A Passive Ankle Dorsiflexion Testing System for an In Vivo Model of Overuse-induced Tendinopathy.

Tendinopathy is a chronic tendon condition that results in pain and loss of function and is caused by repeated overload of the tendon and limited recovery time. This protocol describes a testing system that cyclically applies mechanical loads via passive dorsiflexion to the rat Achilles tendon. The custom-written code consists of pre- and post-cyclic loading measurements to assess the effects of the loading protocol along with the feedback control-based cyclic fatigue loading regimen. We used 25 Sprague-Dawley rats for this study, with 5 rats per group receiving either 500, 1,000, 2,000, 3,600, or 7,200 cycles of fatigue loads. The percentage differences between the pre- and post-cyclic loading measurements of the hysteresis, peak stress, and loading and unloading moduli were calculated. The results demonstrate that the system can induce varying degrees of damage to the Achilles tendon based on the number of loads applied. This system offers an innovative approach to apply quantified and physiological varying degrees of cyclic loads to the Achilles tendon for an in vivo model of fatigue-induced overuse tendon injury.

A passive ankle dorsiflexion testing system to assess mechanobiological and structural response to cyclic loading in rat Achilles tendon.

Tendinopathy is thought to be caused by repeated overload of the tendon with insufficient recovery time, leading to an inadequate healing response and incomplete recovery of preinjury material strength and function. The etiology of tendinopathy induced by mechanical load is being explored with a variety of mechanical load scenarios in small animals. This study establishes a testing system that applies passive ankle dorsiflexion to a rat hindlimb, estimates the force applied to the tendon during cyclic loading and enables the assessment of subsequent structural and biological changes. We demonstrated that the system had no drift in the applied angle, and the registered maximum angle and torque inputs and outputs were consistent between tests. We showed that cyclic loading decreased hysteresis and loading and unloading moduli with increasing cycles applied to the tendon. Histology showed gross changes to tendon structure. This work establishes a system for passively loading the rat Achilles tendon in-vivo in a physiological manner, facilitating future studies that will explore how mechanics, structure, and biology are altered by mechanical repetitive loading.

Effect of intraarticular pressure on glenohumeral kinematics during a simulated abduction motion: a cadaveric study.

BACKGROUND: The current understanding of glenohumeral joint stability is defined by active restrictions and passive stabilizers including naturally-occurring negative intraarticular pressure. Cadaveric specimens have been used to evaluate the role of intraarticular pressure on joint stability, although, while the shoulder's negative intraarticular pressure is universally acknowledged, it has been inconsistently accounted for. HYPOTHESIS: During continuous, passive humeral abduction, releasing the native intraarticular pressure increases joint translation, and restoring this pressure decreases joint translations. STUDY DESIGN: Descriptive Laboratory Study. METHODS: A validated shoulder testing system was used to passively abduct the humerus in the scapular plane and measure joint translations for seven (n = 7) cadaveric specimens. The pressure within the glenohumeral joint was measured via a 25-gauge needle during passive abduction of the arm, which was released and subsequently restored. During motion, the rotator cuff muscles were loaded using stepper motors in a force feedback loop and electromagnetic sensors were used to continuously measure the position of the humerus and scapula. Joint translation was defined according to the instant center of rotation of the glenohumeral head according to the recommendations by the International Society of Biomechanics. RESULTS: Area under the translation versus abduction angle curve suggests that releasing the pressure within the capsule results in significantly less posterior translation of the glenohumeral head as compared to intact (85-90˚, p < 0.05). Posterior and superior translations were reduced after 70˚ of abduction when the pressure within the joint was restored. CONCLUSION: With our testing system employing a smooth continuous passive motion, we were able to show that releasing intraarticular pressure does not have a major effect on the path of humeral head motion during glenohumeral abduction. However, both violating the capsule and restoring intraarticular pressure after releasing alter glenohumeral translations. Future studies should study the effect of simultaneous external rotation and abduction on the relationship between joint motion and IAP, especially in higher degrees of abduction. CLINICAL RELEVANCE: Thoroughly simulating the glenohumeral joint environment in the cadaveric setting may strengthen the conclusions that can be translated from this setting to the clinic.

Minimally invasive, sustained-release relaxin-2 microparticles reverse arthrofibrosis.

