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Observation |

Rapid Healing of Scar-Associated Chronic Wounds After Ablative Fractional Resurfacing FREE

Peter R. Shumaker, MD; Julia M. Kwan, MD; Evangelos V. Badiavas, MD, PhD; Jill Waibel, MD; Stephen Davis, BS; Nathan S. Uebelhoer, DO
[+] Author Affiliations

Author Affiliations: Department of Dermatology, Naval Medical Center San Diego, San Diego, California (Drs Shumaker, Kwan, and Uebelhoer); and Department of Cutaneous Surgery and Dermatology, University of Miami Miller School of Medicine, Miami, Florida (Drs Badiavas and Waibel and Mr Davis).


Arch Dermatol. 2012;148(11):1289-1293. doi:10.1001/2013.jamadermatol.256.
Text Size: A A A
Published online

Background Skin compromised by traumatic scars and contractures can manifest decreased resistance to shearing and other forces, while increased tension and skin fragility contribute to chronic erosions and ulcerations. Chronic wounds possess inflammatory mediator profiles and other characteristics, such as the presence of biofilms, that can inhibit healing.

Observations Three patients with multiple traumatic scars related to blast injuries initiated a course of ablative fractional laser therapy for potential mitigation of contractures, poor pliability, and textural irregularity. Patients also had chronic focal erosions or ulcerations despite professional wound care. All patients experienced incidental rapid healing of their chronic wounds within 2 weeks of their initial ablative fractional laser treatment. Healing was sustained throughout the treatment course and beyond and was associated with gradual enhancements in scar pliability, texture, durability, and range of motion.

Conclusions The unique pattern of injury associated with ablative fractional laser treatment may have various potential wound-healing advantages. These advantages include the novel concept of photomicrodebridement, including biofilm disruption and the stimulation of de novo growth factor secretion and collagen remodeling. If confirmed, ablative fractional resurfacing could be a potent new addition to traditional wound and scar treatment paradigms.

Figures in this Article

Skin compromised by traumatic scarring and split-thickness skin graft placement is often fragile and can manifest decreased resistance to friction and other forces compared with unaffected skin. Scar contractures increase skin tension and decrease mobility, possibly contributing to chronic erosions and ulcerations. These issues may impede rehabilitation after traumatic injuries by limiting prosthetic use, increasing pain, and increasing the risk of infection. One possible barrier to healing in chronic wounds is an exuberant and prolonged inflammatory response, a process that has been linked to bacterial biofilms.1,2 Chronic wounds also possess inflammatory mediator profiles that are inhibitory and characterized by high levels of proteases. These proteases can break down extracellular matrix growth factors and impede wound healing by limiting the proliferation of fibroblasts, endothelial cells, and keratinocytes.35

The association of ablative fractional resurfacing (AFR) with cosmetic enhancements in aged and photodamaged skin is increasingly well documented in the literature.68 Furthermore, several reports have described cosmetic and even functional improvements in traumatic scars and contractures after AFR.917 However, to our knowledge, the potential application of this technique to facilitate the healing of scar-associated chronic wounds has not been addressed specifically. We herein present a series of patients who experienced rapid and sustained healing of long-standing erosions and ulcers associated with traumatic scars and split-thickness skin grafts after initiating a course of AFR. We propose that AFR may exert its effects in part through a microfractional laser debridement phenomenon.

A 26-year-old serviceman presented to the dermatology clinic approximately 5 months after stepping on an improvised explosive device in Afghanistan while on dismounted patrol, resulting in extensive injuries and bilateral above-knee and right above-elbow amputations. He had been engaged in a comprehensive daily or alternate-day rehabilitative program during the preceding months that included skilled physical and occupational therapy and dedicated wound care. Therapy included scar massage, strengthening and range-of-motion exercises, neuromuscular reeducation, prosthetic training, functional activity training, and gait training.

