Adipose stem cells exhibit mechanical memory and reduce fibrotic contracture in a rat elbow injury model.
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SUBMITTER: Dunham C
PROVIDER: S-EPMC8745456 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC8140065 | biostudies-literature
Project description:INTRODUCTION:Posttraumatic elbow contracture is clinically challenging because injury often disrupts multiple periarticular soft tissues. Tissue specific contribution to contracture, particularly muscle, remains poorly understood. METHODS:In this study we used a previously developed animal model of elbow contracture. After surgically inducing a unilateral soft tissue injury, injured limbs were immobilized for 3, 7, 21, and 42 days (IM) or for 42 IM with 42 days of free mobilization (42/42 IM-FM). Biceps brachii active/passive mechanics and morphology were evaluated at 42 IM and 42/42 IM-FM, whereas biceps brachii and brachialis gene expression was evaluated at all time points. RESULTS:Injured limb muscle exhibited significantly altered active/passive mechanics and decreased fiber area at 42 IM but returned to control levels by 42/42 IM-FM. Gene expression suggested muscle growth rather than a fibrotic response at 42/42 IM-FM. DISCUSSION:Muscle is a transient contributor to motion loss in our rat model of posttraumatic elbow contracture. Muscle Nerve 58:843-851, 2018.
| S-EPMC6296879 | biostudies-literature
Project description:BackgroundThe rates of elbow contracture and contracture release after surgically treated elbow trauma are poorly defined. The purpose of this study was to define the incidence of elbow contracture diagnosis and release after surgical treatment for elbow trauma.MethodsThe Humana insurance database was queried using the PearlDiver Patient Records Database between 2007 and 2017. Subjects were identified using International Classification of Diseases (ICD) codes in combination with Current Procedural Terminology codes and were included if they had a minimum of 1-year follow-up. Qualifying operative elbow trauma patients were queried for development of postoperative elbow contracture. Patient demographic characteristics, risk factors for elbow stiffness, and use of postoperative anticoagulation were recorded. Fracture severity was classified based on ICD-9 and ICD-10 codes. Logistic multivariate analysis was performed to determine independent risk factors for postoperative elbow contracture.ResultsThe study population included 10,672 patients who were surgically treated for elbow trauma. In total, 902 patients (8.4%) were diagnosed with a contracture following fracture. Of patients with a diagnosis of elbow contracture, 65 patients (7.2%) underwent contracture release. On average, time to contracture diagnosis was 3.6 months (SD 7 months) and time to contracture release was 8.4 months (SD 3.6 months). The use of postoperative anticoagulation, burn or head injury at the time of fracture, male sex, obesity, opioid use, and moderate or severe fracture severity were significantly associated with progression to elbow contracture.ConclusionThe development of elbow contracture after surgical treatment of elbow trauma has a relatively high incidence of 8.4%.
| S-EPMC6928310 | biostudies-literature
Project description:PurposeTo generate an evidence-based opioid-prescribing guideline by assessing the pattern of total opioid consumption and the factors that may predict opioid consumption following arthroscopic release of elbow contracture and to investigate whether the use of continuous passive motion (CPM), as compared to physical therapy (PT), was associated with a decrease in pain and opioid consumption after arthroscopic release of elbow contracture.MethodsData collected from a randomized controlled trial that compared continuous passive motion (CPM) (n = 24) to physical therapy (PT) (n = 27) following arthroscopic release of elbow contracture was analyzed for opioid use. Fifty-one participants recorded their daily opioid consumption in a postoperative diary for 90 days. Multivariate analysis was performed to identify factors associated with opioid use. Recommended quantities for postoperative prescription were generated using the 50th percentile for patients without and the 75th percentile for patients with factors associated with higher opioid use.ResultsThe median total opioid prescription was 437.5-mg morphine milligram equivalents (MMEs) (58 pills of 5 mg oxycodone) and the median total opioid consumption was 75 MMEs (10 pills of 5-mg oxycodone). Twenty-two percent of patients took no opioid medication, 53% took ≤10 pills, 69% took ≤20 pills and 75% took ≤30 pills. Predictors of higher opioid use were preoperative opioid use, age <60 years and inflammatory arthritis. The total opioid consumption appeared similar between the CPM and the PT group. Seventy-five percent of patient's home opioid requirements would be satisfied using the following guideline: Patients undergoing contracture release for osteoarthritis or post-traumatic contracture should be given a prescription for 10 pills of 5 mg oxycodone or its equivalent at discharge. Patients with inflammatory conditions or those taking preoperative opioids should be prescribed 30 pills of 5 mg oxycodone or its equivalent.ConclusionThis study suggests that most patients undergoing arthroscopic release of elbow contracture use relatively few opioid pills after surgery. Use of an evidence-based guideline could decrease opioid prescriptions substantially, while still effectively treating patients' pain.
