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Burn Scar Lipofilling

September 2013
The Journal of craniofacial surgery 24(5):1806-14

September 2013
24(5):1806-14

DOI:10.1097/SCS.0b013e3182a148b9

Source
PubMed

Authors:

Agostino Bruno

S.Eugenio University Hospital

Giancarlo Delli Santi

aslrm2

Lucio Fasciani

AslRoma2

Show all 6 authorsHide

Over the past years, lipofilling has been used for many pathologies and sequelae; recently, its use has also widened for burn outcomes. A total of 93 burn scars were assessed (from September 2011 to February 2012). Half of scar area was treated through injection of adipose tissue harvested from subcutaneous fat and processed in accordance with the Coleman technique. Biopsy specimens were taken before treatment and at 3 and 6 months after the treatment. Histologic and immunohistochemical evaluations were conducted. In the samples examined, a marked improvement was observed, which can be seen in 3 months, but most of all, documented at 6 months. In addition, from a clinical point of view, an improvement has been documented, both functional and aesthetic. Lipofilling for burn scar complete and improve the results of standard surgical procedures, with long-term care setting and long-acting results.

A, C, and E, Before the treatment. B, D, and F, After the treatment. Preoperative and postoperative pictures show a significant improvement of tissue general structure.

…

A and B, Before the treatment. C and D, After the treatment. After the lipofilling was performed, a remarkable reduction in melanogenic activity is shown.

…

A, Before the treatment. B, After the treatment. In the postoperative biopsy, there was a higher number of collagen fibers that made a fibrillar collagen.

…

A, Before the treatment. B, After the treatment. Increased amount of elastic fibers at the dermopapillary layer.

…

. Summary of Antibody Expression in Preoperative and Postoperative Biopsies

…

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Burn Scar Lipofilling: Immunohistochemical

and Clinical Outcomes

Agostino Bruno, MD, Giancarlo delli Santi, MD, Lucio Fasciani, MD, Michela Cempanari, MD,

Marco Palombo, MD, and Paolo Palombo

Abstract: Over the past years, lipofilling has been used for many

pathologies and sequelae; recently, its use has also widened for burn

outcomes. A total of 93 burn scars were assessed (from September

2011 to February 2012). Half of scar area was treated through

injection of adipose tissue harvested from subcutaneous fat and pro-

cessed in accordance with the Coleman technique. Biopsy speci-

mens were taken before treatment and at 3 and 6 months after the

treatment. Histologic and immunohistochemical evaluations were

conducted. In the samples examined, a marked improvement was

observed, which can be seen in 3 months, but most of all, docu-

mented at 6 months. In addition, from a clinical point of view, an

improvement has been documented, both functional and aesthetic.

Lipofilling for burn scar complete and improve the results of stan-

dard surgical procedures, with long-term care setting and long-acting

results.

Key Words: Lipofilling, burn, scar, histology

(J Craniofac Surg 2013;24: 1806Y1814)

Hypertrophic burn scars occur in approximately 75% of white

patients because of third-degree burns.

They lead to a great

number of adverse consequences such as loss of function or altered

appearance.

Studies have begun to reveal the process of intercellular

communication that regulates this process of burn scar develop-

ment.

In most affected cases, these hypertrophic scars gradually

improve over a period of few years. The final largest hypertrophic

scars are surgically excised often with the creation of Z-plasties or

skin grafts to release scar contractures.

The subscar and intrascar fat grafting is a relatively recent

technique that allows the improvement of the quality of scar as

clinically evaluated from the modified Vancouver Scar scale.

This article investigates the processes of modification of scar

tissue induced by fat grafting.

MATERIALS AND METHODS

For our study, burn scars of at least 200 cm

, divided into

2 homogeneous portions, were selected.

In the first half of the scar area (named A), lipofilling was

performed through an intrascar infiltration; the second half of the

scar area (named B) was the control one.

A total of 93 burn scars were assessed (from September 2011

to February 2012) and were consecutive cases. The mean age of

the scars was 2.3 years (ranging from 8 months to 29 years). We chose

an adult population (mean age, 43 years; range, 18 to 92 years). Bi-

opsies of the 2 areas (A and B) were conducted using a 0.8-cm punch

at 3 different times: before the treatment, after 3 months of the

treatment, and after 6 months of the treatment.

The biopsy specimens were placed, immediately after their

collection, in 10% saline-buffered formalin so as to prevent auto-

lytic putrefactive phenomena. After the fixation, the tissue samples

were vigorously rinsed to remove excess fixative and were then

dehydrated, clarified, and included. The samples included were

cut using a sliding microtome and placed on polarized glass slides.

The following 6 histochemical stains were performed:

1. Hematoxylin-eosin, to assess the nuclear and cytoplasmic struc-

ture of the cells;

2. Masson-Fontana, to evaluate melanocytic activity;

3. Unna, to evaluate the elastic f ibers, which were stained in red

together with the mast cells, whereas the other f ibers were

stained in blue;

4. Silver Gomori methenamine, to evaluate the basal membrane;

5. Weigert elastic fibers, to evaluate the elastic fibers; and

6. Weigert-van Gieson, to assess the elastic fibers and the con-

nective tissue (rapid method) (Bio-Optica).

Immunohistochemical stainings were also conducted using

the following antibodies:

1. Ki-67, to assess the proliferation index (Dako, TEC, 1:100);

2. Vascular endothelial growth factor, to assess angiogenesis

(Santacruz; citrate; 1:100);

3. P63, to assess cell proliferation (Santacruz; citrate; 1:200);

4. P53, to assess the inhibition of cell growth (Dako; TEC; 1:50);

5. S100, to evaluate cell differentiation and melanin (Dako; citrate;

1:100);

6. Monoclonal langerin, to evaluate the Langerhans cells (Ylem;

citrate; 1:100);

7. A-Catenin, to evaluate the stabilization of the cytoskeleton and

the stability of cell junctions (Dako; Citrate; 1:100);

and

8. Transforming growth factor-A, to evaluate the fibrotic response

and neovascularization (Ylem; citrate; 1:20).

