Rotator cuff training with upper extremity blood flow restriction produces favorable adaptations in division IA collegiate pitchers: a randomized trial.

BACKGROUND: Recent evidence indicates that combined upper extremity blood flow restriction (BFR, applied distally to the shoulder) and low-load resistance exercise (LIX) augments clinically meaningful responses in shoulder region tissues proximal to the occlusion site. The purpose of this investigation was to determine the efficacy of BFR-LIX for the shoulder when added to standard offseason training in Division IA collegiate baseball pitchers. We hypothesized that BFR-LIX would augment training-induced increases in shoulder-region lean mass, rotator cuff strength, and endurance. As secondary outcomes, we sought to explore the impact of BFR-LIX rotator cuff training on pitching mechanics. METHODS: Twenty-eight collegiate baseball pitchers were randomized into 2 groups (BFRN = 15 and non-BFR [NOBFR]N = 13) that, in conjunction with offseason training, performed 8 weeks of shoulder LIX (Throwing arm only; 2/week, 4 sets [30/15/15/fatigue], 20% isometric max) using 4 exercises (cable external and internal rotation [ER/IR], dumbbell scaption, and side-lying dumbbell ER). The BFR group also trained with an automated tourniquet on the proximal arm (50% occlusion). Regional lean mass (dual-energy x-ray absorptiometry), rotator cuff strength (dynamometry: IR 0 & 90, ° ER 0 & 90, ° Scaption, Flexion), and fastball biomechanics were assessed pre and post-training. Achievable workload (sets × reps × resistance) was also recorded. An ANCOVA (covaried on baseline measures) repeated on training timepoint was used to detect within-group and between-group differences in outcome measures (α = 0.05). For significant pairwise comparisons, effect size (ES) was calculated using a Cohen's d statistic and interpreted as: 0-0.1, negligible; 0.1-0.3, small; 0.3-0.5, moderate; 0.5-0.7, large; >0.7, and very large (VL). RESULTS: Following training, the BFR group experienced greater increases in shoulder-region lean mass (BFR: ↑ 227 ± 60g, NOBFR: ↑ 75 ± 37g, P = .018, ES = 1.0 VL) and isometric strength for IR 90 ° (↑ 2.4 ± 2.3 kg, P = .041, ES = 0.9VL). The NOBFR group experienced decreased shoulder flexion ↓ 1.6 ± 0.8 kg, P = .007, ES = 1.4VL) and IR at 0 ° ↓ 2.9 ± 1.5 kg, P = .004, ES = 1.1VL). The BFR group had a greater increase in achievable workload for the scaption exercise (BFR: ↑ 190 ± 3.2 kg, NOBFR: ↑ 90 ± 3.3 kg, P = .005, ES = 0.8VL). Only the NOBFR group was observed to experience changes in pitching mechanics following training with increased shoulder external rotation at lead foot contact (↑ 9.0° ± 7.9, P = .028, ES = 0.8VL) as well as reduced forward ↓ 3.6° ± 2.1, P = .001, ES = 1.2VL) and lateral ↓ 4.6° ± 3.4, P = .007, ES = 1.0VL) trunk tilt at ball release. CONCLUSION: BFR-LIX rotator cuff training performed in conjunction with a collegiate offseason program augments increases in shoulder lean mass as well as muscular endurance while maintaining rotator cuff strength and possibly pitching mechanics in a manner that may contribute to favorable outcomes and injury prevention in baseball pitching athletes.

Platelet-rich plasma enhances mechanical strength of strattice in rat model of ventral hernia repair.

Incisional hernia is a common complication of hernia repair despite the development of various synthetic and bio-synthetic repair materials. Poor long-term mechanical strength, leading to high recurrence rates, has limited the use of acellular dermal matrices (ADMs) in ventral hernia repair (VHR). Biologically derived meshes have been an area of increasing interest. Still these materials bring the risk of more aggressive immune response and fibrosis in addition to the mechanical failures suffered by the synthetic materials. Platelet-rich plasma (PRP), a growth-factor-rich autologous blood product, has been shown to improve early neovascularization, tissue deposition, and to decrease the rates of recurrence. Here, we demonstrate that PRP promotes the release of growth factors stromal derived factor (SDF)-1, transforming growth factor-beta, and platelet-derived growth factor in a dose-dependent manner. Additionally, we utilize an aortic ring angiogenesis assay to show that PRP promotes angiogenesis in vitro. A rat model of VHR using StratticeTM ADM demonstrates similar findings in vivo, corresponding with the increased expression of vascular endothelial growth factor and collagen type 1 alpha 1. Finally, we show that the molecular and cellular activity initiated by PRP results in an increased mechanical stiffness of the hernia repair mesh over time. Collectively, these data represent an essential step in demonstrating the utility and the mechanism of platelet-derived plasma in biomaterial-aided wound healing and provide promising preclinical data that suggest such materials may improve surgical outcomes.

