CONNECTIVE TISSUE PROPERTIES

The functions of various connective tissues are to bind cells together to form and organize tissues, organs, and systems and to provide a mechanical link between musculoskeletal junctions and the articulations of joints. Generally, connective tissues are made up of cells and the extracellular matrix that they produce. Extracellular matrix is defined as the noncellular components of connective tissue.⁴

Two classic functions of connective tissues are mechanical support for bone and soft tissues and intercellular exchange of oxygen, blood, water, gases, cells, and wastes. Basic mechanical support functions of connective tissues, such as bone, ligament, tendon, muscle, and cartilage,1,3 are to provide stability and shock absorption in joints,² provide a mechanical link system between bones, and transmit muscle forces.⁴

Intracellular exchange relies on the circulation of blood to supply tissues with nutrients and oxygen, and to provide removal of extracellular waste and gases. The basic aggregate components of the extracellular matrix of connective tissues are I-elastin, II-collagen, III-ground substance, IV-proteoglycans and glycosaminoglycans (GAGs). V-lipids, phospholipids, proteins, and glycoproteins.

Elastin is a noncollagenous glycoprotein in which molecules are arranged randomly as a constituent of extracellular connective tissue matrix. Elastin is found in varying amounts in tissues requiring high levels of physiologic motion (elasticity). Two special amino acids, desmosine and isodesmosine, are found in elastin. They are directly responsible for the cross-linking arrangement of elastin fiber and its unique ability to deform under stress then return to its original orientation and shape. Primarily, elastin fibers contain the amino acids glycine, proline, alanine, and valine. Characteristically, elastin fibers can elongate about 70% without undergoing fiber disruption.⁴

In contrast to elastin, collagen is the most abundant component of the connective tissue matrix, and 12 to 19 distinct types of collagen exist.⁴ Types of collagen are classified according to their structure and tissue distribution. Biochemical properties of connective tissues such as ligament, cartilage, tendon, bone, and muscle are dependent on the specific predominant types of collagen found in the extracellular matrix. The characteristic extensive network of cross-links in collagen significantly contributes to the stability and strength of the extracellular matrix. The basic histochemical profile of collagen includes the amino acids glycine, hydroxyproline, proline, and hydroxylysine. Of these amino acids, proline generally is responsible for resisting tensile forces in collagen.⁴ Fibroblasts stimulate collagen synthesis through assembly of polypeptide chains of proline and lysine, which aggregate into a triple helix monomer.⁴ Ground substance is an amorphous nonfibrous aqueous–gel component of the connective tissue matrix. Generally this substance is responsible for facilitating intercellular exchange of water, oxygen, cells, and gases, as well as providing mechanical support between various tissues.

Proteoglycans are protein and mucopolysaccharide macromolecules subclassified as glycosaminoglycans. Generally, GAGs are responsible for the compressive strength of the cartilage matrix. Proteoglycans are extremely hydrophilic, so they attract and bind water. The major and distinct types of GAGs found in cartilage are chondroitin sulfate, keratan sulfate, and dermatan sulfate, with chondroitin sulfate representing almost 90% of all GAGs in cartilage. These large proteoglycans, specifically chondroitin and keratan, bind together to form a distinct type of GAG referred to as aggrecan. Various types of connective tissues, such as ligament, cartilage, tendon, and muscle, contain varying amounts of these large proteoglycans that relate directly to the specific biomechanical and biochemical nature of all connective tissues. The networking capacity of proteoglycans and collagen within all forms and types of connective tissue contributes to the classically distinct nature of strength, stiffness, rigidity, and flexibility of connective tissues.⁴

Noncollagenous proteins and glycoproteins are relatively minor constituents in terms of volume in the extracellular matrix of connective tissues. Generally, these molecules function in matrix organization and cell matrix interactions. They also help with orientation and maintenance of matrix structure. Two important glycoproteins found in the extracellular matrix are fibronectin and laminin. Fibronectin regulates the spread of cells and has strong chemotactic properties that attract and bind various connective tissue cells. Fibronectin is synthesized by many connective tissue cells, including osteoblasts, and may play a role in cell matrix interactions during osteoblast maturation. Laminin is a multifunctional glycoprotein found in the extracellular matrix that is important in establishing epithelial tissue and basement membranes during wound healing.

Lipids represent less than 1% of human articular cartilage matrix. The specific function of lipids and phospholipids is not clearly known. However, the presence of lipids in extracellular connective tissue matrix varies with the onset of osteoarthritis (OA).⁴

Specific connective tissue organization of muscle fibers is systematically arranged by endomysium connective tissue. Muscle fibers collectively are bound together to form fascicles. These fascicles are supported by perimysium connective tissue. The connective tissue membrane surrounding the entire muscle is called epimysium. Muscle tissue is unique in that it consists of contractile elements that respond to stimuli, as well as passive or elastic elements that resist stretching. Muscle tissue and noncontractile connective tissues such as endomysium, perimysium, and epimysium demonstrate characteristic load deformation viscoelastic properties in response to specific stimuli. Human skeletal muscle exhibits the same viscoelastic properties as other dense connective tissues. In fetal development, these noncontractile connective tissues act as tissue scaffolds to hold, support, and provide continuity of gross form and structure of the muscle’s belly. In addition, loose connective tissue of the perimysium serves as a channel for nutrient arteries and vessels, as well as nerves that supply the muscle fibers.⁴

REVIEW OF TISSUE HEALING

Healing of biological tissue is characterized by predictable, orderly, and sequential phases of repair. In essence, healing can be broadly classified in a series of three overlapping events: (1) inflammatory response, (2) proliferation, and (3) remodeling and tissue maturation. All musculoskeletal tissue proceeds to heal and repair by these individually unique processes.

Inflammatory Response

Acute inflammation is a transient initial phase of injury repair that lasts approximately 5 to 7 days. Directly after trauma, platelets migrate to the injury site and release specific growth factors and chemical mediators, which stimulate homeostasis and initiate the repair process. A fibrin scaffold structure is formed within the trauma bed, creating a matrix that allows for platelet aggregation and adherence to the injury site. This process of platelet activation stimulates synthesis of thrombin, fibrin, and the random organization of clot formation. Platelet plug formation is essentially a four-step process: (1) adhesion, (2) aggregation, (3) secretion, and (4) procoagulant activity (Fig. 7-1).

Adhesion of platelets is the deposition of these cells on the subendothelial matrix. Platelets have a surface receptor glycoprotein that binds to a sticky protein substance referred to as von Willebrand factor (vWF) found in the subendothelial matrix. Endothelial cells synthesize vWF, which is released into the circulating plasma, then deposited in the subendothelial matrix in response to exposure from injury.1,3 Aggregation is simply platelet-to-platelet cohesion via the surface fibrinogen receptor complex of the platelets. Secretion is the release of a number of platelet-derived growth factors (PDGFs) by stimulated platelets. The aggregating stimulators of serotonin, thrombospondin, and thromboxane also are secreted. Procoagulant activity refers to the process of thrombin formation and ensures that coagulation occurs at the site of the platelet plug.