| S-EPMC8689263 | biostudies-literature
Project description:BACKGROUND:Posttraumatic elbow contractures in children and adolescents are challenging to manage, and studies investigating surgical treatment are limited by the rarity of this condition. Small case series have shown variable gains in immediate and long-term elbow arc of motion after open surgical release. We reviewed our experience with open surgical release of posttraumatic elbow contracture in patients <21 years old at 2 institutions. METHODS:A retrospective chart review identified patients who underwent posttraumatic open elbow contracture release by 2 surgeons at 2 institutions between 2006 and 2013. Nontraumatic contractures and arthroscopic releases were excluded. Twenty-six patients were included in this study. Mean age at the time of injury was 12 years (5 to 19 y) and at the time of surgery was 14 years (7 to 20 y). Capsulotomy, osteoplasty, removal of hardware, ulnar nerve release or transposition, and ligament reconstruction were performed through medial and lateral approaches as indicated by the pathology. Ten patients had ligament repair or stabilization, and 16 patients used a continuous passive motion (CPM) postoperatively. Outcomes included active range of motion and complications. RESULTS:Mean time from injury to surgical release was 29 months. Mean postoperative follow-up was 42 months. Elbow active flexion-extension and forearm rotation arcs both increased significantly by a mean of 49 and 70 degrees, respectively, at final follow-up. A mean 85% of intraoperative flexion-extension arc was maintained at final follow-up. Ligament repair or reconstruction and the use of a postoperative CPM did not significantly change these outcomes. Outcomes were not significantly different if our contracture release was performed within a year from injury. Patients who had surgery before our contracture release had decreased restoration of forearm rotation after release. Complications included 2 recurrent contractures (1 used a CPM and 1 did not), and 2 postoperative ulnar neuropathies (1 used a CPM and 1 did not). CONCLUSIONS:Open contracture release for posttraumatic elbow contracture in an adolescent population can significantly improve active range of motion. LEVEL OF EVIDENCE:Level 3-therapeutic.
| S-EPMC6292736 | biostudies-literature
Project description:Abstract Medical devices made from poly(dimethylsiloxane) (PDMS)‐based silicone implants have been broadly used owing to their inert properties, biocompatibility, and low toxicity. However, long‐term implantation is usually associated with complications, such as capsular contracture due to excessive local inflammatory response, subsequently requiring implant removal. Therefore, modification of the silicone surface to reduce a risk of capsular contracture has attracted increasing attention. Human adipose‐derived stem cells (hASCs) are known to provide potentially therapeutic applications for tissue engineering, regenerative medicine, and reconstructive surgery. Herein, hASCs coating on a PDMS (hASC‐PDMS) or itaconic acid (IA)‐conjugated PDMS (hASC‐IA‐PDMS) surface is examined to determine its biocompatibility for reducing capsular contracture on the PDMS surface. In vitro cell cytotoxicity evaluation showed that hASCs on IA‐PDMS exhibit higher cell viability than hASCs on PDMS. A lower release of proinflammatory cytokines is observed in hASC‐PDMS and hASC‐IA‐PDMS compared to the cells on plate. Multiple factors, including in vivo mRNA expression levels of cytokines related to fibrosis; number of inflammatory cells; number of macrophages and myofibroblasts; capsule thickness; and collagen density following implantation in rats for 60 days, indicate that incorporated coating hASCs on PDMSs most effectively reduces capsular contracture. This study demonstrates the potential of hASCs coating for the modification of PDMS surfaces in enhancing surface biocompatibility for reducing capsular contracture of PDMS‐based medical devices.