Substantial advances in biotherapeutics are distinctly lacking for musculoskeletal diseases. Musculoskeletal diseases are biomechanically complex and localized, highlighting the need for novel therapies capable of addressing these issues. All frontline treatment options for arthrofibrosis, a debilitating musculoskeletal disease, fail to treat the disease etiology-the accumulation of fibrotic tissue within the joint space. For millions of patients each year, the lack of modern and effective treatment options necessitates surgery in an attempt to regain joint range of motion (ROM) and escape prolonged pain. Human relaxin-2 (RLX), an endogenous peptide hormone with antifibrotic and antifibrogenic activity, is a promising biotherapeutic candidate for musculoskeletal fibrosis. However, RLX has previously faltered through multiple clinical programs because of pharmacokinetic barriers. Here, we describe the design and in vitro characterization of a tailored drug delivery system for the sustained release of RLX. Drug-loaded, polymeric microparticles released RLX over a multiweek time frame without altering peptide structure or bioactivity. In vivo, intraarticular administration of microparticles in rats resulted in prolonged, localized concentrations of RLX with reduced systemic drug exposure. Furthermore, a single injection of RLX-loaded microparticles restored joint ROM and architecture in an atraumatic rat model of arthrofibrosis with clinically derived end points. Finally, confirmation of RLX receptor expression, RXFP1, in multiple human tissues relevant to arthrofibrosis suggests the clinical translational potential of RLX when administered in a sustained and targeted manner.

Plaster of Paris: Squeeze, But Not Too Hard!

Plaster of Paris (PoP) has been the predominant treatment option for most acute and chronic orthopedic conditions. Water immersion significantly decreases the PoP bandage strength. Moreover, concerns have been raised about the possibility of breaks in PoP splints and cast failures once solid. The current study was designed to account for the increase in weight associated with increased PoP layers. The authors hypothesized that by controlling for weight variation as layers increased, they could determine the number of layers of PoP bandage that truly results in optimal mechanical properties. They assessed whether adequate plaster weight control while increasing layers could improve the mechanical properties of the splint. [Orthopedics. 2022;45(1):e57-e61.].

Tendinopathy and tendon material response to load: What we can learn from small animal studies.

Tendinopathy is a debilitating disease that causes as much as 30% of all musculoskeletal consultations. Existing treatments for tendinopathy have variable efficacy, possibly due to incomplete characterization of the underlying pathophysiology. Mechanical load can have both beneficial and detrimental effects on tendon, as the overall tendon response depends on the degree, frequency, timing, and magnitude of the load. The clinical continuum model of tendinopathy offers insight into the late stages of tendinopathy, but it does not capture the subclinical tendinopathic changes that begin before pain or loss of function. Small animal models that use high tendon loading to mimic human tendinopathy may be able to fill this knowledge gap. The goal of this review is to summarize the insights from in-vivo animal studies of mechanically-induced tendinopathy and higher loading regimens into the mechanical, microstructural, and biological features that help characterize the continuum between normal tendon and tendinopathy. STATEMENT OF SIGNIFICANCE: This review summarizes the insights gained from in-vivo animal studies of mechanically-induced tendinopathy by evaluating the effect high loading regimens have on the mechanical, structural, and biological features of tendinopathy. A better understanding of the interplay between these realms could lead to improved patient management, especially in the presence of painful tendon.

Effect of rotator cuff muscle activation on glenohumeral kinematics: A cadaveric study.

Healthy shoulder function requires the coordination of the rotator cuff muscles to maintain the humeral head's position in the glenoid. While glenohumeral stability has been studied in various settings, few studies have characterized the effect of dynamic rotator cuff muscle loading on glenohumeral translation during shoulder motion. We hypothesize that dynamic rotator cuff muscle activation decreases joint translation during continuous passive abduction of the humerus in a cadaveric model of scapular plane glenohumeral abduction. The effect of different rotator cuff muscle activity on glenohumeral translation was assessed using a validated shoulder testing system. The Dynamic Load profile is a novel approach, based on musculoskeletal modeling of human subject motion. Passive humeral elevation in the scapular plane was applied via the testing system arm, while the rotator cuff muscles were activated according to the specified force profiles using stepper motors and a proportional control feedback loop. Glenohumeral translation was defined according to the International Society of Biomechanics. The Dynamic load profile minimized superior translation of the humeral head relative to the conventional loading profiles. The total magnitude of translation was not significantly different (0.805) among the loading profiles suggesting that the compressive forces from the rotator cuff primarily alter the direction of humeral head translation, not the magnitude. Rotator cuff muscle loading is an important element of cadaveric shoulder studies that must be considered to accurately simulate glenohumeral motion. A rotator cuff muscle activity profile based on human subject muscle activity reduces superior glenohumeral translation when compared to previous RC loading profiles.

Tendon lengthening after achilles tendon rupture-passive effects on the ankle joint in a cadaveric pilot study simulating weight bearing.

