Hyaluronan and the Fascial Frontier

Abstract

The buzz about hyaluronan (HA) is real. Whether found in face cream to increase water volume loss and viscoelasticity or injected into the knee to restore the properties of synovial fluid, the impact of HA can be recognized in many disciplines from dermatology to orthopedics. HA is the most abundant polysaccharide of the extracellular matrix of connective tissues. HA can impact cell behavior in specific ways by binding cellular HA receptors, which can influence signals that facilitate cell survival, proliferation, adhesion, as well as migration. Characteristics of HA, such as its abundance in a variety of tissues and its responsiveness to chemical, mechanical and hormonal modifications, has made HA an attractive molecule for a wide range of applications. Despite being discovered over 80 years ago, its properties within the world of fascia have only recently received attention. Our fascial system penetrates and envelopes all organs, muscles, bones and nerve fibers, providing the body with a functional structure and an environment that enables all bodily systems to operate in an integrated manner. Recognized interactions between cells and their HA-rich extracellular microenvironment support the importance of studying the relationship between HA and the body's fascial system. From fasciacytes to chronic pain, this review aims to highlight the connections between HA and fascial health.

Keywords: HA; connective tissue; densification; extracellular matrix; fascia; fasciacyte; gliding; hyaluronan; hyaluronic acid; myofascial pain.

Figure 1

Properties of HA in the context of the ECM of fascia. Matrix organization of HA varies by tissue type reinforced mechanically by types of collagen fibers and managed by tissue-specific cell types. (a) HA consists of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine structured as a single polysaccharide chain abundantly present in the extracellular matrix (ECM). (b) Extracellular HA plays a role in adhesivity via cell receptors. Mechanical properties of HA are dictated by molecular weight, abundance and fluid dynamics. The cluster determinant 44 (CD44) embedded in the cell membrane mediates adhesion, migration and intracellular signaling. The receptor for HA-mediated motility (RHAMM) modifies intracellular signaling. (c) HA concentration is coordinated by hyaluronan synthases which is (d) balanced by snipping enzymes referred to as hyaluronidases. Based on [17,18,19].

Figure 2

Characteristics of the human fascial system, considered in its three-dimensional continuity. Fascia is composed of soft, collagen-containing loose and dense fibrous connective tissue that permeates the body. (a) From the skin to the deepest plane, we find the epidermis, dermis, superficial fascia, divided into two fibroadipose layers (superficial retinaculum cutis (SRC) and deep retinaculum cutis (DRC)), deep fascia, a loose connective tissue layer, deep fascia and skeletal muscle. (b) In 2020, Purslow established that the configuration of epimysium closely mirrors the organization of aponeurotic fascia with loose connective tissue intervening between two or possibly three sublayers of deep fascia. The main constituents of the loose connective tissue are water, ions, and glycosaminoglycans, with a robust prevalence of HA. Fasciacytes are at home in the loose connective tissue interface between layers of denser, deep fascia covering skeletal muscle of the extremities and regions of the trunk. Based on [17,41,42,43,44].

Figure 3

Normal vs. dysfunctional fascial interface. Illustration of the HA-rich interface between layers of dense connective tissue in normal and dysfunctional scenarios. Each of deep fascia layer is separated from the other by a thin layer of loose connective tissue with normal HA (mean thickness 43 ± 12 μm) that permits the sliding of the several layers upon neighboring ones. When HA is found as short HA chains, its small fragments become adhesive rather than lubricating and the distribution of lines of force within the fascia becomes distorted. This is referred to as the densification of fascia, represented by the lock. The tissue layers around the densification site can be a focal point of intense mechanical stress. Based on [6,24,67,69].