The adipose tissue, which is necessary for the lipofilling

procedure, was collected from the abdomen, the hips, the trochan-

teric region, the inner thigh, and the medial aspect of the knees. A

superwet technique was used with anesthetic solution infiltration

(Ringer-lactate with ropivacaine 2% and epinephrine 1/500000).

TECHNICAL STRATEGY

1806 The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013

From the Burn Center and Plastic Surgery, S. Eugenio Hospital, Rome, Italy.

Received February 3, 2013.

Accepted for publication June 18, 2013.

Address and correspondence and reprint requests to Agostino Bruno, MD, S

Eugenio Hospital, Rome, Italy; E-mail: agostinobruno80@libero.it

The authors report no conflicts of interest.

Presented at the 61st Annual Meeting of the Italian Society of Plastic Surgery,

Panel on lipofilling, September 24Y27, 2012, Palermo, Italy.

This study was performed in accordance with the research ethical guidelines.

ISSN: 1049-2275

DOI: 10.1097/SCS.0b013e3182a148b9

Adipose tissue was therefore aspirated by means of a 2-hole blunt

cannula, of 3 mmin internal diameter, connected to a 10-ml Luer-Lok

syringe; a gentle negative pressure was performed, gradually re-

tracting the syringe plunger.

The adipose tissue thus obtained was centrifuged at 1250 J for

3 minutes; afterward, we removed the upper (oil) and lower (blood

and liquid infiltration) layers. The central layer, consisting of puri-

fied fat, was transferred through a collector to a 1- or 3-cc Luer-

Lok syringes.

The infiltration occurred in the subscar layer, where beads

of adipose tissue were placed, but mainly in the intrascar plane.

To this purpose, the blunt Coleman cannulas were detected

to be ineffective in allowing adequate infiltration because of the

compactness of the scar; we therefore used a sharp angiographic

cannula, which allowed us to easily overcome tissue resistance, thus

enabling grafting of the purified fat directly into the scar. It may

also be argued that the sharp instrument may stimulate a normal

collagen deposition, similar to the needling procedure.

RESULTS

Hematoxylin-Eosin

In the scar tissue, before any kind of treatment, a good

melanocytic activity was observed. The basal layer was evident; less

evident was, on the other hand, the granulous layer.

In the connective tissue, one can see a thickened collagen and

the absence of hyperkeratinization. Six months after the treatment,

there were collagen eruption and, apparently, better vascularization

of the dermal papillae, which are now clearly visible. The collagen,

chaotically organized before the treatment, appeared more organized

with parallel fibers (before the treatment, Figs. 1A, C, and E; after the

treatment, Fig. 1B, D, and F).

Masson-Fontana

In the pretreatment biopsy, there was a strong appreciable

marking at the dermal-epidermal junction that highlighted a large

FIGURE 1. A, C, and E, Before the treatment. B, D, and F, After the treatment. Preoperative and postoperative pictures show a significant improvement of tissue

general structure.

The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013 Burn Scar Lipofilling

*2013 Mutaz B. Habal, MD 1807

FIGURE 3. A, Before the treatment. B, After the treatment. In the postoperative biopsy, there was a higher number of collagen fibers that made a fibrillar collagen.

FIGURE 4. A, Before the treatment. B, After the treatment. Increased amount of elastic fibers at the dermopapillary layer.

FIGURE 2. A and B, Before the treatment. C and D, After the treatment. After the lipofilling was performed, a remarkable reduction in melanogenic activity is shown.

Bruno et al The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013

1808 *2013 Mutaz B. Habal, MD

FIGURE 5. A, Before the treatment. B, After the treatment. After the treatment, papillary dermis seems to reappear.

FIGURE 6. A and C, Before the treatment. B and D, After the treatment. Increased number of elastic fibers, both superficial and deep.

FIGURE 7. A, Before the treatment. B, After the treatment. S-100 expression decreases after the treatment.

The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013 Burn Scar Lipofilling

*2013 Mutaz B. Habal, MD 1809

number of positive melanocytes. This situation appeared to be

strongly reduced because of the lipofilling treatment. The reduction

was not present in the control areas, where we found an unchained

melanocytic activity (before the treatment, Figs. 2A, B; after the

treatment, Fig. 2C, D).

Weigert Elastic Fibers + Tri-Gomori

After the lipofilling treatment, there were more elastic fibers

that made the collagen finely fibrillar. The collagen appeared more

cellular and compact, and the appearance of vessels was observed.

(Fig. 3A, before the treatment; Fig. 3B, after the treatment).

Unna

After the treatment, the collagen fibers increased in the

dermopapillary layer, which is the most superficial reticular dermis

(before the treatment, Fig. 4A; after the treatment, Fig. 4B).

Silver Gomori Methenamine

A change in the organization was observed. The level of or-

ganization of the connective tissue improved in the treated tissue,

but there was also an improvement in the fibrillar organization,

which was best evident after 6 months. After the treatment, the

papillary dermis seemed to reappear. The collagen, initially thick-

ened, became more fibrillar (before the treatment, Fig. 5A; after

the treatment, Fig. 5B).

