ArticlePDF AvailableLiterature Review

Amniotic therapeutic biomaterials in urology: Current and future applications

October 2017
Translational Andrology and Urology 6(5):943-950

October 2017
6(5):943-950

DOI:10.21037/tau.2017.09.01

Authors:

Siam Oottamasathien

Boston Children's Hospital

James Craig

University of Utah

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To examine the rationale and applications of amniotic tissue augmentation in urological surgery. Published literature in English-language was reviewed for basic science and clinical use of amniotic or amnion-chorionic tissue in genitourinary tissues. Basic science and animal studies support the likely benefit of clinical applications of amnion-derived tissues in a variety of urologic interventions. The broad number of properties found in amniotic membrane, coupled with its immunologically privileged status presents a number of future applications in the urological surgical realm. These applications are in their clinical infancy and suggest that further studies are warranted to investigate the use of these products in a systematic fashion.

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Historical medical uses of amniotic membrane

The medical uses of the human placenta probably date back

centuries, with the first description of its use in a treatise

in 1593 by a Chinese clinician Li Shi-Zhen (1). The first

mention of the medical use of amniotic membrane in

the Western literature appeared in 1910 by Davis, who

reported on a series of cases where it was used as a skin

graft in a large case series at Johns Hopkins Hospital (2).

This was shortly followed by Drs. Stern and Sabella,

collaborators who separately published studies using this

material in wounds and burns (3,4). Through the rest of

the 20th century the medical use of the placenta, and more

specifically the amniotic membrane, was described in a

number of medical indications including; but not limited

to, the following types of cases: (I) skin grafting; (II) lower

extremity diabetic ulcers (5); (III) lower extremity venous

leg ulcers (6); (IV) general wounds (7); (V) conjunctival

surgery and repair (8); (VI) burns (9,10); (VII) periodontal

disease and dentistry (11,12); (VIII) vaginal reconstruction

and OB/GYN applications (13); (IX) neurosurgical

applications including spine surgery (14,15); (X) orthopedic

surgery applications (16).

Properties and function of amniotic tissues

While amniotic membrane was originally used because of

its recognized ability to substitute as a skin like tissue with

healing properties, the underlying physiologic, biochemical

and cytological properties of the tissue are reported to

confer a number of additional properties, in addition to

simply performing as a skin substitute. These properties

include: (I) contains essential growth factors (17); (II)

modulation of inflammation (18); (III) reduction of scar

tissue formation (18); (IV) barrier properties (14); (V)

immunologically privileged tissue (19); (VI) enhancement

of wound healing (20); (VII) reduction of pain in burns

and wounds; (VIII) innate antibiotic properties (21). There

Review Article

Amniotic therapeutic biomaterials in urology: current and future

applications

Siam Oottamasathien1,2, James M. Hotaling1,3, James R. Craig1,3, Jeremy B. Myers1,3, William O. Brant1,3

1Department of Surgery and Section of Pediatric Urology, 2Primary Children’s Hospital, 3Department of Surgery and Division of Urology Section of

Men’s Health, University of Utah, Salt Lake City, Utah, USA

Contributions: (I) Conception and design: All authors; (II) Administrative support: All authors; (III) Provision of study materials or patients: All

authors; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII)

Final approval of manuscript: All authors.

Correspondence to: Siam Oottamasathien, MD. University of Utah, 100 North Mario Capecchi Drive, Suite 3550, Salt Lake City, Utah 84113, USA.

Email: siam.oottamasathien@hsc.utah.edu.

Abstract: To examine the rationale and applications of amniotic tissue augmentation in urological surgery.

Published literature in English-language was reviewed for basic science and clinical use of amniotic or

amnion-chorionic tissue in genitourinary tissues. Basic science and animal studies support the likely benet

of clinical applications of amnion-derived tissues in a variety of urologic interventions. The broad number

of properties found in amniotic membrane, coupled with its immunologically privileged status presents a

number of future applications in the urological surgical realm. These applications are in their clinical infancy

and suggest that further studies are warranted to investigate the use of these products in a systematic fashion.

Keywords: Amnion; chorion; dehydrated membranes; hypospadias; urethral reconstruction

Submitted Aug 04, 2017. Accepted for publication Aug 30, 2017.

doi: 10.21037/tau.2017.09.01

View this article at: http://dx.doi.org/10.21037/tau.2017.09.01

950

944 Oottamasathien et al. Amniotic therapeutic biomaterials in urology: current and future applications

are varying degrees of documentation of each of the above

properties, but these attributes appear regularly in the

literature.

The underlying bimolecular mechanisms responsible

for the above properties are becoming increasingly well

characterized, in a growing, robust literature (1,17,22-24)

(Table 1). Briey, active participation of mesenchymal and

circulating stem cells, activated by a wide array of growth

factors and cytokines, and the provision of a collagen based

architecture present a unique structure that promotes

healing and regeneration of tissues in which the amniotic

membrane and its components are applied (22).

