|Year : 2020 | Volume
| Issue : 3 | Page : 151-158
Amniotic membrane for treating chronic cutaneous ulcers: A systematic review and meta-analysis of randomized controlled trials
Xinglong Liang1, Li Zhou2, Jun Yan1, Shivank Singh3, Shantanu Singh4, Ching-Wen Chien5, Tao-Hsin Tung6
1 Department of Dermatology, Maoming People's Hospital, Maoming, Guangdong, China
2 Department of Urology, Maoming People's Hospital, Maoming, Guangdong, China
3 Department of Internal Medicine, Southern Medical University, Guangzhou, China
4 Department of Pulmonary Medicine, Marshall University School of Medicine, Huntington, West Virginia, USA
5 Institute for Hospital Management, Tsinghua University, Shenzhen, China
6 Department of Dermatology, Maoming People's Hospital, Maoming, Guangdong, China; Department of Medical Research and Education, Cheng-Hsin General Hospital, Taipei, Taiwan
|Date of Submission||28-Oct-2019|
|Date of Decision||02-Mar-2020|
|Date of Acceptance||27-Mar-2020|
|Date of Web Publication||09-Jun-2020|
Prof. Ching-Wen Chien
Institute for Hospital Management, Tsing Hua University, Shenzhen Campus, Shenzhen
Dr. Tao-Hsin Tung
Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei; Maoming People's Hospital, Maoming, Guangdong
Source of Support: None, Conflict of Interest: None
Background: In recent years, many studies have reported that amniotic membrane (AM) is an effective adjuvant for promoting the healing of chronic cutaneous ulcers (CCUs). Objectives: The objective of the present study was to evaluate the efficacy and safety of AM for the topical treatment of CCUs. Methods: A literature search was performed using PubMed, Cochrane Library, and Embase for all related studies from inception to May 31, 2019, without restriction on language. A quantitative synthesis of randomized controlled trials (RCTs) was conducted to compare the effectiveness and safety between the AM therapy and standard of care/conventional treatment by employing a random-effect model. Results: Thirteen RCTs with 947 patients were included in the study. Compared to standard of care (SOC), the relative risk (RR) for the healing rate was 1.99 (95% confidence interval [CI]: 1.75–2.26, P < 0.001). A greater percentage area reduction could be found in AM group (mean difference = 70.00%, 95% CI: 15.82–124.17, P = 0.01). There was no statistically significant difference in pain relief (P = 0.36). The RR for adverse events was estimated 0.54 (95% CI: 0.31–0.93) when compared AM group with SOC group (P = 0.03). Conclusion: This systematic review and meta-analysis indicate that it is effective and safe to use AM as an adjuvant treatment for treating CCUs.
Keywords: Amniotic membrane, chronic cutaneous ulcers, meta-analysis, randomized controlled trials
|How to cite this article:|
Liang X, Zhou L, Yan J, Singh S, Singh S, Chien CW, Tung TH. Amniotic membrane for treating chronic cutaneous ulcers: A systematic review and meta-analysis of randomized controlled trials. Dermatol Sin 2020;38:151-8
|How to cite this URL:|
Liang X, Zhou L, Yan J, Singh S, Singh S, Chien CW, Tung TH. Amniotic membrane for treating chronic cutaneous ulcers: A systematic review and meta-analysis of randomized controlled trials. Dermatol Sin [serial online] 2020 [cited 2020 Sep 19];38:151-8. Available from: http://www.dermsinica.org/text.asp?2020/38/3/151/286211
| Introduction|| |
Ulcer healing is a complicated, continuous, and dynamic process that includes coagulation, inflammation, proliferation, and remodeling. Ulcer healing is delayed, and chronic ulcer occurs when the ulcer environment becomes hypoxic, the lymphatic drainage is poor, microbial proliferation, necrotic tissue is present, and proinflammatory cytokines and proteases levels are elevated.,
Chronic cutaneous ulcers (CCUs) are a common problem, with a prevalence of 1%–2% in the general population. CCUs include venous leg ulcers (VLUs), pressure ulcers, diabetic foot ulcers (DFUs), arterial ulcers, neurotrophic ulcers, and so on. More than 70% of CCUs are related to venous diseases, and about 20% are caused by arterial insufficiency or mixed arteriovenous diseases. Atherosclerosis and diabetes are the most common causes for arterial ulcers. CCU management is still a challenging process, requires a long time to heal, and frequently recur.
