Lakmal 

et al. BMC Surg (2021) 21:87

https://doi.org/10.1186/s12893-021-01084-8

RESEARCH ARTICLE Open Access

Systematic review on the rational use

of amniotic membrane allografts in diabetic
foot ulcer treatment
Kasun Lakmal, Oshan Basnayake and D. Hettiarachchi* 

Abstract 
Background:  Diabetic foot ulcer is a complication with multiple aetiological factors which has a significant impact
to patients’ lives and costs to the healthcare system. The potential of human amniotic membrane to act as an allograft
has been studied in relation to this condition. Aim of this study is to evaluate the current scientific evidence on its
effectiveness in healing diabetic foot ulcers.
Methods:  Pubmed, Cochrane library, and Google scholar were searched using the search terms, “Amnion” OR “Pla-
centa” AND “Diabetic foot”. (MeSH terms) in the title or the abstract field from 1st of January 2000 to 30th March 2020.
The quality of published reports was assessed using standard methods. We searched for experimental and observa-
tional studies in terms of randomized control trials, prospective cohort, retrospective cohort studies and case series.
Results:  When searched with Mesh terms, 12 citations in PubMed, 22 citations in Cochrane library and 30 in other
data bases were found. After screening the studies and their reference lists, 12 studies met the inclusion criteria and
the others were excluded. There were 8 randomized control trials (RCTs), 2 prospective studies and 2 retrospective
studies employing different preparation methods of the amniotic membranes. A wide variation in study end points
were noted. Majority of the RCTs (n = 7) were concluded with significantly higher wound closure rate compared to
the conventional treatment groups. In prospective and retrospective studies, it was shown that large chronic ulcers
which were resistant to closure with standard therapy achieved wound closure with amniotic membrane allografts. A
meta-analysis could not be performed due to study heterogeneity, and publication bias was not assessed due to the
small number of available studies which was not sufficient for accurate comparison.
Conclusion:  Even though, the studies had some inherent heterogeneity due to different preparation methods,
different study end points and outcome measurements. According to our review the current studies using amniotic
membrane allografts give reliable evidence of reduction in healing time over conventional methods.
Keywords:  Amniotic membrane, Diabetes, Foot ulcers, Allografts

Background factors and other nutrients that facilitates its intrauter-

The human amniotic membrane has shown immense ine function as it forms the feto-maternal interphase.
potential as an allograft. Owing to its several unique Human Amniotic Allograft Membrane (HAA) can sup-
qualities such as a rich milieu of amino acids, growth port wound healing by facilitating cell migration and
promoting repair [1]. One such use is in the treatment of
chronic wounds, in the early twentieth century this pos-
*Correspondence: [email protected] sibility was explored and further expanded to diabetic
Department of Anatomy, Faculty of Medicine, University of Colombo, 25, neurovascular ulcers. The recent development of gamma
Kynsey Place 8, Colombo, Sri Lanka

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Lakmal et al. BMC Surg (2021) 21:87 Page 2 of 8

