The Biology of Scar Formation Maureen A Hardy PHYS THER. 1989; 69:1014-1024.

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is Director. the reference list will enable interested readers to pursue further information. Jackson. Somehow. they are capable of regenerating exact duplicates of the missing parts. as much as possible. Peripheral nerves heal by axoplasm regeneration distally to restore nerve tracts. 3)to review appropriate intervention methods based on research findings. impart tensile strength. each component of the repair process is an area of intense research efforts. Scar Characteristics How is it possible for the body's repair system to duplicate the original form and function of the injured tissue with only one type of glue? Our body structures can be divided into at least 14 different types of collagen. in its most basic definition. and therapeutic management protocols. The purposes of this overview are 1) to address the three phases of repair (inflammatory. MS. Although a comprehensive treatise on each section is beyond the scope of this manuscript. 2)to discuss the cellular processes occurring in each phase. Scratches and mild burns of the skin are healed by epidermal regeneration. Hepatocytes in the liver are capable of regrowth following mild toxic conditions. 22/1014 Physical Therapy/Volume 69. our body's "glue" is formed through a highly organized sequence of physiologic events. scar does differentiate to become quasi-tissuespecific. but it is the primary means of repair for all vertebrates. Hand injuries. and Instructor. University of Mississippi Medical Center. scar. hand and wrist. Mature scar is formed from type-I collagen. Experience tells us that often this attempt by scar to blend in cosmetically and functionally is not successful. signal the appropriate cells. Maureen A Hardy How We Heal A wound. cirrhosis. flexible tissue. It is an inferior method compared with regeneration. Thus. Primitive animals respond to this threat by mitosis of their cells. Certainly. MS 39216-4699 (USA). is a disruption of unity. MS 39216. and large nerve gaps overwhelm their limited regeneration potential. Certainly. 1989] Key Words: Cicatrix. and carry through the sequence of repair without complications." This body glue is called granulation scar tissue Maintenance of our well-being depends on our body's ability to sense a disruption of unity. that is. Enhancing the potential of scar to duplicate the desired outcome is the basis for surgical. M Hardy. 2012 . Wound healing. Select organs in our body still retain this biological gift of regeneration. Jackson. more devastating insults such as full-thickness burns. Number 12/December 1989 Downloaded from http://ptjournal. Collagen. pharmacological. Hand Management Center. and permit return of function is reviewed. in response to certain internal and external by guest on April 4. 969 Lakeland Dr. School of Health Related Professions. will change in its last phase of healing to reproduce. and 4) to describe complications that interfere with normal healing. Upper extremity. The ability of these tissue examples to regenerate or "reduplicate" their original condition is limited to minor injuries and healing under optimal conditions. Nature has provided us with another means of survival. Phys Ther 69:1014-1024. these physical characteristics. PT.apta. the scar formed in dense tissue "senses" the need for strength and attempts to mimic the surrounding tissue in structure. and remodeling). fibroplastic.The Biology of Scar Formation Scar. St Dominic Hospital. A knowledge of wound healing enables the clinician to design and implement treatment strategies based on scar biology. adapt to their structural integrity. The ability of one type of collagenous tissue to weld various tissues. [Hardy MA: The biology of scar formation. Special cells in our body respond to injury by forming a collagenous "glue. Likewise. yet it is the greatest chameleon in its ability to imitate the structure of other collagen types. This review of scar biology presents an overview of how healing occurs. 2500 N State St. both in the clinic and in the laboratory. filling a defect in loose. Inflammation.

If too little inflammation occurs. 2) thefibroplasticphase. is high in fibrinogen. binding them all together as one unit. either surgically or traumatically by guest on April 4. thus temporarily closing the wound. Yet a balance is needed.2 This gel then does notflow. Timetables for the beginning and end of each phase must be understood as general guides. These channels do not reopen until later in the healing process. The response to injury.The patient's wound-healing status is certainly an integral part of each initial evaluation in acute care. These cut vessels poured whole blood into the wound. require edema care. cauterized. therefore. any blood vessels that traversed the wound were cut at the time of injury. However. thus thinning normal skin in the area. Bradykinins. a descriptive history of how the repair progressed in a patient with wellhealed scar will alert the clinician to certain potential problems. and 3) the remodeling phase. The duration and type of immobilization affects the mobility and stability of the scar. a powerful stimulus to scar formation. noninjured vessels dilate in response to chemicals released from injured tissues. This serous transudate can be diminished by the classic "RICE" regimen of rest. Number 12/December 1989 Downloaded from http://ptjournal. Knowledge regarding injury time frames combined with objective appraisal of the scar give us our best basis on which to make these decisions. sealing off the injured vessels and lymphatic channels. Lymphaticflowis blocked to seal off the wound and prevent the spread of infection.3 This thinning of normal skin is hypothesized to be the cause of the clinical condition of fingertip "pencil pointing" that occurs following chronic edema conditions. The inflammatory phase prepares the area for healing.8 They found that each joint responds to swelling by assuming a Normal Wound-Healing Phases All forms of trauma.1 The mast cells also release hyaluronic acid and other proteoglycans into the wound milieu. and even controlled surgical procedures. the timing of Physical Therapy/Volume 69. If too much inflammation occurs. as long as one month postoperatively. This combination of whole blood exudate and serous transudate creates a reddened. excessive scar is produced. and even one wound can show various areas healing rapidly or slowly. produced by all cells in the body. compression. Hematomas. and elevation. Excessive swelling. Eyring and Murray performed joint distention studies by infusing saline in normal hands. create extra exudate.7 Excessive inflammatory fluid also affects joint positioning. One process is stimulated to begin. Changes in vascular flow are responsible for the clinical symptoms we use to detect an inflammatory response. or one wound (Figure 1A). excessive skin sloughing. derived from the blood. and paresthesias alert us to the presence of associated complications. Most cells in injured tissue release histamine. Primary wound care ensures that all blood vessels have been repaired. Histamine causes brief vasodilation in neighboring noninjured vessels. At what point is healing complete? This question is important in determining return to work. Pharmacological use of steroids and aspirin affects the transudative edema. The sequence of events is highly organized and predictable. Certain prostaglandins further contribute to long-term vascular vasodilation.The inflammatory edema fills all spaces in the wound and surrounds all damaged or repaired structures. dramatic color or temperature changes. and its completion in turn signals another cellular response until the wound is bridged by scar. If there is no inflammation. Prostaglandins. healing is slow. the result of ongoing bleeding in the wound. Reports of prolonged swelling.6 Their action aids in inhibiting prostaglandin release. swollen. healing does not begin. 