Loading, lengthening, healing.

You are doing an excellent job of finding interesting research marinera. As this thread is nearly 200 posts long, it may be worth (at some time) creating an ‘article’ type thread/post to just present all the research (without any comments on it).

It would be a shame if all this research information became ‘lost’ in this long post.

Thank you, firegoat, it’s a nice advice. I was thinking to add the references listed here in the penismith thread :

Science of PE Posts and Threads. Link Here!

but it could appear like an "invasion".

Any idea on how to call such a studies-collection thread? Maybe "Interesting studies"?

Marinera,

Thanks for finding these articles and posting the conclusions on them. A lot of them go over my head since some of them I don’t understand due to the terms they use.

Good job! :)

Many thanks for appreciations. I was commenting these articles because many members with less patience than I have could be confused. What really can confuse mostly is the fact that even authors of those studies aren’t using the same terms when speaking about the same things: we have seen, in example, that some authors call ‘dynamic creep’ what others scientists call ‘fatigue’, saying that it’s a completely different phenomenon.

But of course, my comments could be out-of-place, so everyone should read and try to understand this studies without any ‘interpreter’ or such, as fg in someway suggested.

Another thing to note is: although tendons and ligaments are subjects by far more studied than penile tissues, still there is an incredible lack of knowledge about them, and a lot of controversial thinking about the best ways to make CT grow/lengthen/heal.

So, our attempts to better understand scientific basis of PE are even harder that we could believe at starting.

penismiths thread would be a very good place to link all the articles. I don’t think he’d mind the invasion; it’s what he started the thread for. You could always PM him if you wanted to be sure. :)

Thank you again, fg. I’ll ask to Penismith.

This article is interesting because explain that CT reaction rate and speed of strain is not uniform:

The load-elongation curve of tendon collagen has a characteristic shape with, initially, an increasing slope, corresponding to an increasing stiffness, followed by yielding and then fracture. Cross-link-deficient collagen produces a quite different curve with a marked plateau appearing in some cases, where the length of the tendon increases at constant stress. With the use of in situ X-ray diffraction, it was possible to measure simultaneously the elongation of the collagen fibrils inside the tendon and of the tendon as a whole. The overall strain of the tendon was always larger than the strain in the individual fibrils, which demonstrates that some deformation is taking place in the matrix between fibrils. Moreover, the ratio of fibril strain to tendon strain was dependent on the applied strain rate. When the speed of deformation was increased, this ratio increased in normal collagen but generally decreased in cross-link-deficient collagen, correlating to the appearance of a plateau in the force-elongation curve indicating creep. We proposed a simple structural model, which describes the tendon at a hierarchical level, where fibrils and interfibrillar matrix act as coupled viscoelastic systems. All qualitative features of the strain-rate dependence of both normal and cross-link-deficient collagen can be reproduced within this model. This complements earlier models that considered the next smallest level of hierarchy, describing the deformation of collagen fibrils in terms of changes in their molecular packing.

http://www.jsto … org/pss/3066852

Nonlinear Ligament Viscoelasticity

PAOLO PROVENZANO,1 RODERIC LAKES,2 THOMAS KEENAN,1 and RAY VANDERBY, JR.1
1Department of Biomedical Engineering and Division of Orthopedic Surgery, University of Wisconsin–Madison, Madison, WI and
2Department of Biomedical Engineering and Department of Engineering Physics, University of Wisconsin–Madison,

INTRODUCTION
Ligaments are viscoelastic and thus, display time dependent
and load-history-dependent mechanical behavior.
……….
It is also of interest to know the difference in performance between healthy and damaged ligaments.
For these reasons it is important to understand viscoelastic behavior throughout its functional range.
Prior studies of ligament viscoelasticity often consist of a creep or relaxation test at one load or strain level.

Force versus displacement curves at constant strain rates demonstrate that ligament is nonlinear. The reason is that collagen fibers are recruited as load increases. The stress–strain curves of ligament display a ‘‘toe’’ region where fibers straighten and elongate in a strain-stiffening fashion until the fibers are no longer crimped. At that point the fibers elongate, giving rise to the linear segment of the stress–strain curve. It is this toe region and the lower strain portion of the linear region that is addressed in this study.