Weigert-van Gieson

Before the treatment, the elastic fibers were very thin, short,

not very representative, and confined to the midYsuperficial

reticular dermis. In fact, the elastic fibers were almost absent in the

epithelium, concentrated primarily in the superficial dermis to de-

crease again as one deepens.

After 6 months, the increase in elastic fibers was also evident

in the epithelium; in the deeper layer, one can find thinner ones

because the collagen was more fibrillated (before the treatment,

Figs. 6A, C; after the treatment, Figs. 6B, D).

S-100

In the pretreatment status, there was a high number of me-

lanocytes at the basal membrane level. At this level, there were also

the dendritic cells or the Langerhans cells, whose number was de-

creased in the tissue after 6 months of the treatment. This staining

also revealed nerve endings because S-100 is a calcium-binding

protein (before the treatment, Fig. 7A; after the treatment, Fig. 7B).

Langerin

Before the treatment, the tissue had many Langerhans cells;

after 6 months of the treatment, the Langerhans cells disappeared

in the tissue.

Because of the thermal damage suffered by the skin, there

appeared an erythematous zone with the Langerhans cells. These

cells are antigen-presenting cells and are recalled in the epithelium;

here, they remained trapped in the area of thickened scar connec-

tive tissue. Only after the treatment, the connective tissue became

looser and the Langerhans cells tended to disappear, migrating

downward (before the treatment, Fig. 8A; after the treatment, Fig. 8B).

The cell count of S-100 and Langerin highlighted the evid-

ent decrease in the Langerhans cells after the treatment. This ob-

servation was also confirmed using the Wilcoxon test, which resulted

in a probability equal to 0.005 for S-100 and 0.0043 for Langerin,

which are both highly significant (Tables 1 and 2).

P53

Comparing the preoperative and 6-month postoperative tis-

sues, there appeared an increased positivity after the treatment,

showing an intense proliferative activity at the level of the basal and

spinous layers.

P63

In the pretreatment sample, there was a diffuse proliferative

activity that was widespread in many layers of the epithelium. At

6 months after the treatment, there was a lower proliferative activ-

ity restricted at the level of the basal layer. Hence, where cell

FIGURE 8. B, Before the treatment. C, After the treatment. Downward migration of the Langherans cells.

TABLE 1. S-100 Cellular Count

Fields 1 2 3 4 5 6 Total Mean

Pretreatment 46 30 55 60 40 231 46.2

Posttreatment 10 23 18 9 12 9 81 13.5

Wilcoxon test, P= 0.005.

TABLE 2. Langerin Cellular Count

Fields 1 2 3 4 5 6 Total Mean

Pretreatment 22 25 19 20 20 13 119 19.8333

Posttreatment 5 7 9 8 29 7.25

Wilcoxon test, P= 0.0043.

Bruno et al The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013

1810 *2013 Mutaz B. Habal, MD

FIGURE 10. A, Before the treatment. B, After the treatment. Increased expression in the basal layer in the posttreatment.

TABLE 3. P53 Cellular Count

Fields 1 2 3 4 5 67891011121314Total Mean (ES)

Pretreatment 4 3 0 1 0 20111111 17 1.57 (0.57)

Posttreatment 9 2 15 15 8 33 10 23 22 10 8 7 8 5 175 13.14 (3.71)

Wilcoxon test, P= 0.0048.

TABLE 4. P63 Cellular Count

Fields 1 2 3 4 Total Mean

Pretreatment 158 180 168 170 676 169 (4.5)

Posttreatment 13 8 8 10 39 9.75 (1.18)

Wilcoxon test, P= 0.202.

TABLE 5. Ki-67 Cellular Count

Fields 1 2 3 4567Total Mean

Pretreatment 18 12 23 8 18 12 10 101 14.4286

Posttreatment 30 27 32 30 22 25 32 198 28.2857

Wilcoxon test, P= 0.0032.

FIGURE 9. A, P53 before the treatment. B, P53 After the treatment. C, P63 before the treatment. D1 P63 after the treatment. P53 and P63 are inversely related. The

increased expression of p53 correlates, in fact, with a reduced expression of P63.

The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013 Burn Scar Lipofilling

*2013 Mutaz B. Habal, MD 1811

proliferation increased, P53 increased and P63 decreased. This be-

havior was caused by the expression of P63 that was connected to a

maturation block. After the treatment, P63 was expressed in the

germinal layer and disappeared in the upper layers as in a healthy

skin. P53 was not expressed in the scar tissue before the treatment

because it was blocked by the P63 expression (P53 before the treat-

ment, Fig. 9A; P53 after the treatment, Fig. 9B; P63 before the

treatment, Fig. 9C; P63 after the treatment, Fig. 9D).

Ki-67

Ki-67 is a nuclear antigen expressed by proliferating cells.

In the pretreatment status, its expression was negative,

whereas after the lipofilling treatment, one can observe many posi-

tive cells at the level of the basal layer (before the treatment, Fig. 10A;

after the treatment, Fig. 10B).

The cell count of P53, Ki-67, and P63 as well as the proba-

bility calculated with the Wilcoxon test confirmed the trend of

proliferative activity and its significance (Tables 3Y5).

Vascular Endothelial Growth Factor

In the untreated scar, vascular endothelial growth factor was

expressed mainly from the melanocytes and the keratinocytes; after

the treatment, it was no longer expressed.

The scar tissue after 6 months of the treatment tended to as-

sume a nearly normal morphology (before the treatment, Fig. 11A;

after the treatment, Fig. 11B).

Transforming Growth Factor-A

Before the treatment, there was a positivity in the epithelium

layer. Whereas, after 6 months, there was a net decrease. The positive

FIGURE 11. A, Before the treatment. B, After the treatment. Reduction in the VEGF expression in the postoperative biopsy.