2012 1015/23 . In addition to this direct blood vessel injury. anywhere in the body. are released with any breach of cell membrane integrity. hot. contribute to more prolonged vascular permeability. Inflammatory Phase Inflammation is a normal and necessary prerequisite to healing. This type of edema causes loss of dermal fat. to prevent scar formation is to prevent healing. All wounds. Until then. ice. Obviously. That some swelling in a wound is inevitable and needed is a fact. Different tissues heal at different rates. The extent of wound infection or dehiscence may predict the amount of scar formed in the tissue. progressive pain. Ward showed that the use of a tourniquet in hand surgery significantly increased hand edema. signal the reparative sequence to begin.The coagulated gel will later mature into a dense.4 Fibrinogen coagulates in the wound and in the surrounding tissues that are nowfluidfilled. This inflammatory fluid. The majority of the specialized cells involved in this phase of the woundhealing process come from our blood. which bind with the watery wound fluid to create a gel. or clotted.5 Secondary wound care addresses the contribution made by induced vasodilation. The ultimate goal in collagen research may be the discovery of healing without scar formation. which then coagulated. further surgical intervention. Underlying disease processes and preinjury medications can influence the timing of repair. binding scar (Fig. to any tissue. derived from plasma in the area of the injury. which continues in relation to the severity of the wound. and permanent impairment ratings. 1B). The wound then passes through three phases toward final repair: 1) the inflammatory phase. and the remodeling phase provides the final form. The fibrin plugs that clotted in the wound also form in the lymphatic vessels. is immediate. thefibroplasticphase rebuilds the structure. painful environment.apta. as compared with controls. must not be permitted.

(C) oxygen at over 20% of the scar absorption and reorganization has occurred through successful remodeling. They facilitate As macrophages ingest microorgaillary pores and migrate to the site of muscle action that draws the joint into nisms.13 endothelial walls. 2012 . even edema is first reduced. and 2) a new blood predictable position to lessen tension sues. These short-lived cells begin the process of phagocytosis by fixing to bacteria.apta. 1. peroxide. As a scavenger cell.12 First. hydrogen act at this point by inhibiting the logically inhibit antagonistic muscles. white blood thumb posture confirms their findbreathed. The patient with a wound is a critical factor. topicells begin to stick to the dilated ings. certain vitamin deficiencies. then enzymatically dissolving and digesting the by guest on April 4. Maintenance be available. radiated tissues. Anti-inflammatory steroids also the "comfortable" position and neurodigestion. this phase need to be supported and peroxide aids in controlling anaerobic positioned correctly through the use microbial growth. as opposed to local. Second.teria present.14 Build-up of these acids is wound of infection. The first white blood cells to reach the wound are polymorphonuclear leukocytes. infection developing: the type of bacwound must be decontaminated 24/1016 Physical Therapy/Volume 69.basal rate for enhanced phagocytosis. the inhibitory effect of distended joint from more macrophages. Resolution of repair: (A) Shaded area represents fluid edema bathing all consume injured tissues. has two important roles in the process of repair. Within blood vessels phalangeal (IP) joints. system of defense is adequate to preThe net result of an increased macvent minor contamination from develrophage population is a more intense oping into a major infection. and immunosuppression. two preand prolonged inflammatory conditions can tip the scale in favor of requisite events must occur: l)The response. "dropped" wrist. presence of foreign objects. Each of these processes swollen hand characterized by a of an adequate arterial oxygen supply will be described. flexed interdent on sufficient blood volume and Phagocytosis. the macrophage not only attacks and engulfs bacteria but also disposes of necrotic tissue in the wound. Chemical changes al demonstrated further that swellin the wound induce and attract these ing in a joint causes joint receptors to cells to slip through the enlarged capfire in a biased manner. extending their membrane around them. poor oxygen supply. Hydrogen cells. necrotic tissue. lactic acid are believed to be the subThe main purpose of this portion of Active exercise may be disadvantastances that signal the extent of the phase is to prevent or rid the geous during this phase unless the damage. Number 12/December 1989 Downloaded from http://ptjournal. and lactic acid are byamount and mobility of white blood These findings imply that hands in products of phagocytosis. Ascorbic acid and of external dressings and splints. the macrophage has been termed the "director cell" of repair because of its influence on scar production. it continues the important job of phagocytosis. Because ischemic tissues are more prone to infection than normal tis(phagocytosis). This cell. our receptors. All wounds. (B) the wound fluid has coalesced into one scar binding all tissues. extended metacarfor optimum phagocytosis is depenpophalangeal (MP) joints. they also excrete products of injury. Certain For healing to commence. another type of phagocyte will predominate and remain in the wound until all signs of inflammation cease. More macare contaminated. In a few days. thus removing interpreted as a need for assistance under meticulous sterile conditions. It is capable of phagocytosing in poorly nourished tissues with low oxygen levels or can Fig. the oxygen tension of the supply (neovascularization) must then on joint receptors. Fortunately. Young et al9 and deAndrade et 11 10 cally applied oxygen. Ascorbic acid. rophages produce more by-products. malnutrition. the macrophage. and adducted percentage of atmospheric oxygen adjacent to the wound.

