Mechanical Stimulation of Tendon Tissue Engineered Constructs: Effects on Construct Stiffness, Repair Biomechanics, and Their Correlation

2007 ◽  
Vol 129 (6) ◽  
pp. 848-854 ◽  
Author(s):  
Jason T. Shearn ◽  
Natalia Juncosa-Melvin ◽  
Gregory P. Boivin ◽  
Marc T. Galloway ◽  
Wendy Goodwin ◽  
...  
Keyword(s):  
Mechanical Stimulation ◽  
Maximum Stress ◽  
Tendon Repair ◽  
The Other ◽  
Maximum Force ◽  
In Vivo Studies ◽  
Peak Strain ◽  
Stimulation Of

The objective of this study was to determine how in vitro mechanical stimulation of tissue engineered constructs affects their stiffness and modulus in culture and tendon repair biomechanics 12weeks after surgical implantation. Using six female adult New Zealand White rabbits, autogenous tissue engineered constructs were created by seeding mesenchymal stem cells (0.1×106cells∕ml) in collagen gel (2.6mg∕ml) and combining both with a collagen sponge. Employing a novel experimental design strategy, four constructs from each animal were mechanically stimulated (one 1Hzcycle every 5min to 2.4% peak strain for 8h∕day for 2weeks) while the other four remained unstretched during the 2week culture period. At the end of incubation, three of the mechanically stimulated (S) and three of the nonstimulated (NS) constructs from each animal were assigned for in vitro mechanical testing while the other two autogenous constructs were implanted into bilateral full-thickness, full-length defects created in the central third of rabbit patellar tendons (PTs). No significant differences were found in the in vitro linear stiffnesses between the S (0.15±0.1N∕mm) and NS constructs (0.08±0.02N∕mm; mean±SD). However, in vitro mechanical stimulation significantly increased the structural and material properties of the repair tissue, including a 14% increase in maximum force (p=0.01), a 50% increase in linear stiffness (p=0.001), and 23–41% increases in maximum stress and modulus (p=0.01). The S repairs achieved 65%, 80%, 60%, and 40% of normal central PT maximum force, linear stiffness, maximum stress, and linear modulus, respectively. The results for the S constructs exceed values obtained previously by our group using the same animal and defect model, and to our knowledge, this is the first study to show the benefits of in vitro mechanical stimulation on tendon repair biomechanics. In addition, the linear stiffnesses for the construct and repair were positively correlated (r=0.56) as were their linear moduli (r=0.68). Such in vitro predictors of in vivo outcome hold the potential to speed the development of tissue engineered products by reducing the time and costs of in vivo studies.

scholarly journals Low Intensity Pulsed Ultrasound for Bone Tissue Engineering

Micromachines ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1488
Author(s):  
Colleen McCarthy ◽  
Gulden Camci-Unal
Keyword(s):  
Bone Formation ◽  
Bone Tissue ◽  
Mechanical Stimulation ◽  
Synergistic Effects ◽  
In Vivo Studies ◽  
Pulsed Ultrasound ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity

As explained by Wolff’s law and the mechanostat hypothesis, mechanical stimulation can be used to promote bone formation. Low intensity pulsed ultrasound (LIPUS) is a source of mechanical stimulation that can activate the integrin/phosphatidylinositol 3-OH kinase/Akt pathway and upregulate osteogenic proteins through the production of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). This paper analyzes the results of in vitro and in vivo studies that have evaluated the effects of LIPUS on cell behavior within three-dimensional (3D) titanium, ceramic, and hydrogel scaffolds. We focus specifically on cell morphology and attachment, cell proliferation and viability, osteogenic differentiation, mineralization, bone volume, and osseointegration. As shown by upregulated levels of alkaline phosphatase and osteocalcin, increased mineral deposition, improved cell ingrowth, greater scaffold pore occupancy by bone tissue, and superior vascularization, LIPUS generally has a positive effect and promotes bone formation within engineered scaffolds. Additionally, LIPUS can have synergistic effects by producing the piezoelectric effect and enhancing the benefits of 3D hydrogel encapsulation, growth factor delivery, and scaffold modification. Additional research should be conducted to optimize the ultrasound parameters and evaluate the effects of LIPUS with other types of scaffold materials and cell types.