FIGURE 12. A, Before the treatment. B, After the treatment. Reduction in TGF-Ain the postoperative.

FIGURE 13. A, Before the treatment. B, After the treatment. Downregulation of A-catenin expression.

Bruno et al The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013

1812 *2013 Mutaz B. Habal, MD

epithelium can be attributed to its attempt to repair; after the lipo-

filling was performed, its expression disappeared. In the dermis, ini-

tially, there were fibroblastlike cells that tended to disappear after

the treatment (before the treatment, Fig. 12A; after the treatment,

Fig. 12B).

A-Catenin

In the untreated scar tissue, the A-catenin was expressed

predominantly in the spinous layer, at the membrane level and the

cell junctions, whereas it was not observed at the basal layer. After

6 months of the treatment, however, there was a downregulation.

Thus, the treatment reduced the expression of A-catenin (before

the treatment, Fig. 13A; after the treatment, Fig. 13B).

DISCUSSION

As revealed by these immunohistochemical studies, burn

scars, even old ones, cannot be considered as a quiescent scar be-

cause they are characterized by a maturation block, a proinflamma-

tory and hypervascularized status.

Lipofilling allows a dramatic change of this status, making

the tissue much more similar to a healthy one, which is also from

a histologic point of view.

The positivity of VEGF, A-catenin, and TGF-Athat will be

downregulated after treatment may be associated with the restitutio

ad integrum of the tissue, as well as the considerable amount of

the Langerhans cells that are lost after the treatment, a phenomenon

caused by their nature of antigen-presenting cell, called in the epi-

thelium in defense of the damaged skin and trapped in the scar be-

cause of the very dense connective.

The index of cellular proliferation evaluated using Ki-67 is

also highly significant; this is caused by the adipose-derived stem

cells that once infiltrated at the level of the scar through the

lipofilling technique, engrafted, and proliferated, thus regenerating

a normal environment.

The expression of P53 and the inhibition of P63 are con-

nected. The expression of P63 is closely confined in the nucleus and

is required to maintain the function of proliferative potential, differ-

entiation, and regeneration of the epidermis; although the inhibition

of cell proliferation resulting from the loss of P63 is P53-dependent,

the defects of cell differentiation seem to be independent from P53.

Conversely, P53 is not expressed in the scar tissue because it is

blocked by the expression of P63, which is connected to a cell matu-

ration block.

After complete healing, P63 is still widely expressed not

only in the basal keratinocytes but also within the spinous layer,

whereas the expression of Ki-67 is confined to individual cells of

the basal layer. Apparently, the expression of P63 during wound

healing, when keratinocytes migration is activated, protects mi-

grant cells from apoptosis.

From a clinical point of view, there is a significant reduction

of the time required to improve both functional and aesthetic out-

comes of the treated areas (Table 6).

FIGURE 14. A and C, Before the treatment. B and D, After the treatment.

Six months after the lipofilling, there was a drastic improvement in hypertrophic

scar both functionally and aesthetically.

TABLE 6. Summary of Antibody Expression in Preoperative and

Postoperative Biopsies

Cellular Expression

Antibody Pretreatment Posttreatment (6 mo)

S-100 + j

Langerin + j

VEGF + j

A-Catenin + j

TGF-A+j

Ki-67 j+

P53 j+

P63 + j

þ, positive expression; j, negative expression.

FIGURE 15. A, Before the treatment. B, After the treatment. The postoperative

photograph (B) shows the improvement, both functional and aesthetical.

Increased tissue pliability.

The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013 Burn Scar Lipofilling

*2013 Mutaz B. Habal, MD 1813

For the objective clinical evaluation of the patients, we used a

modified Vancouver scar scale.

The assessment was performed at

time 0, that is, before any type of treatment, and at 3 and 6 months.

We evaluated the vascularization, pigmentation, pliability,

thickness, and the relief on the skin surface. These features have

been selected on the basis of clinical experience and literature. Each

item provides a partial score of up to 10, with 10 indicating the

worst scar. Therefore, the final scoreis the sum of the partial scores of

each item.

The lowest score, namely, 5, indicates normal skin, whereas

a score of 50 suggests the worst imaginable scar.

A double-blind assessment, which was performed by physi-

cians who were not part of the study, has been provided.

The mean score of the objective pretreatment was 41 (range,

34Y49), that of 3 months after the treatment was 29 (range, 22Y35),

and that of 6 months after the treatment was 15 (range, 9Y18).

It was found that the improvement, although present also at

3 months after the treatment, reached the apex at 6 months. This

aspect is also parallel to the histologic evaluations performed be-

cause the maximum histologic improvement was shown at 6 months.

This suggests that lipofilling provides a long-acting, slowly

occurring effect, triggering histologic changes that reach the maxi-

mum level of 6 months after treatment. This also suggests to wait for

5 to 6 months before taking into account the occurrence of a new

treatment.

We also provided a subjective evaluation: we valued appear-

ance, symptoms, awareness of the scar, satisfaction in appearance,

and satisfaction about the symptoms. The questionnaire was given

at time 0, 3, and 6 months. The total score is the sum of the indi-

vidual items, each of which provides a partial score.

The questionnaire oscillates from a minimum score of 28

(maximum degree of dissatisfaction) to a maximum score of 112

(maximum degree of satisfaction).

At time 0, the mean score was 31 (range, 26Y38); at 3 months,

64 (range, 47Y72); and at 6 months, 95 (range, 81Y102). We there-

fore documented, also in the subjective test, an improvement that

reached the maximum degree at 6 months (Figs. 14Y16).

We confirm, therefore, the value of the lipofilling treat-

ment for the improvement of burn scar sequelae, as already emerged

from previous studies.