irradiated or dehydrated amniotic membrane grafts has using Downs and Black checklist. Downs and Black score
enabled us to bypass some of the drawbacks experienced ranges were given corresponding quality levels as previ-
with traditional graphing method including issues with ously reported [8]: excellent (26–28); good (20–25); fair
storage and preparation [2]. (15–19); and poor (≤ 14). Additionally authors attempted
Diabetic foot ulcers (DFU) are estimated to affect 15% to reduce the publication bias and between-study hetero-
of diabetic patients. They experience foot ulcers once geneity by employing standard methods such as extended
in their lifetime with a recurrence rate of 35–50% over funnel plot tests for detecting publication bias, and
3 years to around 70% over 5 years [2–4]. Complications selection modelling and trim-and-fill methods to adjust
of diabetic foot ulcers maybe related to its chronicity, for publication bias in the presence of between-study
osteomyelitis, re-ulceration, gangrene and amputation heterogeneity.
which might be aggravated by concomitant co-morbid- We searched for experimental and observational stud-
ities such as peripheral vascular disease, sub-optimal ies in terms of randomized control trials, prospective
blood glucose control and neuropathy to name a few [5]. cohorts, and retrospective cohort studies. Case reports
The long-drawn healing process in a DFU make them were excluded from this review. Only studies pertaining
more susceptible for infection and resulting complica- to human subjects were selected. The primary objective
tions leading to healthcare economic burden [6]. The of this systematic review was to identify the outcomes of
standard care for a DFU includes management of infec- the use of amniotic membrane in the rate of healing in
tions, local wound care offloading (especially in DFU diabetic foot ulcers (Fig. 1).
complicated with neuropathy) and correcting systemic Initial eligibility screening was performed based on the
factors to promote healing. Some clinicians recom- titles and abstract from electronic databases. Thereafter,
mend advanced treatment such as biological dressings, the full text papers of all studies were assessed based on
collagen, platelet-derived growth factors (PDGF), and the inclusion and exclusion criteria. In doubtful situa-
platelet-rich plasma (PRP) for non-healing ulcers after tions the opinion of the senior investigator was sought.
a\standard wound care [1]. In this light natural amniotic The studies done with both type 1 and type 2 diabetes
membrane wound dressings have been used for over a patients were included. The studies which have used dif-
century as it contains a single epithelial cell layer, a thick ferent preparation of amniotic allografts (dehydrated,
basement membrane and an avascular stroma making it cryopreserved and stem cell extractions) were included.
an ideal biological graft. Human amniotic membrane can When including the RCTs, studies which compared the
assist in wound healing by cell migration into the healing amniotic membrane treatment with standard or conven-
tissue. Acquiring placenta for the harvesting of amniotic tional care were selected. Studies that are designed with
membrane is a challenge in terms of ethical aspects and the aim of analyzing the molecular basis without measur-
the harvesting, processing, and preservation of the mem- ing clinical improvement of the ulcers were also excluded
brane as biological dressing are expensive procedures. from our study. From each study data were extracted on
Products containing amniotic tissue are increasingly trial design, study setting, amniotic membrane prepara-
being manufactured either as cryopreserved or dehy- tion methods used, control interventions, outcome meas-
drated grafts [7]. We sought to investigate the rational ures and statistical analysis. Outcome measures were
use of amniotic membrane allografts in the management extracted in terms of the healing time, healed percentage,
of diabetic foot ulcers by conducting a systemic review recurrences and adverse outcomes.
through published studies. Objective of the study was to
assess the impact on wound closure rates by the use of Results
amniotic membrane in diabetic foot ulcers. When searched with Mesh terms 12 citations in Pubmed,
22 citations in Cochrane library and 30 in other data
Methods bases were found. We couldn’t find new studies by going
PubMed, Cochrane library, CINAHL, Embase, Web through reference lists. By screening the studies total of
of Science, and Clinicaltrials.gov and Google scholar 12 non-duplicated studies met the inclusion and exclu-
engines were searched for the terms “Amnion” OR “Pla- sion criteria. There were 8 randomized control trials, 2
centa” AND “Diabetic foot” (MeSH terms) in the title prospective studies and 2 retrospective studies (Fig.  1).
or in the abstract field from 1st of January 2000 to 3­ 0th Even though the search was done from the studies con-
March 2020. A non-English language database known as ducted since 2000, all the studies that met the criteria
APAMED central was searched using the same criteria to and included in the review were done in the last decade
reduce the publication bias. The reference lists provided i.e. after 2010. We found 8 randomized control trials [1,
in full papers were also used to identify additional papers 2, 5, 9–13] and all were performed in the United States
for review. Quality of published reports was assessed and five of those were multicenter trials. Out of the 2
 Lakmal et al. BMC Surg (2021) 21:87 Page 3 of 8

