeletal growth. Thirty-six male Yorkshire crossbreed pigs were raised to 3 (juvenile), 4.5 (early adolescent), and 6 months (adolescent) of age. Animals were either castrated (barrows) within 2 weeks after birth or were left intact (boars). Posteuthanasia, joint and ACL size were assessed via MRI, and biomechanics were assessed via a robotic testing system. Joint size increased throughout age, yet barrows had smaller joints than boars. ACL cross-sectional area (CSA), length, volume, and in situ stiffness increased with age, as did the percent contribution of the ACL anteromedial (AM) bundle to resisting loads. Boar ACL, AM bundle, and PL bundle volumes were 19%, 25%, and 15% larger than barrows across ages. However, ACL CSA, in situ stiffness, and bundle contribution were similar between boars and barrows. The barrows had smaller temporal increases in AM bundle function than boars, but these data were highly variable. Early and sustained loss in testosterone leads to subtle differences in ACL morphology but may not influence measures associated with increased injury risk, such as CSA or bundle forces in response to applied loads.

  PublisherOA PDFDOI

• Neo-natal castration leads to subtle differences in porcine anterior cruciate ligament morphology and function in adolescence

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-01-25

  preprintOpen access

  Female adolescent athletes are at a higher risk of tearing their anterior cruciate ligament (ACL) than male counterparts. While most work related to hormones has focused on the effects of estrogen to understand the increased risk of ACL injury, there are other understudied factors, including testosterone. The purpose of this study was to determine how surgical castration in the male porcine model influences ACL size and function across skeletal growth. Thirty-six male Yorkshire crossbreed pigs were raised to 3 (juvenile), 4.5 (early adolescent), and 6 months (adolescent) of age. Animals were either castrated (barrows) within 1-2 weeks after birth or were left intact (boars). Post-euthanasia, joint and ACL size were assessed via MRI, and biomechanics were assessed via a robotic testing system. Joint size increased throughout age, yet barrows had smaller joints than boars (p<0.001 for all measures). ACL cross-sectional area (CSA), length, volume, and stiffness increased with age (p<0.0001), as did ACL anteromedial (AM) bundle percent contribution to resisting loads (p=0.012). Boar ACL, AM bundle, and PL bundle volumes were 19% (p=0.002), 25% (p=0.003), and 15% (p=0.04) larger than barrows across ages. However, CSA, stiffness, and bundle contribution were similar between boars and barrows (p>0.05). The barrows had smaller temporal increases in AM bundle percent function than boars, but these data were highly variable. Thus, early and sustained loss in testosterone leads to subtle differences in ACL morphology, but may not influence measures associated with increased injury risk, such as CSA or bundle forces in response to applied loads.

  PublisherOA PDFDOI

• Degenerative changes are associated with severity of anterior cruciate ligament injury within the skeletally immature joint

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-11-13 · 3 citations

  preprintOpen access1st author

  Abstract Anterior cruciate ligament (ACL) injuries are a major problem in the pediatric and adolescent populations. Some of these injuries extend only partially through the tissue cross-section; yet, there is limited data to inform clinical treatment of such partial tears. In particular, it is unknown how injury severity impacts long-term degenerative changes in the joint. Here, we leverage a skeletally immature preclinical porcine model to evaluate joint biomechanics and degeneration after partial (isolated anteromedial (AM) or posterolateral (PL) bundle) or complete ACL injury. Six months after injury, joint laxity increases were minimal after PL bundle injury, minor after AM bundle injury, and major after ACL injury. Joint degeneration (evaluated in the cartilage and meniscus) was minimal after PL bundle injury, moderate after AM bundle injury, and substantial after ACL injury. With subjects grouped by clinical Lachman grade (indicating the extent of joint destabilization), degeneration was associated with increasing grade, irrespective of injury type. These findings point to the importance of considering joint laxity as a factor when treating young patients, particularly those with partial ACL injuries.

  PublisherOA PDFDOI

• Age- and Sex-Specific Joint Biomechanics in Response to Partial and Complete Anterior Cruciate Ligament Injury in the Porcine Model