Preclinical urologic applications of amniotic

tissue products

The general history of the use of amniotic membrane

products and the more recent understanding of the

underlying mechanism of action behind their properties

suggested a number of urologic applications. Preclinical

work has explored a number of urogenital applications.

The use of amniotic membrane as a potential material

for bladder repair extends back to the early 1980s (25).

More recently, Iigma and others demonstrated that

transplantation of preserved human amniotic membrane

could successfully be used for bladder augmentation in

rats, with resulting regeneration of a number of tissues

in the bladder being demonstrated as early as 3 months

postoperatively (26).

Salehipour et al. have evaluated the use of human

amniotic membrane in the reconstruction of long ureteral

defects in dogs (27). In this study, the use of human

amniotic membrane for the reconstruction of ureteral

defects in a canine model was studied. The authors used

chorion prepared and properly treated for surgical insertion

into dogs with circumferentially cut defects, and while they

did not believe the approach to be useful for long (3 cm)

defects, they speculated that use of the amniotic membrane

might be studied for shorter defects or as a patch graft.

Shakeri et al. looked at the use of amniotic membrane

as a xenograft for urethroplasty in rabbits. The authors

concluded that amniotic membrane technology was

an inexpensive, easy, and biodegradable graft yielding

very little antigen effect and a viable option in surgical

urethroplasty approaches (28).

Wang et al. looked at a variation of this idea, namely

using the collagen scaffolding of amniotic membrane

as a potential regenerative material in urethroplasty,

and obtained preliminary success in that approach (29).

The author’s concluded that tissue-engineered denuded

human amniotic scaffold (dHAS) created by separating the

basement membrane layer of amniotic membrane minimizes

potential rejection and maximizes the biocompatibility of

amniotic membrane, making it a potential ideal xenograft

for urethral reconstruction. This concept was also explored

by Gunes and others, who compared the use of buccal

mucosa and amniotic membrane for urethroplasty in a

rabbit model (30). The group examined whether buccal

mucosa, amniotic membrane, or both might be useful

in urethroplasty using epithelial transformation as the

experimental endpoint, noting highest efficacy in the

combined tissue application. After 8 weeks, the best

epithelial transformations were observed in the combined

group.

In another study, Shakeri also noted that amniotic

membrane maybe a substitute for transitional epithelium

of the bladder in dogs. The authors concluded that grafts

remained in place in all cases, except in one of the dogs in

the augmentation group that developed patch perforation,

urine leakage and nally peritonitis. In others, histological

examinations revealed evidence of regeneration of normal-

appearing urothelium, lamina propria, neovascularization,

retracting placental patch, and reconstitution of a normal-

appearing and functioning bladder. This suggests that

placental membranes, because of their low antigenic

properties, easy availability and tolerability by the host

urinary tract, could provide an excellent graft material for

urinary tract reconstructions (31).

Comparison of amniotic membrane with other materials

in preclinical work was conducted by Sharifiaghdas

et al. (32). They examined the use of poly lactic-co-

glycolic acid (PLGA), PLGA/collagen and human amniotic

membrane (hAM) for human urothelial and smooth muscle

cell engineering. The authors demonstrated significant

improvement of cell attachment and growth achieved by

collagen coating (PLGA/collagen) compared to PLGA and

hAM. hAM was a weaker matrix for bladder engineering

purposes.

Human amniotic uid and isolates prepared from human

amniotic membrane derived mesenchymal stem cells have

also had some preliminary scientific work performed on

their inherent biological properties. Human amniotic

membrane mesenchymal stem cells were interestingly noted

to have a suppressive effect on prostate cancer cells (33).

Sedrakyan et al. found that amniotic uid stem cells seemed

to reduce the formation of renal brosis in a mouse model

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Translational Andrology and Urology, Vol 6, No 5 October 2017

Table 1 Regulators of wound healing and inflammation found in dHACM

(17,22)

Regulators of wound healing and inflammation found in dHACM

Regulators of soft tissue healing in dHACM

Cytokines

Angiogenin (Ang)

Angiopoietin-2 (ANG-2)

Basic fibroblast growth factor (bFGF)

Beta nerve growth factor (β-NGF)

Bone morphogenetic protein 5 (BMP-5)

Brain-derived neurotrophic factor (BDNF)

Endocrine gland-derived vascular endothelial growth factor

(EG-VEGF)

Epidermal growth factor (EGF)

Fibroblast growth factor 4 (FGF-4)

Growth hormone (GH)

Heparin binding egf-like growth factor (HB-EGF)

Hepatocyte growth factor (HGF)

Insulin-like growth factor 1 (IGF-I)