About 50% of VLUs cannot heal in 4 months, 20% cannot heal in 2 years, and about 8% cannot heal even after 5 years. The recurrence rate of VLUs could reach 72% and the annual recurrence rate can be up to 27%., In addition, DFUs are another common CCUs. From the clinical viewpoint, the prevalence of diabetes is increasing every year, and 552 million people are estimated to be diabetic by 2030. It is estimated that 25% of diabetic patients will have DFUs during their lifetime. Previous studies indicated that only about 24.2% of DFU healed after 12 weeks of treatment. Delayed healing of DFUs increases the risk of severe wound infection and amputation. It also has been reported that the cost of CCUs exceeded $50 billion, and the cost of pressure ulcers was estimated to exceed $1.3 billion annually in the US., As a result, CCUs drastically reduce the patients' quality of life, who have to live with chronic pain, associated with physical disabilities, and a heavy financial burden. Standard therapies (including debridement, wound offloading, infection control, and moist dressings) for the management of CCUs are not always effective. Many CCUs cannot be cured, last for months or years, and/or recur after healing. Therefore, it is necessary to develop alternative treatment strategies.
Amniotic membrane (AM) (dehydrated, cryopreserved, or acellular) allografts are considered to be a cost-effective therapy. It has many unique properties, including anti-inflammatory effects, epithelialization initialization capacities, bacteriostatic, wound protection, decreased scarring, as well as pain reduction. AM contains many growth factors involved in wound healing, including platelet-derived growth factor, epidermal growth factor, basic fibroblast growth factor, transforming growth factor β1, and placental growth factor. Other cytokines such as interleukins (IL-1Ra, IL-4, and IL-10) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-4, and TIMP-b) are also present in the AM. In recent years, many studies demonstrated the efficacy of AM graft for healing CCUs.,, The objective of this study was to assess the efficacy and safety of AM allografts in CCUs.
| Materials and Methods|| |
The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The literature search was conducted using PubMed, Cochrane Library, and Embase for all related trials published from inception through May 31, 2019, without restriction on language. To identify all relevant studies, the combinations of following terms were used: skin ulcer, wound healing, foot ulcer, diabetic foot, diabetic feet, leg ulcer, varicose ulcer, venous ulcer, stasis ulcer, arterial ulcer, neuropathic ulcer, ischemic wound, ischemic ulcer, ischemic ulcer, ischemic wound, pressure ulcer, decubitus ulcer, chronic wound, chronic ulcer, AM, amnion, bioimplant dressing, GraFix, EpiFix, dehydrated human amnion/chorion membrane (DHACM). Identified reviews, meta-analyses, and relevant references of selected articles were also retrieved manually to identify additional relevant studies. The detailed search strategy is available as shown in [Table 1].
|Table 1: Search strategy in Embase up till May 31, 2019 (similar search run in other databases)|
Click here to view
We included studies that met the following inclusion criteria: (1) Randomized controlled trials (RCTs); (2) the included people aged 18 years or older with CCUs from any cause (such as venous ulcers, pressure ulcers, and DFUs); we also included CCUs with mixed etiology; (3) studies comparing AM with the standard of care/conventional treatment in treating CCUs; (4) one or more of the outcomes available, including healing rate (proportion of ulcers completely healed, defined as 100% epithelialization or skin closure without drainage), healing time (time to complete wound healing), percentage area reduction, wound pain (measured by any validated scale), and infection rate or other adverse events.
Studies that met the following exclusion criteria were excluded as follows: (1) duplicate studies; (2) non-RCTs, such as reviews, case reports, cohort studies, retrospective observational studies, or animal experimental studies; (3) studies that evaluated AM coupled with other treatments; (4) studies focusing on burns, bone fractures, dental or jaw treatment, orthopedic injection, surgery wound, or plastic surgery.
Two authors selected relevant studies independently. Disagreements were resolved via discussion with each other. First, we excluded all duplicate publications, then we scanned the titles and abstracts of the search results and obtained the full text if studies appeared to meet the inclusion criteria; finally, we read the full text carefully based on the inclusion and exclusion criteria. The PRISMA flow diagram of the study selection is shown in [Figure 1].