Intrascar infiltration allows, however, better results because

we are able to bring the ADSC directly into a tissue that would

otherwise be too firm for its diffusion.

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FIGURE 16. A, Before the treatment. B, After the treatment. Six months after

the lipofilling and rigottomies normal limb extension. No Z-plasties were

performed.

Bruno et al The Journal of Craniofacial Surgery &Volume 24, Number 5, September 2013

1814 *2013 Mutaz B. Habal, MD

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Apr 2024
Eur J Plast Surg

Recent advancements in Plastic Surgery and Regenerative MedicineQuery have revolutionized tissue repair, remodeling, and regeneration. A promising approach involves Mesenchymal Stem cells and from the adipose–derived Stromal Vascular Fraction, aimed at improving tissue healing post the use of synthetic materials. This integration shows potential in mitigating adverse effects of synthetic materials like dermal fillers, offering new clinical interventions for tissue repair and regeneration. This article explores the benefits, complications, and applications of these technologies in Plastic Surgery and Cosmetic Medicine, focusing on their mechanisms of action and future perspectives. Level of evidence: Not ratable

Autologous fat grafting and adipose-derived stem cells therapy for acute burns and burn-related scar: A systematic review

Article

Full-text available

Mar 2024

A BSTRACT Objectives The objective of this study was to analyze all available research on the application of autologous fat grafting (AFG) and adipose-derived stem cells (ADSC) to present evidence-based recommendations, particularly in the clinical treatment of acute burns and burn-related scars. Materials and Methods We conducted a systematic search of PubMed, COCHRANE, and EMBASE, as well as a manual search of previous reviews’ reference lists up. The risk of bias (RoB) was assessed using RoB 2.0 and ROBINS-I, where appropriate. Results Six eligible studies were selected (2 randomized clinical trials [RCT], 1 retrospective cohort, and 3 experimental studies) with subjects ranging from 3 to 100. Only one study evaluated the use of AFG for acute burns. Improvements in wound healing, vascularization, scar characteristics, and tissue architecture were generally observed in some studies, supported by molecular markers, while one study reported nonsignificant results. Subjective patient satisfaction was reported to have improved. Functional outcomes improvement in the treated regions was minimal. However, study heterogeneity arose mainly from treatment protocols. Cautious results interpretation due to potential bias, especially in selection and confounding domains, and limited clinical trials are important to note. More studies are needed to evaluate. Conclusion AFG and ADSC hold potential as valuable treatment options for burn-related scars, supported by a body of evidence, but further well-designed RCT are needed. The efficacy of acute burn settings is yet to be further evaluated since evidence is limited.

Autologous nanofat harvested from donor site of full-thickness skin or skin flap grafting for the treatment of early postburn scarring: a case series

Article

Full-text available

Feb 2024

Introduction Postburn scarring often presents a specific reconstructive challenge from both functional and cosmetic perspectives. The purpose of this study was to investigate whether autologous nanofat harvested from the donor site of full skin or a skin flap can be reused for the treatment of early postburn scaring. Methods From July 2018 to April 2022, patients with early postburn scarring underwent scar reconstruction surgery with full-thickness skin or a skin flap for a contour deformity and/or scar contracture, and autologous nanofat grafting was performed during the same operation. The Vancouver Scar Score (VSS) and the itch and pain scores were evaluated at the preoperation time point as well as at 2–3 weeks and 3-months postoperation. A comparison was made among the same patients at different time points. Results A total of 17 patients, aged from 18 months to 62 years old were included in this analysis. The VSS was reduced from 10.00 ± 2.12 to 7.41 ± 1.277 at the 2–3-week postoperation time point, and to 5.53 ± 1.37 at the 3-month postoperation time point. The pain and itch score were reduced from 4.65 ± 1.37 and 6.35 ± 1.27, to 3.70 ± 1.10 and 4.94 ± 1.30 at the 2–3-week postoperation time point, and to 3.00 ± 1.28 and 3.94 ± 0.97 at the 3-month postoperation time point respectively. The VSS and pain and itch scores showed a statistically significant reduction (P < 0.05) at the 2–3-week and 3-month postoperative follow-ups compared with the preoperation time point. Conclusion Autologous nanofat grafting from donor sites of full thickness skin or skin flap may be a promising treatment for an early postburn scaring as it promotes scar softening, improves itching and pain within the scar. However, this is a small case series with only 17 patients. Further conclusions need to be drawn through expanded samples for randomized controlled clinical trials. Lay Summary Hypertrophic scarring is the most common complication after partial thickness burn injury, and the complex pathogenesis and prolonged dynamic process render treatments only marginally effective. In the past few decades, with the technological advances of liposuction and fat grafting, nanofat grafting has been used in a variety of surgical fields, including wound healing, scleroderma, facial rejuvenation, and neuralgia. However, the role of nanofat grafting is not well documented in the prevention and treatment of early postburn scarring. Full-thickness skin grafting or skin flap transplantation is the most common method for the reconstruction of a hypertrophic scaring until now. In the current study, we harvested subcutaneous fat during the preparation of the full-thickness skin or skin flap, prepared nanofat and injected it in the scar located at a nonsurgical site. Comparison of the pre- and postoperation scores for scar color, scar thickness, scar stiffness, and scar regularity showed that the postoperation scores were decreased significantly and that there was a significant improvement in scar pigmentation and thickness as well astheaesthetic outcome after treatment. Most importantly, reductions in the scores for pain and itching could be assessed objectively. It seems that the nanofat grafting is a potential method for prevention and treatment for early postburn scaring.

