Elizabeth Clare Clarke

Introduction: Targeted muscle reinnervation is increasingly being utilized to prevent or manage neuropathic pain in both amputees and non‐amputees. The motor entry points (MEP) to the peroneus tertius provide ideal targets, as they are accessible but deep, and expendable with no donor morbidity. However, there has been no prior study of the neural anatomy of the peroneus tertius in this setting. This study aimed to evaluate the distribution of motor entry points (MEP) to the peroneus tertius, providing an anatomic roadmap to guide its use in targeted muscle reinnervation. Methods: The branches of the deep peroneal nerve to the peroneus tertius were dissected in 12 cadaveric adult lower limbs. The number of MEP, diameter of the terminal branches and distance of each MEP from the tip of the lateral malleolus was recorded, as was the overall length of the fibula. A ratio of the distance of the MEP from the lateral malleolus to the overall length of the fibula was calculated. Results: A mean of 1.9 ± 0.7 [range: 1–3] MEP innervated each peroneus tertius, with the terminal nerve 1.0 ± 0.5 mm [range: 0.5–2] in diameter, located a mean of 144.4 ± 29.1 mm [range: 90–188] cranial to the tip of the lateral malleolus (40.0% ± 8.8% [range: 26.0–56.3] of total fibular length). All specimens had at least a single MEP in the zone spanning 31.4% to 52.2% of the fibular length, located in the plane between the peroneus tertius and extensor digitorum longus. Conclusion: The peroneus tertius has MEP at a consistent location and plane and may be considered an optimal target for targeted muscle reinnervation around the foot and ankle.

Background: Upper limb tendon/ligament injuries are common in sport and may require reconstruction using grafts or tendon transfers. Understanding tissue-specific properties is key to improving graft selection criteria and developing new interventions. Purpose: To characterize morphological, biomechanical, and biochemical properties of clinically important upper limb tendons, expanding available data on upper and lower limb tissues that are commonly injured or used as grafts. Study Design: Descriptive laboratory study. Methods: A total of 31 individual upper limb tendons were each retrieved from 8 fresh-frozen human cadavers (3 female, 5 male; aged 49-65 years): supraspinatus, infraspinatus, subscapularis, long head of biceps, distal biceps, distal triceps, brachioradialis, flexor carpi radialis, flexor carpi ulnaris, palmaris longus, extensor carpi radialis longus and brevis, extensor carpi ulnaris, flexor pollicis longus, abductor pollicis longus, extensor pollicis brevis and longus, extensor indicis proprius, extensor digiti minimi, and from the second to fifth digits, flexor digitorum superficialis and profundus and extensor digitorum communis. Outcome measures included tissue length; cross-sectional area, and major/minor axes; failure load; ultimate tensile strength (UTS); failure strain; elastic modulus; sulfated glycosaminoglycan (sGAG) and hydroxyproline content. Differences were analyzed using mixed linear regression models. Results: Rotator cuff tendons were distinct, exhibiting large, flat cross-sections with high failure loads and sGAG, and low UTS. Supraspinatus was significantly weaker with more sGAG than infraspinatus and subscapularis. Tendon UTS and elastic modulus were largely similar between elbow, wrist, and hand tendons. Exceptions included higher and lower material properties of the extensor pollicis brevis and flexor carpi ulnaris, respectively, than other distal upper limb tendons. Extensor tendons generally had higher sGAG than flexors with significant differences at the wrist and thumb, while hydroxyproline content was significantly higher in digital flexors versus extensors in the fingers. Conclusion: These findings enhance understanding of upper limb tendon properties, providing novel data to inform graft selection and tailor alternative engineered or regenerative strategies. Clinical Relevance: The combined upper/lower limb data sets include 48 unique appendicular tendons and ligaments sourced from the same donors and evaluated using consistent methodologies, providing a robust comparative database to aid selection of suitable donor tendons for the repair/reconstruction of injured tendons/ligaments and the development of graft materials.

Osteoarthritis and polypharmacy are common in older adults. While not consistent with guidelines, opioid analgesia is commonly prescribed to older adults with osteoarthritis and other causes of chronic non-cancer pain. Long term use of opioids is associated with tolerance, addiction, loss of efficacy and adverse events. Thus, deprescribing (reducing or ceasing) opioids is often required. The effect of polypharmacy on the efficacy and safety of opioid prescribing and deprescribing in this setting is poorly understood. Here we aimed to assess the effects of chronic oxycodone, as monotherapy and in polypharmacy (oxycodone, citalopram, simvastatin, oxybutynin, and metoprolol), and of deprescribing oxycodone, on allodynia, physical and cognitive function, and daily activities in middle-aged, osteoarthritic male and female C57BL/6J mice (n=11-15/ group). Only oxycodone monotherapy reduced mechanical allodynia after 6 weeks of treatment. Chronic polypharmacy with oxycodone transiently increased mechanical allodynia in the injured limb and caused marked reductions in mobility, maximum walking speed, activities of daily living, and increased anxiety. Polypharmacy also altered daily activities detected by an automated animal behaviour recognition cage. Sex differences in treatment response were observed in frailty measurements and activity over 23 hours. Deprescribing oxycodone was well tolerated and did not alter physical or cognitive function but did reverse some of the daily activity changes and mechanical allodynia in polypharmacy treated animals only. This clinically relevant preclinical model provides an opportunity to understand the effects of prescribing and deprescribing opioids in older adults with osteoarthritis, including the impact of comedications and sex.