Two authors worked independently to extract the following data from included studies and recorded them using a data extraction sheet: first author's name, publication year, country, study design, study duration, sample size, age and sex, number of ulcers, type of ulcer, ulcer size, and outcomes. If the information was incomplete, attempts were made to contact the author for detailed information.
Risk of bias assessment
Based the assessment on the guidance in Cochrane Handbook for Systematic Reviews of Interventions 5.2.0, we evaluated the following seven domains that are related to biased estimates of intervention effects: random sequence generation, allocation concealment, participant and personnel blinding, outcome assessment blinding, incomplete outcome data, selective reporting, and other biases.
Data synthesis and analysis
We used Review Manager 5.3 (cochrane collaboration DNK), which was provided by the Cochrane library to conduct the meta-analysis (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). P < 0.05 was considered to be statistically significant. Binary outcome measures and continuous variables were pooled by using risk ratios (RRs) and mean differences (MDs) or standard MDs with 95% confidence intervals (CIs), respectively. I2 was used to assess heterogeneity, which describes the percentage of variation across studies that is due to heterogeneity rather than chance alone. If I2< 50%, we used the fixed-effect model, if I2 >50%, we used the random-effects model. A funnel plot was used to assess publication bias.
| Results|| |
Characteristics of included studies
In this study, totally 13 RCTs with sample sizes varying from 14 to 200 were eligible.,,,,,,,,,,,, Totally 947 patients were enrolled, with 482 in the intervention group and 465 in the control group, respectively. The characteristics of the included RCTs are summarized in [Table 2]. At baseline, wound area, gender, and age were similar for both the intervention and control groups.
Risk of bias
All the included studies were involved in random sequence generation. Adequate allocation concealment was reported in six of the studies. Nine studies described the blinding of participants and personnel; only one of the studies used double-blinding, and the rests were open blinded. Blinding of an outcome assessment was undertaken in six studies, whereas the rest were unclear [Figure 2] and [Figure 3].
|Figure 2: Risk of bias' graph: Review authors' judgments about each risk of bias item presented as percentages across all included studies|
Click here to view
|Figure 3: Risk of bias' summary: Review authors' judgments about each risk of bias item for each included study|
Click here to view
The healing rate of chronic cutaneous ulcers
All thirteen trials reported data for the healing rate of CCUs. A fixed-effects model was used to conduct meta-analysis, because there was no significant heterogeneities among studies [χ2 = 23.51, P = 0.02, I2 = 49%; [Figure 4]a and b]. The meta-analysis demonstrated that compared with SOC, AM could significantly improve the healing rate in patients with CCUs (RR = 1.99, 95% CI: 1.75–2.26; P < 0.001). We conducted subgroup analysis to investigate whether different etiology of CCUs and different treatments resulted in diverse clinical outcomes; however, they still revealed statistically differences in favor of AM for the healing rate in subgroups [Figure 4]a and [Figure 4]b.
|Figure 4: Forest plot and meta-analysis for healing rate (a) and stratified by diabetes or nondiabetes (b)|
Click here to view
There were eight studies that reported percentage area reduction.,,,,,,, However, five of these eight studies did not report the standard deviations, and we could not analyze the result.,,,, We pooled the reported data from the other three studies on percentage area reduction.,, Compared with SOC, a greater area reduction could be found in AM groups using the random-effects model (MD = 70.00%, 95% CI: 15.82–124.17; I2 = 82%; P = 0.01) [Figure 5].
Seven studies reported the healing time.,,,,,, Although all the seven studies reported there were statistical differences compared with the SOC, most of them reported the mean healing days without standard deviation, so we could not pool the data for further estimation.
Hanumanthappa et al. (2012) assessed pain score by using a 100-point (0–100) visual analog scale, with 0 indicating no pain and 100 indicating the worst pain. After 3 weeks of treatment, the pain score in the AM group dropped from 70 to 10, whereas the pain score in the SOC group dropped from 60 to 40. Two other studies reported pain relief., However, there was no statistically significant difference between the AM group and the control group (RR = 4.83, 95% CI: 0.16–145.55; I2 = 84%; P = 0.36) [Figure 6].