At presentation, his primary concerns were skin fragility, sensitivity, and multiple nonhealing areas at a split-thickness skin graft site on the lateral aspect of his distal right amputation stump. These issues had precluded progression in the prosthetic rehabilitation of his lower extremity. At presentation, his wound care regimen consisted of daily application of petrolatum or topical bacitracin ointment and intermittent application of silver-impregnated foam dressings (Mepilex Ag; Mölnlycke Health Care). In addition, the patient noted sensitivity of the adjacent skin exacerbated by hair pulling by his prosthetic liner. Examination revealed a maturing split-thickness skin graft with textural and pigmentary irregularity overlying moderate heterotopic ossification. Multiple focal erosions and shallow ulcerations were noted in addition to poor skin pliability and moderate invaginations intermittently at junctions of the graft and adjacent skin (Figure, A).

Place holder to copy figure label and caption
Graphic Jump Location

Figure. Photographs of a 26-year-old patient who underwent bilateral above-knee amputations. A, Approximately 5 months after injury, persistent focal erosions and ulcers are associated with a split-thickness skin graft on his right amputation stump. B, Significant interval healing is observed approximately 1 week after a single fractionated laser treatment. C, Approximately 2 months after a single fractionated laser treatment, almost complete reepithelialization is observed along with enhancements in texture, color, and pliability. A 2-mm erosion at the center of the graft was reportedly the result of trauma from the prosthetic device. Focal laser hair reduction was also performed. D, Cumulative and sustained improvements were observed 8 months after his initial treatment and 6 months after a second fractional laser treatment.

A course of AFR was proposed in an attempt to improve the patient's scar contractures, skin pliability, and textural irregularity. As such, the patient received treatment with a 10.6-μm ablative fractional carbon dioxide laser system (Deep FX laser and UltraPulse Encore system; Lumenis, Ltd) to the entire graft site and a 1- to 2-mm rim of normal skin. The selected pulse energy of 50 mJ was proportional to the perceived scar thickness and desired treatment depth. The spot size (microcolumn width) and pulse width were fixed at approximately 120 μm and 250 microseconds, respectively. All treatments were delivered with a single pulse and single pass, without overlap, at a treatment density of 5%. Postprocedure care included application of petrolatum for 2 to 3 days after treatment. Physical and occupational therapy as already detailed were allowed to resume immediately after treatment.

In addition to AFR, the patient received focal laser hair reduction over the distal aspect of his stump in hair-bearing areas with associated sensitivity. Significant interval wound healing at the graft site was noted at his first follow-up approximately 1 week after his initial treatment (Figure, B). Continued improvement was noted at follow-up approximately 2 months after his initial treatment, with nearly total remission of all previous erosions and ulcers despite significant advancement in his prosthetic use. Interval enhancements in texture, pigmentation, and skin pliability were also appreciated (Figure, C). Persistent and cumulative improvements were noted 8 months after his initial treatment and 6 months after a second AFR treatment, despite extended prosthetic use (Figure, D).

Two additional patients with comparable mechanisms of injury were treated in a similar fashion, yielding equally favorable functional and aesthetic responses (Table).

Table Graphic Jump LocationTable. Summary of Patient Demographic and Treatment Data

Chronic wounds are characterized by phenotypic changes, including evidence of cell senescence with a lack of secretion and response to growth factors.35 Debridement has been long established as a means to remove poorly healing areas from wounds and to promote replacement with healthier tissue. However, this process can be invasive and may require significant downtime, particularly in areas where amputation stumps contact prostheses.