…………..
The onset of mechanical damage in the rat MCL has been shown by Provenzano et al. to be at 5.1% strain after experimental preload ex vivo.
At strains below this threshold the tissue will return to its original, preloaded length after a recovery time equal to ten times the duration of tissue loading during the test. Previous studies have not studied viscoelastic behavior at multiple deformation or load levels throughout the physiologic domain of recoverable loading.

Researchers have tried to quantify fundamental viscoelastic behavior with phenomenological models including
linear, quasilinear, and nonlinear. Linear viscoelasticity is expressed in terms of the Boltzmann
integral………… in which E(t) is a relaxation function, which in the present context refers to deformation in the axial direction, as it depends on time ………..

In the quasilinear viscoelasticity (QLV) formulation of Fung, the relaxation function, which depends on strain,
is separable into the product of a function of time and a function of strain:…………
The stress is clearly dependent on strain level, but its time dependence does not depend on strain. Thus, time
dependence is assumed to be independent of strain.

Analogously, a separable assumption in a creep formulation would imply that time dependence in creep is
independent of stress.

………

In the past, the most common phenomenological model of the viscoelastic behavior of ligaments has been
the QLV model. This model has been useful in describing experiments with ligaments and tendons (seeRefs)….
…………….
In a study by Thornton et al., both creep and relaxation were investigated. They observed that relaxation
proceeded faster than creep and showed that linear viscoelastic theory was not able to phenomenologically
model both behaviors with interrelated constitutive coefficients.

This rate difference between creep and relaxation was also observed in the more clinically focused
experiments of Graf et al. A single linear or QLV model is likely to predict ligament response poorly when components of both creep and relaxation are included in the load history. In consequence, models may be unable to simulate complex joint behavior with fidelity………….

In this study two viscoelastic properties are considered: the increase in tissue deformation over time with a
constant load (creep) and the decrease in load with time at a constant tissue elongation (stress relaxation). The authors’ hypothesis is that nonlinear viscoelasticity of ligament requires a description more general than the separable quasilinear viscoelasticity (QLV) formulation commonly used. To test this hypothesis both creep and relaxation experiments were performed at multiple levels in the physiologic region of recoverable loading.

METHODS
………
Eighteen medial collateral ligaments (MCL) from euthanized Sprague–Dawley male rats (weight about 250g) were used. Each MCL was exposed by carefully dissecting away all extraneous tissue. The MCLs including intact
femoral and tibial bone sections were carefully excised for ex vivo testing with care taken not to disturb the
ligament insertion sites. The tissues were kept hydrated in Hank’s physiologic solution.

Ligaments were divided into three groups: (1) stress relaxation, (2) creep, and (3) stress relaxation and creep
on contralateral ligaments.

Group 1 (n56 ligaments) consists of MCLs subjected to stress relaxation testing for 100 s at varying levels of strain below the damage threshold of 5% for this method of testing.

Group 2 (n56 ligaments) is made up of tissues tested in creep for 100 s at varying levels of load below the loads seen near the damage threshold. None of the group 2 specimens exceeded 5% strain when loaded. The order of the tests was random. A brief test period was chosen for these series to allow sufficient time for recovery between repeated tests and to minimize time spent by the specimen in the bath.

For group 3 (n54 pairs of ligaments) stress relaxation and creep were tested on contralateral ligaments (20 min tests).

Similar methods were used for all ligaments. Ligament cross-sectional area was calculated by optically
measuring the width and thickness of the ligament and assuming an elliptical cross section.
………
Gage length …… was measured at 0.1 N of preload before each test in order to obtain a uniform zero
point.
………………….
Other than the preload, no preconditioning was done, to eliminate the possibility of history effects. For contralateral stress relaxation and creep tests, the relaxation test was performed first and the load history recorded, a creep test was then performed on the contralateral MCL in load control at the maximum load obtained during the relaxation test. For tissue recovery the ligaments were unloaded and allowed to recover for at least ten times the length of the test while remaining hydrated in Hank’s physiologic solution.
…………………..
Statistical analyses were performed on the data in order to determine if the rate of stress relaxation or creep
is strain or stress dependent, respectively, and whether a significant difference in rate of stress relaxation or creep exists for group 3.
………………….