Fig. 1  Prisma flow chart

prospective studies one was done in Spain [14] and the studies ulcer duration was more than 28  days. Mean
other in the United States [15]. Both retrospective stud- size of the ulcers in prospective and retrospective stud-
ies [16, 17] were also performed in the United States. ies were more than 5 c­ m2 and it was less than 5 c­ m2 in
According to the Downs and Black scoring system, 4 majority of participants in randomized control trials
studies [5, 9, 11, 13] were graded as “Good” (score rang- (Table  1). Different amniotic membrane preparations
ing from 20 to 25) and rest of the 8 studies were graded as have been used (Amnioband [9], AMNIOEXCEL [10,
‘Fair” (15–19). 15], Epifix [2,11,12,], Apligraf [11], Grafix [13], NEOX
There were total 244 participants in intervention CORD [16], (dHACM) [5, 17]).
groups and 210 in the control groups of 8 randomized In 6 randomized control trials the follow up duration
control trials, except in in one study. Total of 28 in pro- was 12 weeks and in the rest, it was 6 weeks. Both pro-
spective and total of 92 in retrospective studies were spective and one retrospective study [16] included data
treated with amniotic membrane preparations. The mean until complete wound closure was achieved. Majority
duration of the diabetes mellitus in the participants was of randomized control trials (n = 7) have demonstrated
reported only in one study [13]. There were patients with statistically significant closure rates at the study end-
different ulcer locations in their feet and in all the above point compared to conventional or standard wound care
Table 1  Characteristics of study groups
Lakmal et al. BMC Surg

Author Year Location (setting) Study type Study size Mean age (years)/ Mean duration Ulcer location/s Mean ulcer Mean ulcer size
SD of DM duration (days)/ ­(cm2)/SD
SD

1 Thompson et al. [1] 2019 North Dakota RCT​ 13 I = 58.5(12.96) NA Plantar NA I = 1.54(1.74)
USA (I = 7, C = 6) C = 55.17(18.32 C = 2.78(3.04)
(2021) 21:87

2 Tettebach et al. [5] 2019 Multicenter RCT​ 110 I = 57.4(10.6) NA Toe, forefoot, I = 145.6(129.5) I = 3.2(2.8)
USA (I = 54,C = 56) C = 57.1(10.5) midfoot and C = 149.8(110.6) C = 3.9(3.8)
hindfoot
3 Didomenico et al. 2016 Multicenter RCT​ 40 I-59.0(13) NA Toe, forefoot, mid-  >  = 28.0 I = 2.0(0.90)
[9] USA (I = 20, C = 20) C-58.0(9) foot, heel, ankle, C = 3.3(4.35)
and hindfoot
4 Snyder et al. [10] 2016 Multicenter RCT​ 29 I = 57.9(12.49) NA Forefoot, midfoot,  >  = 28.0 I = 4.7(5.43)
USA (I = 15, C = 14) C = 58.6(6.97) hindfoot, C = 6.9(6.75)
pahanges, meta-
tarsals
5 Zelen et al 2015 Multicenter RCT​ 100 I1 = 63.3(12.25) NA Toe, forefoot, I1 = 121.1(107.1) I1 = 2.6(2.97)
[11] USA (I1 =  32, ­I2 = 33, I2 = 63.8(11.86) midfoot hindfoot, I2 = 133.0(103.46) I2 = 2.7(2.75)
C = 35) C = 60.6(11.55) and ankle C = 98.7(90.3) C = 3.1(3.17)
6 Zelen et al. [12] 2014 Southwest Virginia RCT​ 40 I = 59.6(13.8) NA Toe, forefoot, I = 118.3(151.9) I = 2.4(1.8)
USA (I = 20, C = 60.8(0.9) midfoot and C = 122.5(101.5) C = 2.0(1.3)
C = 20) hindfoot
7 Lavery et al. [13] 2014 Multicenter RCT​ 97 I = 55.5(11.5) I = 15.4(11.1) Dorsal and plantar I = 115.0(72.6) I = 3.41(3.23)
USA (I = 50, C = 47) C = 55.1(12.0) C = 14.0(11.0) C = 122.9(83.9) C = 3.93(3.22)
8 Zelen et al. [2] 2013 Southwest Virginia RCT​ 25 I = 56.4(14.7) NA Forefoot, digital, I = 98.7(91.0) I = 2–6(1.9)
USA (I = 13, C = 61.7(10.3) heel and midfoot C = 114.8(108.5) C = 3.4(2.9)
C = 12)
9 Valiente et al. [14] 2018 El Palmar Prospective N = 14 57 NA Forefoot, midfoot  >  = 56 12.30
Spain Case series and hind foot
10 Abdo [15] 2016 St.Louis Prospective N = 14 56.7(9.1) NA Forefoot, midfoot  >  = 28 6.5(11.6)
USA Cases series and hindfoot
11 Raphael[16] 2016 Georgia Retrospective N = 29 52.9(1.83) NA Forefoot., midfoot 340.2(116.9) 10.6(2.15)
USA study and hindfoot
12 Kirsner et al. [17] 2015 Multicenter Retrospective N = 63 61.1(12.2) NA Planter 128.8 5.2
USA study
SD standard deviation, DM diabetes mellitus, RCT​ randomized control trial, I intervention group, C control group, NA not available
Page 4 of 8
Table 2  Interventions and outcomes of the studies
Author Year Study type Intervention Evaluation Follow-up time Healing Healed Recurrences Adverse outcomes.
and size frequency time(days) /(SD) percentage (amniotic
of the group membrane
product related)
Lakmal et al. BMC Surg

