Hypertrophic scar, poor wound healing, keloid, non-healing wounds

I. Non-Healing Wounds (Chronic Wounds)

  • Generally refers to open wounds that cannot be epithelialized and closed for 30 days.
  • Granulation tissue cannot form.
  • There may be a variety of factors involved; there are more than one theory to explain etiopathogenesis.
  • Medical conditions that prevent wound healing;
  1. Diabetes
  2. Venous diseases
  3. Arterial insufficiency
  4. Lymphedema
  5. Steroid use
  6. Connective tissue diseases
  7. Radiation damage
  8. Pressure necrosis
  9. Infection (especially osteomyelitis)
  10. Skin cancers
  11. Malnutrition
  12. Chronic dermatological diseases
  • For whatever the reason is, treatment for all chronic wounds begins with the debridement of necrotic tissues, if a treatment is available.

Pressure Necroses (Decubitus ulcers, bedsores)

  • In general, they are wounds that develop on bone protrusions of immobilized patients.
  • It more commonly develops in the sacral, ischial, and trochanteric regions. It can also be observed in the metatarsal heads, ankles, heel, and occiput regions.
  • The amount of tissue necrosis depends on the time and magnitude of the pressure. When tissue pressure rises above 25-30mmHg, capillary perfusion and microcirculation get impaired. Pressures persisting for 2 hours at this level cause necrosis.
  • Compared to the deeper fat and muscle tissues, the skin is more resistant to the development of pressure necrosis. This is why larger areas of tissue necrosis are found in tissues under small skin ulcers in clinics.
  • The treatment begins with the elimination of the factors, which cause pressure necrosis (changing the position, using an air mattress).
  • Many pressure necroses heal in consequence of the elimination of the existing pressure. However, wounds heal with scar tissue, which is more pressure-sensitive than normal skin. Therefore, pressure necroses which heal spontaneously are at a greater risk of recurrence, compared to wounds healed with surgical treatment (flap-normal skin).

Lower Extremity Wounds

  • They usually develop due to arterial and venous insufficiency.
  • 80-90% of the causes are venous insufficiency that develops due to valvular insufficiency.

Venous Insufficiency

  • Edema and plasma extravasation develop due to valvular insufficiency and increased lower extremity venous pressure.
  • Fibrinogen deposition causes the formation of a fibrin layer around the capillary, preventing oxygen and substance diffusion.
  • Leukocytes are retained and activated in obstructed capillaries. Released radicals and proteases cause damage and tissue necrosis.
  • Elevation and compression therapy is performed (Coban). Prophylactic stockings that provide 30-40mmHg pressure should be worn after the treatment of venous stasis ulcer.

Arterial Insufficiency

  • Ischemic wounds heal late and carry a higher risk for infection.
  • If the transcutaneous oxygen pressure measured at the wound edge is 30mmHg, the wound is likely to heal.


  • Neuropathy causes loss of sensation and biomechanical joint instability.
  • Many patients have arterial insufficiency.
  • Synthesis of many GFs has been observed to decrease in diabetic wounds (VEGF, IGF-1, FGF-1, PDGF)
  • Apoptosis rates have been observed to increase. Proliferation rates of diabetic fibroblasts and keratinocytes have been observed to decrease. Less collagen synthesis occurs.
  • In cases where blood glucose is well regulated, wound healing is positively affected by the condition as well. This reveals that the mentioned mechanisms are reversible in diabetes.



  • After RT, acute and chronic effects occur on the skin.
  • Self-limited erythema with the potential to develop acutely resolves spontaneously.
  • Late effects are observed on keratinocyte, fibroblast and endothelial cells. The resultant DNA damage causes impaired proliferation of these cells.
  • Endothelial damage causes progressive endarteritis. This causes atrophy, fibrosis, and poor wound healing.