RICE regimen. fewer types of cells operate in thefibroplasticphase. the fibroblast is ready to begin its synthesis of the collagen molecule. Once in place. evacuation of hematomas. Its presence is vital as a phagocytic agent and appraiser of damage. rebuilding can commence. use of wet-to-dry dressings as a form of microdebridement. Number 12/December 1989 Downloaded from http://ptjournal. Once this condition exists. an unknown signal causes the majority of loops to cease functioning and retract. all these events happen within the first four days after injury. These new circulatory loops fill the wound. The capillary sprouts. The inflammatory response so far has proceeded without any new regrowth of blood vessels. Lotz et al's study of the effect of early shoulder motion in the inflammatory phase following mastectomy showed increased serous collection. chronically activated macrophages create a chronically inflamed wound.18 Topical administration of this growth factor is being used to enhance cellular activity in chronic. which renders them delicate and easily disrupted. This phase is named for the primary cell of scar production—the fibroblast.apta. The macrophage thus "directs" the future course of repair by chemically influencing the number of fibroblastic repair cells activated. interrelated dynamics that have occurred in this first phase would lead one to believe that weeks must be necessary for completion. therefore. use of steroids inhibits the macrophage level. Neovascularization. and secondary trauma elsewhere in the body can prolong the inflammatory period. These migratory fibroblasts follow the fibrin meshwork created earlier in the wound fluid milieu. The color of scar. wound cleaning. Three processes occur Physical Therapy/Volume 69.22 As this phase comes to a close. major injuries. Immobilization is essential during this phase to permit vascular regrowth and prevent new microhemorrhages. Fibroblasts originate from mesenchymal cells located in loose tissue around blood vessels and by guest on April 4. In normal conditions. probably directed by ischemia.The significance of thesefindingsis twofold.1617 Hunt and Van Winkle point out that ultrasound agitation is capable of disintegrating macrophages. Our main directive is to minimize all factors that can prevent or prolong inflammation. wound breakdown. Hunt and Van Winkle's statement that "as neovascularization goes. pulsed ultrasound in water baths significantly decreases infection. Removal of all foreign materials. Reviewing the complex.11 Their debris may then signal more phagocytic cells to the infected area.21 They concluded that early motion protocols should commence at the completion of this phase.20 These outgrowths will eventually come in contact with and join other arteriolar or venular buds to form a functioning capillary loop. so goes the wound. As the wound approaches final maturity. lack full thickness. Fibroplastic Phase With the inflammatory phase completed. The purpose of this phase is to resurface and impart strength to the wound. Once again. Paletta et al's work showed that heat application during this portion of the phase will cause increased bleeding from these fragile vessels and is therefore contraindicated. it is suspected that the macrophage may signal this vascular regeneration to begin. creating a highly pink to reddish color throughout the one wound. Because the wound fluid bathed all injured structures. Second. The young wound will remain redder in contrast to the normal adjacent tissues throughout healing because of this inundation of capillary loops. resulting in lack of wound debridement and a delay in scar production.11 Complications. a fully matured scar appears whiter than adjacent tissue. Studies have confirmed the use of low-dosage. debridement. Patent vessels in the wound periphery develop small buds or sprouts that grow into the wound area. the fibroblast has access to all depths of the wound. their work will last about three weeks. and infection as compared with controls. Our body must evaluate the extent of the wound in order to mobilize a sufficient number of repair cells. the inflammatory phase is over. Another cell type (thefibroblast)will soon respond to the chemical signals issued from the macrophage.12 The macrophage has been described as a key factor in regulating events in this inflammatory period. Healing will not proceed unless new. these precursors of the fibroblast transform into cells with migratory ability. Treatment is directed toward assisting the role of the macrophage through the use of antibiotics."11(P14) emphasizes the importance of this phase. and frequent whirlpool cleaning will result in a clean wound bed that is ready for healing. nonhealing wounds. use of antibiotics. First. Areas that remain gray in appearance or have a delayed blanch test following pressure show inadequate circulation. is an excellent prognostic guide as to the potential for further changes in scar characteristics. functioning blood vessels are present to supply oxygen and nourishment to the injured tissue.19 Conversely. fibrinolysin from blood vessels is produced to assist in dissolving clots. debridement of necrotic tissue. A local plateletderived growth factor released from platelets during clotting and from macrophages signals fibroblasts. the fact that most wounds heal without infection is a credit to the microbicidal capacity of the potential macrophage population. In response to chemotactic influence from the injury. Thus. The lymphatic channels open to assist in reducing the wound edema. when first formed. Its role in recruiting fibroblasts is significantly related to the final amount of scar produced. Although many different cells are involved in the inflammatory phase. and proper positioning. 2012 1017/25 . we can potentially mitigate this process by assisting the macrophage in its work.15 Clinically.

