Temporal Patterns of Motion in Flexion-extension and Pronation-supination in a Rat Model of Posttraumatic Elbow Contracture

Dunham, Chelsey L.; Castile, Ryan M.; Havlioglu, Necat; Chamberlain, Aaron M.; Lake, Spencer P.

doi:10.1097/corr.0000000000000388

Cited by 17 publications

(41 citation statements)

References 42 publications

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“…INJ scores slightly varied with previous publications because these sections were blinded and rescored with the data collected in this study; importantly, these subtle differences do not alter the interpretation of the results. 7 While most histological parameters for INJ, INJ-TCP, and INJ-GEL were increased compared to control, indicative of a wound healing response, there were a few notable differences. While INJ-TCP and INJ-GEL capsule thickness values were not different compared to control, both groups exhibited increased myofibroblasts and inflammation.…”

mentioning

confidence: 89%

“…This period of immobilization was selected because it was previously shown to be the earliest time point at which significant contracture developed. 7 Animals were randomized into two groups (n = 6/group): INJ-TCP (injury + immobilization + TCP-expanded ASC injection), and INJ-GEL (injury + immobilization + soft primed ASC injection). Data from control (no injury + no immobilization) and INJ (injury + immobilization) animals were reported in previous studies, but were included here to enable statistical comparison between control, untreated and treated groups.…”

Section: Animal Modelmentioning

confidence: 99%

“…[2][3][4] Notably, fibrosis is believed to drive post-traumatic joint contracture which affects approximately 50% of patients after injury and permanently limits joint function. [5][6][7][8] Currently, there are no treatment strategies which have consistently prevented joint contracture. [9][10][11] Across conditions, fibrosis is thought to derive from a dysregulated wound healing response.…”

Section: Introductionmentioning

confidence: 99%

“…*** P < .001 T A B L E 1 Histological evaluation of the anterior capsule Thickness grading scheme: 0-150 µm (−), 151-300 µm (+), 301-450 µm (+ +), 451-600 µm (+ + +), and >601 µm (+ + + +). Data for control and INJ were scored and published previously 7.…”

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confidence: 99%

“…*P < .05. Data for control and INJ were published previously 7. (INJ-TCP = injured and injected with cells cultured on tissue culture plastic (TCP), INJ-GEL = injured and injected with cells cultured on fibronectin-coated 1 kPa polyacrylamide gels) F I G U R E 5 Adipokine array results: Heatmap of normalized intensity ratio for Soft/Stiff and Soft-to-Stiff (1)/Stiff-to-Stiff (1) with statistical results from two-way analysis of variance (ANOVA) for stiffness and priming with post hoc Bonferroni corrected with False Discovery Rate using the Benjamini-Hochberg method.…”

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confidence: 99%

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Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

et al. 2020

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Fibrosis is driven by a misdirected cell response causing the overproduction of extracellular matrix and tissue dysfunction. Numerous pharmacological strategies have attempted to prevent fibrosis but have attained limited efficacy with some detrimental side effects. While stem cell treatments have provided more encouraging results, they have exhibited high variability and have not always improved tissue function. To enhance stem cell efficacy, we evaluated whether mechanical memory could direct cell response. We hypothesized that mechanically pre‐conditioning on a soft matrix (soft priming) will delay adipose‐derived stem cell (ASC) transition to a pro‐fibrotic phenotype, expanding their regenerative potential, and improving healing in a complex tissue environment. Primary ASCs isolated from rat and human subcutaneous fat exhibited mechanical memory, demonstrated by a delayed cell response to stiffness following two weeks of soft priming including decreased cell area, actin coherency, and extracellular matrix production compared to cells on stiff substrates. Soft primed ASCs injected into our rat model of post‐traumatic elbow contracture decreased histological evidence of anterior capsule fibrosis and increased elbow range‐of‐motion when evaluated by joint mechanics. These findings suggest that exploiting mechanical memory by strategically controlling the culture environment during cell expansion may improve the efficacy of stem cell‐based therapies targeting fibrosis.

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confidence: 89%

Section: Animal Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

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Increased volume and collagen crosslinks drive soft tissue contribution to post‐traumatic elbow contracture in an animal model

Dunham

Steenbock

Brinckmann

et al. 2020

Journal Orthopaedic Research

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Post‐traumatic joint contracture (PTJC) in the elbow is a biological problem with functional consequences. Restoring elbow motion after injury is a complex challenge because contracture is a multi‐tissue pathology. We previously developed an animal model of elbow PTJC using Long‐Evans rats and showed that the capsule and ligaments/cartilage were the primary soft tissues that caused persistent joint motion loss. The objective of this study was to evaluate tissue‐specific changes within the anterior capsule and lateral collateral ligament (LCL) that led to their contribution to elbow contracture. In our rat model of elbow PTJC, a unilateral surgery replicated damage that commonly occurs due to elbow dislocation. Following surgery, the injured limb was immobilized for 42 days. The capsule and LCL were evaluated after 42 days of immobilization or 42 days of immobilization followed by 42 days of free mobilization. We evaluated extracellular matrix protein biochemistry, non‐enzymatic collagen crosslink content, tissue volume with contrast‐enhanced micro‐computed tomography, and tissue mechanical properties. Increased collagen content, but not collagen density, was observed in both injured limb capsules and LCLs, which was consistent with the increased tissue volume. Injured limb LCLs exhibited decreased normalized maximum force, and both tissues had increased immature collagen cross‐links compared to control. Overall, increased tissue volume and immature collagen crosslinks in the capsule and LCL drive their contribution to elbow contracture in our rat model.

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Females and males exhibit similar functional, mechanical, and morphological outcomes in a rat model of posttraumatic elbow contracture

Reiter

Schott

Castile

et al. 2020

Journal Orthopaedic Research

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Posttraumatic joint contracture (PTJC) is a debilitating condition characterized by loss of joint motion following injury. Previous work in a rat model of elbow PTJC investigated disease etiology, progression, and recovery in only male animals; this study explored sex-based differences. Rat elbows were subjected to a unilateral anterior capsulotomy and lateral collateral ligament transection followed by 42 days of immobilization and 42 days of free mobilization. Grip strength and gait were collected throughout the free mobilization period while joint mechanical testing, microcomputed tomography and histological analysis were performed postmortem. Overall, few differences were seen between sexes in functional, mechanical, and morphological outcomes with PTJC being similarly debilitating in male and female animals. Functional measures of grip strength and gait showed that, while some baseline differences existed between sexes, traumatic injury produced similar deficits that remained significantly different long-term when compared to control animals. Similarly, male and female animals both had significant reductions in joint range of motion due to injury. Ectopic calcification (EC), which had not been previously evaluated in this injury model, was present in all limbs on the lateral side. Injury caused increased EC volume but did not alter mineral density regardless of sex.Furthermore, histological analysis of the anterior capsule showed minor differences between sexes for inflammation and thickness but not for other histological parameters. A quantitative understanding of sex-based differences associated with this injury model will help inform future therapeutics aimed at reducing or preventing elbow PTJC.

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Temporal Patterns of Motion in Flexion-extension and Pronation-supination in a Rat Model of Posttraumatic Elbow Contracture

Abstract: A rat model of posttraumatic elbow contracture quantitatively described contracture development/progression and reiterates the need for rehabilitation strategies that consider both flexion-extension and pronation-supination elbow motion.

Cited by 17 publications

References 42 publications

Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model

Increased volume and collagen crosslinks drive soft tissue contribution to post‐traumatic elbow contracture in an animal model

Females and males exhibit similar functional, mechanical, and morphological outcomes in a rat model of posttraumatic elbow contracture

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