Fractionated lasers create microscopic wounds that can reach greater dermal depths than previously attainable with full-field devices, while relatively large adjacent areas of untreated skin may facilitate rapid healing. Several histopathologic studies1826 involving AFR in normal skin demonstrate the sequential generation of a multitude of growth factors and cytokines at the treatment site with varying dynamics over time. The coordinated expression of heat shock proteins, matrix metalloproteinases, growth factors, and other mediators leads to early epidermal regrowth and the induction of a collagen-remodeling response that has been shown to persist 6 months or more after treatment. Histologically, reepithelialization occurs within 24 to 48 hours, with epidermal invagination into the ablated zones during the first week. This process is followed by replacement of the ablation zone with newly synthesized collagen and long-term remodeling.1821

Although little is known about the details of the histopathologic response of scar tissue to AFR, the process probably follows similar molecular pathways. This unique pattern of discrete ablative microcolumns may provide various wound-healing advantages, affording a means to reverse the long-standing changes seen in these chronic wounds with a minimally invasive treatment. One putative mechanism that may have applications across all types of chronic wounds is the disruption of bacterial biofilms. We propose the term photomicrodebridement for the process of applying AFR to vaporize a portion of dysfunctional scar tissue and wound debris.

Alterations in adjacent skin from burns or other trauma, such as increased tension and fragility, likely contribute to a microenvironment that promotes chronic wounds. Although normal dermis has a relatively fine 3-dimensional basket-weave pattern, scar tissue is characterized by the presence of thick parallel bundles of cellular collagen.27 The controlled removal of a portion of dysfunctional scar and the stimulation of deep dermal cells to promote diffuse collagen remodeling may provide a second possible mechanism facilitating the healing of chronic wounds associated with scars and contractures.19,23,25 The principle of deliberately producing a pixilated skin injury to stimulate a wound-healing response with associated neocollagenesis and collagen remodeling has long been practiced in the form of skin needling.28,29 The enhancements in scar texture, pliability, durability, mobility, and dyschromia observed in the cases described herein are consistent with our overall experience during the course of thousands of AFR treatments. Although future confirmatory histopathologic studies are required, we hypothesize that a relative normalization of the epidermal and dermal architecture is responsible for the improvements in appearance and functionality of the treated skin.

In summary, we present herein a series of cases in which AFR was associated with incidental rapid and sustained healing of scar-related chronic erosions and ulcers, with clear benefits to the patients in terms of enhanced rehabilitation. Based on our experience, indications in this series suggest that AFR demonstrates efficacy for scars in patients with a range of ages and wound locations. Two of the patients in this series were treated less than 1 year after injury, in contrast to existing scar treatment paradigms for procedural intervention.30 In our experience, treatment variables should be individualized at each therapy session largely on the basis of estimated scar thickness and degree of restriction. Higher pulse energies selected for thicker, restrictive scars require a concomitant decrease in treatment density to avoid bulk heating and potentially worse scarring. In our practice, traumatic scars are treated usually at the lowest available density setting. Atrophic scars or areas with minor textural or pigmentary irregularity may be treated with lower pulse energies and a somewhat higher density. Less mature scars within 1 year of injury seem to be more susceptible to breakdown with aggressive multimodal treatment. Therefore, judicious settings and single-modality treatment sessions are recommended within the first year of injury. Future prospective studies will be required to determine optimal treatment variables inclusive of other factors, such as the age and location of the scar and adjunctive treatments.

We must consider limitations when drawing conclusions from this series. Although histological analysis of pretreatment and posttreatment scar tissue would strengthen the association of AFR with the observed clinical enhancements, the risks of additional poorly healing wounds or infections in this setting precluded the use of such tests. Furthermore, the inherent heterogeneity of traumatic injuries makes the accumulation of a large homogeneous series particularly challenging and will have to be accounted for during future inquiry. Prospective studies are certainly required to clarify any potential role for AFR as an adjunct to traditional wound management and in applications for the management of traumatic scars in general. If confirmed, traditional wound and scar treatment paradigms could shift toward earlier intervention with anticipated benefits in rehabilitation and a more favorable trajectory for wound healing.

Correspondence: Peter R. Shumaker, MD, Department of Dermatology, Naval Medical Center San Diego, 34520 Bob Wilson Dr, Ste 300, San Diego, CA 92134 (peter.shumaker@med.navy.mil).