If contraction occurs. Permitting an open wound on the hand to heal by uncontrolled contraction is inviting trouble. and hypertrophic scars. The advancing edge of the epithelium seeks out moist. the goal should be inhibition of wound contraction. tendons. square or rectangular wounds contract at a moderate pace. and sheaths all joined by fascial connections requires every millimeter of skin and tissue length. Some investigators claim beneficial effects of local application of oxygen in accelerating the migration process. Although clean. avoidance of chemical irritants or infection. it will dive downward to maintain contact with the vascularloop network in the wound.simultaneously in this phase to achieve coalescence and closure: l)epithelialization. If the wound bed is viable and good blood supply available. protecting the wound from minor repetitive trauma. undamaged epithelial cells at the wound margin begin to reproduce. If the necrotic tissue or the wound is too extensive or oxygen availability is poor. This specialized cell was identified in 1971 by Gabbiani et al28 and named a myofibroblast. Unlike epithelialization. The myofibroblast is derived from the same blood vessel adventitia and fat cells as are fibroblasts. epithelial migration cannot proceed. The close interplay of multi- ple joints. The myofibroblasts attach to the skin margins and pull the entire epidermal layer inward. and possibly topical oxygen therapy. which act to cleave the attachments of nonviable tissue from the viable wound bed. tenosynovitis. Joint contractures. muscles. There is another force at work aimed at closing the wound. It is hypothesized that the stimulus for this epithelial mitosis is a loss of restraint that cells in contact exhibit over each other. the centripetal force will pull all structures toward the wound. There is a priority of nature inherent in healing. therefore. and in fibrous capsules formed around implants.23 This accelerated reproduction causes a ridge to form around the periphery.apta. Factors critical to survival such as phagocytosis. the dressings will adhere to this thin skin. forming a "picture frame" that will move inward. Dressings. These unusual cells have been identified in other conditions associated with a contraction process. deep structures covered by mobile. Within hours after injury. If sufficient capillary circulation is not available to maintain epithelial integrity.31 the shape of the picture frame predicts the resultant speed of contraction: Linear wounds contract rapidly. Wound contraction begins about four days postinjury. will facilitate this by guest on April 4. These migratory cells remain attached to their parent cells. therefore.26 Epithelialization can be facilitated by maintaining moist dressings. or blood clots. debridement. open wounds require a longer period. oxygen-rich tissue. Epithelialization. the eschar loosens and detaches from the wound. 2) wound contraction. The new cells are true epithelial cells. approximated wounds are clinically resurfaced within 48 hours. foreign material. Approximated and sutured wounds minimize the need for contraction Physical Therapy/Volume 69.24 Surviving epidermal structures such as hair shafts and sweat glands also give rise to epithelial mitosis. decreasing the size of the wound. however. as sometimes seen in full-thickness hand burns. may be harmful in the hand. If allowed to dry. and 3) collagen production. are often the result of uncontrolled wound contraction. 2012 .29 The "picture-frame theory" identifies the wound margin beneath the skin as the location of myofibroblast action. contraction is a process that actually pulls the entire wound together.11 but further research is needed to validate this claim.32 Because contraction in the hand results in deformities. The difference is that these cells contain the contractile properties of smooth muscle cells.27 Wound contraction. This phenomenon is an active event dependent on an active cell. Successful contraction results in a smaller wound to be repaired by scar formation. sutures. however. such as Dupuytren's contracture. and circular wounds contract slowly. Minimizing the area to be healed is truly beneficial in certain tissues with fixed. their movement causes a "pull" on the normal skin around the wound edge. As it gradually 26/1018 undermines. in effect shrinking the defect. larger. contact inhibition causes cessation of movement. and removal will result in microdebridement of this healing tissue. Wound contraction. If the wound is not closed by 14 to 21 days postinjury. with those from the periphery moving in and those from appendages moving out. A red. highly vascular wound with a thin. Skin healed in this manner. Although contractile forces start out equal in all wounds. blood flow. this is a regeneration process. It is believed that the scab forms a temporary barrier for the wound and should not be disturbed until epithelialization is complete. contraction stops because of the restraint of the surrounding stretched tissue.30 A ring of these contractile fibroblasts convene near the wound perimeter. Providing even a one-cell layer of its own covering will reduce the chances for infection. Number 12/December 1989 Downloaded from http://ptjournal. wound dehiscence can occur. then migration of these new cells begins.2 Should the epithelial edge meet eschar. never truly develops a full basal layer of cells and will always be thinner in appearance. The body "knows" invading organisms are from the outside environment.25 When epithelial cells from one direction meet similar migratory cells. The epithelial margin must release lytic enzymes. such as on the abdomen or gluteal area. which closes the wound surface. almost transparent covering is now visible. kept moist and not permitted to dry out. The thickening process of skin healing is called intussusceptive growth. Several weeks are required for this thin covering to become multilayered and to differentiate into the various strata of normal epidermis. A protective barrier will further aid healing by preventing loss of fluid from the wound. and surface covering occur early in healing. loose skin.

These spiraled chains.34 The thickness of the graft correlates with the degree to which contraction is suppressed. The climax of wound healing occurs with collagen production. then excision of the wound margins prior to graft application is necessary to prevent contraction from occurring beneath the graft. Salt water application. the triple-helical molecule undergoes cleavage at specific terminal sites. These ionic charges together with early hydrogen bonds keep the molecule weakly stable. still in a gelatinous state. Fig. now called procollagen. Once exocytosed. the build-up of lactic acid will influence the amount of collagen produced. The early combined use of full-thickness grafts with splinting inhibits contraction by 77%. and copper are needed to create the proper background forfibroplasia. Adequate supplies of oxygen. Number 12/December 1989 Downloaded from http://ptjournal. The only difference Physical Therapy/Volume by guest on April 4. the fibroblast synthesizes three polypeptide chains. ascorbic acid. 2012 1019/27 . Studies have shown that contraction is diminished through the use of skin grafts. but not all wounds can be closed primarily. is dependent on the microscopic welding that must occur within each filament and from onefilamentto another. 2). Initially. 3A). Wound durability. 2. and this dense connective tissue can be considered highly cross-linked. and other cofactors such as zinc. The number of intermolecular bonds formed will enhance the strength of the filament. The amount of collagen filaments formed does not build strength. opaque gel on the plate is also collagen. They are the major force holding tropocollagen filaments together. vibration. If this event does not occur. the wound will not heal.apta. which enhance stability but remain soluble. 3B). are then extruded from thefibroblastout into the extracellular space. in the inflammatory phase before contraction is initiated.35 If the myofibroblasts are already mobilized and functioning. thus imparting tensile strength to the wound. Figure 4 depicts a clear solution of collagen in a beaker. These sites of bonding are called cross-links.Having its metabolic needs met for nutrients. With further maturation into tropocollagen. Split-thickness grafts diminish contraction of the wound bed by 31%. and enzymes can easily denature and separate the chains.36 These cross-links are called intramolecular cross-links because they occur within a single tropocollagen molecule (Fig. Rudolph points out that grafts must be applied early. Collagen aggregation from one helicalfilamentamassing with others to formfibrilsand collagen fibers. Collagen production. iron..forces. These chains coil to form a right-handed helix. The rigid. Bone tissue has the highest ratio of intermolecular bonds. Migratoryfibroblastsare now present throughout the wound. The wound environment is responsible for stimulating thefibroblaststo synthesize and secrete collagen. weak electrostatic forces aid in attracting and holding the three chains together at the procollagen stage. Tropocollagens spontaneously associate in an overlapping array. The amassing continues as tropocollagen convolves with other tropocollagen molecules to form a collagen fibril (Fig. The helix is now called a tropocollagen molecule. Covalent bonds are now in place. the chains change at specific sites to permit stronger cross-links to form. or tensile strength. Thesefilamentslay disorganized in the wound.33. Intermolecular bonds form from one tropocollagen molecule to another (Fig. heat. full-thickness grafts diminish contraction by 55%. As described earlier.

