Fascia Research 2015 – State Of The Art

hypothesize that the “structure probably has a direct role inforce transmission during muscle contraction, establishinga synergy between the gluteus maximus muscle and the longhead of the biceps femoris.” They further hypothesize thatthis structure is likely involved in injury of the proximalattachment of long head of biceps femoris and highlight theimportance of mobilization of this fascial tissue especiallyin sciatic nerve involvement. 1.1.2 This paper comprehensively reviews theorganization and composition of the thoracolumbar fascia(TLF), a girdling structure consisting of several aponeuroticand fascial layers which separate the paraspinal musclesfrom the muscles of the posterior abdominal wall. Thesuperficial lamina of the posterior layer of the TLF (PLF) isdominated by the aponeuroses of the latissimus dorsi andthe serratus posterior inferior. The deeper lamina of thePLF forms a retinacular sheath encapsulating the paraspinalmuscles. The middle layer of the TLF (MLF) is derivedfrom an intermuscular septum, which separates musclesthat develop anterior (hypaxial) and posterior (epaxial) tothe transverse processes of the vertebrae. The paraspinalretinacular sheath (PRS) forms a lumbar interfascial triangle(LIFT) with the MLF and PLF, which is in a key positionto act as a ‘hydraulic amplifier;’ assisting the paraspinalmuscles to support the lumbosacral spine. Along the lateralborder of the PRS, a thickened complex of dense connectivetissue, the lateral raphe, arises from the junction of thehypaxial myofascial compartment (the abdominal muscles)with the paraspinal sheath of the epaxial muscles and iswell positioned to distribute tension from the surroundinghypaxial and extremity muscles into the layers of the TLF.At the base of the lumbar spine all of the layers of the TLFfuse together to attach firmly to the posterior superior iliacspine and the sacrotuberous ligament. This thoracolumbarcomposite (TLC) is suggested to assist in maintaining theintegrity of the lower lumbar spine and the sacroiliac joint.This is an important concept for clinicians involved in themanagement of back pain and its biomechanical role isfurther investigated and explained in section 2.1.3. 1.1.3 This study evaluated the gross and histologicalanatomy of the bicipital aponeurosis (BA), a fascialexpansion which arises from the tendon of biceps brachii.In the 30 cadaveric upper limbs examined, fibres fromthe short head of the biceps brachii contributed to theformation of the proximal part of the aponeurosis, while itsdistal part was continuous with the fascial sheath overlyingthe tendon of the long head of biceps brachii. The BAwas angled at about 22 to the tendon and both bloodvessels and adipose tissue were found between the tendonand the fascial sheath. The authors suggest that the BAtttFascia Research 2015 – State of the Artplays an important role in dissipating force away fromthe attachment site of the biceps tendon and may assist indual action of the biceps brachii as a supinator and flexorof the forearm.In brief: what is known and what is new In contrast to its depiction in many textbooks, fascia formsa complex network of sheets, bags, and strings that act todivert and transmit forces to assist in body movement. Itwas previously suggested in Fascia III, that muscles maynot transmit their full force directly to the skeleton viatendons, but rather distribute a portion of their contractileor tensile force to other structures via fascial sheets. Fascialsheets transmit these forces to synergistic as well asantagonistic muscles to stiffen the respective joint, but alsoexert these effects on other regions, several joints furtheraway, by forming a complex network of fascial sheets,bags, and strings. The relative importance of myofascialversus myotendinous force pathways in many commonmovements are currently being investigated (see section 2).The papers in this section begin to map out the details ofthis network in specific parts of the body, highlighting theirpotential neuromechanical role and raising new questionsabout the importance of these tissues in common injuries,such as muscle strains and chronic low back pain.2Biomechanics of Fascia 2.1.1 The structural organization of fascia intosheet-like layers with multiple orientations, attachmentsand its intimacy with muscle groups provides fascia with adistinctly functional anisotropy. This has been investigatedin fascia lata, using a biaxial mechanical test to determinethe effect of interactions between lateral and longitudinalloading on overall material properties such as stiffness andstrain energy storage. Histological sectioning and scanningelectron micrographs provide anatomical evidence thatcorrelates with the observed mechanical properties. Thegreater stiffness observed in the longitudinal directioncorresponds with a thicker layer of longitudinally orientedcollagen fibres which are of large diameter. The thinnerlayer, containing small diameter collagen fibres, providesa lower transverse stiffness thereby permitting muscleexpansion with minimal influence on the mechanicalproperties in the longitudinal direction. 2.1.2 A cadaveric investigation into the complexinteractions between myofascial structures and functionalmovement attempts to answer questions about the relativefunctional importance of myofascial versus myotendinousforce pathways. The relative contributions made by theset3

