Skin Substitutes: Filling the Gap in the Reconstructive Algorithm

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors,

Thank you for your submission. Overall this is a good review filling in the gaps of the reconstruction algorithm. My minor editing comments:

- Line 97 - 'specially' should be 'especially'

- Line 104 - 'while' should be 'which'

- Line 126 - 'temporally' should be 'temporarily'

Comments on the Quality of English Language

Minor editing as outlined above. 

Author Response

Dear Reviewer,

Thank you for your feedback and constructive comments on our submission. We have carefully reviewed your suggestions and have made the necessary corrections accordingly.

• Line 97: We have amended "specially" to "especially".
• Line 104: The word "while" has been replaced with "which".
• Line 126: The term "temporally" has been corrected to "temporarily".

Regarding the quality of English language, we have addressed the minor editing suggestions as outlined in your review.

We appreciate your time and effort in reviewing our work.

Sincerely,

The authors

Reviewer 2 Report

Comments and Suggestions for Authors

This is an interesting review article summarising the use of skin substitutes in filling soft tissue defects following trauma. This is a relevant topic and overall the manuscript is reasonably well written. However there are a number of parts of the manuscript that require further attention:

Line 68 - a figure or table would be nice to visually represent the various classifications and subtypes of skin substitutes and how they relate to one another.   

Line 91 - 'composed' is written twice, one shoulde be removed.

  Lines 163-65: "Secondary intention healing is indicated in patients without exposed bone or tendon and less than 2 cm of skin loss, or children with exposed bone." Please provide a citation to support this statement.   Lines 170-72 - A lot more specific detail is needed here. Which skin substitutes in particular are associated with better scar quality, , shorter surgical times, etc? And compared to which alternative treatments? There are a lot of possible skin substitutes, and various alternative treatment options which you have listed. These broad sweeping statement make it very hard to take away anything meaningful. I would also find it useful to include some images of skin substitues being used in the treatment of fingertip injuries. Many readers of Trauma Care would not have seen this.   Lines 174-64: "This approach can also be considered in cases with exposed tendons and bones according to some authors. [50]" - Likewise, a lot more detail is needed. Which skin substitues in particular are you talking about, and on the basis of what studies can can it be used for exposed tendon and bone. Much more specific detail required.    Lines 200-02: "Moreover, skin substitutes alone can achieve reconstruction success of 70-80%, which is remarkable compared to the 91% and 93% for local and free flaps, respectively". Please provide detailed information about the studies that support these claims. Is reconstructive success to be considered avoiding amputation? What types of studies were these (retrospective vs propspective, case series vs cohort studies vs case-control studies etc)? Were the patients undergoing free flaps highly comparable with regards their injuries and patient factors to the patients being treated with skin substitutes?   Lines 213-14: 25% reduction in healing time compared to what? More detail required.   Line 218: "can see positive outcomes" - please provide more detail about exactly what positive outcomes you are talking about.   Figure 5 - Very interesting and relevant clinical photos. Please provide the timeline for these photos with regards the initial injury so they can be more meaningfully interpreted.   Lines 235 -239: - "Literature contains detailed strategies that incorporate the use of autologous tissue, with or without synthetic and biological materials. [71,72]...". Suggest removing these sentences or replacing them with more relevan comparison of the use of skin subsitues to alternative techniques.   Lines 246-48; ' Also, when utilized for abdominal wall hernia repair, current research recommends the use of retromuscular or underlay mesh placement due to their lower risk of hernia recurrence. [83-85]". Could you please comment in more detail on what the current research is that you allude to?

 

Author Response

Dear Reviewer,

Thank you for your feedback and constructive comments on our submission. We have carefully reviewed your suggestions and have made the necessary corrections accordingly. Please see manuscript attached.

We appreciate your time and effort in reviewing our work.

Sincerely,

The authors

.......................

Line 68 - a figure or table would be nice to visually represent the various classifications and subtypes of skin substitutes and how they relate to one another. 

See manuscript attached 

Line 91 - 'composed' is written twice, one should be removed.

Done

 Lines 163-65: "Secondary intention healing is indicated in patients without exposed bone or tendon and less than 2 cm of skin loss, or children with exposed bone." Please provide a citation to support this statement.  

[47]  Kawaiah A, Thakur M, Garg S, Kawasmi SH, Hassan A. Fingertip Injuries and Amputations: A Review of the Literature. Cureus. 2020 May 26;12(5):e8291. doi: 10.7759/cureus.8291. PMID: 32601565; PMCID: PMC7317129.