Despite the fact that collagen synthesis continues at a high rate. bone. Remodeling requires the scar to change to fit the tissue. which fill in the space between and around collagen fibers. with thin and lengthy adhesions to permit motion between parts. controlled motion without fear of disruption."43 Synthesis-lysis balance. of normal. Breaking the bonds causes the molecule to become soluble and excreted from the body as waste by-products. that is.42 A secondarily inflamed wound results in collagen deposition in addition to that already present.41 37 eling scheme. The quantity of scar produced at this time is an indication of final outcome.apta. they make new collagen and break down old collagen in a balanced fashion. and rough handling can cause the wound to become reinflamed. the tissues are in a steady state. and arrangement of collagen fibers.45 Col- Physical Therapy/Volume 69.39 When this important buffer interface is diminished. no further increase in scar mass occurs. A bulky. infection. It is believed that the composition of this nonfibrous substance is also related to the amount and location of cross-links formed.Remodeling Phase Successful wound healing requires more than closing the wound with sufficient tensile strength. Akeson et al have shown that immobilization causes a loss of ground substance. Repaired ligaments must have firm. combined with water. however. provides lubrication and acts as a spacer between moving collagen fibers. Mobilization aimed at breaking scar will create a new wound. is responsible for the final aggregation. The formation of cross-links in this phase allows the wound to tolerate early. and postpartum uterine tissues. Number 12/December 1989 Downloaded from http://ptjournal. In adults. but the 28/1020 red scar is visible and palpable. Inflammation from injury causes hormonal stimulation for increased collagen destruction by the enzyme collagenase. Several factors assist in the maturation Fig. and the wound granulation bed. Collagen bonding increases tensile strength: (A) Weak intramolecular and final physical characteristics of the crosslinks form between amino acid chains within one collagenfilament.44 It is a pervasive enzyme found also in rheumatoid synovial cells. Wound repair is optimal when this remodeling of scar tissue occurs and less than optimal when it does not occur. orientation. cross-linkage. 3 . Brand summarizes this point as follows: "The amount of scar to be remodeled is inversely related to the return of function. balance and fiber orientation will be described as they relate to the remodbetween the two is in their degree of tensile strength is roughly only 15% 40. 2012 . Thus.(B) stronger interscar. Edema.38 This GAG ground substance. Just millimeters away. the scar formed between ligaments and bone or moving parts must have a random orientation of scar fibers. The influence of synthesis-lysis molecular cross-links form from one collagenfilamentto another. Collagenase is capable of cleaving the strong cross-links in the tropocollagen molecule. ultimately with further scar formation. new cross-links are formed. a relationship between GAG ground substance and collagen dictates scar architecture. The fibroblast also synthesizes glycosaminoglycans (GAG). the migrating epithelium. they proceed to the next phase. The process of scar remodeling. which is not fully understood. The ultimate goal is the return of function. Collagenase is derived from polymorphonuclear leukocytes. by guest on April 4. rendering mobile tissue immobile. tender. under optimal healing circumstances. The wound at the end of this threeweek time frame has the greatest mass of collagen assembled. but complications can cause a recurrence of inflammation. Wounds are bidirectional at this time. yet the scar fibers must pleat with relaxation when tension is removed. intransigent scar formed with a parallel weave in order to resist deforming joint forces during stretching activities.