A low-cost, novel endoscopic repeated-access port for small animal research.

Repeated endoscopic access to the abdominal cavity of animal models is useful for a variety of research applications. However, repeated surgical access may affect the welfare of the animal and compromise results. We present the design and benchtop manufacturing process for a self-sealing endoscopic port requiring surgical incision only at implantation. It can be used for repeated body cavity access over a long time period. This device reduces costs, animals required for a given study, and potential suffering for each animal. This novel endoscopic port is designed for low-cost benchtop manufacturing without expensive equipment such as injection molding facilities. Devices manufactured using the method described in this work have been implanted successfully in hen models for investigation of ovarian cancer for over two years. All work followed Texas A&M University institutional guidelines and was covered under Animal Use Protocol 2017-0172, approved by TAMU Animal Care and Use Committee (IACUC). This method can be translated to produce similar devices for use in other small animal models besides the galline model used in this work. This method can be used to produce devices for slightly different purposes than repeated endoscopic access, such as production of an entry port for surgical tools.

The Usefulness of Meta-Analyses to Hip and Knee Surgeons.

BACKGROUND: Comprehensive systematic reviews of results from homogenous or heterogeneous clinical trials, meta-analyses are used to summarize and to interpret studies. Proponents believe that their use can increase study power and improve precision results. Critics emphasize that heterogeneity between studies and bias of individual studies compromise the value of results. The methodology of meta-analyses has improved over time, utilizing statistical analysis to reduce bias and examining heterogeneity. With an increasing trend of meta-analyses in orthopaedic literature, this study aimed to investigate quality and clinical utility of meta-analyses for total knee arthroplasty and total hip arthroplasty. METHODS: A systematic review of total knee arthroplasty and total hip arthroplasty meta-analyses in 3 major orthopaedic journals from January 2000 to August 2017 was performed. Three authors independently reviewed eligible meta-analyses. A quality assessment was conducted using the Oxman-Guyatt Index. Reporting quality was assessed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Two high-volume, fellowship-trained, attending surgeons specializing in total hip arthroplasty and total knee arthroplasty independently, in a blinded fashion, reviewed 24 of the highest-scored meta-analyses. RESULTS: There were 114 studies meeting eligibility criteria, 25 published from 2000 to 2009 and 89 published from 2010 to 2017, a 3.6-fold increase. The mean Oxman-Guyatt Index score was 3.89 points, with 12 high-quality studies, 87 moderate-quality studies, and 15 low-quality studies. The mean PRISMA score for all meta-analyses was 22.2 points, with 79% classified as low to moderate. Only 23 studies listed the Level of Evidence, and 8 were Level-I studies and 9 were Level-II studies. Studies with >15 randomized controlled trials were associated with higher PRISMA and Oxman-Guyatt Index scores. In 12 articles, we were unable to decipher the types of studies included. Only 39.4% of studies showed the risk of bias. Of the 24 studies identified as high quality per the PRISMA statement, 71% were determined to be either clinically unimportant or inconclusive. CONCLUSIONS: The number of total hip arthroplasty and total knee arthroplasty meta-analyses has markedly increased over the past decades. The majority of published meta-analyses from 3 major orthopaedic journals were not performed in accordance with established PRISMA guidelines. CLINICAL RELEVANCE: Many published meta-analyses are low to moderate quality, and clinicians should cautiously draw conclusions from poorly executed meta-analyses.

Biomimetic collagen/elastin meshes for ventral hernia repair in a rat model.