Introduction: Complications arising from the patellofemoral joint (PFJ) represent the third most common cause for revision in total knee arthroplasty (TKA). Previous in vitro biomechanical studies have altered the native attachments of muscles controlling the PFJ. The purpose of this study was to design an in vitro biomechanical setup that would allow testing of both native and arthroplasty knee joints, specifically the PFJ, without disturbing the native attachments of the quadriceps and hamstrings muscles. Methods: After finalising a prototype, a pelvis-to-toe human cadaver specimen was tested. The simVITRO platform was used to simulate movement and control force trajectories. A motion capture system was used to capture the motion of the bones and to measure knee flexion angle and patellar movement with respect to the femur. The forces applied in the PFJ were measured using a custom patella sensor. Results: Displacement of the reflective cluster attached to the femur was measured during compression loading at different flexion angles, passive flexion and stairs descent trajectory. The femur showed less than 1 mm and 3 mm displacement with respect to the femur clamp in passive flexion and stairs descent. The most translation of 8.37 mm (Conclusion: This novel design provides a methodology for studying the biomechanics of the PFJ in vitro that preserves the soft tissues influencing the behaviour of the joint. This setup provides a biomechanics model that can be utilised to better understand and study the PFJ in vitro.

Tendons are force‐transmitting structures which facilitate musculoskeletal functioning. Characterizing variations between different anatomical tendons, regions within tendons, as well as between the sexes and with age can improve understanding of tendon physiology and pathology. A systematic search of the literature was conducted to identify and summarize microscopic structural (histological) variations in normal/healthy tendons in relation to these variables (Tendon, Region, Age, Sex, and Other). Regional differences within individual tendons have been investigated in numerous studies, however investigations comparing histological variations between a range of different tendons are sparse, with most focusing on a few select tendons. When injured, ageing tendons typically have a greater degree of pathological changes than younger tendons, but few studies have documented variations in tendon histology throughout typical (uninjured) ageing or across large age spans. Similarly, sex‐related observations of tendon structure are underreported. This narrative review summarizes studies on these topics and explores interactions between these variables, as well as the implications of these in the context of selecting control samples for studies of tendon pathology. Future studies should endeavour to improve knowledge of tendon structural variations—specifically focusing on normal tendons—to facilitate understanding of tendon structure‐function relationships, physiological mechanisms involved in tendon damage/healing, and to aid clinical research and practice.

Tendon allograft and xenograft processing often involves one or more steps of freezing and thawing. As failure strength is an important graft consideration, this study aimed to evaluate effects on failure properties when varying freeze‐thaw conditions. Kangaroo tendons, a potential xenograft source, were used to evaluate changes in ultimate tensile strength (UTS), failure strain and elastic modulus after exposure to different freezer‐storage temperatures (−20°C vs. −80°C), storage durations (1, 3, 6, 9, or 12 months), number of freeze‐thaw cycles (1, 2, 3, 4, 5, or 10), or freeze‐thaw temperature ranges (including freezing in liquid nitrogen to thawing at 37°C). Tendons stored for 6 or more months had significantly increased UTS and elastic modulus compared with 1 or 3 months of storage. This increase occurred irrespective of the freezing temperature (−20°C vs. −80°C) or the number of freeze‐thaw cycles (1 vs. 10). In contrast, UTS, failure strain and the elastic modulus were no different between storage temperatures, number of freeze‐thaw cycles and multiple freeze‐thaw cycles across a range of freeze and thaw temperatures. Common freeze‐thaw protocols did not negatively affect failure properties, providing flexibility for graft testing, storage, transportation and decellularisation procedures. However, the change in properties with the overall storage duration has implications for assessing the consistent performance of grafts stored for short versus extended periods of time (6 months), and the interpretation of data obtained from tissues of varying or unknown storage durations.

Increasing anterior cruciate ligament (ACL) rupture rates are driving the need for new graft materials which undergo testing to characterize material properties and function. The in vitro collagenase assay is routinely used to determine the degradation rate of collagenous materials. At times, it is used to screen new biomaterials on the basis that results reflect breakdown rates in vivo. However, its predictive potential is inconclusive with no guidelines for acceptable in vitro rates of degradation. Reference data from target tissue/s or existing clinical materials are needed to determine appropriate thresholds. From a summary of reported protocols, the most common bench conditions (bacterial collagenase; unloaded samples) were used to evaluate the in vitro degradation of human tendons used as ACL allografts: patellar, semitendinosus, gracilis, Achilles, tibialis anterior and posterior. Tendons were sectioned in equal volumes and exposed to 100 U collagenase for 1, 2, 4 or 8 h. The change in dry weight was analysed using mixed linear regression. All tendon samples demonstrated a significant reduction in mass over time but the patellar tendon degraded significantly faster than all other tendons (P ≤ 0.004). As all tendons used in this study are clinically accepted, this study provides a range of human tendon reference data for comparative assessment of new tendon and ligament biomaterials. However, the more rapid degradation of the patellar tendon, one of the most successful ACL graft materials, also highlights the limitations of common collagenase assay conditions for predicting in vivo performance, particularly in the absence of suitable comparative controls.

Cite this article: Bone Joint Res 2022;11(8):514–517.