balance is achieved when scar bulk is flattened to approximate normal tissue. Ann Surg 155251-257. (Reprinted with permission from Peacock EE. remodeling is underway. Collagen synthesis and lysis are in balance with each other in a normal wound. Production and polymerization of collagen in healing wounds of rats: Some rate-regulating factors. depending on the extent of the injury. coiled.51 Thus. The "one-wound concept" of similar scar found throughout the wound is resolved (Fig. they can also regain it quickly with proper management. the entire organ suffers"47 reminds us that a fundamental principle of hand management is to keep all noninjured structures normal throughout the repair process. dense tissues induce dense. synthesis is depressed. held immobile throughout all three phases. We can restore the balance in hypertrophic scarring by the application of pressure to the scar. Inc. *James Industries. Seyfer and Bolger used a scanning electron microscope to visualize the form of adhesions that affect tendon gliding. The physical weave of the collagen fibers is largely responsible for the final functional behavior of the wound. whereas lysis continues. noninjured tissues are also affected. What forces are at play to direct this collagen realignment? Two theories are given regarding these forces: 1) the induction theory and 2) the tension theory. if one part is injured. Scar is nonelastic. Using principles inherent in the induction theory. the surgeon attempts to design the repair field by separating dense and soft tissues. The tissue structure induces the collagen weave. The high rate of collagen turnover in this phase can be either beneficial or detrimental. This process continues until the remodeling phase ends at six months to a year postinjury.46 This finding explains why an injured hand.) lagenase action is highest at the site of injury.apta. Synthesis is oxygen dependent. but neighboring. Collagen turnover is accelerated as old fibrous tissue is removed and new fibrous tissue is formed. PO Box 230.Collagen fiber orientation. highly cross-linked scar. Hypertrophic scar and keloids are examples of normal synthesis following wounding combined with a genetic inhibition of lysis. Two important questions must be addressed: 1) How does a change in scar orientation change tissue function? and 2) What forces direct the alignment of the collagen fibers? The first question can be answered with a common household example. pliable tissues induce a loose. dense adhesions. Studies on fascial wounds have revealed that not only does the area of injury experience this accelerated synthesis-lysis process. although to a lesser degree. 1C).11 This fact becomes important when the balance between the two processes is abnormal. Hollidaysburg. This pressure treatment must be continued until remodeling is complete and all collagen turnover returns to a normal level. Scar can adapt through the remodeling forces of synthesis and lysis. The induction theory hypothesizes that scar attempts to mimic the characteristics of the tissue it is healing. PA 16648. 2012 1021/29 . like a Slinky. whereas lysis is not. As long as the scar exhibits a rosier appearance than normal. Prolonged pressure renders an ischemic condition. in both linear and lateral orientation.Beaker of clear collagen solution and rigid collagen gel produced as result of collagen bonding. Physical Therapy/Volume 69. even though both rates are higher than preinjury rates. 1962. During remodeling. collagen turnover allows the randomly deposited scar tissue to be rearranged.49 A Slinky* toy is made from nonelastic metal. Number 12/December 1989 Downloaded from http://ptjournal. less crosslinked scar.50 They found that gliding tendons had lengthy. can have multiple contractures in injured and noninjured structures alike. Dense tissues seem to have preference or greater influence when multiple tissue types are found in close proximity. Merritt's statement that "the hand is an organ.43 Tendon repairs left immobile over bone fractures will ultimately resolve into bony adhesions encasing the nongliding tendon. Scar that forms with redundant folds will permit mobility of the structures to which it is affixed. elongated adhesions. by guest on April 4. Fig. If joints and tissues can lose mobility quickly. With lowered oxygen tension. Its spiral shape allows it to expand and contract with play. whereas restricted tendons had short.48 Eventually.

The recovery curves for tissue experimentally immobilized for two to four weeks reveals that reversibility requires months to complete and often is never fully successful. The current clinical advances in tissue remodeling are taking place in controlled-motion protocols. Other studies have demonstrated that the application of tension causes an increase in tensile strength during healing. 2012 . joint movement. positioning. They found that two variables were most responsible for successful remodeling: the phase of the repair process when forces are introduced and low-loadlong-duration application of stress.65 When the rod is removed. a dense. positional heat and stretching techniques. Bora et al demonstrated that gentle tension over time results in a repair site that is stretched and taut † Dow Corning Corp. temperature changes. and rational postoperative care. Even in the area of nerve regeneration. (Repr ed with permission from Arem and Madden. Upper sponge pair from unstressed control side.57.52) Remodeling factors. splinting. Permanent elongation of scar requires long-duration application of stress for scar tissues to remodel to the new position. Controlling the amount and location of scar can be addressed.53 Dynamic splints. Appearance of three-week-old scar following four weeks of tension.56 tendon. Changing the wound chemistry. yet permit forces through the tissue and wound bed. Midland. restrictive motion is used so as not to disrupt the repair or incite inflammation. in an attempt to influence scar formation. the hand has a new scar tunnel ready to accept a tendon graft.60 and bone61 have all been shown to lose tensile strength and normal collagen array with immobilization and stress deprivation. to a limited degree.63.54-62 Fascia. 5. lower sponge pair from stressed side. which requires redundancy for movement into flexion and extension.59 capsule.55 skin. The lateral sides of the new scar capsule are permitted to form denser scar to resist deviation deformities. serial casting. sequencing of repair. selectively inhibiting or enhancing synthesis-lysis. and controlled motion is then initiated. and selective hand activities are examples of methods used to achieve the lowload-long-duration stress necessary to change scar configuration. parallel union of scar to tissue is the desirable outcome. by gentle inspection of the wound. we are concerned with remodeling.58 Controlled. The clinical implication is that stretching scar achieves only a temporary lengthening. Muscle tension.apta. and mobilization are all examples of forces acting on the collagen array.64 These advances remain limited in clinical application because of their generalized effect on normal and healing tissues. Joint implants in the hand enable us to remodel the new scar formed around the implant as close to normal capsule architecture as possible. and controlling cross-linking are areas of intense research.57 ligament. Silastic†rods used in two-stage tendon reconstruction depend upon the induction theory of remodeling to form a smooth-surfaced scar around the entire length of the rod. Pharmacological manipulation of scar seeks to alter metabolism at specific sites. soft tissue loading and unloading.When repair sites cannot be separated by hand positioning.52 The results of their study confirmed that a physical change of scar length could be achieved through the application of stress during the appropriate healing phase (Fig.66 Through splinting forces.43 The tension theory refers to internal and external stresses that affect the wound area during the remodeling phase. planned surgical procedures.58 cartilage. functional electrical stimulation. and selective exercises. Tendon and ligament repairs are held immobile for two to three days during the inflammatory by guest on April 4. I 30/1022 Physical Therapy/Volume 69.62 Fig. In both types of tissue. The tension theory was given validity by the work of Arem and Madden. M 48640. tension is exerted on the dorsal and volar sides of the capsule. or interposition of fat and areolar tissues. 5). Number 12/December 1989 Downloaded from http://ptjournal. Each type of tissue depends on some type of stress for its functional integrity. The goal during the remodeling phase is to reintroduce a controlled stress as the scar matures. then early controlledmovement protocols are beneficial. or protective. passive gliding of fascial planes.