 

Lines 170-72 - A lot more specific detail is needed here. Which skin substitutes in particular are associated with better scar quality, , shorter surgical times, etc? And compared to which alternative treatments? There are a lot of possible skin substitutes, and various alternative treatment options which you have listed. These broad sweeping statement make it very hard to take away anything meaningful. I would also find it useful to include some images of skin substitues being used in the treatment of fingertip injuries. Many readers of Trauma Care would not have seen this.  

The adjunct use of skin substitutes for second intention healing of fingertip injuries is a feasible option. In a recent retrospective cohort study the use of a collagen-elastin-template scaffold treated with autologous adipose-derived stromal vascular fraction cells has led to promising results including better scar quality, higher tactile recovery, improved range of motion, higher patient satisfaction, shorter surgical times and hospital stays, and lower surgical costs when compared to the reverse digital artery island flap. [48] Cell therapy using autologous cells accelerates wound healing by reducing invasion time of host cells and early skin synthesis, and while cell-only treatment quickens healing, it doesn't affect wound contraction, hence, cells are often used with artificial dermal scaffolds to optimize healing and minimize wound contraction without delay in healing for skin and soft tissue defects. [49]

[48] Namgoong S, Jung JE, Han SK, Jeong SH, Dhong ES. Potential of Tissue-Engineered and Artificial Dermis Grafts for Fingertip Reconstruction. Plast Reconstr Surg. 2020 Nov;146(5):1082-1095. doi: 10.1097/PRS.0000000000007258. PMID: 32915527.

[49] You HJ, Han SK. Cell therapy for wound healing. J Korean Med Sci. 2014 Mar;29(3):311-9. doi: 10.3346/jkms.2014.29.3.311. Epub 2014 Feb 27. PMID: 24616577; PMCID: PMC3945123.

 

Lines 174-64: "This approach can also be considered in cases with exposed tendons and bones according to some authors. [50]" - Likewise, a lot more detail is needed. Which skin substitues in particular are you talking about, and on the basis of what studies can can it be used for exposed tendon and bone. Much more specific detail required.   

Limited case series have indicated that complex cases with exposed tendons and joints following burns, traumatic injuries, and oncological resections have been successfully treated with either single or staged composite applications of dermal substitutes and split-thickness skin grafts. [40, 50-52] Some of these injuries necessitate that the dermal substitutes be piled or stacked to increase the thickness and sturdiness of coverage when applied over exposed bone and tendon [53]. Some of the matrices reported for this use include collagen-elastin templates, esterified hyaluronic acid matrices, and dermal regeneration templates[50-53].  

40. Bhavsar D, Tenenhaus M. The use of acellular dermal matrix for coverage of exposed joint and extensor mechanism in thermally injured patients with few options. Eplasty. 2008;8: e33. Published 2008 Jun 24.
41. Rehim SA, Singhal M, Chung KC. Dermal skin substitutes for upper limb reconstruction: current status, indications, and contraindications. Hand Clin 2014; 30: 239–52, vii.
42. Graham GP, Helmer SD, Haan JM, Khandelwal A. The use of Integra® Dermal Regeneration Template in the reconstruction of traumatic degloving injuries. J Burn Care Res. 2013; 34(2):261–6
43. Taras JS, Sapienza A, Roach JB, et al. Acellular dermal regeneration template for soft tissue reconstruction of the digits. J Hand Surg Am. 2010; 35(3):415–21.
44. Helgeson MD, Potter BK, Evans KN, et al. Bioartificial dermal substitute: a preliminary report on its use for the management of complex combat-related soft tissue wounds. J Orthop Trauma. 2007; 21(6):394–9.

 

Lines 200-02: "Moreover, skin substitutes alone can achieve reconstruction success of 70-80%, which is remarkable compared to the 91% and 93% for local and free flaps, respectively". Please provide detailed information about the studies that support these claims. Is reconstructive success to be considered avoiding amputation? What types of studies were these (retrospective vs propspective, case series vs cohort studies vs case-control studies etc)? Were the patients undergoing free flaps highly comparable with regards their injuries and patient factors to the patients being treated with skin substitutes?  