Adverse events were reported in eleven studies.,,,,,,,,,, Using the random-effects model, indicated that there was a statistically significant difference between AM group and SOC group (RR = 0.54, 95% CI: 0.31–0.93; I2 = 0.79; P = 0.03) [Figure 7]. Four studies reported serious adverse events (adverse events that resulted in death, required hospitalization, or caused significant disability), and meta-analysis demonstrated that compared with SOC, AM group had a lower incidence (RR = 0.61, 95% CI: 0.25–1.49), but did not have a statistically significant difference (P = 0.07) [Figure 8].
A funnel plot was used to assess publication bias. As displayed in [Figure 9], there was no significant publication bias among most of the included studies.
| Discussion|| |
To the best of our knowledge, this is the first systematic review and meta-analysis on this topic. This study of 13 RCTs, including 947 patients comparing the efficacy of AM and SOC shows that AM is effective, with significantly improved healing rate, higher percentage area reduction, and less adverse events. There was no significant difference in pain relief. We could not pool the data for healing time because the standard deviations were not available.
We analyzed the overall effect of AM on healing rate with data from thirteen RCTs, and the result reveals that AM is effective in treating CCUs. In subgroup analyses, the results confirmed this finding. The RR in venous ulcer group, pressure ulcer group, diabetic ulcer group, and mix etiology group were all >1 with P < 0.05, which suggested there were significant differences. This study indicated that AM might be effective for treating different ulcers (different etiologies). Our finding was consistent with previous studies.,, For diabetic ulcers, peripheral vascular disease, neuropathy, and poor blood glucose control are the main causes of poor prognosis. In addition, the delayed healing of ulcers increases the risk for wound infection and amputation. In our study, the results of diabetic ulcer group and nondiabetic ulcer group reveal that there are no significant differences between these two groups. Compared with standard therapy, AM promotes wound closure, resulting in more consistent and faster healing of chronic diabetic ulcers.,,, Am can stimulate the migration, proliferation, and change the expression of cytokines of diabetic adipose-derived stem cells, to promote the healing of diabetic ulcers. Given that most included studies were about diabetic ulcers and some studies had small sample sizes, future well-designed studies concerning different cutaneous ulcers with larger sample sizes are needed.
The assessment of percentage area reduction showed a statistically significant difference in the two groups. An early decrease in the ulcer area indicates a good prognosis. If the wound area does not reduce by ≥40% in 4 weeks, it has little chance to heal in 12 weeks. Serena et al. observed that in 20 patients with wound area reduction ≥40% within the first 4 weeks, 16 were completely healed within 24 weeks, whereas only 8 of the 24 patients who had <40% healing in the first 4 weeks were completely healed.
Previous studies showed that AM was thought to have an analgesic effect, but the mechanism was not well understood.,,, It may be associated with reduced inflammation, better contact between the wound bed and the external environment, protection of exposed nerve terminals, and less frequent dressing changes. In this study, the overall pooled data was in favor of the AM group for pain relief, which was consistent with previous studies. However, there was no statistically significant difference. This might be due to the limited number of studies and sample sizes included.
Regarding adverse events, this study also indicated that there was a significant difference between AM group and SOC group. This finding suggested that there were fewer adverse events in the AM group, and it was relatively safe in the short term. In addition, none of the adverse events were related to the product or any study procedures. However, long-term adverse events were still unclear in previous studies. In recent years, commercially dehydrated human amnion/chorion membranes (such as Grafix®, EpiFix®) are available, and hence, they may enhance safety and reduce the adverse events in clinical applications.
There were some limitations to this study. First, the sample size in some included studies was too small, which might contribute to statistical bias. Second, most of the included RCTs in our study were related to DFUs, and more RCTs concerns in other CCUs (such as pressure ulcers, venous ulcers, and neuropathic ulcers) are needed in future. Third, most patients enrolled in the studies were males with their ages range from 18 to 78. Sex and age could be risk factors in CCUs healing, which might be a potential source of clinical heterogeneity that affects the results. Fourth, the preparation of AM varied, and there was no uniform standard, which might be a potential source of clinical heterogeneity. Different techniques may affect the quality of AM products; however, these do not seem to be clinically relevant. Finally, the observation period in the included studies ranged from 3 to 12 weeks, some of which were between 3 and 6 weeks, however, since CCUs often require a long time to heal and frequently recur, it is necessary to assess the efficacy and safety of AM with a longer period of follow-up.
| Conclusion|| |
This systemic review and meta-analysis demonstrate that AM is effective and safe in treating CCUs. AM may be used as an adjuvant treatment for CCUs. Well-designed and large-size RCTs and systemic reviews are needed to confirm our findings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
McCarty SM, Percival SL. Proteases and delayed wound healing. Adv Wound Care (New Rochelle) 2013;2:438-47.