Insulin-like growth factor binding protein 1 (IGFBP-1)

Insulin-like growth factor binding protein 2 (IGFBP-2)

Insulin-like growth factor binding protein 3 (IGFBP-3)

Insulin-like growth factor binding protein 4 (IGFBP-4)

Insulin-like growth factor binding protein 6 (IGFBP-6)

Keratinocyte growth factor (KGF/FGF-7)

Placental growth factor (PlGF)

Platelet-derived growth factor AA (PDGF-AA)

Platelet-derived growth factor BB (PDGF-BB)

Transforming growth factor alpha (TGF-α)

Transforming growth factor beta 1 (TGF-β1)

Vascular endothelial growth factor (VEGF)

Vascular endothelial growth factor D (VEGF-D)

Matrix metalloproteinases

Matrix metalloproteinase 1 (MMP-1)

Matrix metalloproteinase 2 (MMP-2)

Matrix metalloproteinase 3 (MMP-3)

Matrix metalloproteinase 8 (MMP-8)

Matrix metalloproteinase 9 (MMP-9)

Matrix metalloproteinase 10 (MMP-10)

Matrix metalloproteinase 13 (MMP-13)

Table 1 (continued)

Protease inhibitors

Alpha 1 antitrypsin (α1AT)

Alpha 2 macroglobulin (α2M)

Tissue inhibitor of metalloproteinase 1 (TIMP-1)

Tissue inhibitor of metalloproteinase 2 (TIMP-2)

Tissue inhibitor of metalloproteinase 4 (TIMP-4)

Regulators of inflammation in dHACM

Cytokines

Granulocyte colony-stimulating factor (GCSF)

Granulocyte macrophage colony-stimulating factor (GM-CSF)

Growth differentiation factor 15 (GDF-15)

Interferon gamma (IFNγ)

Interleukin 1 alpha (IL-1α)

Interleukin 1 beta (IL-1β)

Interleukin 1 receptor antagonist (IL-1RA)

Interleukin 4 (IL-4)

Interleukin 5 (IL-5)

Interleukin 6 (IL-6)

Interleukin 7 (IL-7)

Interleukin 10 (IL-10)

Interleukin 12 p40 (IL-12p40)

Interleukin 12 p70 (IL-12p70)

Interleukin 15 (IL-15)

Interleukin 17 (IL-17)

Macrophage colony-stimulating factor (MCSF)

Osteoprotegerin (OPG)

Prostaglandin E2 (PGE2)

Chemokines

B lymphocyte chemoattractant (BLC/CXCL13)

Chemokine ligand 1 (I-309/CCL1)

Eotaxin 2

Interleukin 8 (IL-8)

Interleukin 16 (IL-16)

Macrophage inflammatory protein 1 alpha (MIP-1α/CCL3)

Macrophage inflammatory protein 1 beta (MIP-β1/CCL4)

Macrophage inflammatory protein 1 delta (MIP-1δ/MIP-5/

CCL15)

Monocyte chemotactic protein 1 (MCP-1/CCL2)

Monokine induced by gamma interferon (MIG/CXCL9)

Regulated on activation, normal t-cell expressed and

secreted (RANTES/CCL5)

dHACM, dehydrated human amnion/chorion membrane.

946 Oottamasathien et al. Amniotic therapeutic biomaterials in urology: current and future applications

of acute tubular necrosis (34).

Amniotic membrane has also been used as a supportive

scaffold for other procedures. For example, Burgers et al.

used nerve grafts, nerve growth factor and a supportive

scaffold made from amniotic membrane to repair surgically

induced erectile dysfunction in rats. In this study, the use

of fetal amniotic membrane as an alternative growth factor

matrix was used to improve the regeneration of ablated

cavernous nerves in rats as a model to study surgically

damaged nerves. The use of membrane as an alternative

nerve growth matrix improved electrically stimulated

erections and mating behavior in these mice (35).

The underlying logic in many of these preclinical studies

focuses on both the structural and regenerative properties

of amniotic membrane. In the first case, the underlying

structure of the membrane, created by various collagen

types, forms an architecture or scaffold that assists in

the re-creation of normal tissue. In the second case, the

biologically active growth factors, cytokines and other

biomolecules initiate and modulate the regenerative process

that involves the recruitment and activation of stem cells

and broblasts in the area under consideration.

Clinical urological applications of amniotic

tissues in humans

The broadly recognized ability of amniotic tissues to help

in healing and regenerative repair of tissues suggested a

number of other direct clinical applications. Preclinical

work and initial evaluation of these tissues have been

attempted in a number of urogenital indications. Koziak

et al. built on the previous preclinical work described above

and investigated the use of amniotic membrane in the

reconstruction of long ureteral strictures in 11 patients

(36,37). Several reports of the use of amniotic membrane

to repair vesicovaginal stulas have also been reported. In

each case, successful use of the material has permitted a

less aggressive operative or non-operative approach to this

problem (38).