  • Bacterial infections disturb healing through different mechanisms. Acute and conical inflammatory infiltrates slow down the fibroblast proliferation, preventing the synthesis of ECM components. Sepsis causes systemic effects and disrupts wound healing through an unknown mechanism.
  • The number of bacteria that clinically causes the development of wound infection and affects the healing is 105 per gram of tissue.
  • Similarly, when the number of bacteria per gram tissue in the culture is 105, the skin graft placed on an open wound is more likely to fail; and in such cases, impaired wound healing is observed.
  • Desired healing with well-vascularized muscle flaps in open wounds can be achieved until the number of bacteria per gram of tissue exceeds 105.
  • Signs of wound site infection are fever, tenderness, erythema, edema, and drainage.
  • Treatment of an infected closed wound depends on the availability of discharge and necrotic tissue. Wounds with no accumulation to drain can be treated with appropriate antibiotics.
  • In cases with the accumulation of necrotic tissue and purulent fluid, sutures should be removed, debridement and washing processes should be carried out, and drainage should be provided. When necessary, selected appropriate antibiotics should be changed in accordance with the culture result obtained.


  • Wound healing that is an anabolic process causes the need for additional calories. The amount of calories required for optimal wound healing has yet to be defined.
  • Vit A (Retinoic Acid)

- It is effective at stages such as fibroplasia, collagen synthesis, cross-linking and epithelialization.

- Since it is a fat-soluble vit, attention should be paid to its toxicity. Its oral dose is 25,000 IU/day.

- Animal studies have revealed that it reverses the effects of steroid intake on wound healing. Its effect has not been proven in humans, but postoperative vit A is commonly used by many surgeons for patients treated with steroid.

Impaired collagen cross-linking is observed in vitamin B6 (pyridoxine) deficiency.

  • Syndromes characterized by impaired wound healing are observed in Vit B1 (Thiamine) and Vit B2 (Riboflavin) deficiency.
  • Vit C

- It is needed in the hydroxylation stage of collagen synthesis. Proline and Lysine

are converted to hydroxylysine and hydroxylysine by hydroxylation.

- In cases of hydroxyproline deficiency, newly synthesized collagen cannot be transported out of the cell.

- In cases of lack of hydroxylysine, collagen cross-linking does not occur.

- Despite the availability of normal amounts of fibroblasts at the wound site, adequate collagen synthesis does not occur (scurvy disease)

  • In patients with no vitamin deficiencies, vitamins given have no effect on wound healing.
  • Divalent cations such as copper and zinc functions as cofactors in enzymatic reactions. In cases of their deficiency, slowed epithelialization and healing are observed.


  • There is a slowdown in the wound healing process independently of diabetes.
  • In obese patients with diabetes, the wound healing process is disrupted independently of glucose control and insulin use.


  • The use of topical and systemic steroid adversely affects the healing process, especially in the 3 days after trauma.
  • Although the basic mechanism of action has yet to be defined, inflammation disrupts the collagen synthesis and contraction stages.
  • In experimental wounds, they have been observed to reduce the expression of PDGF and KGF.
  • Steroids stabilize the lysosomal membrane, reduce inflammation and slow down the healing process. They increase the rate of bacterial infection.
  • The use of Vit A can reverse the effects of steroids.


  • Radiation and chemotherapy manifest their main effects on dividing cells. Especially the Proliferative Phase of Wound Healing is affected.
  • In the oncologic surgical procedures, chemotherapeutics cannot be used until the 5-7th postoperative days.
  • Normally, when the dermal defect is closed and epithelialization is completed, the signals stopping the healing process are activated. Insufficiency or failure of this process leads to hypertrophic scar formation.
  • Although the basic molecular mechanism has yet to be revealed, Profibrotic Cytokine overexpression has been exhibited. Insufficiency of the apoptosis mechanisms and the continuing ECM synthesis of activated fibroblasts are among the possible causes.
  • There are important clinical factors which affect the formation of scar tissue. Making elective incisions parallel to Langer’s lines and not closing the wound tightly are among the preventive measures in this regard.
  • Incisions in parallel to Langer’s lines are positioned in natural skin folds, camouflage the scar, and minimize the tension.
  • Infection, scab formation on the wound lips and secondary healing lead to more scar tissue.
  • Hyperpigmentation or hypopigmentation makes the resultant scar tissue more visible. It is necessary to avoid direct sunlight to prevent the formation of scar pigmentation.
  • Hypertrophic scar and keloid formation are unique to human beings. The reason is unknown, but it is not seen in animals.


  • The scar tissue does not extend beyond the original boundaries of the wound, but it is too high.
  • Hypertrophic scar is a type of over-healing that limits itself and can regress over time.
  • It is usually observed in areas creating excessive tension. It is commonly observed in the extremities, articular surfaces, sternum, shoulders and neck regions.