Accepted for Publication: August 4, 2012.

Author Contributions: All the authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Shumaker, Kwan, Badiavas, and Uebelhoer. Acquisition of data: Shumaker, Kwan, and Uebelhoer. Analysis and interpretation of data: Shumaker, Kwan, Badiavas, Waibel, Davis, and Uebelhoer. Drafting of the manuscript: Shumaker, Kwan, and Waibel. Critical revision of the manuscript for important intellectual content: Shumaker, Kwan, Badiavas, Waibel, Davis, and Uebelhoer. Administrative, technical, or material support: Shumaker, Badiavas, Waibel, and Davis. Study supervision: Shumaker and Uebelhoer.

Conflicts of Interest Disclosures: Dr Waibel has been employed by Palm Beach Aesthesis Dermatology, Miami Dermatology and Laser Institute, and Dermatology Institute of Southwest Ohio; has consulted for Medicis and Lumenis; has received honoraria from Sciton, Lumenis, Syneron/Candela, Medicis, Allergan, and Solta; has served on the speakers bureau of Sciton, Lumenis, Syneron/Candela, Medicis, Allergan, and Solta; has provided expert testimony for renewed cases; has received grants from Sciton, ASDS, and Lumenis; receives royalties for patent UMK-193 at the University of Miami; and has received donated equipment from Palomar, Alma, Celleration, Syneron/Candela, Sciton, Deka, and Solta.

Disclaimer: The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US government.