Most recently, the use of an amniotic membrane

protective layer in the surgical eld of patients undergoing

robotic assisted laparoscopic prostatectomy as a means of

protecting adjacent nerve bundles from scarring has been

advanced by a number of clinicians (39,40). The notion that

amniotic membrane might be useful in preventing adhesions

at the surgical site in DaVinci robot prostatectomies was

initially developed and evolved across a number of sites.

Patel et al. published a retrospective series of these patients

demonstrating improvement in both urinary incontinence

and erectile function in the short-term post-operative

period (41). For completeness, it is worth noting that

amniotic membrane has found numerous applications in

OB/GYN surgery as well, with applications in the repair

of various abnormalities of the vagina, uterus and related

structures in patients (42-49).

At our institutions, we have applied amniotic membrane

technology in the following four realms of adult and

pediatric urology: (I) proximal and redo-hypospadias

repairs; (II) complex penile reconstruction in Peyronie’s

disease; (III) microsurgical cord denervation procedures;

(IV) posterior urethroplasty in the male with a history of

pelvic radiation.

In the eld of hypospadias surgery, proximal hypospadias

comprises most of the severe cases and results in higher

surgical complication rates (50). Between 6–20% of

hypospadias patients are diagnosed with proximal

hypospadias (51,52). Hypospadias is corrected surgically

with the goal of improving cosmetic appearance as well as

normalizing erectile function and voiding. Surgery creates

a straight phallus, with the meatus residing at the tip of the

glans, with a proper and symmetrical appearance of both

the glans and penile shaft. For more severe hypospadias,

specifically for proximal hypospadias, a variety of surgical

techniques can be employed. Unfortunately, even the most

skilled surgeons cannot guarantee a positive outcome.

Complications from proximal hypospadias repair range

from 6–30% depending on the severity of the defect,

the surgical technique utilized, and the experience of the

surgeon (53). Surgical results are also poorer in re-operative

cases. Common complications include urethrocutaneous

fistulas (UCF), urethral stricture, urethral diverticulum,

and persistent ventral curvature (54). UCF, or a reopening

of the surgical site, can occur in 13–33% of patients,

depending on the different surgical techniques utilized

(50-52,55-58). Current data suggests that an experienced

pediatric urologist successfully can close fistulas in 71%,

72%, 77%, 100%, and 100% of patients after stula repairs

1 to 5, respectively (59). With these high reoperation

rates, there is a significant need to investigate innovative

approaches to reduce complication rates. One such

approach is the potential application of dehydrated human

amnion/chorion membrane (dHACM). The underlying

premise is to provide a barrier layer with a robust source

of tissue and vascular growth factors and provide a local

anti-inammatory environment, thus optimizing soft tissue

healing of the surgical site (20,41,60-62).

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Translational Andrology and Urology, Vol 6, No 5 October 2017

In the eld of Peyronie’s disease, surgical correction of

curvature with either permanent plication sutures or graft

material usually requires full or partial mobilization of

the deep dorsal neurovascular bundle to allow for proper

placement of surgical material as well as to avoid potentially

devastating complications such as glans numbness and

ischemia. Typically, the neurovascular bundle is placed

back in its anatomical position and in most cases, it will

overly the site of surgical curvature correction. The

inflammatory response associated with healing and the

subsequent formation of fibrotic tissue and neuroma has

been theorized as the cause for post-operative pain with

the associated graft material or suture knots. The use of

dHACM has been postulated to be used as an interposition

graft in between the plication knots or graft material and

the neurovascular bundle in an effort to reduce brosis and

neuroma formation and therefore improve pain outcomes.

Anecdotally, we have noticed diminished postoperative pain

and more rapid recovery, and are currently studying, in a

more formal manner, the utility of using this interposition

graft in these cases.

In the eld of chronic orchialgia, management strategies

are aimed at identifying specic etiologies of the pain and

managing those directly (i.e., varicocelectomy, vasectomy

reversal, epididymectomy). When a specific etiology

cannot be identied, the individual has failed conservative

management, or has failed surgical management and

spermatic cord denervation may be discussed. Methods that

have been employed to improve outcomes of spermatic cord

denervation include the use of a provocative pre-operative

spermatic cord block and the intraoperative use of the

operating room microscope. Even with these improvements

in pre-operative screening and surgical techniques the

success rate of the procedure is still not 100% (current

studies success rates range from 70–90%) and there is a

reported orchiectomy rate of 10–20% after the surgery due

to persistent pain (63,64). The utilization of dHACM as a

wrap at the site of denervation has been theorized to reduce

the formation of brosis and neuroma and therefore reduce

persistent pain post-operatively (63).