The claims regarding reconstructive success and the comparative analysis between different procedures, namely bilayer wound matrix, local tissue rearrangement, and free flap reconstruction, are supported by a retrospective study conducted by Kozac et al [66]. This study analyzed over 300 adult patients with lower extremity wounds and assessed the success of each procedure based on specific criteria. For the bilayer wound matrix, success was defined as providing an adequate wound bed for split-thickness skin grafting, while for local tissue rearrangement and free flaps, success meant not requiring additional coverage procedures. The primary outcome measured was graft success at 180 days, with secondary outcomes including amputation rates, readmissions, reoperations, and costs. The study found varying success rates for the three procedures: 69.2% for bilayer wound matrix, 91.3% for local tissue rearrangement, and 93.3% for free flaps. Notably, free flap reconstructions had the lowest amputation rates despite longer hospital stays and higher costs. However, the study acknowledges significant heterogeneity in data, including comparability of injuries and patient factors between groups, suggesting the need for further studies to directly compare these factors for a more comprehensive understanding. Reconstructive success, in this context, is indeed associated with avoiding amputation but encompasses other crucial factors such as graft success, readmissions, reoperations, and costs. While this study is retrospective, other study designs such as prospective studies, case series, cohort studies, or case-control studies could also provide valuable insights into this field.

66. Kozak GM, Hsu JY, Broach RB, et al. Comparative Effectiveness Analysis of Complex Lower Extremity Reconstruction: Outcomes and Costs for Biologically Based, Local Tissue Rearrangement, and Free Flap Reconstruction. Plast Reconstr Surg. 2020 Mar;145(3):608e-616e. doi: 10.1097/PRS.0000000000006589. PMID: 32097331; PMCID: PMC7043725..

 

Lines 213-14: 25% reduction in healing time compared to what? More detail required.  

In the study by Pontell et al., [67]  two groups of patients with foot and ankle wounds were compared: Four patients underwent reverse sural adipofascial flap (RSAF) with immediate STSG. The average healing time for this group was 141.2 days.

Four patients underwent RSAF with the placement of an acellular dermal matrix (ADM) and negative-pressure wound therapy (NPWT), followed by STSG at a later date. The average healing time for this group was 104.5 days. The second group, which used ADM and NPWT in conjunction with RSAF, demonstrated a reduction in healing time by an average of 36.7 days. This reduction represents a 25% decrease in healing time compared to the group that underwent RSAF with immediate STSG. Therefore, the 25% reduction refers to the comparison between these two different treatment approaches. It’s important to note that all 8 patients achieved successful wound closure, and the study suggests that using ADM and NPWT in conjunction with RSAF may decrease the overall healing time compared with RSAF with immediate STSG. However, more extensive studies may be needed to confirm these findings.

67. Pontell ME, Saad N, Winters BS, et al. Reverse sural adipofascial flaps with acellular dermal matrix and negative pres-sure wound therapy. Adv Skin Wound Care 2018; 31: 612–617.

 

Line 218: "can see positive outcomes" - please provide more detail about exactly what positive outcomes you are talking about.  

In a study by Kavros et al., [69] a fetal bovine acellular dermal matrix, was used to treat 46 patients with chronic diabetic foot ulcers. The study found that 76% of the patients healed within 12 weeks, with an average healing time of 53.1 days, a relatively brief period considering that these chronic ulcers had persisted for an average of 286 days. Most healed wounds required only one or two applications of the ADM. Even for ulcers not fully healed within 12 weeks, the wound area was reduced by 71.4% on average. The study suggests that this ADM, combined with standard care, can effectively treat diabetic foot ulcers, although results may vary and further research is needed.

69. Kavros SJ, Dutra T, Gonzalez-Cruz R, et al. The use of PriMatrix, a fetal bovine acellular dermal matrix, in healing chronic diabetic foot ulcers: a prospective multicenter study. Adv Skin Wound Care 2014; 27: 356–362.

 

Figure 5 - Very interesting and relevant clinical photos. Please provide the timeline for these photos with regards the initial injury so they can be more meaningfully interpreted.  

Figure 5. Application of porcine urinary bladder matrix and split-thickness skin graft in a diabetic foot ulcer. a. A 28-year-old male, with type I diabetes, presented with a necrotizing infection. b. Multiple debridements were performed for local infection control, which exposed the extensor tendons. c. Urinary bladder ECM was applied over the wound 10 days after the initial presentation. STSG was applied 6 weeks later over a healthy granulated wound bed as an outpatient procedure (not shown). d. Eight months after the initial presentation, the patient achieved complete healing and foot salvage, despite an initially poor prognosis.