Purcell A, Buckley T, Fethney J, King J, Moyle W, Marshall AP. The effectiveness of EMLA as a primary dressing on painful chronic leg ulcers: Effects on wound healing and health-related quality of Life. Int J Low Extrem Wounds 2017;16:163-72.
Alavi A, Sibbald RG, Phillips TJ, Miller OF, Margolis DJ, Marston W, et al
. What's new: Management of venous leg ulcers: Approach to venous leg ulcers. J Am Acad Dermatol 2016;74:627-40.
Zapata MJ, Carvajal AJ, Solà I, Expósito JA, Bolíbar I, Rodríguez L, et al
. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev 2016;5:CD006899.
Gordon P, Widener JM, Heffline M. Venous leg ulcers: Impact and dysfunction of the venous system. J Vasc Nurs 2015;33:54-9.
Morimoto N, Kakudo N, Matsui M, Ogura T, Hara T, Suzuki K, et al
. Exploratory clinical trial of combination wound therapy with a gelatin sheet and platelet-rich plasma in patients with chronic skin ulcers: Study protocol. BMJ Open 2015;5:e007733.
Gohel MS, Barwell JR, Taylor M, Chant T, Foy C, Earnshaw JJ, et al
. Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): Randomised controlled trial. BMJ 2007;335:83.
Bakker K, Schaper NC; International Working Group on Diabetic Foot Editorial Board. The development of global consensus guidelines on the management and prevention of the diabetic foot 2011. Diabetes Metab Res Rev 2012;28 Suppl 1:116-8.
Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005;293:217-228.
Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis. Diabetes Care 1999;22:692-5.
Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, et al
. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012;54:e132-73.
Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care (New Rochelle) 2015;4:560-82.
Diegelmann RF, Evans MC. Wound healing: An overview of acute, fibrotic and delayed healing. Front Biosci 2004;9:283-9.
Rodrigues I, Mégie MF. Prevalence of chronic wounds in Quebec home care: An exploratory study. Ostomy Wound Manage 2006;52:46-8, 50, 52-7.
ElHeneidy H, Omran E, Halwagy A, Al-Inany H, Al-Ansary M, Gad A. Amniotic membrane can be a valid source for wound healing. Int J Womens Health 2016;8:225-31.
Koob TJ, Rennert R, Zabek N, Massee M, Lim JJ, Temenoff JS, et al
. Biological properties of dehydrated human amnion/chorion composite graft: Implications for chronic wound healing. Int Wound J 2013;10:493-500.
Zelen CM, Serena TE, Gould L, Le L, Carter MJ, Keller J, et al
. Treatment of chronic diabetic lower extremity ulcers with advanced therapies: A prospective, randomised, controlled, multi-centre comparative study examining clinical efficacy and cost. Int Wound J 2016;13:272-82.
Dehghani M, Azarpira N, Mohammad Karimi V, Mossayebi H, Esfandiari E. Grafting with cryopreserved amniotic membrane versus conservative wound care in treatment of pressure ulcers: A randomized clinical trial. Bull Emerg Trauma 2017;5:249-58.
Bianchi C, Cazzell S, Vayser D, Reyzelman AM, Dosluoglu H, Tovmassian G, et al
. A multicentre randomised controlled trial evaluating the efficacy of dehydrated human amnion/chorion membrane (EpiFix®
) allograft for the treatment of venous leg ulcers. Int Wound J 2018;15:114-22.