1 Thompson et al. 2019 RCT​ Human amniotic Weekly 12 weeks I-29.50(15.41) NA 90-day recurrence NA
[1] allograft 7 C- 26.20(8.93) rate
SOC-6 (p value has not I-14.29%
been calculated C-83.3%
due to small
(2021) 21:87

sample size)
2 Tettebach et al. [5] 2019 RCT​ dHACM – 54 Weekly 12 weeks P = 0.0187 I-70% 112-day recur- 3 product related
SOC- 56 (Kaplan–Meier C-50% rence events
plot of time to P = 0.0338 I-5%
heal) C-14%
3 Didomenico et al. 2016 RCT​ AmnioBand 20 Weekly 12 weeks I – 36.0 I-85%, C-25% NA NA
[9] SOC 20 C – 70.0 P = 0.00073
P = 0.00073 Odds ratio = 17
4 Snyder et al. [10] 2016 RCT​ AMNIOEXCEL 15 Weekly 6 weeks NA I-35%, NA Not observed
SOC 14 C-0%
P = 0.017
5 Zelen et al.[11] 2015 RCT​ EpiFIx 32 Weekly 12 weeks I1-23.6 I1-97% NA Not observed
Apligraf 33 I2- 47.9 I2-73%
SOC 35 C = 57.4 C-51
P = 0.0019
6 Zelen et al. [12] 2014 RCT​ Epifix 20 I – weekly 12 weeks I-16.8(12.6) I-85% NA Not observed
SOC 20 C—biweekly C-29.0(17) C-100%
P = 0.039
7 Lavery et al. [13] 2014 RCT​ Grafix 50 Weekly 12 weeks I-42.0 I-62.0% NA Would infections
SCO 47 C-69.5 C-21.3% were low in inter-
P = 0.019 P = 0.0001 ventional group
(p = 0.044)
8 Zelen et al. [2] 2013 RCT​ Epifix 13 Weekly 6 weeks I-17.5(13.3) I-92% NA NA
SOC 12 C-35.0 C-8%
P = 0.0001
9 Valiente et al. [14] 2018 Prospective Cryopreserved Weekly Until complete Median time NA NA Not observed
Case series amniotic mem- closure 20 weeks (range
brane 14 7–56)
10 Abdo [15] 2016 Prospective AMNIOEXCEL 14 Weekly Until complete Median 5 weeks NA NA NA
Cases series closure (range
1014 weeks)
Page 5 of 8
 Lakmal et al. BMC Surg
(2021) 21:87

Table 2  (continued)
Author Year Study type Intervention Evaluation Follow-up time Healing Healed Recurrences Adverse outcomes.
and size frequency time(days) /(SD) percentage (amniotic
of the group membrane
product related)

11 Raphael [16] 2016 Retrospective NEOX CORD 1 K Weekly Until complete Mean 96.6(13.65) 87.5% NA NA
study (cryopreserved closure days
amniotic mem- Median 9 weeks
brane) 29
12 Kirsner et al. [17] 2015 Retrospective dHACM 63 NA 24 weeks Median time At 12 weeks-28% NA NA
study 26 weeks At 24 weeks-47%