Hypertrophic Scar - Keloid

The both type involve the fibroproliferative process characterized by excessive wound healing.

They are distinguished with their clinical appearances and characters.

In a hypertrophic scar, the scar does not exceed the original wound margins, but in a keloid scar, the scar tissue is larger than the original wound.

Histopathologically, there is no significant difference between these two types. In the both types, fibroblasts produce and accumulate excessive amount of collagen.

Keloid fibroblasts are more responsive to signals that lead to scar tissue formation.

Keloid scars may act like a benign skin tumor, and they keep growing slowly.

Those with OD have a genetic predisposition to keloid. It is less common in black people.



  • Scar classification should be performed before treatment.
  • Clinical scar classification was prepared by Plastic surgeons and dermatologists in 2002; (International Advisory Panel on Scar Management)




Mature Scar

Light colored, not raised; flat


Immature Scar

Red-pink, itchy, sometimes painful, raised from the skin (in the remodeling phase). Most of them turn into mature scars over time.


Linear Hypertrophic Scar

(surgery, traumatic)

Red-pink, at the incision line, raised from the skin, itchy.

It usually develops within weeks in the postoperative period. They may enlarge in size between the 3-6th months, and regression is observed after the static phase. Full maturation may take more than 2 years.


Wide Hypertrophic Scar


Observed in the burn area, becomes red-pink, mostly itchy.


Minor Keloid

Expanded beyond the wound margin to normal tissue, itchy.

It may keep growing for 1 year after the trauma. It does not regress.

It recurs after surgical excision.

Typical observed in the ear lobule.


Major Keloid

Expanded beyond the wound margin to normal tissue, large (> 0.5cm), painful, can be pruritic.

It can develop after a minor trauma and expands over the years.


  • Appropriate surgical manipulation (approach towards the tissue, suturation), wound care, protection from infection and direct sunlight are the rules that must be followed.
  • As a method of prevention, the following practices can be applied to patients in the risk group against hypertrophic scar formation:

1.Silicone gel application

2.Silicon-oil-containing creams

3.Hypoallergenic Microporous Tape

4.Intralesional Steroid injection.

Silicone gel is commonly used in the treatment of hypertrophic scars and keloids. It can also be easily used in children as it is painless and easy to apply.

  • The effectiveness of silicone has been proven by randomized controlled studies. Therefore, it can be considered as the method to choose first.
  • The mechanisms of action of silicone gel include;
  1. Causes hydration and occlusion,
  2. Causes local temperature rise (1 C or less); (leads to changes in collagenase kinetics and in adhesion molecule expression of lymphocytes).
  • Steroid injection reduces collagen gene expression.




  1. Immature Hypertrophic Scar (Red, slightly raised)
  • Silicone gel, steroid injection, localized pressure are applied.
  • The probability of its regression or progression is unpredictable. If erythema lasts more than 1 month, there is a high risk of linear hypertrophic scarring. Many authors recommend laser therapy to reduce its vascularity in such a case (pulsed dye laser).

2.Linear Hypertrophic Scar (Red, slightly raised)

  • Local compression (with a compression garment), silicone gel, 585nm pulsed dye laser therapy and re excision can be applied.
  • Re-excision is usually not preferred due to the high recurrence rate.
  • If there is wound infection or dehiscence accompanying the hypertrophic scar tissue, re-excision is the most appropriate procedure among the options.
  • Steroid therapy is useful for pruritic and resistant patients.
  • The 585nm pulsed dye laser is an alternative technique in the treatment of hypertrophic scars, but it has not been considerably supported by controlled studies.
  1. Wide Burn Hypertrophic Scars (Red, raised)
  • Silicone gel, compression garments, physical therapy (alone or in conjunction with massage, electrical stimulation, or USG)
  • Surgical treatment (z-plasty, excision-grafting, reconstruction with flap) can be performed.
  1. Minor Keloid (Red, raised)
  • A successful method for keloid treatment is not yet available. Steroid administration can be useful especially in the early period.
  • Patients become less responsive to steroid and silicone gel treatments in the course of time.
  • Short-low-dose RT administered immediately after keloid excision may reduce the recurrence rates.
  1. Major Keloid (Dark, raised)
  • They are quite resistant to treatments. After all the treatment options described above including the surgical treatment, the recurrence rates are still significantly high.
  • Despite the risk of cancer development it carries, RT is a widely performed procedure in elderly patients.
  • In cases where a surgical operation is planned, the patient should be preoperatively informed of the fact that the risk of recurrence is quite high and a new keloid will be more resistant to treatment.
  • The new treatment approaches include; Intralesional
  1. Interferon (α,β,γ)
  2. 5-FU
  3. Bleomycin applications are today a subject of research. The mechanisms of action have yet to be fully defined.


