The process of wound healing differs markedly in utero compared with life after birth. In the first and second trimesters, fetal wounds heal by regeneration and without scarring. In contrast adult healing occurs via a series of processes starting with hemostasis, followed by inflammation, cellular proliferation, and remodeling. This process results in the formation of scar tissue to replace lost or damaged tissue. At the skin level this is seen as a visible linear scar, for example, after direct wound closure. As a result of this knowledge, there has been much research into the process of fetal wound healing in order to help adults ultimately achieve scarless wound healing. Thus far, however, this objective has never been met and we have, at best, approaches that minimize scar tissue formation by reducing inflammation, tissue loss, and improving the remodeling phase. Such modalities include steroid injection, scar massage, laser therapy, and radiotherapy.1
The process of wound healing in fetal tissue differs significantly from adult healing in a number of ways. Research into the differences to identify the reason/s has shown that there are different ratios of TGF-β subtypes, namely, that TGF-β3 is seen in much higher quantities in fetal tissue compared with adults. Furthermore, TGF-β1 and TGF-β2 are found in low concentration in fetal wounds whereas they are increased in adult healing wounds. The TGF-β family has multiple functions in both tissue repair and scarring. The addition of TGF-β3 to a wound model has been shown to decrease scar formation.1,2 It has roles in both fibroblast migration and proliferation. In contrast, TGF-β1 and TGF-β2 are considered to be profibrotic. Fetal healing displays many other differences including reduced immune cell activation, and lower cytokine and growth factor levels, which lead to lower inflammation. Specifically, there is decreased expression of interleukins, interleukin (IL)-6, -8, and -10. In addition, there is a higher expression of hyaluronic acid, altered collagen cross linking, and increased levels of matrix metalloproteinases (MMPs). Myofibroblasts are present but have a transitory appearance. The role that angiogenesis and vascular endothelial growth factor (VEGF) have in scar formation remains unclear but it is generally accepted that both are reduced in fetal scarless repair. VEGF is important in endothelial cell proliferation.
Following injury and complete healing, the ideal scar will be subtle to visualize, be soft, smooth, and similarly colored and textured to the adjacent uninjured tissues. Ideally scars will be barely visible. In reality scarring can be considered to be on a spectrum with model scarring at one end and extremely poor scarring at the other. Poor scarring may involve tissue thickening or thinning, scar stretch, abnormal pigmentation (either hypo- or hyperpigmentation), and patient discomfort leading to functional as well as aesthetic concerns. At one extreme there lies keloid scarring, where poor features are seen as just described extending beyond the original zone of injury. Further along the scar spectrum lies hypertrophic scarring, which may too have many of the poor features described within the confines of injured tissue. It is this key finding that differentiates keloid from hypertrophic scarring, the extension of the keloid scar beyond the initial scar edge. Keloids grow like a soft tissue tumor and are thus essentially scar growths rather than poor scars alone. They can continue to grow for weeks, months, or even years after the original injury. In contrast, a hypertrophic scar may have many similar features of a keloid clinically but will remain within the borders of the original scar and will not grow further over time. Keloid scars tend to occur on specific body sites including the sternum following chest wall surgery, and on the ear after ear piercing or surgery. Hypertrophic scars tend to occur on the knees, ankles, and other areas of high tension wound closure, or following burn injury treated with skin grafting or secondary intention healing.
Being able to evaluate a scar using a scoring system can be useful for a given scar to compare the effects before and after treatment, and also to compare scars between patients and different treatment modalities within a research setting. There are a number of different scoring systems described, including the Vancouver score and the Patient and Observer Scar Assessment Scale (POSAS). The Vancouver score involves a clinician’s assessment of the following points: vascularity, pigmentation, pliability, and thickness or height. The POSAS also considers vascularity, pigmentation, pliability, and thickness or height from the clinician’s perspective, as well as surface area and overall opinion on scar. The patient assessment considers pain, itching, color, stiffness, thickness, irregularity, and overall opinion. Other commonly used scar assessment tools include the Visual Analog Scale (VAS) and Stony Brook Scar Evaluation Scale (SBSES).1,2
Silicone is used topically for scar management in either sheet or gel forms. The medical form used for scars is polydimethylsiloxane. Application should ideally be started 1–2 weeks after surgery once the wound has completely epithelialized, and continued for at least 3 months following this. It is thought that silicone works by improving scar hydration and can decrease fibroblast activity. In addition, it may act by scar warming, leading to increased collagenase activity and by applying a static negative charge leading to tissue polarization. It is proven to decrease the formation of hypertrophic scar after surgery and help improve established hypertrophic scars too.1,2,3 Vitamin E causes mild inhibition of collagen synthesis but most studies show no real efficacy in scar improvement.4,5,6 Onion extract is the main active ingredient in Mederma (Merz Pharmaceuticals, Raleigh, NC). This is thought to inhibit fibroblast proliferation, inhibit histamine, and upregulate matrix metalloproteinase with improved collagen organization. However, clinical evidence on effectiveness for hypertrophic scar prevention and scar improvement is mixed.7,8,9 Anti-TGF-β1 antibodies do not represent a topical agent but are injected into the scar. Although they have been effective in animal models, they have not been shown to be effective in humans.10,11,12 5-Fluocouracil inhibits fibroblast proliferation and can be effective in the treatment of hypertrophic scars and keloids when combined with steroids and pulsed dye laser (PDL) as well as in its role in treatment of actinic keratosis. However, it can lead to skin ulceration and pain.13
Fat transfer has become very popular in a number of body sites for increasing tissue volume and contour irregularities, particularly within breast tissue and the reconstructed breast. Fat is obtained from a distant body site, most commonly the abdomen, flanks, or thighs, and reinjected at the recipient site. This approach has found widespread use in breast after wide local excision and radiotherapy for breast cancer. Initially it was intended as a contour filler, but it has been found that the scar quality also improves following this treatment. The precise mechanism for this is not known, but it is thought that the fat cell solution also contains adipose derived stem cells which induce neoangiogenesis. Both fat grafts and adipose derived stem cells have been shown to improve scar pliability in irradiated fields as well as their volumetric effect on depressed scars.1 Corticosteroids have a major role in scar management but not specifically in irradiated tissue. They are often part of a multimodality approach to scar management. Bleomycin is an antineoplastic agent that causes DNA damage, leading to fibroblast apoptosis. It has many clinical uses including treatment of vascular malformations and scar management. Bleomycin is a particularly good option for hypertrophic scars and keloids in patients with dark skin at risk of depigmentation with steroids. Scar massage is regularly recommended to patients following surgery to facilitate remodeling of the scar and soften the feel and appearance. Hyaluronic acid is used to volumize the face in the aesthetic setting. It is a synthetic nonpermanent filler that helps draw fluid into the injected site and reduce static rhytids, deep nasolabial folds, and enhance the lips, cheeks, and nose.