tttFascia Research 2015 – State of the Artpathways have been estimated by tracking the kinematicsof cadaveric limbs following sequential tenotomiesin procedures that mimic surgical harvesting of thesemitendinosus and gracilis tendons widely used in kneereconstructions. It was shown that the forces generatedaround the joint, are mostly dependent on the myofascialpathway and less reliant on the myotendinous connection.Supporting the notion that tendons are no longer the uniquestructures that transmit motive force to the skeleton. 2.1.3 Stability of the thoraco-lumbar spineis dependent on the highly complex arrangement ofaponeurotic and fascial layers that surround the paraspinaland abdominal muscle groups. A recent cadaveric studyused an ingenious arrangement of inflation devicesto mimic muscle expansion and load cells to monitortension generated within fascial layers in a series oftransverse segments through the mid-lumbar region whileunder fluoroscopic visualization to explore load-sharingpathways. This study was able to simulate and manipulatethe effects of paraspinal and abdominal muscle contractionson the throacolumbar fascia (TLF). Noticeable increases inthe moment arms about the spinal axis were observed asposterior and lateral displacements in the TLF, highlightingthe importance of this mechanism in spinal stability. Inaddition, this study demonstrated the essential interplaybetween paraspinal and abdominal muscle contractionsthat are necessary for optimizing musculoskeletal bracingmechanisms in the spine.tIn brief: what is known and what is new These three papers highlight the complexity andfunctionality of major fascial groups throughout thebody. The directional variability (anisotropy) and multipleinteractions between neighbouring myofascial systemscombine to enhance the overall efficiency and stabilityof functional movement patterns. Fascia has highlydirectional properties that correspond with the transferand redirection of forces while simultaneously permittinglength and shape changes in muscle groups. There alsoappears to be some advantageous interplay between themyotendionus and myofascial force transmission pathwaysthat provides sufficient redundancy between these systemsto accommodate varying degrees of injury or surgicalinsults while still remaining a functional force transmissionsystem. The most complex myofascial arrangementsare seen in the back where they help to enhance spinalstability during complex movement patterns. Stability isachieved by the multi-directional bracing forces generatedduring muscle contraction and further assisted by fascialrealignment resulting from changes of shape and pressurewithin the muscle groups.43Cytology and Histology of Fascia 3.1.1 Fibroblasts are responsible for the productionof collagen and elastin within the extracellular matrix(ECM). However, the discovery of separate lineages offibroblasts helps to explain why scar formation in the skinfails to replicate true epidermal tissue. There are two linesof fibroblasts, arising separately from the upper dermal andlower dermal layers. Differences in the way cells respondto external protein triggers, via Wnt signalling (a pathwaythat regulates crucial aspects of cell fate determination,cell migration, cell polarity, neural patterning and organdevelopment during embryonic development) and theinterplay with T cell immune responses, are deemedresponsible for the mechanism that influences dermal cellproliferation and hair follicle formation. Since it is the lowerdermal lineage that dominates during the healing process,scar tissue is devoid of hair follicles that typify normalskin architecture. This linkage between tissue of originfor fibroblasts and variations in their functional responseto Wnt activation provides new avenues for exploringmechanisms that underpin age related and pathologicalchanges in the ECM. 3.1.2 The influence of mechanical therapies onchronic tendinopathies at the tissue level are exploredby a murine model where tendinopathy is induced byinjection of a transforming growth factor, TGF-β1. Thisreduces tendon strength and induces cellular changes thatclosely typify the chondroid populations and raised levelsof glycosaminoglycans seen in injured tendon. Presence oftendinopathy was validated by histological, gene expressionand mechanical testing techniques. Following exposure toa controlled exercise regime, treadmill exercise was ableto elicit in pathological tendon, a return to near normalstrength, cellular make up and gene expression within fourweeks. These results provide direct evidence for the role andefficacy of mechanical stimulation in the tendon healingprocess, albeit in the acute phase. It is anticipated that thismurine model of tendinopathy will facilitate more detailedquantitative assessment of tissue repair processes inducedby physical therapies and exercise-based rehabilitationmodalities.In brief: what is known and what is new Previously in Fascia III, the question was asked whethermanual treatments might have beneficial effects duringearly development of fibrotic processes. A useful modelfor addressing this issue has since been demonstrated andprovides some necessary supporting evidence (see paper3.1.2). Cells within the ECM are demonstrably influencedby external mechanical factors resulting in an ECM protein