Ventral hernia repair remains a major clinical need. Herein, we formulated a type I collagen/elastin crosslinked blend (CollE) for the fabrication of biomimetic meshes for ventral hernia repair. To evaluate the effect of architecture on the performance of the implants, CollE was formulated both as flat sheets (CollE Sheets) and porous scaffolds (CollE Scaffolds). The morphology, hydrophylicity and in vitro degradation were assessed by SEM, water contact angle and differential scanning calorimetry, respectively. The stiffness of the meshes was determined using a constant stretch rate uniaxial tensile test, and compared to that of native tissue. CollE Sheets and Scaffolds were tested in vitro with human bone marrow-derived mesenchymal stem cells (h-BM-MSC), and finally implanted in a rat ventral hernia model. Neovascularization and tissue regeneration within the implants was evaluated at 6weeks, by histology, immunofluorescence, and q-PCR. It was found that CollE Sheets and Scaffolds were not only biomechanically sturdy enough to provide immediate repair of the hernia defect, but also promoted tissue restoration in only 6weeks. In fact, the presence of elastin enhanced the neovascularization in both sheets and scaffolds. Overall, CollE Scaffolds displayed mechanical properties more closely resembling those of native tissue, and induced higher gene expression of the entire marker genes tested, associated with de novo matrix deposition, angiogenesis, adipogenesis and skeletal muscles, compared to CollE Sheets. Altogether, this data suggests that the improved mechanical properties and bioactivity of CollE Sheets and Scaffolds make them valuable candidates for applications of ventral hernia repair. STATEMENT OF SIGNIFICANCE: Due to the elevated annual number of ventral hernia repair in the US, the lack of successful grafts, the design of innovative biomimetic meshes has become a prime focus in tissue engineering, to promote the repair of the abdominal wall, avoid recurrence. Our meshes (CollE Sheets and Scaffolds) not only showed promising mechanical performance, but also allowed for an efficient neovascularization, resulting in new adipose and muscle tissue formation within the implant, in only 6weeks. In addition, our meshes allowed for the use of the same surgical procedure utilized in clinical practice, with the commercially available grafts. This study represents a significant step in the design of bioactive acellular off-the-shelf biomimetic meshes for ventral hernia repair.

Fabrication of macromolecular gradients in aligned fiber scaffolds using a combination of in-line blending and air-gap electrospinning.

Although a variety of fabrication methods have been developed to generate electrospun meshes with gradient properties, no platform has yet to achieve fiber alignment in the direction of the gradient that mimics the native tendon-bone interface. In this study, we present a method combining in-line blending and air-gap electrospinning to address this limitation in the field. A custom collector with synced rotation permitted fiber collection with uniform mesh thickness and periodic copper wires were used to induce fiber alignment. Two poly(ester urethane ureas) with different hard segment contents (BPUR 50, BPUR 10) were used to generate compositional gradient meshes with and without fiber alignment. The compositional gradient across the length of the mesh was characterized using a fluorescent dye and the results indicated a continuous transition from the BPUR 50 to the BPUR 10. As expected, the fiber alignment of the gradient meshes induced a corresponding alignment of adherent cells in static culture. Tensile testing of the sectioned meshes confirmed a graded transition in mechanical properties and an increase in anisotropy with fiber alignment. Finite element modeling was utilized to illustrate the gradient mechanical properties across the full length of the mesh and lay the foundation for future computational development work. Overall, these results indicate that this electrospinning method permits the fabrication of macromolecular gradients in the direction of fiber alignment and demonstrate its potential for use in interfacial tissue engineering. STATEMENT OF SIGNIFICANCE: The native tendon-bone interface contains a gradient of properties that ensures stability of the joint. Without this transition, failure can occur due to stress concentration at the bone insertion site. Electrospinning is a method commonly used to produce fibrous grafts with gradient properties; however, no current method allows for gradients in the direction of fiber alignment. This work details a novel electrospinning method to produce gradients in the direction of fiber alignment in order to better mimic transitional zones and improve regeneration of the tendon-bone interface. In addition to the biomechanical gradients demonstrated here, this method may also be used to generate gradients of macromolecular, biochemical, and cellular cues with broad potential utility in tissue engineering.

In vitro biomechanical comparison of 3.5 mm LC-DCP/intramedullary rod and 5 mm clamp-rod internal fixator (CRIF)/intramedullary rod fixation in a canine femoral gap model.