Contraction and the wound contents. 1975 35 Rudolph R: Contraction and the control of contraction. 1976 Physical Therapy/Volume 69. 1962 38 Dingman RO: Factors of clinical significance affecting wound healing. Larrabee WF: Controversies in wound management. 1961 4 Witte CL. Dixon ASJ: Joint distension and reflex muscle inhibition in the knee. Grillo HC. The role of granulation tissue in contraction. Plast Reconstr Surg 72:66-73. 1976. 1962 42 Cummings G: Selection of Treatment of Soft Tissue Contractures. Moltke E. 1983 33 Sawhney CP. 1984 26 Douglas DM. 1981 22 Paletta FX. MI. 2012 1023/31 . Adverse reactions and complications should be recognized and addressed. 1984 48 Hunt TK. Gross J: Studies in wound healing: II. 1986 28 Gabbiani G. J Invest Dermatol 32:505507. 1977 40 Howes EL. Understanding the sequence of repair permits flexibility in management as the wound changes. Harvey SC: Strength of healing wounds in relation to holding strength of catgut suture. PA. Hand 8:179185. Dumont AE: Significance of protein in edema by guest on April 4. Ann Surg 204:322-330.67 The nerve can then be stretched again and the stretched position maintained until the scar and tissues around the nerve remodel. Cohen IK: Biology of wound healing. Experientia 27:549-550. Perspectives in Plastic Surgery 2:89120. GA. Spector WG: Macrophage turnover in inflamed connective tissue. Br J Surg 56:219-222. Lymphology 4:29-31. Ann Surg 164:1-12. Stokes M. MO. Inc. Atlanta. 1970 16 Schoenbach S. 1980 36 Peacock EE. 1965 24 Bryant WM: Wound healing. J Exp Med 167:975987. Surg Gynecol Obstet 146:641-649. Ross R: The role of the macrophage in wound repair. J Bone Joint Surg [Am] 46:1235-1241. South Plainfield. 1985. Eriksson E: A double-blind trial of NSAID versus placebo during rehabilitation. In Peacock EE. Song I: Ultrasound debridement: A new approach in the treatment of burn wound. Mustoe TA. Clin Plast Surg 3:3-11. Philadelphia. J Invest Dermatol 36:451-456. Madden JW: Biological factors affecting wound contraction. Senia RM. Ross R: Platelet factors stimulate fibroblasts and smooth muscle cells quiescent in plasma serum to proliferate. 1976 49 Peacock EE: Some biochemical and biophysical aspects of joint stiffness: Role of collagen synthesis as opposed to altered molecular bonding. et al: Tissue edema: A stimulus of connective tissue regeneration. Majeno G: Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Proc Soc Exp Biol Med 124:207-210. Connect Tissue Res 5:15-19. NJ. J Cell Biol 69:196-203. 1980 46 Merritt WH. 1988 19 Knighton DR. 1984. et al: Wound Care. Ann Surg 148:145-152. Grant C. Peacock EE: Identification. et al: Collagen cross-linking alterations in joint contractures: Changes in the reducible cross-links in periarticular connective tissue collagen after nine weeks of immobilization. 1971 29 Guber S. Stokesville Publishing Co. Over six weeks of gradual repositioning. Laryngoscope 83:1540-1544. Br J Plast Surg 23:318321. Ciba Found Clin 29(3):3-6. South Plainfield. 1976 12 Leibovich SJ. 1929 41 Levenson S: Practical applications of experimental studies in the care of primary closed wounds. 1966 50 Seyfer AE. 1975 47 Merritt WH: Complications of hand surgery and trauma. Fiegel VD. 1977 25 Carrico TJ. Weber and Davis have defined hand therapy based on scar biology as follows: "Hand therapy is behavioral modification of thefibroblastduring the healing response. Am J Pathol 78:7191. World J Surg 4:279-287. Mudd JG: Hypothermia and tourniquet ischemia. 1965 11 Hunt TK. In Greenfield L (ed): Complications in Surgery and Trauma. 1980 17 Nichter L. Ann Surg 148:153-160. 1958 32 McGrath MH. 1986 3 Houck JC. J B Lippincott Co. Watts GT. 1958 31 Grillo HC. Jacob RA: The chemistry of local dermal inflammation. Proc R Soc Lond [Biol] 174:269-292. Ann Surg 155:251-257. 1987 10 deAndrade JR. 1975 13 Mathes S: Roundtable discussion: Problem wounds. Ogilvie RP: Physical characteristics of collagen in the later stages of wound healing. 1962 23 Carter SB: Principles of cell motility: The directional control of cell movement. Mehrhof AI. Nature 208:1183-1187. distribution and significance of a collagenolytic enzyme in human tissues. Plast Reconstr Surg 83:122-128. Rudolph R: The myofibroblast. et al: Classification and treatment of chronic nonhealing wounds: Successful treatment with autologous platelet-derived wound-healing factors. Surg Clin North Am 64:721733. Plast Reconstr Surg 29:531-538. NJ. Monga HL: Wound contraction in rabbits and the effectiveness of skin grafts in preventing it. J Bone Joint Surg [Am] 47:313-322. White RR. 1969 27 Borges AF. Majno G: Inflammation. Inc. 1976 15 Ryan GB. 1967 45 Peacock EE: Collagenolysis: The other side of the equation. Bolger WE: Effects of unrestricted motion on healing: A study of posttraumatic adhesions in primate tendon.apta. Ann Surg 193:288-295. Amiel D. NY.but that will respond by increasing its cross-sectional area. J Hand Surg [Am] 13:142-146. Chirurgecom. J B Lippincott Co. et al: In vivo incisional wound healing augmented by PDGF and recombinant c-sis gene homodimeric proteins. 