RESULTS
Stress relaxation and creep were both nonlinear in that their rates (slopes on log–log plots) are dependent on
strain and stress, respectively (Figs. 1 and 2). In both stress relaxation and creep, rates changed by approximately an order of magnitude throughout this low load region ………

Statistical analysis for group 1 indicated that the rate n (slope in a log–log plot) of stress relaxation is strongly dependent upon strain………

Statistical analysis for group 2 indicated that the rate of creep is strongly dependent upon stress …….
To ensure specimen recovery from serial testing, the preloaded gage length was measured before each
test. Each ligament subjected to multiple tests showed gage length differences less than 0.5% for stress relaxation and less than 0.75% for creep.

Multiple stress relaxation tests from group 1 demonstrate a decrease in stress with time and a decrease in the rate of stress relaxation with increasing strain.

In addition, the elastic moduli at 10 s for increasing strain are 129.6, 290.0, 396.0, and 396.4 MPa, respectively.
Creep data at multiple levels of stress from group 2 display increasing strain with time and a reduction in
creep rate with increasing levels of stress.……….

Group 3 data (stress relaxation and creep on contralateral ligaments) demonstrate a statistically significant difference in the rate of stress relaxation and creep (p 50.0009) and that the rate of stress relaxation proceeds
faster than creep by 1.96 +/- 0.57 times.
The separable form of the nonlinear constitutive equation (QLV) does not describe the above results. For these data the rate of creep depends on load level and the rate of relaxation depends on strain level.
The rate of relaxation varied by more that an order of magnitude from -0.163 for 0.27% strain to -0.0125 for 5.10% strain.
Creep rate also varied by nearly an order of magnitude between 0.058 for 3.72 MPa and 0.007 for 9.88 MPa
stress. In QLV the time dependence and stress or strain dependence are assumed to be independent, and the same (separable) function of time is used regardless of applied stress (in creep) or applied strain (in relaxation).

………
Fluid present in ligament tissue has been shown to play a role in the mechanical response. As for tendon, when they are loaded, water content decreases with static and cyclic loading. Chimich et al. showed that ligaments with higher water content demonstrated greater relaxation than ligaments with lower water content and stated that water content has a significant effect on viscoelastic behavior.
………..The authors speculate that the decrease in relaxation rate with increasing strain could be the result of larger strains causing greater water loss (wringing out effect) which causes the tissue to be more elastic (less viscous) than tissues subjected to lower strains.

Chimich et al. showed that rabbit MCLs with larger water content showed greater relaxation. Hannafin and Arnoczky reported that as tendons are loaded to 100 g water content decreases with static and cyclic loading, probably due to fluid being driven out of the ligament during loading.

In combination these studies show that load influences hydration and that differences in the rate of stress relaxation with strain are due in part to water content. Further study of fluid content under varying levels of strain could add insight into the mechanism by which stress relaxation varies with strain.

Thornton et al. speculated that differences in stress relaxation and creep behavior are due to progressive recruitment of collagen fibers during creep and that this microstructural behavior is unlikely to have as significant an effect on stress relaxation as on creep. If this concept is correct, then the progressive recruitment of collagen fibers could also explain the decrease in the rate of creep with increasing load. As larger loads are applied to the ligament more fibers are recruited leaving fewer fibers to be progressively recruited after initial loading and therefore decreasing the creep response.

http://silver.n … akes/LigNLV.pdf

I think the study resumed in the last post is interesting because it shows how creep adaptation happens in a different way when a load is applyed right after stress-relaxation - in this case, the rate of creep augment with the load, when in normal circumstances happens just the opposite.

If this phenomenon was true for TA, it would means that, in example, wearing an extender or doing ligth progressive stretches before hanging could speed the creep adaptation because, at that moment, creeps are more dependant on load that on time.It recall close the “2-phase PE approach” discussed before in this same thread.

Very interesting :)

Thanks for the clarification on the articles and your interpretations.

Thanks ShMM. Of course everybody is entitled to post their interpretations of these findings, and I would be glad of hearing others opinions - don’t let me do all the work, friends :) .