In the eld of posterior urethral contracture in the male

with a history of pelvic radiation, surgical management is

aimed at resecting the affected scarred or infected tissue,

achieving a watertight tension free anastomosis, and

providing a healthy bed of tissue to allow for good wound

healing. However, even with these surgical tenants, necrosis

and reformation of scar tissue still may occur even in the

most skilled hands. The use of dHACM as a wrap at the

site of urethral anastomosis has been theorized to recruit

healthy tissue ingrowth and improve surgical outcomes.

Clinical outcomes are currently being evaluated.

Potential future applications of human amniotic

tissues

The broad number of properties found in amniotic

membrane, coupled with its immunologically privileged

status presents a number of future applications, particularly

given the historical preclinical and clinical uses described

above. New applications continue to be proposed, and the

potential for combining amniotic membrane allografts with

other biomaterials expands this horizon further.

Acknowledgements

The authors are indebted to Dr. Donald E. Fetterolf for

providing critical suggestions to this review surrounding

amnion/chorion technology.

Footnote

Conicts of Interest: William O. Brant: proctor, consultant,

and grant recipient, Boston Scientic; Siam Oottamasathien:

scientic advisory consultant, GlycoMira Therapeutics Inc.

The other authors have no conicts of interest to declare.

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Around the Prostatic Neurovascular Bundle Accelerates

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Urethral reconstruction using amniotic membrane allograft in hereditary androgen insensitivity syndrome: a case series

Article

Full-text available

Dec 2023

Partial androgen insensitivity syndrome is a rare X-linked disorder. While most cases are sporadic, familial cases are less frequent. The management of this syndrome follows a multidisciplinary approach involving hormone substitution, psychological counseling, and surgical procedures. We present a case series of three young siblings with familial partial androgen insensitivity syndrome who presented with a female phenotype. All of them were managed with hormonal treatment for 6 months followed by surgical reconstruction. The operative procedure involved phalloplasty and urethroplasty using amniotic membrane transplant, which is considered a novel technique in this group of patients. No intraoperative or postoperative complications were observed and good results were achieved within 2 years of follow-up.

Low-dose prednisone is an effective rescue for deteriorating semen parameters following vasovasostomy

Article

Full-text available

Apr 2024

Objective: This retrospective study aimed to evaluate the effectiveness of low-dose prednisone as a rescue therapy for patients with deteriorating semen parameters following vasovasostomy. Materials and methods: Electronic medical records were queried at the University of Miami with documented CPT code 55400 (Bilateral Vasovasostomy) between January 2016 and April 2023. Records were then reviewed to identify patients who demonstrated ≥50% decrease in semen parameters, specifically sperm concentration, motility and total motile sperm count. Patients who were treated with 6 weeks of low-dose prednisone were identified, and baseline semen parameters and subsequent changes after prednisone therapy were assessed. A Mann-Whitney U Test was used to compare semen parameter changes before and after prednisone. Adverse effects associated with prednisone were monitored. Results: A total of 8 patients were identified with deteriorating semen parameters who were treated with 6 weeks of low-dose prednisone. Following prednisone therapy, all patients demonstrated improvements in total motile sperm count (TMSC), with a median improvement of 6 million. The median relative improvement in TMSC was 433%. Sperm concentration and motility also improved compared to post-operative baseline. No adverse effects were reported during the treatment period. Conclusions: Low-dose prednisone therapy appears to be a safe and effective intervention for managing deteriorating semen parameters following VV. The observed improvements in TMSC suggest the potential of prednisone to rescue patients with delayed failure after VV. Further research with larger sample sizes is warranted to confirm the safety and efficacy of low-dose prednisone as a rescue therapy in this specific patient population. Optimizing VV outcomes is crucial in male infertility, and further exploration of steroid therapy and innovative biotechnologies is warranted.

The Effect of Multilayered Electrospun PLLA Nanofibers Coated with Human Amnion or Bladder ECM Proteins on Epithelialization and Smooth Muscle Regeneration in the Rabbit Bladder