1970 34 Stone PA. Mechanic GL. C V Mosby Co. Van Winkle W (eds): Wound Repair. 1973 39 Akeson WH. Philadelphia. Lynch DJ. 1988 18 Pierce GF. Williams J: Ultrasonic wound debridement. Surg Forum 26:547-548. Forrester JC. Kalamazoo. World J Surg 4:297-302. Plast Reconstr Surg 66:34-37. synthesis. 1977 21 Lotz M. 1964 9 Young A. Orthopedics 10:1007-1013. Summary These examples show that a knowledge of wound healing and repair enables the clinician to design and implement treatment regimens based on scar biology. References 1 Asboe-Hansen G. 1976 8 Eyring EJ. Murray WR: The effect of joint position on the pressure of intra-articular effusion. Surg Forum 26:553-554. Simon RH: Wound geometry and the kinetics of wound contraction. 1986 20 Ryan G. In Brand PW (ed): Clinical Mechanics of the Hand. Gross J: Studies in wound healing: I. 1971 5 Cohen IK: Complications of wound healing. 1989 51 Madden JW: Wound healing: The biological basis of hand surgery. Am J Surg 104:273-282. PA. " 6 8 ( P 5 2 9 ) HOW to apply the correct stress to the correct tissue at the correct time is the "behavioral modification" of scar that we strive to achieve. Philadelphia. Churchill Livingstone Inc. In Greenfield L (ed): Complications in Surgery and Trauma. Witte MH. 1987 7 Ward CM: Oedema of the hand after fasciectomy with or without tourniquet. vol 2 43 Brand PW: Drag. PA. Upjohn Co. W B Saunders Co. American Journal of Cosmetic Surgery 3:5-9. Austin LL. the subject in Bora et al's study was able to achieve full limb mobility without jeopardizing the repair. 1988 14 Rutherford RB. and interaction of fibrous protein and matrix. Chirurgecom. Duncan M. Chvapil M: Studies on the inductive capacity of canine fascia lata. Shehadi SI. Gerber L: Early versus delayed shoulder motion following axillary dissection. Dunphy JE: Wound Healing: Disorders of Repair—Fundamentals of Wound Management in Surgery. pp 61-87 44 Riley WB. Dyrbye MO. pp 3-8 6 Arvidsson RP. Ryan G.I l e sJF: Effects of joint pathology on muscle. Van Winkle W: Wound Healing: Normal Repair—Fundamentals of Wound Management in Surgery. New York. Number 12/December 1989 Downloaded from http://ptjournal. 1959 2 Cocke WM. N Engl J Med 200:1285-1291. Van Winkle W: Structure. Peacock EE. pp 145-203 37 Peacock EE: Production and polymerization of collagen in healing wounds of rats: Some rate-regulating factors. St Louis. 1982. Clin Orthop 219:21-27. 1978 30 Watts GT.

1975 63 Kulick MI. Madden JW: Effects of stress on healing wounds: I. 1976 53 Light KE. 1977 67 Bora by guest on April 4. 1987 60 Akeson WH. 1941 55 Thorngate S. high-load brief stretch in treating knee contractures. 1966 57 Gelberman RH. J Surg Res 20:93-102. Woo SL. et al: Effects of immobilization on joints. Smith S. 1969 62 Finsterbush A. Davis J: Rehabilitation following hand surgery. Lothringer K. et al: Effects of early intermittent passive mobili- zation on healing canine flexor tendons. World J Surg 4:289-295. Adv Surg 5:145-188. Nuzik S. Clin Orthop 111:290-298. Allen HS: The rate of healing of tendons: An experimental study of tensile strength. J Hand Surg [Am] 7:170-175. J Hand Surg [Am] 2:358-366. Surgery 44:619-624. 1978 32/1024 Physical Therapy/Volume 69. 1982 58 Noyes FR: Functional properties of knee ligaments and alterations induced by immobilization. Proc Soc Exp Biol Med 123:38-41.52 Arem AJ. 1980 68 Weber E. et al: Lowload prolonged stretch vs. Ann Plast Surg 13:459-467. J Hand Surg [Am] 5:21-25. Personius W. Brazlow R. Ferguson DJ: Effect of tension on healing of aponeurotic wounds. Clin Orthop 64:128. et al: Injectable ibuprofen: Preliminary evaluation of its ability to decrease peritendinous adhesions. Clin Orthop 123:210-242. DeVore G: A rational postoperative management program for metacarpophalangeal joint implant arthroplasty. 1971 66 Madden JW. Peacock EE: Biologic principles affecting repair of flexor tendons. Phys Ther 64:330-333. Richardson S.apta. 1958 56 Sussman MD: Effect of increased tissue traction upon tensile strength of cutaneous incisions in rats. 2012 . 1984 64 Cohen IK. Clin Orthop 221:26-32. Ann Surg 113:424-456. McCoy B: The biology and control of surface overhealing. Ing D. Intermittent noncyclical tension. 1986 61 Jenkin D. Amiel D. Friedman B: Reversibility of joint changes produced by immobilization in rabbits. Clin Orthop 219:28-37. 1977 59 Videman T: Connective tissue and immobilization. Number 12/December 1989 Downloaded from http://ptjournal. 1984 54 Mason ML. Black J: The biomechanical response to tension in a peripheral nerve. Orthop Clin North Am 92:529542. Cochrans T: Osteoporosis: The dramatic effect of disuse of an extremity. 1980 65 Weiner LJ.

org/site/misc/ Permissions and Reprints by guest on April Cited by This article has been cited by 2 HighWire-hosted articles: http://ptjournal. 2012 . 1989. Subscription Information http://ptjournal.xhtml Information for Authors http://ptjournal.xhtml Downloaded from http://ptjournal.apta.The Biology of Scar Formation Maureen A Hardy PHYS THER.apta.

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