SD standard deviation, RCT​ randomized control trials, SOC standard of care, I intervention group, C control group, dHACM dehydrated human amnion/chorionic membrane
Page 6 of 8
 Lakmal et al. BMC Surg (2021) 21:87 Page 7 of 8

procedures (p < 0.05). Adverse graft outcomes were low in and publication bias was not assessed due to the small
studies where safety evaluation data was available (n = 6). number of available studies for each comparison. Fur-
One study [13] showed statistically significant low infec- thermore, this study findings are in-line with previously
tion rate in the intervention group (p < 0.044). Thompson conducted study on the efficacy and time sensitivity of
et al. evaluated 90-day recurrence rates in both interven- human amnion/chorion membrane treatment in patients
tion and control group and a lower recurrence rate was with diabetic foot ulcers which concluded that when
observed in the intervention group (14.29% versus 83.3%) amniotic membranes were combined with standard care
similarly Tettlebatch et  al. also showed a lower recur- diabetic foot ulcers healed significantly faster than stand-
rence rate at 112 days (5% versus 14%). ard care alone [18]. However, we recommend that further
In one prospective study [14], the mean duration of prospective randomized control trials with larger popula-
ulcer was more than 56 days and the mean ulcer size was tion with long term follow-up have to be performed for
12.30 ­cm2 in comparison the other prospective study better evidence. The current evidence suggests the use
[15] these two parameters were more than 28  days and of amniotic membrane preparations for resistant dia-
6.5 ­cm2. Median ulcer closure times were 20  weeks and betic foot ulcers can achieve relatively fast wound closure
5 weeks, respectively. The mean ulcer duration was long- rates.
est in one retrospective study [16], which was 340  days
with mean ulcer size of 10.6 ­cm2. This study concluded Conclusions
that the median ulcer closure time was 9  weeks. In the According to our review the current studies summarize
other retrospective study [17], mean ulcer duration was reliable evidence to suggest reduction in healing time
128.8  days and mean ulcer size was 5.2cm2 and this with amniotic membrane preparations in the treatment
study demonstrated that the median time of healing was of refractory chronic diabetes foot ulcers compared to
26 weeks (Table 2). conventional methods.

Discussion Abbreviations
This study aimed to evaluate the current scientific evi- DFU: Diabetic foot ulcer; dHACM: Dehydrated human amniotic chorionic
dence on effectiveness of use of amniotic membrane in membrane; DM: Diabetes mellitus; HAA: Human amniotic allograft membrane;
NA: Not available; PDGF: Platelet Derived Growth Factors; PRP: Platelet-rich
healing the diabetic foot ulcers. In the analysis of retro- Plasma; RCT​: Randomized control trials; SD: Standard deviation; SOC: Standard
spective studies, majority of the RCTs (n = 7) were con- of care; USA: Untied States of America.
cluded with significantly higher wound closure rates
Acknowledgements
compared to the conventional treatment group. One None.
randomized control trial showed less recurrent rate of
the healed ulcers after treatment. In prospective and ret- Authors’ contributions
KL wrote the first draft of the manuscript with contributions from OB and DH.
rospective studies showed that larger and more chronic All authors read and approved the final manuscript.
ulcers which are resistant to close with the standard
therapy achieve wound closure with amniotic membrane Funding
No funding for this project.
allografts. Minimal numbers of adverse effects attribut-
able to amniotic membrane product were observed in the Availability of data and materials
included studies. Not applicable.
Only two RCTs aimed at assessing the recurrence rate Ethics approval and consent to participate
following total closure of the ulcers [1, 5]. Follow up Not applicable.
details were not included in the other studies in terms
Consent for publication
of recurrent rates and further complications. Amniotic Not applicable.
membrane preparations used in different studies were
different to each other. Currently commercially available Competing interests
Authors declare that there are no competing interests.
amniotic membranes are expensive and median graft
costs in some studies were between 2000 and 10,000 of Received: 20 May 2020 Accepted: 1 February 2021
dollars [11, 12]. The main limitations of these studies
were the heterogeneity study methods and outcomes,
limited number of RCTs and small number of the of
study participants. Except one study [14] other studies References
were conducted in the USA limiting the generalization 1. Thompson P, et al. Comparing human amniotic allograft and standard
wound care when using total contact casting in the treatment of patients
of the results to the global population. A meta-analy- with diabetic foot ulcers. Adv Skin Wound Care. 2019;32(6):272–7.
sis could not be performed due to study heterogeneity,
Lakmal et al. BMC Surg (2021) 21:87 Page 8 of 8