 

Lines 235 -239: - "Literature contains detailed strategies that incorporate the use of autologous tissue, with or without synthetic and biological materials. [71,72]...". Suggest removing these sentences or replacing them with more relevan comparison of the use of skin subsitues to alternative techniques.  

Strategies for the reconstruction of partial and complete defects of the abdominal wall encompass the utilization of autologous tissue for local and free flaps. [73] These strategies can include the addition of synthetic and biological materials for reinforcement. Promising results have been observed when full-thickness abdominal wall defects were addressed with component separation in a multilayer fashion using an acellular dermal allograft. [74,75] This approach suggests a safe profile and good integration with the surrounding tissues, as well as a low rate of infection, erosion, extrusion, and rejection compared to synthetic materials. [76] However, it can be associated with hernia recurrence rates of 11.5% and 14.6% at 3 and 5-year follow-ups, respectively according to a single-center prospective series of 191 patients [77].

73. Rohrich RJ, Lowe JB, Hackney FL, Bowman JL, Hobar PC. An algorithm for abdominal wall reconstruction. Plast Re-constr Surg 2000; 105:202e16.
74. Kolker AR, Brown DJ, Redstone JS, Scarpinato VM, Wallack MK. Multilayer reconstruction of abdominal wall defects with acellular dermal allograft (AlloDerm) and component separation. Ann Plast Surg 2005; 55:36e41.
75. Buinewicz B, Rosen B. Acellular cadaveric dermis (AlloDerm): a new alternative for abdominal hernia repair. Ann Plast Surg 2004; 52:188e94.
76. De Moya MA, Dunham M, Inaba K, et al. Long-term outcome of acellular dermal matrix when used for large traumatic open abdomen. J Trauma 2008; 65:349e53.
77. Garvey PB, Giordano SA, Baumann DP, Liu J, Butler CE. Long-Term Outcomes after Abdominal Wall Reconstruction with Acellular Dermal Matrix. J Am Coll Surg. 2017 Mar;224(3):341-350. doi: 10.1016/j.jamcollsurg.2016.11.017. Epub 2016 Dec 18. PMID: 27993696.

 

Lines 246-48; ' Also, when utilized for abdominal wall hernia repair, current research recommends the use of retromuscular or underlay mesh placement due to their lower risk of hernia recurrence. [83-85]". Could you please comment in more detail on what the current research is that you allude to?

The current research on abdominal wall hernia repair indicates that the location of mesh placement significantly impacts the recurrence rates of hernias. Sosin et al. [83] have shown that retromuscular (5.8%) and underlay (10.9%) mesh placements have lower recurrence rates compared to onlay (12.9%) and interposition (21.6%) placements. Furthermore, a systematic review from John Hopkins University concluded that underlay or retrorectus mesh placements are associated with lower recurrence rates, with the lowest seroma rates observed following a retrorectus repair. [84] Additionally, a study on robotic ventral/incisional hernia repair with hernia defect closure and intraperitoneal onlay mesh reported a hernia recurrence rate of 14.81%. [85] Therefore, while the choice of technique depends on various factors, including patient-specific circumstances and surgeon’s expertise, retromuscular or underlay mesh placements are generally associated with lower hernia recurrence rates.

83. Sosin M, Nahabedian MY, Bhanot P. The Perfect Plane: A Systematic Review of Mesh Location and Outcomes, Update 2018. Plast Reconstr Surg. 2018 Sep;142(3 Suppl):107S-116S. doi: 10.1097/PRS.0000000000004864. PMID: 30138278.
84. Albino FP, Patel KM, Nahabedian MY, Sosin M, Attinger CE, Bhanot P. Does mesh location matter in abdominal wall reconstruction? A systematic review of the literature and a summary of recommendations. Plast Reconstr Surg. 2013 Nov;132(5):1295-1304. doi: 10.1097/PRS.0b013e3182a4c393. PMID: 24165612.
85. Fuenmayor P, Lujan HJ, Plasencia G, Karmaker A, Mata W, Vecin N. Robotic-assisted ventral and incisional hernia re-pair with hernia defect closure and intraperitoneal onlay mesh (IPOM) experience. J Robot Surg. 2020 Oct;14(5):695-701. doi: 10.1007/s11701-019-01040-y. Epub 2020 Jan 2. PMID: 31897967.

 

 

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thanks for the edits. 

Reviewer 2 Report

Comments and Suggestions for Authors

The concerns I raised have been adequately addressed. The manuscript is now suitable for publication.