In the next posts I will expose some articles referring to another way the CT seems to adapt to loads/stretches: the phenomenon of cellular proliferation.

Cellular proliferation should be, intuitively, linked with cellular damage; we could expect to see cellular proliferation in consequence of cellular damage. So it could be interesting to know at which strain/load level cellular damage starts:

Subfailure damage in ligament: a structural and cellular evaluation

PAOLO P. PROVENZANO,1 DENNIS HEISEY,2 KEI HAYASHI,3

RODERIC LAKES,4 AND RAY VANDERBY, JR.1

J Appl Physiol

92: 362–371, 2002.

"Microtrauma or sub-failure injury in tendon and ligament may occur either as the result of overuse or a single traumatic event.

Pathologies of the musculoskeletal system in which microtrauma is thought to play a role include: tendinitis and tendinosis …………………………

Tendon and ligament microtrauma and partial tears may accumulate damage to the point where load bearing is compromised and complete rupture occurs.

A sprain is defined as an acute injury to a ligament or joint capsule without dislocation. Grade I sprains are mild stretches with no discontinuity of the ligament. Grade II sprains are moderate stretches in which some fibers are torn. Grade III sprains are severe and consist of a complete or nearly complete ligament disruption. Grade III sprains constitute less than 15% of all ligament sprains (Andriacchi et

al., 1987). This leaves more than 85% of the sprains where sub-failure damage is the dominant issue.

METHODS

Fifty-seven medial collateral ligaments from male Sprague- Dawley rats (weight = 250 ± 25 g) were used as our animal model.

Structural damage and cellular damage was evaluated after a subfailure stretch. For structural damage (n=25) the tissue was pre-loaded (10g), measured for gage length (LO), preconditioned (10 cycles at 1%

strain), subjected to a sub-failure stretch in displacement control (grip speed 1mm/s), allowed to recover (10 min.). After recovery the length (LS) was measured at the preload level (10g). The difference was

normalized by original length and represents laxity (DS is a measure of permanent strain).

DS = 100*[(LS-LO)/LO

Stress strain behavior was evaluated in after a sub-failure stretch in 4 additional pairs of ligaments. Cellular damage (n=22) was measured by stretching ligaments in the same fashion as the structural damage

group and using confocal microscopy with a cell viability assay to detect live and dead cells.

……………………….

Statistical analysis was performed in order to determine the strain at which the onset of damage occurs from a structural and cellular standpoint, and to determine if the two were different from one

another.

RESULTS

Results indicate that tissue stretch induced laxity and cell death are fundamentally different in their behaviors when analyzed as a function of applied strain. Qualitatively, cellular damage can be seen to increase with strain by examination of the confocal microscopic images and damage to individual cells is seen in TEM images at 3.2% tissue strain ….

………….

Statistically, the onset of structural damage (θs) was found to be ε = 5.14% (4.50 to 5.69 confidence intervals), while the onset of cellular damage (θc) was found to be ε = 0%. That is, statistically, cellular

damage in rat MCLs begins with the application of tissue strain and structural damage occurs at strains greater than 5.14%.

…………

DISCUSSION

…………….

Results from this study indicate that rat medial collateral ligaments strained above 5.14% do not regain their original length after significant recovery time and hence remain stretched.

The authors speculate that this increase in elongation is the result of fiber damage in the form of torn or plastically deformed fibers. The resulting increase in tissue length represents tissue laxity and can be

hypothesized to increase joint laxity.

………………….

our data reveal that grade II tissue sprains occur after 5.14% strain in rat MCLs. In addition, it is reasonable to hypothesize that a grade I tissue sprain occurs at strains just prior to this onset of tissue damage (5.14%). Here, some cellular damage has occurred but no macroscopic laxity can be detected.

The threshold of cellular damage was found to be at 0% strain in the rat MCL. That is, statistically, cellular damage begins with the application of tissue strain. It should be noted that physically one would not expect an increase in cellular damage at infinitesimal strains as our statistical analysis implies. However, necrotic cells are present in the control tissues (ε = 0) and are present after very small strains.