The Effect of Fat Grafting on Scars Hyperpigmentation: A Systematic Review and Meta-Analysis

Article

Jan 2024

Hyperpigmented scars, particularly in exposed body areas, can be difficult to conceal and may evoke psychological distress. While the precise causes of scar dyschromia are not fully understood, alterations in melanogenic activity appear to hold more significance than changes in melanocyte quantity. Current treatments encompass laser interventions. However, it is essential to consider their costs and potential complications in relation to their limited proven effectiveness. Fat grafting has gained interest as a scar modulation technique due to its regenerative properties, and its efficacy in reducing scar hyperpigmentation is currently under investigation. A systematic review and meta-analysis was reported according to PRISMA guidelines. PubMed, Embase, and Cochrane Library databases were accessed. PROSPERO registration number is CRD42023457778. The primary outcome was a change in scar pigmentation after fat grafting. Pigmentation changes after fat grafting were calculated using the standardized mean difference (SMD) between baseline and postoperative scores according to POSAS and VSS scales. Bias assessment was conducted according to the National Institute for Health and Clinical Excellence quality assessment tool. A total of 8 articles meeting inclusion and exclusion criteria were identified, involving 323 patients with hyperpigmented scars treated with fat grafting. A significant difference in scar pigmentation was noted after treatment with fat grafting according to observers’ ratings, with a SMD of − 1.09 [95% CI: − 1.32; − 0.85], p<0.01. The SMD for patient-reported scar pigmentation after treatment with fat grafting was − 0.99 [96% CI: − 1.31; − 0.66], p<0.01. Four studies provided objective measurements of melanin changes after fat grafting and revealed inconsistent findings compared to subjective observations. Fat grafting shows promise in ameliorating hyperpigmented scars based on subjective assessments, but further corroborating evidence from objective measures is required. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review

Article

Full-text available

Jan 2024
PLOS ONE

Aim Radiation-induced fibrosis is a recognised consequence of radiotherapy, especially after multiple and prolonged dosing regimens. There is no definitive treatment for late-stage radiation-induced fibrosis, although the use of autologous fat transfer has shown promise. However, the exact mechanisms by which this improves radiation-induced fibrosis remain poorly understood. We aim to explore existing literature on the effects of autologous fat transfer on both in-vitro and in-vivo radiation-induced fibrosis models, and to collate potential mechanisms of action. Method PubMed, Cochrane reviews and Scopus electronic databases from inception to May 2023 were searched. Our search strategy combined both free-text terms with Boolean operators, derived from synonyms of adipose tissue and radiation-induced fibrosis. Results The search strategy produced 2909 articles. Of these, 90 underwent full-text review for eligibility, yielding 31 for final analysis. Nine conducted in-vitro experiments utilising a co-culture model, whilst 25 conducted in-vivo experiments. Interventions under autologous fat transfer included adipose-derived stem cells, stromal vascular function, whole fat and microfat. Notable findings include downregulation of fibroblast proliferation, collagen deposition, epithelial cell apoptosis, and proinflammatory processes. Autologous fat transfer suppressed hypoxia and pro-inflammatory interferon-γ signalling pathways, and tissue treated with adipose-derived stem cells stained strongly for anti-inflammatory M2 macrophages. Although largely proangiogenic initially, studies show varying effects on vascularisation. There is early evidence that adipose-derived stem cell subgroups may have different functional properties. Conclusion Autologous fat transfer functions through pro-angiogenic, anti-fibrotic, immunomodulatory, and extracellular matrix remodelling properties. By characterising these mechanisms, relevant drug targets can be identified and used to further improve clinical outcomes in radiation-induced fibrosis. Further research should focus on adipose-derived stem cell sub-populations and augmentation techniques such as cell-assisted lipotransfer.

Exploring the mechanisms behind autologous lipotransfer for radiation-induced fibrosis: A systematic review

Article

Jan 2024
PLOS ONE

Combined Synergetic Effect of Lipoconcentrate Fat Grafting, Nanofat Transfer, Platelet-Rich Plasma, Microneedling, and CO2 Fractional Laser for Plastic Regenerative and Esthetic Surgery and Cosmetic Care

Article

Full-text available

Aug 2023

The advancements in skin care methods and products show the rising interest in cosmetics. Recent studies emphasize the regenerative potential of fat grafting, platelet-rich plasma (PRP), microneedling, and carbon dioxide (CO2) fractional laser techniques. Combining these strategies into a protocol is yet to be explored. In this article, we demonstrate different types of fat grafts and their versatility in treating different facial problems found in our patient. This study evaluated the synergistic effect of lipoconcentrate and nanofat grafting, PRP, microneedling, and CO2 fractional laser to provide esthetic and regenerative facial skin care. This case report was conducted in Dr. Soliman Fakeeh Hospital, Saudi Arabia. Our case involved a 53-year-old woman who had traumatic facial injuries due to a car accident years ago that buried asphalt particles in her facial scars, causing bluish skin discoloration. She suffered from multiple deep atrophic scars in several areas on the left side of her face, causing asymmetry. She was treated using lipoconcentrate and nanofat grafting, followed by three PRP with microneedling sessions and then a final CO2 fractional laser session. The evaluation was based on the physician’s clinical assessment, image documentation, and patient satisfaction, which revealed significant improvement in skin appearance with respect to texture, color, symmetry, and overall health of the skin over a period of four months. The potentiality and efficacy of the combination therapy of lipoconcentrate, nanofat, PRP, microneedling, and CO2 fractional laser for skin rejuvenation and scar treatment showed promising results in this case report.