Pulsed dye laser (PDL) can be a useful adjunct to scar management in order to reduce scar pigmentation and vascularity, i.e., pinkness, by destruction of small blood vessels. During the early phases of wound healing there is increased vascularity within a wound and this serves to improve blood supply to the area and allow delivery of key cells and growth factors required for healing. In a normal wound this vascularity will subside later in the healing process. This increased vascularity is why immature scars are pink and mature ones tend to be pale. In cases where the paling process is not occurring, laser treatment with PDL may be helpful. The most likely mechanism is the destruction of small blood vessels. In addition to the color change, scar hypoxia with PDL can also lead to decreased fibroblast activity which can help a treated scar to become less active and reduce the appearance of hypertrophic scars. For this reason, it has been used on both new and pre-existing scars to determine whether hypertrophic or keloid scarring can be avoided or treated once established. Studies on the use of PDL early after surgery have shown mixed results in the prevention of hypertrophic scars, but PDL has been shown to be effective in the treatment of established hypertrophic scars,1,2,3 CO2 laser and erbium-doped yttrium aluminum garnet (Er:YAG) lasers are both ablative lasers used most commonly for skin resurfacing in the cosmetic setting. These lasers can also be used to thin hypertrophic scars and improve their pliability by induction of collagen remodeling. Intense pulsed light (IPL) is a nonlaser modality that is also used for cosmetic surgical applications. For scars it can be helpful to treat scar dyschromia. Treatment modalities which modulate TGF-β should, in theory, help modify scar development given that fetal wound healing is scarless in contrast to healing after birth, and that one factor in this is the different ratios of TGF-β1, TGF-β2, and TGF-β3. In fetal wounds there is a proportionally higher amount of TGF-β3.1 However, anti-TGF-β1 antibodies and human recombinant TGF-β3 have only shown to be effective in animal models rather than in humans.4 Scar massage can be helpful to optimize scar quality outcomes and may work by reducing fibroblast activity or helping collagen remodeling. There is no evidence to suggest it works by reducing vascularity of the tissues by destruction of small blood vessels. Alexandrite laser has a target chromophore of oxyhemoglobin and is therefore useful in the management of tattoos, hair removal, and treating pigmented skin lesions.
Patients should be advised to start firm scar massage several times a day starting 2–3 weeks after surgery to help improve the scar pliability and appearance. Scar massage probably works in a number of ways to help the remodeling phase of healing in terms of collagen formation and alignment, and one particular aspect of the mechanism is to cause fibroblast apoptosis. Many patients will ask about the effectiveness of one massage product over another, e.g., oil, cream, and emollient, and it is most likely that the product used has less importance than the massage process itself.1,2,3 Following surgery, it is important to protect the new scar from ultraviolet (UV) radiation both with physical barriers such as clothing or dressings and sun block because UV exposure to immature scars leads to hyperpigmentation which can be difficult to correct subsequently. Sunscreen should be worn from the second or third week following surgery once the wound has epithelialized and continued for 18 months. Application of pressure to scars can help flatten them and improve their appearance. However, pressure therapy is not routinely indicated for most scars. It is used most commonly in burn scars in children and adults, where grafting has been performed or where healing has occurred by secondary intention. Pressure therapy can also be helpful for keloid scars, particularly those on the ear. One of the most challenging aspects to pressure garment use is achieving patient compliance as pressure needs to be maintained for 24 hours each day in most circumstances.4
Keloid scars are notoriously challenging to treat as although there are a number of potentially effective treatment options, there is also a high risk of recurrence. Multimodality treatment is most likely to provide a meaningful and lasting result. The two main approaches are steroid and surgery or radiotherapy and surgery. Evidence suggests that the combination of radiotherapy and surgery has the lowest recurrence rates. When surgery and radiotherapy are combined, surgery can either be performed first and then radiotherapy is commenced on postoperative day 2, in three fractions or doses with a total dose of 15–30 Gy· Alternatively, radiotherapy may be commenced on the day of surgery. In general radiotherapy is ideally done within 3 days of surgery. Reported recurrence rates with such treatment are 10–30% compared to recurrence rates of 40–50% for surgery and steroid.1,2 Steroid therapy alone is not completely ineffective, but it is unlikely to help even a small keloid to resolve fully. The effects of steroid injection on a keloid can be seen within a week or two following injection. The clinical signs include softening of the keloid and some reduction in size. The key point to communicate to patients when selecting treatment is that treatment may not be effective particularly in the longer term and recurrence is a potential risk so that they enter the treatment plan with realistic expectations.