James GA, Swogger E, Wolcott R,  et al.  Biofilms in chronic wounds.  Wound Repair Regen. 2008;16(1):37-44
PubMed   |  Link to Article
Bjarnsholt T, Kirketerp-Møller K, Jensen PØ,  et al.  Why chronic wounds will not heal: a novel hypothesis.  Wound Repair Regen. 2008;16(1):2-10
PubMed   |  Link to Article
Falanga V. Wound bed preparation and the role of enzymes: a case for multiple actions of therapeutic agents.  Wounds. 2002;14(1):47-57
Bucalo B, Eaglstein WH, Falanga V. Inhibition of cell proliferation by chronic wound fluid.  Wound Repair Regen. 1993;1(3):181-186
PubMed   |  Link to Article
Trengove NJ, Stacey MC, MacAuley S,  et al.  Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors.  Wound Repair Regen. 1999;7(6):442-452
PubMed   |  Link to Article
Tierney EP, Kouba DJ, Hanke CW. Review of fractional photothermolysis: treatment indications and efficacy.  Dermatol Surg. 2009;35(10):1445-1461
PubMed   |  Link to Article
Bogdan Allemann I, Kaufman J. Fractional photothermolysis: an update.  Lasers Med Sci. 2010;25(1):137-144
PubMed   |  Link to Article
Tierney EP, Hanke CW, Watkins L. Treatment of lower eyelid rhytids and laxity with ablative fractionated carbon-dioxide laser resurfacing: case series and review of the literature.  J Am Acad Dermatol. 2011;64(4):730-740
Link to Article
Waibel J, Beer K. Ablative fractional laser resurfacing for the treatment of a third-degree burn.  J Drugs Dermatol. 2009;8(3):294-297
PubMed
Haedersdal M. Fractional ablative CO2 laser resurfacing improves a thermal burn scar.  J Eur Acad Dermatol Venereol. 2009;23(11):1340-1341
PubMed   |  Link to Article
Bowen RE. A novel approach to ablative fractional treatment of mature thermal burn scars.  J Drugs Dermatol. 2010;9(4):389-392
PubMed
Weiss ET, Chapas A, Brightman L,  et al.  Successful treatment of atrophic postoperative and traumatic scarring with carbon dioxide ablative fractional resurfacing: quantitative volumetric scar improvement.  Arch Dermatol. 2010;146(2):133-140
PubMed   |  Link to Article
Cervelli V, Gentile P, Spallone D,  et al.  Ultrapulsed fractional CO2 laser for the treatment of post-traumatic and pathological scars.  J Drugs Dermatol. 2010;9(11):1328-1331
PubMed
Cho SB, Lee SJ, Chung WS, Kang JM, Kim YK. Treatment of burn scar using a carbon dioxide fractional laser.  J Drugs Dermatol. 2010;9(2):173-175
PubMed
Kwan JM, Wyatt M, Uebelhoer NS, Pyo J, Shumaker PR. Functional improvement after ablative fractional laser treatment of a scar contracture.  PM R. 2011;3(10):986-987
PubMed   |  Link to Article
Kineston D, Kwan JM, Uebelhoer NS, Shumaker PR. Use of a fractional ablative 10.6-μm carbon dioxide laser in the treatment of a morphea-related contracture.  Arch Dermatol. 2011;147(10):1148-1150
PubMed   |  Link to Article
Uebelhoer NS, Ross EV, Shumaker PR. Ablative fractional resurfacing for the treatment of traumatic scars and contractures.  Semin Cutan Med Surg. 2012;31(2):110-120
PubMed   |  Link to Article
Helbig D, Bodendorf MO, Grunewald S, Kendler M, Simon JC, Paasch U. Immunohistochemical investigation of wound healing in response to fractional photothermolysis.  J Biomed Opt. 2009;14(6):064044