Article

Nov 2023
MACROMOL BIOSCI

Nanofibrous scaffolds have attracted much attention in bladder reconstruction approaches due to their excellent mechanical properties. In addition, their biological properties can be improved by combination with biological materials. Taking into account the advantages of nanofibrous scaffolds and decellularized extracellular matrix (dECM) in tissue engineering, scaffolds of poly‑L‑lactic acid (PLLA) coated with decellularized human amnion membrane (hAM) or sheep bladder (SB)‐derived ECM proteins are developed (amECM‐coated PLLA and sbECM‐coated PLLA, respectively). The bladder regenerative potential of modified electrospun PLLA scaffolds is investigated in rabbits. The presence of ECM proteins is confirmed on the nanofibers’ surface. Coating the surface of the PLLA nanofibers improves cell adhesion and proliferation. Histological and immunohistochemical evaluations show that rabbits subjected to cystoplasty with a multilayered PLLA scaffold show de novo formation and maturation of the multilayered urothelial layer. However, smooth muscle bundles (myosin heavy chain [MHC] and α‐smooth muscle actin [α‐SMA] positive) are detected only in ECM‐coated PLLA groups. All groups show no evidence of a diverticulumor fistula in the urinary bladder. These results suggest that the biofunctionalization of electrospun PLLA nanofibers with ECM proteins could be a promising option for bladder tissue engineering. Furthermore, hAM can also replace animal‐sourced ECM proteins in bladder tissue regeneration approaches. This article is protected by copyright. All rights reserved

Early three-month report of amniotic bladder therapy in patients with interstitial cystitis/bladder pain syndrome

Article

Full-text available

Jun 2023
INT UROL NEPHROL

Background Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by symptomatic frequency and urgency, as well as chronic pelvic pain. Disruption of the urothelial barrier is closely associated with IC/BPS. As amniotic membranes (AM) offer capabilities of wound healing in many other fields of medicine, likewise amniotic bladder therapy (ABT) may offer capability of urothelial healing in IC/BPS. Methods Under general anesthesia, 10 consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized AM (Clarix Flo) diluted in 10 ml 0.9% preservative-free sodium chloride. Clinical evaluation and questionnaires (Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS), Overactive Bladder Assessment Tool, and SF-12 Health Survey) were repeated at pre-op and 2, 4, 8 and 12 weeks post-op. Results Ten females (47.4 ± 14.4 years) who had recalcitrant IC/BPS for 7.8 years (5.2–12.1 years) received injection of micronized AM uneventful in all cases. After treatment, voiding symptoms and bladder pain significantly improved from pre-injection to 3 months. BPIC-SS significantly decreased from 37.4 ± 0.70 at baseline to 12.2 ± 2.90 at 3 months (p < 0.001). This corresponded to a significant improvement in their overall physical and mental quality of life. No adverse events occurred related to micronized AM injections, such as UTIs or acute urinary retention. Conclusion ABT could be an innovative treatment option for IC/BPS patients in terms of improving clinical symptoms based on preliminary outcomes at 3 months. Further studies are warranted to confirm the usefulness of ABT in patients with IC/BPS and to determine the duration of the effect.

A comprehensive review on methods for promotion of mechanical features and biodegradation rate in amniotic membrane scaffolds

Article

Full-text available

Mar 2022
J MATER SCI-MATER M

Amniotic membrane (AM) is a biological tissue that surrounds the fetus in the mother’s womb. It has pluripotent cells, immune modulators, collagen, cytokines with anti-fibrotic and anti-inflammatory effect, matrix proteins, and growth factors. In spite of the biological characteristics, some results have been released in preventing the adhesion on traumatized surfaces. Application of the AM as a scaffold is limited due to its low biomechanical resistance and rapid biodegradation. Therefore, for using the AM during surgery, its modification by different methods such as cross-linking of the membrane collagen is necessary, because the cross-linking is an effective way to reduce the rate of biodegradation of the biological materials. In addition, their cross-linking is likely an efficient way to increase the tensile properties of the material, so that they can be easily handled or sutured. In this regard, various methods related to cross-linking of the AM subsuming the composite materials, physical cross-linking, and chemical cross-linking with the glutraldehyde, carbodiimide, genipin, aluminum sulfate, etc. are reviewed along with its advantages and disadvantages in the current work.

Future of Bovine Amniotic Membrane: Bovine Membrane Application on Wound Healing, Surgery and Prospect of Use for Urethral Reconstruction

Chapter

Full-text available

Aug 2021

This chapter describes how bovine amniotic membrane could be indicated for wound healing, especially in complex surgery such as urethral reconstruction. Chemical studies have assessed both histologically and immunohistochemically that bovine amniotic membrane creates scaffold for wound healing. Whereas, clinical studies have shown that bovine amniotic membrane property could be substituted for wound dressing hence improving skin or mucosal integrity. Bovine membrane has been known to be used for many specialties such as ocular surgery, neurosurgery, maxillofacial and orthopedic surgery. This chapter includes such studies and shows the usage possibility of bovine amniotic membrane for other complex defect as shown in urethral reconstruction.

