**1. Introduction**

Fetal development in mammals is a complex pathway which occurs after prenatal embryonic development [1]. Fetal development system is achieved by meticulous interactions consisting in umbilical cord, amniotic fluid and placenta. Fetal membrane is part of the system, composed of two layers: an outer layer (chorion), which contacts maternal cells and an inner layer (amniotic membrane; AM). Fetal membrane holds important role in fetal development, essential for protection, breathing, nutrition and excretion. Amniotic membrane or amnion is a thin membrane on the inner side of the placenta forming a sac that completely surrounds the embryo/fetus and delimits the amniotic cavity, which contains amniotic fluid [2, 3]. AM holds important metabolic roles by transporting water, other soluble materials and the production of bio-active factors, including vasoactive peptides, growth factors and cytokines. AM also provides the fetus with protection against dessication and environment of suspension, thus promoting embryonal growth. This function is mainly attributed by tractional resistance

mainly related to the condensed layer of interstitial collagen type I, II and elastin [2, 4]. Toda et al. mentions that amnion also holds pluripotent differentiation ability with low immunogenicity and anti-inflammation property [5]. These properties creates opportunities and interest on the use of amniotic membrane for regenerative medicine.

The usage for human amnion as a surgical material for skin substitute was first suggested and reported by Davis in 1910. Sabella in 1913 performed the first human trial for skin grafting [6–8]. Bovine amnion first use for absorbable insulating material and suture material was described by Johnson in 1937. Bovine amniotic membrane (bAM) and bovine allantoic membrane was suggested as biological dressing [9]. A study by Rao stated that further preliminary experimental study using bovine amnion xenograft was suggested by Silvetti et al. in 1957 [6]. Since then, there are many basic and clinical researches regarding usage of bovine amnion on regenerative medicine.

Bovine amnion was worth noting, due to its wide surface area compared with human amnion (6000–7500 sq. cm vs. 1600 sq. cm) and similar histological appearance. Both amnion characteristic is marked with single layer of cuboid epithelium [6]. Consideration should be taken for the AM harvest timing due to morphological change during gestational period. Morphological change of bovine amniotic membrane has been observed between 40 and 230 days of gestation. The epithelium changes from a single layer of flattened, squamous cell containing conspicuous cytoplasmic organelles into single or multi-layered cuboidal cells with numerous microvilli. This epithelium is further supported by a basement membrane rich in collagen. The extracellular matrix is infiltrated with fibroblasts, mesenchymal stromal cells, and tissue macrophages ("Hoffbauer cells") [10].

Proteomic profile of bovine amniotic membrane is proved rich in proteins and signaling pathways. An analysis study by da Silva in 2021 identified 2105 proteins with an interactive network of 1271 nodes (proteins) and 8757 edges (interactions), some of which are known to be present in healing pathway. Notable proteins such as albumin, actin, collagen, fibronectin, histone, protein s100, vimentin, tubulin are abundant in its composition [11, 12]. Epithelial cell in amniotic membrane also secretes several growth factors and cytokines such as epidermal growth factor, vascular endothelial growth factor, keratinocyte growth factor, basic fibroblast growth factor, transforming growth factors alpha and beta (TGF-a and TGF-b), interleukin-8 (IL-8), angiogenin, dipeptidyl peptidase IV (DPPIV/CD26), serine protease inhibitor (serpin) E1, also known as type 1 plasminogen activator inhibitor (PAI-1), and insulin-like growth factors [3, 13–16].