PubMed  |  Link to Article   |  Link to Article
Hantash BM, Bedi VP, Kapadia B,  et al.  In vivo histological evaluation of a novel ablative fractional resurfacing device.  Lasers Surg Med. 2007;39(2):96-107
PubMed   |  Link to Article
Reilly MJ, Cohen M, Hokugo A, Keller GS. Molecular effects of fractional carbon dioxide laser resurfacing on photodamaged human skin.  Arch Facial Plast Surg. 2010;12(5):321-325
PubMed   |  Link to Article
Xu X-G, Luo Y-J, Wu Y,  et al.  Immunohistological evaluation of skin responses after treatment using a fractional ultrapulse carbon dioxide laser on back skin.  Dermatol Surg. 2011;37(8):1141-1149
PubMed   |  Link to Article
Grunewald S, Bodendorf M, Illes M, Kendler M, Simon JC, Paasch U. In vivo wound healing and dermal matrix remodeling in response to fractionated CO2 laser intervention: clinicopathological correlation in non-facial skin.  Int J Hyperthermia. 2011;27(8):811-818
PubMed   |  Link to Article
Prignano F, Campolmi P, Bonan P,  et al.  Fractional CO2 laser: a novel therapeutic device upon photobiomodulation of tissue remodeling and cytokine pathway of tissue repair.  Dermatol Ther. 2009;22:(suppl 1)  S8-S15
PubMed   |  Link to Article
Rahman Z, MacFalls H, Jiang K,  et al.  Fractional deep dermal ablation induces tissue tightening.  Lasers Surg Med. 2009;41(2):78-86
PubMed   |  Link to Article
Capon A, Mordon S. Can thermal lasers promote skin wound healing?  Am J Clin Dermatol. 2003;4(1):1-12
PubMed   |  Link to Article
Orringer JS, Kang S, Johnson TM,  et al.  Connective tissue remodeling induced by carbon dioxide laser resurfacing of photodamaged human skin.  Arch Dermatol. 2004;140(11):1326-1332
PubMed   |  Link to Article
Weedon D, Strutton G. Skin Pathology. 2nd ed. New York, NY: Churchill Livingstone; 2002
Aust MC, Fernandes D, Kolokythas P, Kaplan HM, Vogt PM. Percutaneous collagen induction therapy: an alternative treatment for scars, wrinkles, and skin laxity.  Plast Reconstr Surg. 2008;121(4):1421-1429
PubMed   |  Link to Article
Fernandes D. Minimally invasive percutaneous collagen induction.  Oral Maxillofac Surg Clin North Am. 2005;17(1):51-63, vi
PubMed   |  Link to Article
Wainwright DJ. Burn reconstruction: the problems, the techniques, and the applications.  Clin Plast Surg. 2009;36(4):687-700
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure. Photographs of a 26-year-old patient who underwent bilateral above-knee amputations. A, Approximately 5 months after injury, persistent focal erosions and ulcers are associated with a split-thickness skin graft on his right amputation stump. B, Significant interval healing is observed approximately 1 week after a single fractionated laser treatment. C, Approximately 2 months after a single fractionated laser treatment, almost complete reepithelialization is observed along with enhancements in texture, color, and pliability. A 2-mm erosion at the center of the graft was reportedly the result of trauma from the prosthetic device. Focal laser hair reduction was also performed. D, Cumulative and sustained improvements were observed 8 months after his initial treatment and 6 months after a second fractional laser treatment.