  • In the body, it is not just the skin where scarring and fibrosis are important.
  • Joint capsule fibrosis results in contractures.
  • Fibrosis developing in the anastomotic lines between the free jejunal flaps and the esophagus or pharynx may lead to lumen obstruction.
  • Capsule formation around the breast implant is a response to a normal damage. If the amount of fibrosis here is excessive, capsular contractures develop.
  • Excessive fibrosis in neural repair areas results in Neuroma.
  • Scar tissue that develops in the tendon repair area causes limitation of movement.
  • Dupuytren's disease is a fibroproliferative disease that involves the palmar fascia and deep dermis.


  • In a study on postnatal rodent wound, the use of Anti-TGF-β antibodies was observed to reduce the inflammatory response and scar formation.
  • In the rabbit flexor tendon repair model, the use of Anti-TGF-β1 antibody was observed to reduce adhesions and increase the rate of postoperative ROM.
  • In the rodent skin wound model, the use of TGF-β3 was observed to reduce scar formation (an opposite of the results of the others).
  • In the rabbit ear wound model, the use of TGF-β3 was observed to be unable to reduce scar formation.
  • The use of fibromodulin (TGF-β modulator) was observed to reduce the scar tissue.
  • In an adult mouse wound model, the use of IL-10 was observed to reduce inflammation and scar tissue formation.


  • The approach varies depending on the type of wound.


  • Incisional wounds heal with primary care.
  • Deep sutures are placed in the layers rich in collagen, such as the dermis and fascia. Since the adipose tissue has not significant collagen content, the sutures placed cannot bear the load. Therefore, many surgeons don’t prefer the technique that involves the closure of the sc (subcutaneous) adipose tissue with sutures. Instead, they use negative pressure drains, especially in obese patients. They ensure better obliteration of the dead space, and reduce the risk of seroma-infection.
  • To reduce the risk of infection and the amount of scar tissue, hematoma should be avoided and hemostasis should be provided properly.
  • Dermal and epidermal trauma should be avoided using appropriate forceps and hooks. Necrosis that may develop on the wound lips lead to increases in inflammatory response, necrotic debris and scar tissue formation.
  • Closed wounds should be kept in sterile condition for 24-48 hours until the epithelialization. Since the water barrier function is provided as well, water contact can be allowed at the end of this period.
  • During the dressings, the old serum and blood are removed using SF. Thus, the risk of infection is reduced.
  • The wound tensile strength reaches 20% in the 3rd week and 70% in the 6th week.
  • Self-dissolving sutures effectively carry tension forces in tense areas (abdominal fascia) for a period of up to 6 weeks (Therefore, strenuous exercises should be avoided for at least 6 weeks after operations, involving interventions in the abdominal fascia.)


  • Like closed wounds, open wounds also heal by following the inflammation, proliferation and remodelingphases. The main difference is that these processes in open wounds take longer. As a result, more granulation tissue, contraction, and scar tissue are observed.
  • The healing process that progresses in this way is called Secondary Healing.


  • Necrotic tissues should be removed as they form a culture medium for bacteria.
  • The non-infected chronic dry eschar tissue observed in Arterial Insufficiency is exceptional for early debridement.
  • Open wounds tend to heal faster in a sterile and moist environment.


  • Although a wide variety of medical dressing materials are available, none of them can be claimed to affect healing quicker than the others.
  • An ideal dressing material to be used for open wounds;
  • Should be able to maintain the moist and clean environment,
  • Should be able to protect the wound from pressure and mechanical trauma,
  • Should be able to reduce edema,
  • Should be able to simulate repair steps,
  • Should be cheap,
  • Should be able to be replaced less often.
  • Should not cause skin irritation.