CORTICOID PRODUCTION IN VITRO AS A TEST OF ADRENOCORTICAL FUNCTION IN RATS

1960 ◽  
Vol XXXIII (I) ◽  
pp. 59-66 ◽  
Author(s):  
J. van der Vies
Keyword(s):  
Adrenal Cortex ◽  
Adrenal Function ◽  
The Other ◽  
Adrenocortical Function ◽  
Experimental Conditions ◽  
Adrenal System ◽  
Other Hand ◽  
Stimulation Of

ABSTRACT Adrenal function in rats under various experimental conditions was studied by incubating the adrenals in vitro and determining the corticosteroid output during one hour. This in vitro corticoid production was reduced after hypophysectomy, hypothalamus-lesioning and treatment with hydrocortisone or with Nembutal and morphine. On the other hand, an increased production was observed following stimulation of the pituitary-adrenal system by exogenous histamine or corticotrophin. From these experiments it is concluded that the corticoid production in vitro reflects the activity of the adrenal cortex in vivo and hence can be used for the study of the latter function.

Extreme hyperinsulinemia unmasks insulin’s effect to stimulate protein synthesis in the human forearm

1998 ◽  
Vol 274 (6) ◽  
pp. E1067-E1074 ◽  
Author(s):  
Teresa A. Hillier ◽  
David A. Fryburg ◽  
Linda A. Jahn ◽  
Eugene J. Barrett
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
In Vivo Studies ◽  
Skeletal Muscle Protein ◽  
High Concentrations ◽  
Arterial Plasma ◽  
Stimulation Of

Insulin clearly stimulates skeletal muscle protein synthesis in vitro. Surprisingly, this effect has been difficult to reproduce in vivo. As in vitro studies have typically used much higher insulin concentrations than in vivo studies, we examined whether these concentration differences could explain the discrepancy between in vitro and in vivo observations. In 14 healthy volunteers, we raised forearm insulin concentrations 1,000-fold above basal levels while maintaining euglycemia for 4 h. Amino acids (AA) were given to either maintain basal arterial ( n = 4) or venous plasma ( n = 6) AA or increment arterial plasma AA by 100% ( n = 4) in the forearm. We measured forearm muscle glucose, lactate, oxygen, phenylalanine balance, and [3H]phenylalanine kinetics at baseline and at 4 h of insulin infusion. Extreme hyperinsulinemia strongly reversed postabsorptive muscle’s phenylalanine balance from a net release to an uptake ( P < 0.001). This marked anabolic effect resulted from a dramatic stimulation of protein synthesis ( P < 0.01) and a modest decline in protein degradation. Furthermore, this effect was seen even when basal arterial or venous aminoacidemia was maintained. With marked hyperinsulinemia, protein synthesis increased further when plasma AA concentrations were also increased ( P< 0.05). Forearm blood flow rose at least twofold with the combined insulin and AA infusion ( P< 0.01), and this was consistent in all groups. These results demonstrate an effect of high concentrations of insulin to markedly stimulate muscle protein synthesis in vivo in adults, even when AA concentrations are not increased. This is similar to prior in vitro reports but distinct from physiological hyperinsulinemia in vivo where stimulation of protein synthesis does not occur. Therefore, the current findings suggest that the differences in insulin concentrations used in prior studies may largely explain the previously reported discrepancy between insulin action on protein synthesis in adult muscle in vivo vs. in vitro.

scholarly journals Studies on Agranulocytosis. II. The Effect of Chlorpromazine upon the Influx of S35 L-Cystine and L-Methionine into Human Leukocytes

Blood ◽  
1960 ◽  
Vol 16 (4) ◽  
pp. 1456-1468 ◽  
Author(s):  
ANTHONY V. PISCIOTTA ◽  
SHIRLEY N. EBBE ◽  
MARY DALY ◽  
MONA RUWALDT ◽  
MILTON GLASER ◽  
...  
Keyword(s):  
Whole Blood ◽  
Blood Cells ◽  
The Other ◽  
In Vivo Studies ◽  
Human Leukocytes ◽  
In Vivo Administration

Abstract 1. When whole blood was incubated in vitro with S-35 L-cystine and L-methionine, the blood cells became radioactive. 2. Preincubation of whole blood from normals and from patients susceptible to agranulocytosis with chlorpromazine showed no effect upon uptake of S-35 L-cystine and L-methionine by leukocytes. 3. The in vivo administration of S-35 L-cystine was followed by the appearance of radioactive leukocytes. Peak radioactivity occurred in leukocytes in 5 to 12 days. 4. Pretreatment of test subjects with large doses of chlorpromazine did not block the uptake of S-35 L-cystine by leukocytes in vivo. Leukocytes of women showed an increase in the incorporation of S-35 L-cystine, in vivo. Studies performed in vivo on two persons during recovery from agranulocytosis showed enhanced uptake of L-cystine in one and a normal uptake in the other.

