Human Amniotic Membrane Usage from Bench to Bedside in Congenital Defects and Wounds in Paediatric Surgery: A Systematic Review

Abstract

Background: The restricted donor area in paediatric patients demands the use of Human Amniotic membrane (hAM) in the management of difficult-to-manage wounds. It can be used directly over wounds or used to grow stem cells by different culture methods. The hAM can be used “fresh” i.e., +4O glycerol preserved or “cryopreserved”. Methods: In this literature review, we searched ‘PubMed’, ’Web of Science’ and ’SCOPUS’ for experimental models, RCT, Observational studies, case series, and case reports involving the usage of hAM in the treatment of neonatal and paediatric (​<14 yrs.) patients, published in from 1993 to April 2022. The search included the keywords, “amnion”, “biomaterials”, “biological dressing”, “clinical study”, “congenital defects”, “human amniotic membrane”, “paediatric wound”, “neonatal wounds”, and “regenerative medicine”. The Search was extended by snowballing the reference list of all included studies. Results: The final analysis included one experimental RCT, three review articles, and twelve case reports. The experimental studies were in rat, pup, and porcine models. The paediatric second-and third-degree thermal burn followed by paediatric ocular diseases viz corneal epithelial ulcers, conjunctiva reconstruction following Steven Johnson Syndrome, and scarring after surgery of strabismus were the most common indications for the usage of AM. Five cases of meningomyelocele repair (intradural & extradural placement of AM) and 2 cases of gastroschisis repair (as an antiadhesive layer) were reported. Freeze-dried hAM is most frequently used in clinical practice. Autologous hAM was used in antenatally detected birth defects. In the adults, the fresh hAM was found equally effective as freeze-dried AM, but with the risk of transmission of contagious diseases. The literature on Fresh amnion is deficient in paediatric patients. Conclusion: hAM as a skin substitute in paediatric wounds/defects has shown an enhanced rate of healing. However, further studies, regarding the utility of hAM in the management of paediatric wounds, congenital anatomical defects, and diseases along with analysis of outcome and economic constraints in developing countries are needed.

Innovative Biologic Dressings for Neonatal and Pediatric Wounds

“…The organizational framework of the basement membrane, provided by the ECM, contains not only an intricate network of macromolecules produced and assembled by surrounding cells but also numerous growth factors along with collagens, laminins, nidogen-1 and 2, fibronectin, fibulin-2, fibrillin-2, perlecan, and agrin. Collagen in BM decreases microbial accumulation, along with cystatin-E, an anti-infective inhibitor, and beta 3-defensin, an antimicrobial peptide [38][39][40][41]. Additionally, many growth factors are found within basal membrane ECM.…”

“…ECM also contains fibroblasts and neonatal mesenchymal cells (MSCs). MSCs release soluble factors that stimulate proliferation and migration within the wound [39,40]. MSCs also provide anti-scarring properties via stimulation of the release of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF).…”

“…EVs are known for their cell-to-cell communication, genetic information transfer via mRNA, and guidance to macrophage differentiation from pro-inflammatory to prorepair phenotype [38,40]. The anti-inflammatory effect is moderated by the release of interleukin 10 and thrombospondin-1 [39].…”

“…All show successful epithelization with minimum dressing manipulation, softer scars, and shortened time to closure compared to other modalities. Pediatric literature focuses on burn care, while neonatal report superior results with extravasation injuries [39][40][41][42][43][44][45].…”