Higgins JP, Altman DG, Sterne JA. Assessing risk of bias in included studies. Ch 8. In: Higgins JPT, Churchill R, Chandler J, Cumpston MS, editors. Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0. [Last updated on 2017 Jun]: Cochrane; 2017. Available from: https//www.training.cochrane.org/handbook
DiDomenico LA, Orgill DP, Galiano RD, Serena TE, Carter MJ, Kaufman JP, et al
. Use of an aseptically processed, dehydrated human amnion and chorion membrane improves likelihood and rate of healing in chronic diabetic foot ulcers: A prospective, randomised, multi-centre clinical trial in 80 patients. Int Wound J 2018;15:950-7.
Hanumanthappa MB, Gopinathan S, Suvarna R, Guruprasad RD, Shetty G, Shetty K, et al
. Amniotic membrane dressing versus normal saline dressing in non-healing lower limb ulcers: A prospective comparative study at a teaching hospital. J Clin Diagn Res 2012;6:423-7.
Lavery LA, Fulmer J, Shebetka KA, Regulski M, Vayser D, Fried D, et al
. The efficacy and safety of Grafix(®
) for the treatment of chronic diabetic foot ulcers: Results of a multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J 2014;11:554-60.
Tehrani MR, Variji Z, Mohseni S, Firuz A, Annabestani Z, Zartab H, et al
. Comparison of a bioimplant dressing with a wet dressing for the treatment of diabetic foot ulcers: A randomized, controlled clinical trial. Wounds 2016;28:248-54.
Serena TE, Carter MJ, Le LT, Sabo MJ, DiMarco DT; EpiFix VLU Study Group. A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. Wound Repair Regen 2014;22:688-93.
Snyder RJ, Shimozaki K, Tallis A, Kerzner M, Reyzelman A, Lintzeris D, et al
. A Prospective, randomized, multicenter, controlled evaluation of the use of dehydrated amniotic membrane allograft compared to standard of care for the closure of chronic diabetic foot ulcer. Wounds 2016;28:70-7.
Tettelbach W, Cazzell S, Reyzelman AM, Sigal F, Caporusso JM, Agnew PS. A confirmatory study on the efficacy of dehydrated human amnion/chorion membrane dHACM allograft in the management of diabetic foot ulcers: A prospective, multicentre, randomised, controlled study of 110 patients from 14 wound clinics. Int Wound J 2019;16:19-29.
Zelen CM, Gould L, Serena TE, Carter MJ, Keller J, Li WW. A prospective, randomised, controlled, multi-centre comparative effectiveness study of healing using dehydrated human amnion/chorion membrane allograft, bioengineered skin substitute or standard of care for treatment of chronic lower extremity diabetic ulcers. Int Wound J 2015;12:724-32.
Zelen CM, Serena TE, Denoziere G, Fetterolf DE. A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers. Int Wound J 2013;10:502-7.
Laurent I, Astère M, Wang KR, Cheng QF, Li QF. Efficacy and time sensitivity of amniotic membrane treatment in patients with diabetic foot ulcers: A systematic review and meta-analysis. Diabetes Ther 2017;8:967-79.
Massee M, Chinn K, Lim JJ, Godwin L, Young CS, Koob TJ. Type I and II diabetic adipose-derived stem cells respondin vitro
to dehydrated human amnion/chorion membrane allograft treatment by increasing proliferation, migration, and altering cytokine secretion. Adv Wound Care (New Rochelle) 2016;5:43-54.
Steed DL, Attinger C, Colaizzi T, Crossland M, Franz M, Harkless L, et al
. Guidelines for the treatment of diabetic ulcers. Wound Repair Regen 2006;14:680-92.
Serena TE, Yaakov R, DiMarco D, Le L, Taffe E, Donaldson M, et al
. Dehydrated human amnion/chorion membrane treatment of venous leg ulcers: Correlation between 4-week and 24-week outcomes. J Wound Care 2015;24:530-4.
Loeffelbein DJ, Rohleder NH, Eddicks M, Baumann CM, Stoeckelhuber M, Wolff KD, et al
. Evaluation of human amniotic membrane as a wound dressing for split-thickness skin-graft donor sites. Biomed Res Int 2014;2014:572183.
Lo V, Pope E. Amniotic membrane use in dermatology. Int J Dermatol 2009;48:935-40.
Hoeynck FV, Steinfeld AP, Becker J, Hermel M, Rath W, Hesselbarth U. Sterilization and preservation influence the biophysical properties of human amnion grafts. Biologicals 2008;36:248-55.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
[Table 1], [Table 2]