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Table 3 Overview of the advanced modalities used to enhance Amnio-M for clinical applications

From: Applications of the amniotic membrane in tissue engineering and regeneration: the hundred-year challenge

Enhancement modalities

Additives

Purpose

Membrane status

Study type

Outcome

Ref

Cross-linking

Glutaraldehyde

γ-ray and electron beam irradiation

Testing degradation rate

Decellularized Amnio-M

In vitro & in vivo

GA-cross-linked Amnio-Ms were degraded more slowly with a slight tissue response. γ-ray and electron beam irradiation decreased the tensile strength

[157]

 

Glutaraldehyde

Corneal regeneration

Intact Amnio-M

In vitro and clinical cases

High mechanical properties in comparison with fresh and cryopreserved membranes. Low degradation rate and better transparency

[158]

 

Al2(SO4)3

Corneal regeneration

Intact Amnio-M

In vitro

Al2(SO4)3 increased the tensile strength of the membrane

[160]

 

Carbodiimide

Corneal regeneration

Decellularized Amnio-M

In vitro & in vivo

0.05 mmol EDC/mg support cell proliferation and maintained differentiation of LEC

[190]

 

Photo cross-linking

UV irradiation

Corneal regeneration

Intact Amnio-M

In vitro

Biocompatible membrane, with detectable maintenance of cell stemness

[159]

Hybridization

With natural or synthetic materials

Atelocollagen skin collagen

Skin regeneration

Bovine decellularized Amnio-M

In vivo/ pig model

Inhibit inflammatory reactions and promote wound healing

[191]

 

Hyaluronic acid hydrogel

Skin regeneration

Human solubilized Amnio-M

In vitro & in vivo

In vitro, the proposed scaffold enhanced cell proliferation. In vivo, it enhanced wound healing, reepithelization, and vascularization

[171]

 

GelMA hydrogel

Oral mucosa regeneration

Decellularized Amnio-M particles

In vitro & in vivo

GelMA–dAmnio-M Particles scaffold has been proven to be effective in neovascularization and mucosa repair

[172]

 

Aloe vera gel

Skin regeneration (burn)

Non-decellularized membrane (powder)

In vitro and in vivo

Significantly enhance burn wound healing

[175]

 

Nano-fibrous Fibroin

Skin regeneration

Decellularized hAmnio-M

In vitro

Bilayer Amnio-M/nano-fibrous fibroin scaffold represents an efficient natural construct with broad applicability to generate keratinocytes from Menstrual stem cells

[174]

 

POC polymer

Cleft palate repair

Decellularized hAmnio-M

In vitro & in vivo

The biocompatible scaffold could regenerate both soft and hard tissue effectively

[192]

Combination with cells

Dental pulp derived cells

Periodontal tissue regeneration

Decellularized hAmnio-M

In vitro

cell sheet that contained MSC may be helpful for application in periodontal tissue regeneration

[182]

 

TGF‐β3 BMSCs

Skin regeneration

dehydrated Amnio-M (hDAM) commercial

In vitro & in vivo

Wound healing with a minimal scar in a full-thickness wound in rat back

[183]

 

Corneal stromal cells (CSCs)

Cornea regeneration

ultrathin Amnio-M

In vitro and in vivo

UAM provided a suitable scaffold for CSCs to generate tissue mimic the native cornea

[193]

 

ASCs

Skin regeneration

Decellularized hAmnio-M

In vitro and in vivo

AM-ASCs accelerated the wound healing with a less inflammatory response in a third-degree burns rat model

[184]

Drug carrier

Nanoreservoir

Cefazolin

Cornea regeneration

hAmnio-M

In vitro

High drug entrapment was achieved by incubation of Amnio-M for 3 h at 4C

[179]

 

Moxifloxacin

Cornea regeneration

hAmnio-M

In vitro

Thick HAM entraps moxifloxacin efficiently higher than thin HAM. 3 h incubation was sufficient for entrapment

[180]

Other additives

Tissue glue

Cornea regeneration

Intact Amnio-M

Clinical trial (After dermoid removal)

Rapid corneal reepithelization and smooth healing

[194]

 

Amino acids

Cornea regeneration

Carbodiimide cross-linked Amnio-M

In vitro and in vivo

Lysine amino acid could increase the cross-linking efficiency of Amnio-M

[195]

 

Calcium and Phosphate

Bone regeneration

Decellularized hAmnio-M

In vitro and in vivo

The mineralized Amnio-M enhanced ASCs osteogenic differentiation in vitro and bone regeneration in a calvarial bone defect in vivo

[181]