Applications of Human Amniotic Membrane for Tissue Engineering

Article

Full-text available

May 2021

An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and provide an excellent environment for cell growth and differentiation. Human amniotic membrane (hAM) is considered as a surgical waste without ethical issue, so it is a highly abundant, cost-effective, and readily available biomaterial. It has biocompatibility, low immunogenicity, adequate mechanical properties (permeability, stability, elasticity, flexibility, resorbability), and good cell adhesion. It exerts anti-inflammatory, antifibrotic, and antimutagenic properties and pain-relieving effects. It is also a source of growth factors, cytokines, and hAM cells with stem cell properties. This important source for scaffolding material has been widely studied and used in various areas of tissue repair: corneal repair, chronic wound treatment, genital reconstruction, tendon repair, microvascular reconstruction, nerve repair, and intraoral reconstruction. Depending on the targeted application, hAM has been used as a simple scaffold or seeded with various types of cells that are able to grow and differentiate. Thus, this natural biomaterial offers a wide range of applications in TE applications. Here, we review hAM properties as a biocompatible and degradable scaffold. Its use strategies (i.e., alone or combined with cells, cell seeding) and its degradation rate are also presented.

Recent Trends and Advances in Anterior Urethroplasty

Article

Jun 2022
UROL CLIN N AM

While patient preference often helps guide treatment decisions, poor long-term success combined with cumulative risk of repeat endoscopic treatments and the complications innately associated with urethral stricture emphasize that urethroplasty is most often the best choice for successful treatment in the long-term. This has led to the need to better refine urethroplasty techniques and optimize patient outcomes. Urethroplasty has now largely transitioned to a day-surgery procedure in the majority of centers. Some evidence suggests that avoiding urethral transection and/or avoiding overzealous urethral mobilization may lead to a reduction in post-operative sexual dysfunction. The trend toward single stage penile urethroplasty with buccal mucosal grafts likely minimizes patient morbidity without compromising urethroplasty success. For urethroplasty success to further improve particularly in patients at high risk for stricture recurrence, the synergistic potential of combining wound healing enhancing agents with evolving tissue-engineering represents an exciting future opportunity in the quest to perfect urethroplasty outcomes.

Placental Tissues as Biomaterials in Regenerative Medicine

Article

Full-text available

Apr 2022
BMRI

Placental tissues encompass all the tissues which support fetal development, including the placenta, placental membrane, umbilical cord, and amniotic fluid. Since the 1990s there has been renewed interest in the use of these tissues as a raw material for regenerative medicine applications. Placental tissues have been extensively studied for their potential contribution to tissue repair applications. Studies have attributed their efficacy in augmenting the healing process to the extracellular matrix scaffolds rich in collagens, glycosaminoglycans, and proteoglycans, as well as the presence of cytokines within the tissues that have been shown to stimulate re-epithelialization, promote angiogenesis, and aid in the reduction of inflammation and scarring. The compositions and properties of all birth tissues give them the potential to be valuable biomaterials for the development of new regenerative therapies. Herein, the development and compositions of each of these tissues are reviewed, with focus on the structural and signaling components that are relevant to medical applications. This review also explores current configurations and recent innovations in the use of placental tissues as biomaterials in regenerative medicine.

Flaps and Grafts in Hypospadias Repair

Chapter

Mar 2022

This chapter describes the roles, types, brief history, and basic principles of flaps and grafts used in hypospadias repair. Different tissues are used to optimize individual penile reconstructions, including the prepuce, buccal mucosa, penile skin, and scrotum. Various techniques for urethral substitution, augmentation, and layer interposition are available to address different patient pre-operative characteristics. Summary tables describing flap and graft comparisons, technique advantages and disadvantages, and outcomes of current literature provide brief overviews of the chapter. As for future direction, an introduction to tissue engineering and nanotechnology provides a glimpse of how the field of hypospadiology may change in the coming years.

Robotic repair of a vesicovaginal fistula in an irradiated field using a dehydrated amniotic allograft as an interposition patch

Article

Full-text available

Dec 2015

We report the case of a 66 year old female with a supratrigonal vesicovaginal fistula (VVF) that developed after undergoing radical hysterectomy, chemotherapy and pelvic radiation therapy for advanced cervical cancer. VVF repairs in an irradiated field are known to be complicated procedures with significant morbidity and a high rate of failure due to the effect of radiation. Amniotic membranes have been demonstrated to improve healing rates in difficult to heal wounds. To decrease morbidity a minimally invasive robotic procedure was performed and a dehydrated amniotic allograft patch was used to augment tissue healing. The VVF was repaired using the da Vinci Surgical System and the amniotic membrane was used as an interposition patch over the repair. There were no operative or postoperative complications and the patient was discharged home on postoperative day one. A cystogram performed 3 weeks postoperatively demonstrated a healed fistula. Follow-up at 5 months revealed no incontinence. This is the first reported case of a robotic VVF repair performed in an irradiated pelvis and the first use of an amniotic membrane allograft in the repair a VVF. Electronic supplementary material The online version of this article (doi:10.1007/s11701-015-0546-8) contains supplementary material, which is available to authorized users.