………

"

http://jap.phys iology.org/cgi/ … nt/92/1/362.pdf

Now let’s see some studies about mechanical stimuli and cellular proliferation:

Cyclic mechanical stretching modulates secretion pattern of growth factors in human tendon fibroblasts.

Skutek M, van Griensven M, Zeichen J, Brauer N, Bosch U.

Department of Trauma Surgery, Hannover Medical School, Germany. skutek@aol.com

The objective of the study was to investigate whether the response profile of the growth factor of human tendon fibroblasts could be beneficially influenced through the application of mechanical stretch.
……………………
Human tendon fibroblasts were experimentally stretched for 15 and 60 mm at a frequency of 1 Hz and an amplitude of 5%.
……….
All the growth factors investigated were indeed secreted by human tendon fibroblasts both in stretched cells and controls. Mechanical stretch increased the secretion pattern of the growth factors. The increased concentrations of TGF-beta bFGF and PDGF after cyclical mechanical stretching may have a positive influence on tendon and ligament healing through stimulation of cell proliferation, differentiation and matrix formation.

Cyclic mechanical stretching modulates secretion pattern of growth factors in human tendon fibroblasts

Time-dependent Modulation of Alignment and Differentiation of Smooth Muscle Cells Seeded on a Porous Substrate Undergoing Cyclic Mechanical Strain
Jae Min Cha*, Si-Nae Park*†, Sung Hoon Noh‡, and Hwal Suh*†

ABSTRACT
………
Cyclic mechanical strain has been applied to modulate the alignment, proliferation, and differentiation of smooth muscle cells.
………
The cells were primary cultured from rabbit esophageal smooth muscle layer, and a self-designed stretching chamber was used to modulate the cells on porous polyurethane (PU) scaffolds with 10% strain at a frequency of 1 Hz. The applied cyclic strain induced cellular alignment.
……..
In terms of proliferation, the strained groups differed significantly from the statically cultured group, but no difference was observed between groups that were subjected to straining for different lengths of time. Quantitative analysis of α-smooth muscle actin (SMA) showed that differentiation was significantly promoted at 18 h of strain. Penetration of primary cultured cells into the pores of PU scaffolds was shown after cyclic strain application, especially in 18 and 24 h of strain. Consequently, it is expected that myofibroblast/scaffold hybrids, cyclically strained in the defined time course, could be practically applied to organize functional smooth muscle tissues having consistent cell alignment and up-regulated SMA.

http://www3.int erscience.wiley … 627829/abstract

-Assisted Closure: Microdeformations of Wounds and Cell Proliferation.

ORIGINAL ARTICLES

Plastic & Reconstructive Surgery. 114(5):1086-1096, October 2004.
Saxena, Vishal S.M.; Hwang, Chao-Wei M.D., Ph.D.; Huang, Sui M.D., Ph.D.; Eichbaum, Quentin M.D., Ph.D., M.P.H.; Ingber, Donald M.D., Ph.D.; Orgill, Dennis P. M.D., Ph.D. [/b]

Abstract:
The mechanism of action of the Vacuum Assisted Closure Therapy (VAC; KCI, San Antonio, Texas), a recent novel innovation in the care of wounds, remains unknown. In vitro studies have revealed that cells allowed to stretch tend to divide and proliferate in the presence of soluble mitogens, whereas retracted cells remain quiescent. The authors hypothesize that application of micromechanical forces to wounds in vivo can promote wound healing through this cell shape-dependent, mechanical control mechanism. The authors created a computer model (finite element) of a wound and simulated VAC application.
…………
In this model, the authors altered the pressure, pore diameter, and pore volume fraction to study the effects of vacuum-induced material deformations. The authors compared the morphology of deformation of this wound model with histologic sections of wounds treated with the VAC. The finite element model showed that most elements stretched by VAC application experienced deformations of 5 to 20 percent strain, which are similar to in vitro strain levels shown to promote cellular proliferation. Importantly, the deformation predicted by the model also was similar in morphology to the surface undulations observed in histologic cross-sections of the wounds. The authors hypothesize that this tissue deformation stretches individual cells, thereby promoting proliferation in the wound microenvironment. The application of micromechanical forces may be a useful method with which to stimulate wound healing through promotion of cell division, angiogenesis, and local elaboration of growth factors. Finite element modeling of the VAC device is consistent with this mechanism of action.