2. Zelen CM, et al. A prospective randomised comparative parallel study of 12. Zelen CM, Serena TE, Snyder RJ. A prospective, randomised compara-
amniotic membrane wound graft in the management of diabetic foot tive study of weekly versus biweekly application of dehydrated human
ulcers. Int Wound J. 2013;10(5):502–7. amnion/chorion membrane allograft in the management of diabetic foot
3. Zubair M. Prevalence and interrelationships of foot ulcer, risk-factors and ulcers. Int Wound J. 2014;11(2):122–8.
antibiotic resistance in foot ulcers in diabetic populations: a systematic 13. Lavery LA, Fulmer J, Shebetka KA, et al. The efficacy and safety of Grafix
review and meta-analysis. World J Diabetes. 2020;11(3):78. for the treatment of chronic diabetic foot ulcers: results of a multi-
4. Harris-Hayes M, et al. The role of physical therapists in fighting the type 2 centre, controlled, randomised, blinded, clinical trial. Int Wound J.
diabetes epidemic. J Orthopaed Sports Phys Therapy. 2020;50(1):5–16. 2014;11(5):554–60.
5. Tettelbach W, et al. A confirmatory study on the efficacy of dehydrated 14. Valiente MR, Nicolás FJ, García-Hernández AM, Fuente Mora C, Blanquer
human amnion/chorion membrane dHACM allograft in the manage- M, Alcaraz PJ, Almansa S, Merino GR, Lucas MDL, Algueró MC, Insausti CL,
ment of diabetic foot ulcers: a prospective, multicentre, randomised, Piñero A, Moraleda JM, Castellanos G. Cryopreserved amniotic membrane
controlled study of 110 patients from 14 wound clinics. Int Wound J. in the treatment of diabetic foot ulcers: a case series. J Wound Care.
2019;16(1):19–29. 2018;27(12):806–15.
6. Driver VR, de Leon JM. Health economic implications for wound care and 15. Abdo RJ. Treatment of diabetic foot ulcers with dehydrated amni-
limb preservation. J Manag Care Med. 2008;11(1):13–9. otic membrane allograft: a prospective case series. J Wound Care.
7. Ya-Na S, et al. Human amniotic membrane allograft, a novel treatment 2016;25(Sup7):S4–9.
for chronic diabetic foot ulcers: a systematic review and meta-analysis of 16. Raphael A. A single-centre, retrospective study of cryopreserved umbili-
randomised controlled trials. Int Wound J. 2020;17(3):753–64. cal cord/amniotic membrane tissue for the treatment of diabetic foot
8. Phil H, et al. Age-related macular degeneration and low-vision rehabilita- ulcers. J Wound Care. 2016;25(Sup7):S10–7.
tion: a systematic review. Can J Ophthalmol. 2008;43(2):180–7. 17. Kirsner RS, Sabolinski ML, Parsons NB, Skornicki M, Marston WA. Com-
9. DiDomenic LA, Orgill DP, Galiano RD, et al. Aseptically processed parative effectiveness of a bioengineered living cellular construct vs
placental membrane improves healing of diabetic foot ulcerations: a dehydrated human amniotic membrane allograft for the treatment
prospective, randomized clinical trial. Plast Reconstr Surg Glob Open. of diabetic foot ulcers in a real world setting. Wound Repair Regen.
2016;4(10):e1095. 2015;23(5):737–44.
10. Snyder RJ, Shimozaki K, Tallis A, et al. A prospective, randomized, multi- 18. Irakoze L, et al. Efficacy and time sensitivity of amniotic membrane
center, controlled evaluation of the use of dehydrated amniotic mem- treatment in patients with diabetic foot ulcers: a systematic review and
brane allograft compared to standard of care for the closure of chronic meta-analysis. Diabetes Therapy. 2017;8(5):967–79.
diabetic foot ulcer. Wounds. 2016;28(3):70–7.
11. Zelen CM, Gould L, Serena TE, et al. A prospective, randomised, con-
trolled, multi-centre comparative effectiveness study of healing using Publisher’s Note
dehydrated human amnion/corion membrane allograft, bioengineered Springer Nature remains neutral with regard to jurisdictional claims in pub-
skin substitute or standard of care for treatment of chronic lower extrem- lished maps and institutional affiliations.
ity diabetic ulcers. Int Wound J. 2015;12(6):724–32.

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