Evidence for a thyroid-inhibiting factor of adenohypophysial origin

1964 ◽  
Vol 206 (5) ◽  
pp. 1145-1150 ◽  
Author(s):  
Israel Posner ◽  
Enrique Pimentel
Keyword(s):  
Anterior Pituitary ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Pituitary Extract ◽  
Inhibiting Factor ◽  
Rat Thyroid ◽  
Tsh Stimulation ◽  
Stimulation Of

Thyroids of normal or thyroxine ( T4)-pretreated rats were incubated in vitro in a serum medium containing I131. It was found that the addition of either a whole rat adenohypophysis, a crude rat anterior pituitary extract, or of commercial bovine thyrotrophin (TSH) to the medium caused a slight stimulation of I131 release and no apparent stimulation but rather an immediate and considerable inhibition of thyroid-I131 uptake. Preincubation of rat thyroid with crude anterior pituitary extract resulted in a prolonged inhibitory effect on the thyroid-I131 uptake. In vivo studies showed that shortly after TSH administration a similar inhibition of uptake occurred in normal rats, although allowing 24 hr for TSH stimulation brought about no change in iodine uptake in thyroids of normal and a marked increase in uptake by thyroids of T4-pretreated rats. The inhibition of thyroid-I131 uptake was assumed to have been caused either by TSH itself, or by a thyroid-inhibiting factor of adenohypophysial origin present in commercial TSH preparations as a contaminant.

Multiscale Modeling of Trabecular Bone Marrow: Understanding the Micromechanical Environment of Mesenchymal Stem Cells During Osteoporosis

2015 ◽  
Vol 137 (1) ◽  
Author(s):  
T. J. Vaughan ◽  
M. Voisin ◽  
G. L. Niebur ◽  
L. M. McNamara
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Trabecular Bone ◽  
Mechanical Stimulation ◽  
Cell Level ◽  
Mechanical Environment ◽  
Stimulation Of

Mechanical loading directs the differentiation of mesenchymal stem cells (MSCs) in vitro and it has been hypothesized that the mechanical environment plays a role in directing the cellular fate of MSCs in vivo. However, the complex multicellular composition of trabecular bone marrow means that the precise nature of mechanical stimulation that MSCs experience in their native environment is not fully understood. In this study, we developed a multiscale model that discretely represents the cellular constituents of trabecular bone marrow and applied this model to characterize mechanical stimulation of MCSs in vivo. We predicted that cell-level strains in certain locations of the trabecular marrow microenvironment were greater in magnitude (maximum ε12 = ∼24,000 με) than levels that have been found to result in osteogenic differentiation of MSCs in vitro (>8000 με), which may indicate that the native mechanical environment of MSCs could direct cellular fate in vivo. The results also showed that cell–cell adhesions could play an important role in mediating mechanical stimulation within the MSC population in vivo. The model was applied to investigate how changes that occur during osteoporosis affected mechanical stimulation in the cellular microenvironment of trabecular bone marrow. Specifically, a reduced bone volume (BV) resulted in an overall increase in bone deformation, leading to greater cell-level mechanical stimulation in trabecular bone marrow (maximum ε12 = ∼48,000 με). An increased marrow adipocyte content resulted in slightly lower levels of stimulation within the adjacent cell population due to a shielding effect caused by the more compliant behavior of adipocytes (maximum ε12 = ∼41,000 με). Despite this reduction, stimulation levels in trabecular bone marrow during osteoporosis remained much higher than those predicted to occur under healthy conditions. It was found that compensatory mechanobiological responses that occur during osteoporosis, such as increased trabecular stiffness and axial alignment of trabeculae, would be effective in returning MSC stimulation in trabecular marrow to normal levels. These results have provided novel insight into the mechanical stimulation of the trabecular marrow MSC population in both healthy and osteoporotic bone, and could inform the design three-dimensional (3D) in vitro bioreactor strategies techniques, which seek to emulate physiological conditions.

scholarly journals In Vitro and In Vivo Activities of Syn2836, Syn2869, Syn2903, and Syn2921: New Series of Triazole Antifungal Agents

2001 ◽  
Vol 45 (9) ◽  
pp. 2420-2426 ◽  
Author(s):  
S. M. Salama ◽  
H. Atwal ◽  
A. Gandhi ◽  
J. Simon ◽  
M. Poglod ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Survival Rates ◽  
Systemic Infection ◽  
Kinetic Studies ◽  
The Other ◽  
In Vivo Studies ◽  
Infection Model ◽  
Time Kill