OBJECTIVE: To compare the biomechanical properties of clamp rod internal fixation (CRIF)/rod and LC-DCP/rod constructs in a canine femoral gap model. STUDY DESIGN: Cadaveric biomechanical study. SAMPLE POPULATION: Canine femora (n = 10 pair). METHODS: Femora with 40 mm ostectomies were assigned to LC-DCP/rod or CRIF/rod treatment groups. Five construct pairs had 4-point bending and 5 pairs had torsional loading. Construct stiffness, strength, and bending angle at failure or permanent angular deformation (torsional loading) were determined. Statistical comparisons were performed using Student t tests; significance was set at P ≤ .05. RESULTS: There was significantly greater permanent angular deformation, or residual twist, in the CRIF/rod constructs (23.1 ± 0.89°) compared with LC-DCP/rod constructs (7.47 ± 2.08°). Whereas there was no significant difference in torsional stiffness of these constructs at torsional loads <4.92 N m (P = .819), LC-DCP/rod constructs had significantly greater torsional stiffness (0.303 ± 0.079 N m/°) and strength (11.546 ± 2.79 N m) than CRIF/rod construct stiffness (0.06 ± 0.013 N m/°) and strength (6.078 ± 0.527 N m) at torsional loads >4.92 N m. Differences in stiffness and strength in 4-point bending were not statistically significant. CONCLUSIONS: LC-DCP/rod constructs had significantly less permanent angular deformation than CRIF/rod constructs. CRIF/rod constructs became less stiff as torsional load was increased, thus the LC-DCP/rod constructs had significantly greater torsional stiffness and strength under high torsional loads. LC-DCP/rod and CRIF/rod constructs performed similarly under 4-point bend loading conditions.

A device to study the effects of stretch gradients on cell behavior.

Mechanical forces are key regulators of cell function with varying loads capable of modulating behaviors such as alignment, migration, phenotype modulation, and others. Historically, cell-stretching experiments have employed mechanically simple environments (e.g., uniform uniaxial or equibiaxial stretches). However, stretch distributions in vivo can be highly non-uniform, particularly in cases of disease or subsequent to interventional treatments. Herein, we present a cell-stretching device capable of subjecting cells to controllable gradients in biaxial stretch via radial deformation of circular elastomeric membranes. By including either a defect or a rigid fixation at the center of the membrane, various gradients are generated. Capabilities of the device were quantified by tracking marked positions of the membrane while applying various loads, and experimental feasibility was assessed by conducting preliminary experiments with 3T3 fibroblasts and 10T1/2 cells subjected to 24 h of cyclic stretch. Quantitative real-time PCR was used to measure changes in mRNA expression of a profile of genes representing the major smooth muscle phenotypes. Genes associated with the contractile state were both upregulated (e.g., calponin) and downregulated (e.g., α-2-actin), and genes associated with the synthetic state were likewise both upregulated (e.g., SKI-like oncogene) and downregulated (e.g., collagen III). In addition, cells aligned with an orientation perpendicular to the maximal stretch direction. We have developed an in vitro cell culture device that can produce non-uniform stretch environments similar to in vivo mechanics. Cells stretched with this device showed alignment and altered mRNA expression indicative of phenotype modulation. Understanding these processes as they relate to in vivo pathologies could enable a more accurately targeted treatment to heal or inhibit disease, either through implantable device design or pharmaceutical approaches.

Effects of stent design and atherosclerotic plaque composition on arterial wall biomechanics.

PURPOSE: To examine the solid mechanical effects of varying stent design and atherosclerotic plaque stiffness on the biomechanical environment induced in a diseased artery wall model. METHODS: Computational modeling techniques were employed to investigate the final radius of the lumen and artery wall stresses after stent implantation. Two stent designs were studied (one stiff and one less stiff). The stenotic artery was modeled as an axisymmetrical diseased vessel with a 20% stenosis by diameter. The material properties of the diseased tissue in the artery models varied. Atherosclerotic plaques half as stiff (0.5x), of equal stiffness (1.0x), or twice as stiff (2.0x) as the artery wall were investigated. RESULTS: Final lumen radius was dependent on stent design, and the stiffer stent deformed the artery to an approximately 10% greater radius than the more compliant design. Alternatively, circumferential stress levels were dependent on both stent design and plaque material properties. Overall, the stiffer stent subjected the artery wall to much higher stress values than the more compliant design, with differences in peak values of 0.50, 0.31, and 0.09 MPa for the 2.0x, 1.0x, and 0.5x stiff plaques, respectively. CONCLUSION: Evidence suggests that a judicious choice of stent design can minimize stress while maintaining a patent lumen in stenotic arteries. If confronted with a rigid, calcified plaque, stent design is more important, as design differences can impose dramatically different stress fields, while still providing arterial patency. Alternatively, stent design is not as much of an issue when treating a soft, lipid-laden plaque, as stress fields do not vary significantly among stent designs.