milieu that is modulated by exercise, inflammation anddisease processes. A regular exercise protocol that is shownto be sufficient in countering some early degenerativechanges within tendon permits more detailed mechanisticevaluations. For example, the relative contribution andexplanatory mechanisms behind the different responsesseen in concentric as opposed to eccentric exercise needfurther clarification. And can this difference be explainedby the variations in load distribution and shear betweenmuscle fascicles during contraction? (see papers 2.1.2 and7.1.2)4Fascia Pathology 4.1.1 The complexity of the fascial structure andits intricate connectivity throughout the body makeit vulnerable to strain and overuse injuries resultingin a number of chronic musculoskeletal pathologiesand pain syndromes. The pathomechanics of painfulmusculoskeletal conditions is further complicated bythe sensory and reactive capability of the myofascia tomechanical stimulii. Fascia is no longer considered tobe a passive supporting structure within the body dueto the presence and motility of contractile elements ofactin containing myofibroblasts. The mechanosensorycapacity of myofascial tissue is increasingly implicatedin many painful conditions and diseases such as chronicneck and back pain, frozen shoulder and nerve entrapmentsyndromes. Extremes in movement, from hyperlaxity toincreased stiffness and restricted shear in the fascial tissuesare often found in painful conditions. Hence, more detailedinvestigations into the causal mechanisms of myofacial painare required if we are to properly understand the rationalebehind various massage and manipulative therapies. Forexample, how does reduction of compartmental pressure ormobilization of fibrous adhesions within the tissues help toresolve pain? Further information and some explanationsare proposed in paper 11.1.4. 4.1.2 High levels of myofibroblast proliferation withuneven distribution are seen in the fascia of certain diseasessuch as Dupuytren’s. Detailed analysis of the histology,immunohistochemistry and genetic factors within the ECMof tissues from symptomatic, asymptomatic and healthytissue has helped to shed light on regional differences indisease development. This particular disease presents asa progressive flexion contracture of the fingers leadingto disabling deformities. The main treatment for severecases of Dupuytren’s disease is fasciotomy, or failing thatfasciectomy, of the affected tissue only. However, thispaper cautions against considering asymptomatic tissuetttFascia Research 2015 – State of the Artas “normal” due to certain similarities in cellular make upand activity to the clinically affected tissue. This finding hasimplications for potential improvements to treatment andinvestigating the bilateral nature of some disease symptomsand processes.In brief: what is known and what is new Previously in Fascia III, proprioception in ligamentswas discussed as a trigger for reflex muscle activity thathelps protect the joint. In this issue a similar mechanismis also described in relation to the functional responseof the fascia via mechanosensory pathways. Anomaliesor resultant imbalances in this response are found in anumber of movement disorders, such as hyperlaxity ofjoints or hypermobility syndrome; increased stiffnesse.g. Dupuytren’s contractures or restricted tissue shear,as in Duchenne dystrophy all of which, lead to painfulmusculoskeletal conditions. Since current treatments areoften based on reversing the triggering conditions of eitherexcessive laxity or stiffness, detailed investigations intothe cellular responses to mechanical stimuli are becomingincreasingly relevant. Understanding how the cellular makeup and physical properties of tissue change with diseaseis proving increasingly beneficial to the advancement ofsurgical and manipulative therapies, as discussed in 9 and10.5Fluid Dynamics in Fascia 5.1.1 The ability of myofibroblasts to directly exerttension on the ECM through integrin-mediated contractionis now well established. Less is known, however, aboutthe contractile nature of fibroblasts. This paper suggeststhat healthy fibroblasts embedded within fascia may alsodynamically influence the tension of connective tissueby rapidly remodelling their cytoskeleton but withouttransforming into myofibroblasts. Tension modulation byfibroblasts is suggested to regulate interstitial fluid pressureand flow by altering the permeability (pore size) of theECM, and thus the movement of water toward the normallyunder-hydrated glycosaminoglycans. Movement of waterin or out of the tissue also serves as the mechanism bywhich fibroblasts sense a change in osmotic pressure andaccordingly adjust their size, to control fluid movement.These cytoskeletal responses appear to be unique toloose connective tissues, such as those forming interfacesbetween subcutaneous and perimuscular layers, and doesnot occur in other more densely packed connective tissues. 5.1.2 Nearly every cell in the human body has aprimary cilium, a solitary, non-motile, microtubule-basedt5