ABSTRACT The in vitro and in vivo activities of four azole compounds belonging to a new series of 2(2,4-difluorophenyl)-3-(4-substituted piperazin-1-yl)-1-(1,2,4-triazol-1-yl) butanol antifungal agents is described. The compounds were selected from a library of azole compounds synthesized by our group. The in vitro activities of Syn2869, Syn2836, Syn2903, and Syn2921 against a panel of over 240 recently collected clinical isolates of yeast and molds were determined, and the results were compared with those obtained with fluconazole (FLC), itraconazole (ITC), and amphotericin B (AMB). The MICs at which 90% of the isolates were inhibited (MIC90s) for the four test compounds for strains of Candida spp. ranged from <0.048 to 0.78 μg/ml. All compounds were also active against FLC-resistant Candida albicans and otherCandida sp. strains. Moreover, MIC90s for strains of Cryptococcus neoformans,Aspergillus spp., Trichophyton spp., andMicrosporum spp. were also low and ranged from <0.048 to 0.39 μg/ml. The test compounds produced a fungistatic pattern during the time-kill kinetic studies. In vivo studies indicated that all four test compounds have good efficacies against C. albicans in a murine systemic infection model and significantly improved the survival rates of the infected mice. The results for Syn2903 were similar to those for FLC, while the other compounds were slightly less effective but had ranges of activities similar to the range of activity of ITC. The compounds were also evaluated against anAspergillus fumigatus systemic infection. Syn2903 was also superior to ITC, whereas the efficacy data for the other compounds were similar to those for ITC. It was concluded from the data generated for this new series of azole compounds in the studies described above that further pharmacokinetic and toxicologic evaluations are warranted prior to selection of a candidate compound for preclinical testing.

The Myogenic Response

Physiology ◽  
1991 ◽  
Vol 6 (1) ◽  
pp. 41-42 ◽  
Author(s):  
Paul C. Johnson
Keyword(s):  
Ion Channel ◽  
Experimental Evidence ◽  
Adrenergic Receptors ◽  
In Vitro Studies ◽  
In Vivo Studies ◽  
Myogenic Response ◽  
Intravascular Pressure ◽  
Stimulation Of

New experimental evidence from in vitro studies supports the concept that small arterial vessels and arterioles constrict in response to intravascular pressure elevation (myogenic response). A stretch-dependent ion channel may be involved. In vivo studies show that stimulation of α-adrenergic receptors enhances the response, suggesting that the myogenic mechanism may be partly under autonomic control.

Mechanical Stimulation of Tissue Engineered Tendon Constructs: Effect of Scaffold Materials

2007 ◽  
Vol 129 (6) ◽  
pp. 919-923 ◽  
Author(s):  
Victor S. Nirmalanandhan ◽  
Matthew R. Dressler ◽  
Jason T. Shearn ◽  
Natalia Juncosa-Melvin ◽  
Marepalli Rao ◽  
...  
Keyword(s):  
Mechanical Stimulation ◽  
Type I Collagen ◽  
Collagen Gel ◽  
Mechanical Stimulus ◽  
Collagen Sponge ◽  
The Other ◽  
Type I ◽  
Peak Strain ◽  
Bovine Collagen

Our group has shown that numerous factors can influence how tissue engineered tendon constructs respond to in vitro mechanical stimulation. Although one study showed that stimulating mesenchymal stem cell (MSC)–collagen sponge constructs significantly increased construct linear stiffness and repair biomechanics, a second study showed no such effect when a collagen gel replaced the sponge. While these results suggest that scaffold material impacts the response of MSCs to mechanical stimulation, a well-designed intra-animal study was needed to directly compare the effects of type-I collagen gel versus type-I collagen sponge in regulating MSC response to a mechanical stimulus. Eight constructs from each cell line (n=8 cell lines) were created in specially designed silicone dishes. Four constructs were created by seeding MSCs on a type-I bovine collagen sponge, and the other four were formed by seeding MSCs in a purified bovine collagen gel. In each dish, two cell-sponge and two cell-gel constructs from each line were then mechanically stimulated once every 5min to a peak strain of 2.4%, for 8h∕day for 2 weeks. The other dish remained in an incubator without stimulation for 2 weeks. After 14 days, all constructs were failed to determine mechanical properties. Mechanical stimulation significantly improved the linear stiffness (0.048±0.009 versus 0.015±0.004; mean±SEM (standard error of the mean ) N/mm) and linear modulus (0.016±0.004 versus 0.005±0.001; mean±SEM MPa) of cell-sponge constructs. However, the same stimulus produced no such improvement in cell-gel construct properties. These results confirm that collagen sponge rather than collagen gel facilitates how cells respond to a mechanical stimulus and may be the scaffold of choice in mechanical stimulation studies to produce functional tissue engineered structures.

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