| S-EPMC8780897 | biostudies-literature
Project description:OBJECTIVE:To investigate the protective effect of melatonin against myocardial ischemia reperfusion (IR) injury in isolated rat hearts and explore the underlying mechanisms. METHODS:The isolated hearts from 40 male SD rats were randomly divided into 4 groups (n=10): the control group, where the hearts were perfused with KH solution for 175 min; IR group, where the hearts were subjected to global ischemia for 45 min followed by reperfusion for 120 min; IR+melatonin (Mel+IR) group, where melatonin (5 ?mol/L) was administered to the hearts 1 min before ischemia and during the first 5 min of reperfusion, followed by 115 min of reperfusion; and IR+2, 3-butanedione monoxime (IR+BDM) group, where the hearts were treated with BDM (20 mmol/L) in the same manner as melatonin treatment. Myocardial injury in the isolated hearts was assessed based on myocardial injury area, caspase-3 activity, and expressions of cytochrome C and cleaved caspase-3 proteins. Cardiac contracture was assessed using HE staining and by detecting lactate dehydrogenase (LDH) activity and the content of cardiac troponin I (cTnI) in the coronary outflow, measurement of left ventricular end-diastolic pressure (LVEDP) and electron microscopy. The content of ATP in the cardiac tissue was also determined. RESULTS:Compared with those in the control group, the isolated hearts in IR group showed significantly larger myocardial injury area and higher caspase-3 activity and the protein expressions of cytochrome C and cleaved caspase-3 with significantly increased LDH activity and cTnI content in the coronary outflow and elevated LVEDP at the end of reperfusion; HE staining showed obvious fractures of the myocardial fibers and the content of ATP was significantly decreased in the cardiac tissue; electron microscopy revealed the development of contraction bands. In the isolated hearts with IR, treatment with Mel or BDM significantly reduced the myocardial injury area, caspase-3 activity, and protein expressions of cytochrome C and cleaved caspase-3, obviously inhibited LDH activity, lowered the content of cTnI and LVEDP, reduced myocardial fiber fracture, and increased ATP content in the cardiac tissue. Both Mel and BDM inhibited the formation of contraction bands in the isolated hearts with IR injury. CONCLUSIONS:Mel can alleviate myocardial IR injury in isolated rat hearts by inhibiting cardiac contracture, the mechanism of which may involve the upregulation of ATP in the cardiac myocytes to lessen the tear of membrane and reduce cell content leakage.
| S-EPMC7386215 | biostudies-literature
Project description:The etiology of elbow flexion contracture in children with brachial plexus birth palsy remains unclear. We hypothesized that the long head of the biceps brachii muscle assists with shoulder stabilization in children with brachial plexus birth palsy and that overactivity of the long head during elbow and shoulder activity is associated with an elbow flexion contracture.Twenty-one patients with brachial plexus birth palsy-associated elbow flexion contracture underwent testing with surface electromyography. Twelve patients underwent repeat testing with fine-wire electromyography. Surface electrodes were placed on the muscle belly, and fine-wire electrodes were inserted bilaterally into the long and short heads of the biceps brachii. Patients were asked to perform four upper extremity tasks: elbow flexion-extension, hand to head, high reach, and overhead ball throw. The mean duration of muscle activity in the affected limb was compared with that in the contralateral, unaffected limb, which was used as a control. Three-dimensional motion analysis, surface dynamometry, and validated function measures were used to evaluate upper extremity kinematics, elbow flexor-extensor muscle imbalance, and function.The mean activity duration of the long head of the biceps brachii muscle was significantly higher in the affected limb as compared with the contralateral, unaffected limb during hand-to-head tasks (p = 0.02) and high-reach tasks (p = 0.03). No significant differences in mean activity duration were observed for the short head of the biceps brachii muscle between the affected and unaffected limbs. Isometric strength of elbow flexion was not significantly higher than that of elbow extension in the affected limb (p = 0.11).Overactivity of the long head of the biceps brachii muscle is associated with and may contribute to the development of elbow flexion contracture in children with brachial plexus birth palsy. Elbow flexion contracture may not be associated with an elbow flexor-extensor muscle imbalance, as previously hypothesized. The negative impact of elbow flexion contracture on upper extremity function warrants future research in the development of preventive and therapeutic techniques to address elbow flexion contractures in children with brachial plexus birth palsy.
