Optimized Modeled Myofascial Release Enhances Wound Healing in 3-Dimensional Bioengineered Tendons: Key Roles for Fibroblast Proliferation and Collagen Remodeling.

Objective: The purpose of this study was to evaluate the mechanisms of action of optimized myofascial release (MFR) on wound healing using a 3-dimensional human tissue construct.

Methods: Bioengineered tendons were cultured on a deformable matrix, wounded using a steel cutting tip, then strained in an acyclic manner with a modeled MFR paradigm at 103% magnitude for 5 minutes. Imaging and measurements of the width and wound size were performed daily, and the average tissue width of the entire bioengineered tendon was measured, and wound size and major and minor axes of the elliptical wound were additionally measured.

Modeled Osteopathic Manipulative Treatments: A Review of Their in Vitro Effects on Fibroblast Tissue Preparations.

A key osteopathic tenet involves the body's ability to self-heal. Osteopathic manipulative treatment (OMT) has been evolved to improve this healing capacity. The authors' in vitro work has focused on modeling 2 common OMT modalities: myofascial release (MFR) and counterstrain.

Duration and magnitude of myofascial release in 3-dimensional bioengineered tendons: effects on wound healing.

Context: Myofascial release (MFR) is one of the most commonly used manual manipulative treatments for patients with soft tissue injury. However, a paucity of basic science evidence has been published to support any particular mechanism that may contribute to reported clinical efficacies of MFR.

Objective: To investigate the effects of duration and magnitude of MFR strain on wound healing in bioengineered tendons (BETs) in vitro.

Biomechanical strain vehicles for fibroblast-directed skeletal myoblast differentiation and myotube functionality in a novel coculture.

Skeletal muscle functionality is governed by multiple stimuli, including cytokines and biomechanical strain. Fibroblasts embedded within muscle connective tissue respond to biomechanical strain by secreting cytokines that induce myoblast differentiation and, we hypothesize, regulate myotube function. A coculture was established to allow cross talk between fibroblasts in Bioflex wells and myoblasts on nondeformable coverslips situated above Bioflex wells.

In vitro biomechanical strain regulation of fibroblast wound healing.

Context: Strain-directed therapy such as vacuum compression and manual manipulative therapies are clinically effective, but their cellular and molecular mechanisms are not well understood.

Objective: To determine the effects of modeled myofascial release (MFR) on fibroblast wound healing and to investigate the potential role of nitric oxide (NO) in mediating these responses.

Methods: Using an in vitro scratch wound strain model, the authors investigated human fibroblast wound healing characteristics in response to injurious repetitive motion strain (RMS) and MFR.

Dosed myofascial release in three-dimensional bioengineered tendons: effects on human fibroblast hyperplasia, hypertrophy, and cytokine secretion.

Objective: The purpose of this study was to investigate potential differences of magnitudes and durations associated with dosed myofascial release (MFR) on human fibroblast proliferation, hypertrophy, and cytokine secretions.

Methods: Bioengineered tendons (BETs) attached to nylon mesh anchors were strained uniaxially using a vacuum pressure designed to model MFR varying in magnitudes (0%, 3%, 6%, 9%, and 12% elongation) and durations (0.5 and 1-5 minutes).

Mechanical strain applied to human fibroblasts differentially regulates skeletal myoblast differentiation.

Cyclic short-duration stretches (CSDS) such as those resulting from repetitive motion strain increase the risk of musculoskeletal injury. Myofascial release is a common technique used by clinicians that applies an acyclic long-duration stretch (ALDS) to muscle fascia to repair injury. When subjected to mechanical strain, fibroblasts within muscle fascia secrete IL-6, which has been shown to induce myoblast differentiation, essential for muscle repair.

Cyclic strain upregulates VEGF and attenuates proliferation of vascular smooth muscle cells.

Objective: Vascular smooth muscle cell (VSMC) hypertrophy and proliferation occur in response to strain-induced local and systemic inflammatory cytokines and growth factors which may contribute to hypertension, atherosclerosis, and restenosis. We hypothesize VSMC strain, modeling normotensive arterial pressure waveforms in vitro, results in attenuated proliferative and increased hypertrophic responses 48 hrs post-strain.

Methods: Using Flexcell Bioflex Systems we determined the morphological, hyperplastic and hypertrophic responses of non-strained and biomechanically strained cultured rat A7R5 VSMC.

In vitro modeling of repetitive motion injury and myofascial release.

Objective: In this study we modeled repetitive motion strain (RMS) and myofascial release (MFR) in vitro to investigate possible cellular and molecular mechanisms to potentially explain the immediate clinical outcomes associated with RMS and MFR.

Method: Cultured human fibroblasts were strained with 8h RMS, 60s MFR and combined treatment; RMS+MFR. Fibroblasts were immediately sampled upon cessation of strain and evaluated for cell morphology, cytokine secretions, proliferation, apoptosis, and potential changes to intracellular signaling molecules.