Repair of a vesico-vaginal fistula with amniotic membrane –Step 1 of the IDEAL recommendations of surgical innovation

Article

Full-text available

Nov 2015

Introduction: Complex vesico-vaginal fistula (VVF) has a high recurrence rate and so the repair with graft tissues seems to be favorable. Amniotic membrane (AM) plays an increasing role as a scaffold for the repair of defect tissue due to its unique biological properties with regard to promoting wound healing. Material and methods: An innovative surgical procedure for AM-assisted repair of a complex vesico-vaginal fistula as the Idea Stage following the IDEAL recommendations is presented. The development of amnion preparation and the involved surgical steps are described. Results: We are able to report a successful repair of VVF by abdominal approach with an amniotic membrane graft. Good functional results, no adverse events and no graft rejection have been detected. Conclusions: Favorable results confirm the technical simplicity, safety and efficacy of this procedure. Following the IDEAL recommendations, consecutive animal experiments and a cohort study are in progress.

The Long Path of Human Placenta, and Its Derivatives, in Regenerative Medicine

Article

Full-text available

Oct 2015

In the 1800s, a baby born with a caul, a remnant of the amniotic sack or fetal membranes, was thought to be lucky, special, or protected. Over time, fetal membranes lost their legendary power and were soon considered nothing more than biological waste after birth. However, placenta tissues have reclaimed their potential and since the early 1900s an increasing body of evidence has shown that these tissues have clinical benefits in a wide range of wound repair and surgical applications. Nowadays, there is a concerted effort to understand the mechanisms underlying the beneficial effects of placental tissues, and, more recently, cells derived thereof. This review will summarize the historical and current clinical applications of human placental tissues, and cells isolated from these tissues, and discuss some mechanisms thought to be responsible for the therapeutic effects observed after tissue and/or cell transplantation.

Prevalence, repairs and complications of hypospadias: An Australian population-based study

Article

Full-text available

Aug 2015
Arch Dis Child

To investigate hypospadias' prevalence and trends, rate of surgical repairs and post-repair complications in an Australian population. Hypospadias cases were identified from all live-born infants in New South Wales, Australia, during the period 2001-2010, using routinely collected birth and hospital data. Prevalence, trends, surgical procedures or repairs, hospital admissions and complications following surgery were evaluated. Risk factors for reoperation and complications were assessed using multivariate logistic regression. There were 3186 boys with hypospadias in 2001-2010. Overall prevalence was 35.1 per 10 000 live births and remained constant during the study period. Proportions of anterior, middle, proximal and unspecified hypospadias were 41.3%, 26.2%, 5.8% and 26.6%, respectively. Surgical procedures were performed in 1945 boys (61%), with 1718 primary repairs. The overall post-surgery complication rate involving fistulas or strictures was 13%, but higher (33%) for proximal cases. Complications occurred after 1 year post-repair in 52.3% of cases and up to 5 years. Boys with proximal or middle hypospadias were at increased risk of reoperation or complications, but age at primary repair did not affect the outcome. One in 285 infants were affected with hypospadias, 60% required surgical repair or correction and one in eight experienced complications. The frequency of late complications would suggest that clinical review should be maintained for >1 year post-repair. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

179 Use of Dehydrated Amniotic Membrane Allograft at the Time of Microscopic Denervation of the Spermatic Cord for Chronic Orchialgia Improves Outcomes

Article

Feb 2017

Skin transplantation with a review of 550 cases at the Johns Hopkins Hospital

Article

Jan 1910

JW Davis

Human term placenta as a therapeutic agent: From the first clinical applications to future perspectives

Article

Jan 2010

The placenta is a fetomaternal organ provided by nature to aid development of the growing embryo by facilitating gas and nutrient exchange between the mother and fetus and by helping to maintain fetomaternal tolerance. Aside from playing an age-old and essential role in fetal development, placental tissues have also attracted the interest of clinical scientists due to their potential utility as a therapeutic agent. For decades, the human term placenta, which is available in plentiful supply and raises no ethical concerns for its procurement, has been used as a surgical material in skin transplantation, as a biological dressing for treatment of skin wounds, burn injuries and chronic leg ulcers, for prevention of tissue adhesion in surgical procedures, and in ocular surface reconstruction. More recently, human placenta has also attracted increasing attention from cell and molecular biologists, who have turned to this tissue in the search for a novel stem cell source. Indeed, cells derived from the amniotic and chorionic fetal membranes have been shown to present with high plasticity and to possess low immunogenicity as well as immunomodulatory properties, thereby making them prime candidates for development of cell therapy-based tissue regeneration strategies. This chapter will provide an overview of the clinical applications which have been described for placental tissue or which are currently applied, and will also give a summary of the most recent results obtained in preclinical studies, which present promising perspectives for the future clinical application of placenta-derived cells.

A literature review of the safety and biocompatibility of amnion tissue

Article