Lipofilling—A Regenerative Alternate for Remodeling Burn Scars: A Clinico-Immunohistopathological Study

Article

Full-text available

Aug 2023
Indian J Plast Surg

Introduction Any injury involving the dermis will lead to scarring. Scar tissue can cause functional limitations, cosmetic impairments, pain, and itch. Adipose-derived stem cells have also been shown to play a role in scar modulation. This study evaluates changes in lipofilled scar over the period of time and compares it with non-lipofilled scar tissue. Materials and Methods A prospective case–control study with intraindividual follow-up was performed on 30 adult patients with post-burn scars from November 2016 to May 2019. Clinical, histopathological, and immunohistochemical parameters were assessed among the case and control regions of the scar. Results Mean age of the study population was 30.6 years. The duration of the scar included in this study ranged from 1 to 28 years, with a mean duration of 5.91 years. There was a significant reduction in pain, itch, stiffness, and an increase in the pliability of the scar, and a substantial improvement in the modified Vancouver Scar Score in the lipofilled group. In histopathological analysis, the case group showed organized parallel collagen fibers, a significant reduction in melanocytes, improvement in vascularity, and a significantly increased amount of collagen fibers at the reticular dermis. Immunohistochemical analysis indicated new cell synthesis in the scar tissue and reduced melanocytes. Conclusion The remodeling effect of adipocyte-derived stem cells is long-lasting, and there is a gradual improvement in most of the parameters. Lipofilling has regenerative capacity, which leads to the improved overall appearance of scar and improvement at the cellular level.

The Patient and Observer Scar Assessment Scale: A reliable and feasible tool for scar evaluation

Article

Full-text available

Jun 2004
PLAST RECONSTR SURG

At present, various scar assessment. scales are available, but not one has been shown to be reliable, consistent, feasible, and valid at the same time. Furthermore, the existing scar assessment scales appear to attach little weight to the opinion of the patient. The newly developed Patient and Observer Scar Assessment Scale consists of two numeric scales: the Patient Scar Assessment Scale (patient scale) and the Observer Scar Assessment Scale (observer scale). The patient and observer scales have to be completed by the patient and the observer, respectively. The patient scale's consistency and the observer scale's consistency, reliability, and feasibility were tested. For the Vancouver Scar Scale, which is the most frequently used scar assessment scale at present, the same statistical measurements were examined and the results of the observer scale and the Vancouver scale were compared. The concurrent validity of the observer scale was tested with a correlation to the Vancouver scale. Furthermore, the authors examined which specific characteristics significantly influence the general opinion of the patient and the observers on the scar areas. Four independent observers have each used the observer scale and the Vancouver scale to assess 49 burn scar areas of 3 X 3 cm belonging to 20 different patients. Subsequently, the patients completed the patient scale for their scar areas. The (internal) consistency of both the patient and the observer scales was acceptable (Cronbach's alpha, 0.76 and 0.69, respectively), whereas the consistency of the Vancouver scale appeared not to be acceptable (alpha, 0.49). The reliability of the observer scale completed by a single observer was acceptable (r = 0.73). The reliability of the Vancouver scale completed by a single observer was lower (r = 0.69). The observer scale showed better agreement than the Vancouver scale because the coefficient of variation was lower (18 percent and 22 percent, respectively). The concurrent validity of the observer scale in relation to the Vancouver scale is high (r = 0.89, p < 0.001). Linear regression of the general opinions on scars of the observer and the patient showed that the observer's opinion is influenced by vascularization, thickness, pigmentation, and relief, whereas the patient's opinion is mainly influenced by itching and the thickness of the scar. Such an impact of itching and thickness of the scar on the patient's opinion is an important and novel finding. The Patient and Observer Scar Assessment Scale offers a suitable, reliable, and complete scar evaluation tool.

Penn JW, Grobbelaar AO, Rolfe KJThe role of the TGF-β family in wound healing, burns and scarring: a review. Int J Burns Trauma 2:18-28

Article

Full-text available

Aug 2012

It is estimated worldwide that over 6 million people per annum experience a burn injury. Despite advances in management and improved survival rates, the incidence of hypertrophic scarring remains high. These scars are particularly common after burns and are often raised, red, hard and may cause abnormal sensations. Such pathological scarring can lead to severe functional impairment, psychological morbidity, and costly long term healthcare. Wound healing is an inherent process which restores the integrity of the skin after injury and although scarring is a frequent by-product, the scarless wound healing observed in early human gestational fetuses suggests that it is not an essential component of the response. This has lead to a large body of research attempting to understand the mechanisms behind scarring and in turn prevent it. One of the main focuses of recent research has been the role played by the growth factor TGF-β in the process of both wound healing and scar formation. The three isoforms (TGF-β1, TGF-β2 and TGF-β3) appear to have overlapping functions and predominantly mediate their effects through the intracellular SMAD pathway. Initial research suggested that TGF-β1 was responsible for the fibrotic scarring response whereas the scarless wound healing seen in fetal wounds was due to increased levels of TGF-β3. However, the reality appears to be far more complex and it is unlikely that simply altering the ratio of TGF-β isoforms will lead to scarless wound healing. Other aspects of the TGF-β system that appear promising include the downstream mediator CTGF, the proteoglycan decorin and the binding protein p311. Other putative mechanisms which may underlie the pathogenesis of hypertrophic scars include excessive inflammation, excessive angiogenesis, altered levels of matrix metalloproteinases, growth factors, and delayed apoptosis of fibrotic myofibroblasts either due to p53 genetic alterations or tensile forces across the wound. If an effective treatment for hypertrophic scars following burns injury is to be developed then further work must be carried out to understand the basic mechanisms of pathological scarring.

Epidermal Langerhans Cells Rapidly Capture and Present Antigens from C-Type Lectin-Targeting Antibodies Deposited in the Dermis

Article

Full-text available

Nov 2009
J INVEST DERMATOL

Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.