  Journal of Athletic Training · 2021 · 6 citations

  1st authorCorresponding
  • Medicine
  • Anatomy
  • Surgery

  CONTEXT: Pediatric anterior cruciate ligament (ACL) injury rates are increasing and are highest in female adolescents. Complete ACL tears are typically surgically reconstructed, but few guidelines and very limited data exist regarding the need for surgical reconstruction or rehabilitation for partial ACL tears in skeletally immature patients. OBJECTIVE: To evaluate the effects of partial (anteromedial bundle) and complete ACL transection on joint laxity and tissue forces under anterior and rotational loads in male and female stifle joints throughout skeletal growth in the porcine model. DESIGN: Descriptive laboratory study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: We studied 60 male and female Yorkshire crossbreed pigs aged 1.5, 3, 4.5, 6, and 18 months (n = 6 pigs per age per sex). MAIN OUTCOME MEASURE(S): Joint laxity was measured in intact, anteromedial bundle-transected, and ACL-transected joints under applied anterior-posterior drawer and varus-valgus torque using a robotic testing system. Loading of the soft tissues in the stifle joint was measured under each condition. RESULTS: Anterior-posterior joint laxity increased by 13% to 50% (P < .05) after anteromedial bundle transection and 75% to 178% (P < .05) after ACL transection. Destabilization after anteromedial bundle transection increased with age (P < .05) and was greater in late female than late male adolescents (P < .05). In anteromedial bundle-transected joints, the posterolateral bundle resisted the anterior load. In ACL-transected joints, the medial collateral ligament (MCL) contribution was largest, followed by the medial meniscus. The MCL contribution was larger and the medial meniscus contribution was smaller in male versus female specimens. CONCLUSIONS: Partial ACL transection resulted in moderate increases in joint laxity, with the remaining bundle performing the primary ACL function. Destabilization due to partial ACL transection (anteromedial bundle) was largest in late adolescent joints, indicating that operative treatment should be considered in active, late-adolescent patients with this injury. Increased forces on the MCL and medial meniscus after ACL transection suggested that rehabilitation protocols may need to focus on protecting these tissues.

  PublisherDOI

• Sex-Specific Function and Morphology of the Anterior Cruciate Ligament During Skeletal Growth in a Porcine Model

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-05-10 · 4 citations

  preprintOpen access1st author

  Abstract Pediatric anterior cruciate ligament (ACL) injuries are on the rise, and females experience higher ACL injury risk than males during adolescence. Studies in skeletally immature patients indicate differences in ACL size and joint laxity between males and females after the onset of adolescence. However, functional data regarding the ACL and its anteromedial and posterolateral bundles in the pediatric population remain rare. Therefore, this study uses a porcine model to investigate the sex-specific morphology and function of the ACL and its bundles throughout skeletal growth. Hind limbs from male and female Yorkshire pigs aged early youth to late adolescence were imaged using magnetic resonance imaging to measure the size and orientation of the ACL and its bundles, then biomechanically tested under anterior-posterior drawer using a robotic testing system. Joint laxity decreased (p&lt;0.001) while joint stiffness increased (p&lt;0.001) throughout skeletal growth in both sexes. The ACL was the primary stabilizer against anterior tibial loading in all specimens, while the functional role of the anteromedial bundle increased with age (p&lt;0.001), with an earlier shift in males. ACL and posterolateral bundle cross-sectional area and ACL and anteromedial bundle length were larger in males than females during adolescence (p&lt;0.01 for all), while ACL and bundle sagittal angle remained similar between sexes. Additionally, in situ ACL stiffness correlated with cross-sectional area across skeletal growth (r 2 =0.75, p&lt;0.001 in males and r 2 =0.64, p&lt;0.001 in females), but not within age groups. This study has implications for age and sex-specific surgical intervention strategies and suggests the need for human studies.

  PublisherOA PDFDOI

• A Direct Comparison of Node and Element-Based Finite Element Modeling Approaches to Study Tissue Growth

  Journal of Biomechanical Engineering · 2021-07-06

  articleOpen access1st authorCorresponding

  Finite element analysis is a useful tool to model growth of biological tissues and predict how growth can be impacted by stimuli. Previous work has simulated growth using node-based or element-based approaches, and this implementation choice may influence predicted growth, irrespective of the applied growth model. This study directly compared node-based and element-based approaches to understand the isolated impact of implementation method on growth predictions by simulating growth of a bone rudiment geometry, and determined what conditions produce similar results between the approaches. We used a previously reported node-based approach implemented via thermal expansion and an element-based approach implemented via osmotic swelling, and we derived a mathematical relationship to relate the growth resulting from these approaches. We found that material properties (modulus) affected growth in the element-based approach, with growth completely restricted for high modulus values relative to the growth stimulus, and no restriction for low modulus values. The node-based approach was unaffected by modulus. Node- and element-based approaches matched marginally better when the conversion coefficient to relate the approaches was optimized based on the results of initial simulations, rather than using the theoretically predicted conversion coefficient (median difference in node position 0.042 cm versus 0.052 cm, respectively). In summary, we illustrate here the importance of the choice of implementation approach for modeling growth, provide a framework for converting models between implementation approaches, and highlight important considerations for comparing results in prior work and developing new models of tissue growth.

  PublisherOA PDFDOI

Recent grants

• Effect of Age, Sex, and Injury on Regional Stresses and Resulting Growth of the Anterior Cruciate Ligament

  NIH · $54k · 2021–2024

Frequent coauthors

• Matthew B. Fisher

  North Carolina State University

  39 shared

• Jacob D. Thompson

  16 shared

• Stephanie G. Cone

  University of Wisconsin–Madison

  15 shared

• Jeffrey T. Spang

  14 shared

• Emily H. Griffith

  11 shared

• Stephanie D. Teeter

  North Carolina State University

  8 shared

• Lynn Ansley Fordham

  6 shared

• Margaret Easson

  North Carolina State University

  6 shared

Labs

• The Alliance for Inclusive Design Practice and ResearchPI

Education

• Ph.D., Biomedical Engineering

  North Carolina State University

• B.S., Biomedical Engineering

  College of New Jersey

  2017

Awards & honors

• American Society of Landscape Architects College of Fellows…