BACKGROUND: In recent years, primary Achilles tendon ruptures have increased due to the aging population's participation in physically demanding activities. These injuries commonly occur during recreational sports and frequently lead to a long-term reduction in activity despite treatment. Non-operative methods of treatment for Achilles tendon ruptures may result in the Achilles healing in a lengthened position compared to the pre-injury state. This study uses a cadaveric model that simulates static weight bearing to explore the effect of a lengthened Achilles tendon on ankle joint load distribution. METHODS: Five lower limb cadaveric specimens were placed on a custom jig, where a 334 N (75 lb) load was applied at the femoral head, and the foot was supported against a plate to simulate static double-leg stance. A pressure mapping sensor was inserted into the ankle joint. A percutaneous triple hemiresection tendo-Achilles lengthening procedure (Hoke procedure) was performed on each specimen to simulate tendon lengthening after conservative treatment. Contact pressure, peak pressure, and center-of-pressure were measured for native and tendon-lengthened conditions. RESULTS: Tendon rupture did not significantly alter average contact pressure, peak contact pressures, or center-of-pressure in the ankle joint compared with native tendon. CONCLUSION: Achilles lengthening does not significantly change contact pressures of the ankle joint in this model . This result suggests that the passive restraint on ankle joint translation imposed by the Achilles tendon is minimal without muscle activation.

Intraarticular injection of relaxin-2 alleviates shoulder arthrofibrosis.

Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesive capsulitis (frozen shoulder) and to restore glenohumeral ROM in shoulder arthrofibrosis. Recombinant human relaxin-2 down-regulates type I collagen and α smooth muscle actin production and increases intracellular cAMP concentration in human fibroblast-like synoviocytes, consistent with a mechanism of extracellular matrix degradation and remodeling. Pharmacokinetic profiling of a bolus administration into the glenohumeral joint space reveals the brief systemic and intraarticular (IA) half-lives of relaxin-2: 0.96 h and 0.62 h, respectively. Furthermore, using an established, immobilization murine model of shoulder arthrofibrosis, multiple IA injections of human relaxin-2 significantly improve ROM, returning it to baseline measurements collected before limb immobilization. This is in contrast to single IA (sIA) or multiple i.v. (mIV) injections of relaxin-2 with which the ROM remains constrained. The histological hallmarks of contracture (e.g., fibrotic adhesions and reduced joint space) are absent in the animals treated with multiple IA injections of relaxin-2 compared with the untreated control and the sIA- and mIV-treated animals. As these findings show, local delivery of relaxin-2 is an innovative treatment of shoulder arthrofibrosis.

Diagnostic Modalities for Acute Compartment Syndrome of the Extremities: A Systematic Review.

IMPORTANCE: Acute compartment syndrome (ACS) can cause catastrophic tissue damage leading to permanent muscle and nerve loss. Acute compartment syndrome is a clinical diagnosis, with intracompartmental pressure (ICP) used in equivocal cases. There are no reliable diagnostic methods. The clinical evaluation is impossible to standardize, and the threshold for ICP has been known to be unreliable; thus, guidelines for diagnosis can result in overtreatment or delayed diagnosis. OBJECTIVE: To present and review the advantages and disadvantages of each diagnostic modality and identify gaps that need to be addressed in the future and to review the most used and appropriate animal and human ACS models. EVIDENCE REVIEW: We included clinical studies and animal models investigating diagnostic modalities for ACS of the extremities. A MEDLINE and Web of Science search was performed. The protocol for the study was registered on PROSPERO (CRD42017079266). We assessed the quality of the clinical studies with Newcastle-Ottawa scale and reported level of evidence for each article. FINDINGS: Fifty-one articles were included in this study, reporting on 38 noninvasive and 35 invasive modalities. Near-infrared spectroscopy and direct ICP measurement using a Stryker device were the most common, respectively. Cadaveric studies used saline infusions to create an ACS model. Most studies with human participants included injured patients with acquired ACS or at risk of developing ACS. In healthy human participants, tourniquets formed the most commonly used ACS model. Application of tourniquets and infusion of saline or albumin were the most used ACS models among animal studies. CONCLUSIONS AND RELEVANCE: This article reports on the most common as well as many new and modified diagnostic modalities, which can serve as inspiration for future investigations to develop more effective and efficient diagnostic techniques for ACS. Future studies on diagnostic modalities should include the development of tools for continuous assessment of ICP to better identify the earliest alterations suggestive of impending ACS. With the advent of such technologies, it may be possible to develop far less aggressive and more effective approaches for early detection of ACS.