The role of the TGF-β family in wound healing, burns and scarring: A review

Article

Feb 2012

Hypertrophic scars, keloids, contractures

Article

Jun 1997
SURG CLIN N AM

Keloids and hypertrophic scars (HSc) are unique human dermal fibroproliferative disorders (FPD) that occur following trauma, inflammation, surgery, and burns and possibly spontaneously. Keloids occur in individuals with a familial predisposition, enlarge and extend beyond the margins of the origin wounds, and rarely regress (Fig. 1). HSc are raised, erythematous, pruritic, fibrous lesions that typically remain within the confines of the original wound, usually undergo at least partial spontaneous resolution over widely varying time courses, and are often associated with contractures of the healing tissues (Fig. 2). The development of contractures is by definition the pathologic shortening of scar tissue, resulting in deformities as opposed to wound contraction, which occurs in an open wound with the positive outcome of reducing the wound surface area. These disorders represent aberrations in the fundamental processes of wound healing, which include cell migration and proliferation, inflammation, increased synthesis and secretion of cytokines and extracellular matrix (ECM) proteins, and remodeling of the newly synthesized matrix. Conceptually, it is the goal of individuals caring for wounds to facilitate regeneration of the injured skin and associated structures (Fig. 3); however, at present adult mammalian healing occurs by the formation of scar, characterized by a disordered architecture, which, in the case of HSc and keloids, is also associated with excessive deposition of extracellular matrix proteins.

Mechanosignaling pathways in cutaneous scarring

Article

Aug 2012
ARCH DERMATOL RES

Mechanotransduction is the process by which physical forces are sensed and converted into biochemical signals that then result in cellular responses. The discovery and development of various molecular pathways involved in this process have revolutionized the fundamental and clinical understanding regarding the formation and progression of cutaneous scars. The aim of this review is to report the recent advances in scar mechanosignaling research. The mechanosignaling pathways that participate in the formation and growth of cutaneous scars can be divided into those whose role in mechanoresponsiveness has been proven (the TGF-β/Smad, integrin, and calcium ion pathways) and those who have a possible but as yet unproven role (such as MAPK and G protein, Wnt/β-catenin, TNF-α/NF-κB, and interleukins). During scar development, these cellular mechanosignaling pathways interact actively with the extracellular matrix. They also crosstalk extensively with the hypoxia, inflammation, and angiogenesis pathways. The elucidation of scar mechanosignaling pathways provides a new platform for understanding scar development. This better understanding will facilitate research into this promising field and may help to promote the development of pharmacological interventions that could ultimately prevent, reduce, or even reverse scar formation or progression.

Employment of Needles: A Different Technique for Fat Placement

Article

Aug 2012

Keloids: What do we know and what do we do next?

Article

Mar 2012

Evaluation of Ki-67 as a Histological Index of Burn Damage in a Swine Model

Article

Oct 2011
J BURN CARE RES

Histological diagnosis of burn depth lacks consensus. The purpose of this study was to determine whether Ki-67, a cell proliferation marker, provides an index of integument viability after burn injury. Induction of thermal burn injuries (3, 12, 20, 30, 75, 90, and 120 seconds) were made with a brass rod heated to 100°C on the dorsal trunk of the swine. Controls were created with a brass rod heated to 37.5°C. Four 6-mm biopsies were obtained from each site for histological analysis of Ki-67. Biopsies were taken at the following times postinjury: 1, 12, 24, 36, 48, 72, and 96 hours. The results illustrate a characteristic Ki-67 nuclear staining in the basal layer of the epidermis and in the hair follicle. With increasing thermal injury, the nuclei of the cells changed morphology: condensing, fragmenting, and elongating. The uniqueness of the labeling index was to include only morphologically intact nuclei as having capacity to proliferation. Quantitative analysis showed a reduction in the mean number of Ki-67-positive cells, suggesting a reduced regenerative capacity. This study supports using this index as a means of performing histology for burn depth analysis. In future studies, determining viability of partial-thickness burns will require multiple histological markers such as Ki-67 in addition to hematoxylin and eosin staining.

Myofibroblastic differentiation in atypical fibroxanthomas occurring on sun-exposed skin and in a burn scar: An ultrastructural and immunohistochemical study

Article

May 2011
J CUTAN PATHOL

Herein, we report the investigation of two cases of atypical fibroxanthoma (AFX). One AFX developed within actinically damaged skin, as is typical, while the other developed within a burn scar within non-sun-exposed skin. The two tumors showed almost identical histopathological, immunohistochemical and ultrastructural features. The tumors were composed of pleomorphic spindled, epithelioid, multinucleated and bizarre cells with enlarged atypical nuclei. Most tumor cells expressed vimentin and about 50% expressed CD10. Some tumor cells also expressed α-smooth muscle actin and CD68. However, there was no expression of cytokeratins, p63, S-100 protein, melan-A, HMB 45, desmin, epithelial membrane antigen or CD34. Ultrastructurally, the tumor cells contained myofilaments with dense patches but lacked plasmalemmal caveolae and basal lamina. The most prominent finding was the identification of fibronexus junctions. In addition, there were tumor cells containing numerous lysosomal granules. In conclusion, we clearly showed myofibroblastic differentiation in AFX by electron microscopy. We report also a case of AFX directly developing within a burn scar in the absence of actinic damage. Ito A, Yamada N, Yoshida Y, Morino S, Yamamoto O. Myofibroblastic differentiation in atypical fibroxanthomas occurring on sun-exposed skin and in a burn scar: an ultrastructural and immunohistochemical study.

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