In vitro modeling of repetitive motion strain and manual medicine treatments: potential roles for pro- and anti-inflammatory cytokines.

Despite positive clinical outcomes documented post-treatment with a variety of manual medicine treatments (MMT), the underlying cellular mechanisms responsible remain elusive. We have developed an in vitro human fibroblast cell system used to model various biomechanical strains that human fibroblasts might undergo in response to repetitive motion strain (RMS) and MMT. Our data utilizing this system suggest that RMS induces disruption of cell-cell and cell-matrix contacts, which appear are reversed when a modeled MMT is also added to the treatment protocol.

Treadmill exercise training fails to reverse defects in glucose, insulin and muscle GLUT4 content in the db/db mouse model of diabetes.

Objective: Regular exercise is recommended for the treatment of type 2 diabetes because of the benefits on body weight and glycemic control. The present study was designed to compare the impact of voluntary wheel and forced treadmill running on the metabolic state in the db/db mouse model of type 2 diabetes. Our hypothesis is that voluntary exercise training reduces body weight, blood glucose and insulin levels and restores GLUT4 levels in skeletal muscle, whereas forced exercise training produces a greater effect.

Modeled repetitive motion strain and indirect osteopathic manipulative techniques in regulation of human fibroblast proliferation and interleukin secretion.

Context: Clinical studies have supported the efficacy of a variety of osteopathic manipulative techniques. However, an evidence base for the cellular mechanisms underlying these clinical findings is lacking.

Objective: To investigate human fibroblast proliferation and interleukin secretory profiles in response to modeled repetitive motion strain (RMS) and modeled indirect osteopathic manipulative techniques (IOMT).

Importance of strain direction in regulating human fibroblast proliferation and cytokine secretion: a useful in vitro model for soft tissue injury and manual medicine treatments.

Objective: Manual medicine treatments (MMTs) rely on biophysical techniques that use manually guided forces in numerous strain directions to treat injuries and somatic dysfunctions. Although clinical outcomes post-MMT are positive, the underlying cellular mechanisms responsible remain elusive. We previously described an in vitro model of strain-induced tissue injury and MMTs.

In vitro biophysical strain model for understanding mechanisms of osteopathic manipulative treatment.

Context: Normal physiologic movement, pathologic conditions, and osteopathic manipulative treatment (OMT) are believed to produce effects on the shape and proliferation of human fibroblasts. Studies of biophysically strained fibroblasts would be useful in producing a model of the cellular mechanisms underlying OMT.

Objective: To investigate the effects of acyclic in vitro biophysical strain on normal human dermal fibroblasts and observe potential changes in cellular shape and proliferation, as well as potential changes in cellular production of nitric oxide, interleukin (IL) 1beta, and IL-6.

Prevention of ischemic heart failure by exercise in spontaneously diabetic BB Wor rats subjected to insulin withdrawal.

Poor metabolic control resulting from insulin withdrawal in chronic type 1 diabetic rats results in ischemic heart failure. In the present study, we determined whether heart failure occurs in acute type 1 diabetic rats following insulin withdrawal and if prior exercise training can prevent this dysfunction. Four-week-old diabetic prone BB Wor rats were either sedentary or moderately exercised by daily treadmill running.

Altered insulin-like growth factor-1 and nitric oxide sensitivities in hypertension contribute to vascular hyperplasia.

Vascular medial thickening, a hallmark of hypertension, is associated with vascular smooth muscle cell (VSMC) hypertrophy and hyperplasia. Although the precise mechanisms responsible are elusive, we have shown that strain induced regulation of autocrine insulin-like growth factor-1 (IGF-1) and nitric oxide (NO) reciprocally modulate VSMC proliferation. Therefore, we investigated potential IGF-1 and NO abnormalities in young (10-week-old) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and their respective VSMC ex vivo.

Cyclic stretch induces vascular smooth muscle cell alignment via NO signaling.

We investigated the effects of cyclic stretch on vascular smooth muscle cell (VSMC) alignment and potential overlap of signaling modalities with stretch-induced proliferation. VSMC were subjected to graded stretch (1 Hz at 100-124% of resting length) for 48 h. Graded stretch resulted in graded VSMC alignment from a minimum of completely random orientation to a maximum of ~80-85 degrees to the stretch vector.

Identification of a functional Na+/Mg2+ exchanger in human trophoblast cells.

Background: Ionized magnesium levels are elevated in fetal blood compared with maternal blood, suggesting that the placenta may possess an active transport mechanism for magnesium. In the present study, we sought to determine the existence of an active transport mechanism for magnesium in the placenta using cultured trophoblast cells.

Methods: Using choriocarcinoma cells as a model system, we attempted to demonstrate the presence of a functional Na+/Mg2+ exchanger.