tttFascia Research 2015 – State of the Artantenna that extends from the cell surface. The primarycilium controls the balance between the canonical and noncanonical Wnt pathways (see 3.1.1 for example), whichregulate gene transcription, intra-cellular calcium levelsand components of the cytoskeleton responsible for cellshape. Recently, the primary cilium has also been shown toplay an important mechanosensory role, and in particular,in sensing fluid flow. Application of oscillating fluid flowto cultured cells that have an intact primary cillium wasshown to alter the microtubule network within the cell;increasing the number and density of microtubules in amagnitude- and time-dependent manner. Cytoskeletalmicrotubules are thought to work together with integrinsin extracellular matrix adhesions and cadherins in cellcell junctions to resist tensile forces generated withinthe actin component of the cytoskeleton and therebyestablish a mechanical force balance that stabilizes theshape of the entire cell. This reinforcement mechanismdid not occur after primary cilia removal from the cell.It is possible therefore that, following fluid shear across acell, microtubule networks are developed to stabilize thecell in response to the mechanical stimulus.influence the tension of adjacent tissues by remodellingtheir cytoskeleton but without stress fibre formation andtransforming into myofibroblasts. This restrains the fluidretaining capacity of the adjacent proteoglycans, which arenormally under hydrated. Stretching of the matrix or partialdetachment of the cell, likely increases the permeabilityof the tissue allowing flux of fluid into the peri-cellularground substance. Local changes in osmolarity or fluidshear stress are sensed by cell structures, such as theprimary cilia, which influence gene transcription, intracellular calcium levels and provide a direct connection tothe cytoskeletal machinery, which governs cell shape andmotility. Such changes in cell shape may oppose furtherfluid movement and stabilize the cell but may also directthe migration of fibroblasts toward the flow of fluid ina dose-dependent manner. Thus therapies that promoteinterstitial fluid flow could have the potential to acceleratecellular migration, healing and tissue repair. Care is needed,however, when manipulating these tissues to avoid theformation of myofibroblasts and caution is also requiredin cancer-associated tissues. 5.1.3 Numerous in vitro studies have shown thatfibroblasts regulate their cellular functions in response tofluid flow over a range of shear stress (0.005 to 2.5 Pa).During inflammation and in certain cancers, interstitialfluid flow can increase 10-fold ( 10 μm/s) and caninfluence cell migration. This in vitro study used a novelculture chamber to investigate the migration behaviourof human breast cancer cells to physiologically relevantfluid shear flows. Interstitial flow increased the percentageof migratory cells, and also increased migration speedin about 20 % of cancer cells. The migratory behaviorof cancer cells, however, was heterogeneous, with somecells migrating towards flow and others migrating againstflow. Flow-directed invasion occurred in roughly 10% ofcells, suggesting that fluid flow can enhance tumor cellinvasion by directing a subpopulation towards the draininglymphatic vessels, a major route of metastasis.6tIn brief: what is known and what is new In Fascia II and III it was shown that in scar, chronicallyinflamed tissue and cancer-associated tissues, fibroblastshave the ability to transform into contractile cells, ormyofibroblasts, which can increase ECM stiffness bygenerating sustained and continued tension on theECM. This increase in ECM stiffness is accompanied bygreater interstitial pressure and lymphatic flow, whichmay predispose an individual to fibrosis, cancer invasionand metastasis. Healthy fibroblasts embedded withinloose fascia, however, would also appear to dynamically6Fascia and Cancer 6.1.1 Tumor associated Collagen Signature (TACS)outside the immediate tumor in surgical samples of breastsurgery for cancer, independent of the cancer lesion itself,is correlated with patient outcome. 10-year survival ratesare 46 % for those with increased collagen depositionnear the tumor, compared to 78 % without. This paperexplores potential mechanisms. The adult mammary glandresponds to biochemical and mechanical signaling fromthe extracellular matrix. The stroma outside the tumoraffects survival in several ways: 1) Reorganization of theextracellular matrix to promote tumor invasion – increasedbreast density, increased collagen alignment, increasedexpression of syndecan-1 (which promotes alignment),and higher expression of COX-2 and the gene for type Icollagen, COL1A1; 2) changes in expression of stromal celltypes – beta lymphocytes, macrophages (which stimulatecollagen fibrillogenesis and remodel and align collagen),and carcinoma associated fibroblasts (CAF); 3) changes instromal gene expression, including changes associated withthe wound healing response of fibroblasts and 4) stromaland mechanical signaling pathways – increased caveolin-1,matrix metalloproteinase (MMP) and chemokines. 6.1.2 There is recent interest in structural components of the extracellular matrix (ECM) and how they playan active and not just a passive role in adult tissue changes.This paper reviews the collagens and proteoglycans in the

ECM and highlights recent research of individual components and their effects on cells through speci

Fascia Research Congress in Boston (2007), fascia has aroused increasing interest from scientists, clinicians and manual body therapists. The number of research papers on fascia appearing in peer-reviewed journals has rapidly increased, particularly since the late 1980s and mid 2000 (see Fig. 1). Since the publication of the proceedings of the