Tables

Table Graphic Jump LocationTable. Summary of Patient Demographic and Treatment Data

References

James GA, Swogger E, Wolcott R,  et al.  Biofilms in chronic wounds.  Wound Repair Regen. 2008;16(1):37-44
PubMed   |  Link to Article
Bjarnsholt T, Kirketerp-Møller K, Jensen PØ,  et al.  Why chronic wounds will not heal: a novel hypothesis.  Wound Repair Regen. 2008;16(1):2-10
PubMed   |  Link to Article
Falanga V. Wound bed preparation and the role of enzymes: a case for multiple actions of therapeutic agents.  Wounds. 2002;14(1):47-57
Bucalo B, Eaglstein WH, Falanga V. Inhibition of cell proliferation by chronic wound fluid.  Wound Repair Regen. 1993;1(3):181-186
PubMed   |  Link to Article
Trengove NJ, Stacey MC, MacAuley S,  et al.  Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors.  Wound Repair Regen. 1999;7(6):442-452
PubMed   |  Link to Article
Tierney EP, Kouba DJ, Hanke CW. Review of fractional photothermolysis: treatment indications and efficacy.  Dermatol Surg. 2009;35(10):1445-1461
PubMed   |  Link to Article
Bogdan Allemann I, Kaufman J. Fractional photothermolysis: an update.  Lasers Med Sci. 2010;25(1):137-144
PubMed   |  Link to Article
Tierney EP, Hanke CW, Watkins L. Treatment of lower eyelid rhytids and laxity with ablative fractionated carbon-dioxide laser resurfacing: case series and review of the literature.  J Am Acad Dermatol. 2011;64(4):730-740
Link to Article
Waibel J, Beer K. Ablative fractional laser resurfacing for the treatment of a third-degree burn.  J Drugs Dermatol. 2009;8(3):294-297
PubMed
Haedersdal M. Fractional ablative CO2 laser resurfacing improves a thermal burn scar.  J Eur Acad Dermatol Venereol. 2009;23(11):1340-1341
PubMed   |  Link to Article
Bowen RE. A novel approach to ablative fractional treatment of mature thermal burn scars.  J Drugs Dermatol. 2010;9(4):389-392
PubMed
Weiss ET, Chapas A, Brightman L,  et al.  Successful treatment of atrophic postoperative and traumatic scarring with carbon dioxide ablative fractional resurfacing: quantitative volumetric scar improvement.  Arch Dermatol. 2010;146(2):133-140
PubMed   |  Link to Article
Cervelli V, Gentile P, Spallone D,  et al.  Ultrapulsed fractional CO2 laser for the treatment of post-traumatic and pathological scars.  J Drugs Dermatol. 2010;9(11):1328-1331
PubMed
Cho SB, Lee SJ, Chung WS, Kang JM, Kim YK. Treatment of burn scar using a carbon dioxide fractional laser.  J Drugs Dermatol. 2010;9(2):173-175
PubMed
Kwan JM, Wyatt M, Uebelhoer NS, Pyo J, Shumaker PR. Functional improvement after ablative fractional laser treatment of a scar contracture.  PM R. 2011;3(10):986-987
PubMed   |  Link to Article
Kineston D, Kwan JM, Uebelhoer NS, Shumaker PR. Use of a fractional ablative 10.6-μm carbon dioxide laser in the treatment of a morphea-related contracture.  Arch Dermatol. 2011;147(10):1148-1150
PubMed   |  Link to Article
Uebelhoer NS, Ross EV, Shumaker PR. Ablative fractional resurfacing for the treatment of traumatic scars and contractures.  Semin Cutan Med Surg. 2012;31(2):110-120
PubMed   |  Link to Article
Helbig D, Bodendorf MO, Grunewald S, Kendler M, Simon JC, Paasch U. Immunohistochemical investigation of wound healing in response to fractional photothermolysis.  J Biomed Opt. 2009;14(6):064044
PubMed  |  Link to Article   |  Link to Article
Hantash BM, Bedi VP, Kapadia B,  et al.  In vivo histological evaluation of a novel ablative fractional resurfacing device.  Lasers Surg Med. 2007;39(2):96-107
PubMed   |  Link to Article
Reilly MJ, Cohen M, Hokugo A, Keller GS. Molecular effects of fractional carbon dioxide laser resurfacing on photodamaged human skin.  Arch Facial Plast Surg. 2010;12(5):321-325
PubMed   |  Link to Article
Xu X-G, Luo Y-J, Wu Y,  et al.  Immunohistological evaluation of skin responses after treatment using a fractional ultrapulse carbon dioxide laser on back skin.  Dermatol Surg. 2011;37(8):1141-1149
PubMed   |  Link to Article
Grunewald S, Bodendorf M, Illes M, Kendler M, Simon JC, Paasch U. In vivo wound healing and dermal matrix remodeling in response to fractionated CO2 laser intervention: clinicopathological correlation in non-facial skin.  Int J Hyperthermia. 2011;27(8):811-818
PubMed   |  Link to Article
Prignano F, Campolmi P, Bonan P,  et al.  Fractional CO2 laser: a novel therapeutic device upon photobiomodulation of tissue remodeling and cytokine pathway of tissue repair.  Dermatol Ther. 2009;22:(suppl 1)  S8-S15
PubMed   |  Link to Article
Rahman Z, MacFalls H, Jiang K,  et al.  Fractional deep dermal ablation induces tissue tightening.  Lasers Surg Med. 2009;41(2):78-86
PubMed   |  Link to Article
Capon A, Mordon S. Can thermal lasers promote skin wound healing?  Am J Clin Dermatol. 2003;4(1):1-12
PubMed   |  Link to Article
Orringer JS, Kang S, Johnson TM,  et al.  Connective tissue remodeling induced by carbon dioxide laser resurfacing of photodamaged human skin.  Arch Dermatol. 2004;140(11):1326-1332
PubMed   |  Link to Article
Weedon D, Strutton G. Skin Pathology. 2nd ed. New York, NY: Churchill Livingstone; 2002
Aust MC, Fernandes D, Kolokythas P, Kaplan HM, Vogt PM. Percutaneous collagen induction therapy: an alternative treatment for scars, wrinkles, and skin laxity.  Plast Reconstr Surg. 2008;121(4):1421-1429
PubMed   |  Link to Article
Fernandes D. Minimally invasive percutaneous collagen induction.  Oral Maxillofac Surg Clin North Am. 2005;17(1):51-63, vi
PubMed   |  Link to Article
Wainwright DJ. Burn reconstruction: the problems, the techniques, and the applications.  Clin Plast Surg. 2009;36(4):687-700
PubMed   |  Link to Article

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