| S-EPMC3273876 | biostudies-other
Project description:Cancer patients often require radiotherapy (RTx) to enhance their survival. Unfortunately, RTx also damages nearby healthy non-cancer tissues, leading to progressive fibrotic soft-tissue injury, consisting of pain, contracture, tissue-breakdown, infection, and lymphoedema. Mechanisms underlying the clinically observed ability of fat grafting to ameliorate some of these effects, however, are poorly understood. It was hypothesized that RTx significantly alters fibroblast cell function and the paracrine secretome of adipose-derived stem cells (ADSC) may mitigate these changes. Methods:To investigate cellular changes resulting in the fibrotic side-effects of RTx, cultured normal human dermal fibroblasts (NHDF) were irradiated (10Gy), then studied using functional assays that reflect key fibroblast functions, and compared with unirradiated controls. RNA-Seq and targeted microarrays (with specific examination of TGF?) were performed to elucidate altered gene pathways. Finally, conditioned-media from ADSC was used to treat irradiated fibroblasts and model fat graft surgery. Results:RTx altered NHDF morphology, with cellular functional changes reflecting transition into a more invasive phenotype: increased migration, adhesion, contractility, and disordered invasion. Changes in genes regulating collagen and MMP homeostasis and cell-cycle progression were also detected. However, TGF? was not identified as a key intracellular regulator of the fibroblast response. Finally, treatment with ADSC-conditioned media reversed the RTx-induced hypermigratory state of NHDF. Conclusions:Our findings regarding cellular and molecular changes in irradiated fibroblasts help explain clinical manifestations of debilitating RTx-induced fibrosis. ADSC-secretome-mediated reversal indicated that these constituents may be used to combat the devastating side-effects of excessive unwanted fibrosis in RTx and other human fibrotic diseases.
| S-EPMC7253248 | biostudies-literature
Project description:BackgroundElbow flexion contracture is a well-known complication of brachial plexus birth palsy that adversely affects upper-extremity function. The prevalence, risk factors, and rate of progression of elbow flexion contracture associated with brachial plexus birth palsy have not been established, and the effectiveness of nonoperative treatment involving nighttime splinting or serial casting has not been well studied.MethodsThe medical records of 319 patients with brachial plexus birth palsy who had been seen at our institution between 1992 and 2009 were retrospectively reviewed to identify patients with an elbow flexion contracture (≥10°). The chi-square test for trend and the Kaplan-Meier estimator were used to evaluate risk factors for contracture, including age, sex, and the extent of brachial plexus involvement. Longitudinal models were used to estimate the rate of contracture progression and the effectiveness of nonoperative treatment.ResultsAn elbow flexion contracture was present in 48% (152) of the patients with brachial plexus birth palsy. The median age of onset was 5.1 years (range, 0.25 to 14.8 years). The contracture was ≥30° in 36% (fifty-four) of these 152 patients and was accompanied by a documented radial head dislocation in 6% (nine). The prevalence of contracture increased with increasing age (p < 0.001) but was not significantly associated with sex or with the extent of brachial plexus involvement. The magnitude of the contracture increased by 4.4% per year before treatment (p < 0.01). The magnitude of the contracture decreased by 31% when casting was performed (p < 0.01) but thereafter increased again at the same rate of 4.4% per year. The magnitude of the contracture did not improve when splinting was performed but the rate of increase thereafter decreased to <0.1% per year (p = 0.04).ConclusionsThe prevalence of elbow flexion contracture in children with brachial plexus birth palsy may be greater than clinicians perceive. The prevalence increased with patient age but was not significantly affected by sex or by the extent of brachial plexus involvement. Serial casting may initially improve severe contractures, whereas nighttime splinting may prevent further progression of milder contractures.
| S-EPMC3284859 | biostudies-literature