Link

In Vitro Biophysical Strain Model for Understanding Mechanisms of Osteopathic Manipulative Treatment
John G. Dodd, BS; Meadow Maze Good, BS; Tammy L. Nguyen, BS; Andersen I. Grigg, BS; Lyn M. Batia, BS; Paul R. Standley, PhD
From the Department of Physiology at the Midwestern University/Arizona College of Osteopathic Medicine (MWU/AZCOM) in Glendale, Ariz.

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) 1ß, and IL-6.

Design and Methods: Randomized controlled trial. Human fibroblasts were subjected in vitro to control conditions (no strain) or biophysical strain of various magnitudes (10%–30% beyond resting length) and durations (12–72 hours). After control or strain stimuli, fibroblasts were analyzed for potential changes in cell shape, proliferative capacity, nitric oxide secretion, and cytokine (IL-1ß, IL-6) secretion.

Results: Low strain magnitudes (<20%) induced mild cellular rounding and pseudopodia truncation. High strain magnitudes (>20%) decreased overall cell viability and the mitogenic response, and induced cell membrane decomposition and pseudopodia loss. No basal or strain-induced secretion of IL-1ß was observed. Interleukin 6 concentrations increased two-fold, while nitric oxide levels increased three-fold, in cells strained at 10% magnitude for 72 hours (P<.05).

Conclusion: Human fibroblasts respond to in vitro strain by secreting inflammatory cytokines, undergoing hyperplasia, and altering cell shape and alignment. The in vitro biophysical strain model developed by the authors is useful for simulating a variety of injuries, determining in vivo mediators of somatic dysfunction, and investigating the underlying mechanisms of OMT.

Distributing a fixed amount of cyclic loading to tendon explants over longer periods induces greater cellular and mechanical responses
Aaditya C. Devkota 1 2, Mari Tsuzaki 1, Louis C. Almekinders 3, Albert J. Banes 2 4, Paul S. Weinhold 1 2 *
1Department of Orthopaedics, CB 7055, University of North Carolina, Chapel Hill, North Carolina 27599-7055
2Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, North Carolina
3North Carolina Orthopaedic Clinic, Durham, North Carolina
4Flexcell International Corporation, Hillsborough, North Carolina

Abstract
……………
The purpose of this study was to examine the biochemical and biomechanical tendon response after applying cyclical loading over varying durations. Avian flexor digitorum profundus tendons were loaded (3 or 12 MPa) to a fixed number of cycles across either 1 or 12 days in vitro. The tendon response evaluations included biomechanical data gathered during loading and subsequent failure testing. Evaluations also included cellular viability, cell death, and proteoglycan, collagen, collagenase, and prostaglandin E2 (PGE2) content measurements obtained from tissue specimens and media samples.

Significant strains (up to 2%) accumulated during loading. Loading to 12 MPa significantly reduced maximum stress (33% and 27%) and energy density (42% and 50%) when applied across 1 or 12 days, respectively. Loading to 3 MPa also caused a 40% reduction in energy density, but only when applied across 12 days. Cell death and collagenase activity increased significantly with increasing magnitude and duration. However, no differences occurred in cell viability or collagen content. Glycosaminoglycan content increased 50% with load magnitude, while PGE2 production increased 2.5-fold with loading magnitude and 11-fold with increased duration. Mechanical fatigue-induced mechanical property changes were exhibited by the tendons in response to increased loading magnitude across just 1 day. However, when the same loading was applied over a longer period, most outcomes were magnified substantially, relative to the short duration regimens. This is presumably due to the increased response time for the complex cellular response to loading. A key contributor may be the inflammatory mediator, PGE2, which exhibited large magnitude and duration dependent increases to cyclic loading.

http://www3.int erscience.wiley … ETRY=1&SRETRY=0

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Pea Awards 2008. Best Non-Commercial PE Site
Pea Awards 2008. Best PE Site

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This is another interesting study, in my personal opinion:

Effects of continuous and Intermittent forces on human fibroblasts in vitro

Aldo Carano, Giuseppe Siciliani

Department of Orthodontics, University of Ferrara, Ferrara, Italy

SUMMARY

Orthodontics is based upon the cellular response to biomechanical forces.

However, little is known about the way cells respond to such forces. An experimental model has been designed to study the morphological and metabolic behaviour of human cells, subjected to cyclical or static mechanical loads.

The model involves attaching human fibroblasts to silicone collagen-coated membranes, which are subjected to either continuous or cyclical stretching by a motor coupled with a movable supporting frame.

The effect of continuous or cyclical stretching on the secretion of collagenase, an enzyme thought to play an important role in the process of tooth movement, was measured. Cyclical stretching of fibroblasts over a 4-day period, approximately doubled collagenase production as compared with the control. Continuous stretching, on the other hand, was only 50 per cent as effective in enhancing enzyme release. In contrast, the secretion of the collagenase inhibitor was unaffected by either form of mechanical deformation.

To understand the effect of cyclical forces further, a morphological study using human fibroblasts was performed. It was found that stretching or compression delivered an immediate and proportional deformation of the cells. After 10-15 minutes the morphology of cells readapted to the new mechanical environment, causing a loss of the biological activation. This suggests that a new mechanical stimulus is necessary to induce a new biological reaction.

Introduction

The effect of mechanical forces on bone, cartilage, and connective tissue has been central to a

number of studies in different branches of medicine. Although the human body is continuously

stimulated by mechanical stresses, their regulatory effect on the biology of tissues is not well

known and only recently has the effect of mechanical deformation on cell biology been

investigated

………………

Orthodontics and orthopaedics, besides sharing with other medical fields an interest in the biomechanical aspects of human physiology, are particularly relevant to this field because their therapeutic approaches are mainly based on the application of mechanical forces to teeth and the facial skeleton. All orthodontic appliances exert forces on tissues, inducing either a stimulatory or an inhibitory effect on cellular

activities, which form the basis of tissue remodelling.

Results

The fibroblasts, stimulated by a cyclical mechanical deformation (3 minutes stress, 3minutes relaxation) of about 7 per cent of their length, produced 200 per cent more collagenase in comparison with the control ….. The production of collagenase inhibitor (TIMP) remained unchanged when compared to the control …

During the experiments the practically unchanged level of total protein synthesis in relation to the control indicatedthat the effect of mechanical stimulus was specific to collagenase synthesis.

Although it is reasonable to think that whenever a force is applied to a cell this could alter the cell morphology, there are no reports in the literature to substantiate this. The morphological study conducted in this experiment was designed to investigate this topic by observing what happened to the cell during and after

application of the stimulus.

Discussion

………..

This morphological study showed an immediate proportionate cellular deformation following the application of tensile or compressive forces. After 10-15 minutes, even if the substrate was still elongated,

the fibroblasts changed their morphology. Although at present it is not clear what actually

happens when cells are distorted, it is reasonable to suggest that the mechanism which activates

them diminishes when the cells rearrange their morphology.

……………

it can be concluded that the cells loose their sensitivity to the mechanical

deformation applied to the substratum over a time range of 10-15 minutes. In order to reactivate

the cells a new deformation of the substratum would be necessary. This observation

could help to explain the reason why intermittent forces have a higher inductive capacity on

tissues, compared with a continuous force of the same magnitude.

Conclusions

1. Cyclical forces are more effective than continuous

forces in stimulating human

fibroblast production of collagenase.

2. The differential cellular behaviour to

differing modalities of application of

mechanical deformations could be found in

the quick cellular morphological readaptation

to the new physical conditions of the

substrate.

http://ejo.oxfo rdjournals.org/ … reprint/18/1/19

Why all that is interesting to us? Penis-extenders sellers claim on their sites that the basic mechanism of penile elongation obtained with extenders is a result of cellular proliferation. IF (a big IF) this study has some meaning for connective tissue of penis, cellular proliferatin it’s not the major process involved in penis-extenders gains.

It’s adversely much more probable that cellular proliferation, as a reaction to intermittent mechanics stimuli, is, at some significant amount, produced by manual stretches.