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

The amniotic membrane (Amnio-M) has various applications in regenerative medicine. It acts as a highly biocompatible natural scaffold and as a source of several types of stem cells and potent growth factors. It also serves as an effective nano-reservoir for drug delivery, thanks to its high entrapment properties. Over the past century, the use of the Amnio-M in the clinic has evolved from a simple sheet for topical applications for skin and corneal repair into more advanced forms, such as micronized dehydrated membrane, amniotic cytokine extract, and solubilized powder injections to regenerate muscles, cartilage, and tendons. This review highlights the development of the Amnio-M over the years and the implication of new and emerging nanotechnology to support expanding its use for tissue engineering and clinical applications. Graphical Abstract

Comparison of Collagen and Human Amniotic Membrane Nerve Wraps and Conduits for Peripheral Nerve Repair in Preclinical Models: A Systematic Review of the Literature

Introduction Collagen and human amniotic membrane (hAM) are Food and Drug Administration (FDA)-approved biomaterials that can be used as nerve wraps or conduits for repair of peripheral nerve injuries. Both biomaterials have been shown to reduce scarring and fibrosis of injured peripheral nerves. However, comparative advantages and disadvantages have not been definitively shown in the literature. The purpose of this systematic review is to comprehensively evaluate the literature regarding the roles of hAM and collagen nerve wraps and conduits on peripheral nerve regeneration in preclinical models. Methods The MEDLINE database was queried using the PubMed search engine on July 7, 2019, with the following search strategy: (“amniotic membrane” OR “amnion”) OR (“collagen conduit” OR “nerve wrap”)] AND “nerve.” All resulting articles were screened by two independent reviewers. Nerve type, lesion type/injury model, repair type, treatment, and outcomes were assessed. Results Two hundred and fifty-eight articles were identified, and 44 studies remained after application of inclusion and exclusion criteria. Seventeen studies utilized hAM, whereas 27 studies utilized collagen wraps or conduits. Twenty-three (85%) of the collagen studies utilized conduits, and four (15%) utilized wraps. Six (35%) of the hAM studies utilized conduits and 11 (65%) utilized wraps. Two (9%) collagen studies involving a conduit and one (25%) involving a wrap demonstrated at least one significant improvement in outcomes compared with a control. While none of the hAM conduit studies showed significant improvements, eight (73%) of the studies investigating hAM wraps showed at least one significant improvement in outcomes. Conclusion The majority of studies reported positive outcomes, indicating that collagen and hAM nerve wraps and conduits both have the potential to enhance peripheral nerve regeneration. However, relatively few studies reported significant findings, except for studies evaluating hAM wraps. Preclinical models may help guide clinical practice regarding applications of these biomaterials in peripheral nerve repair.

Experience of using a thrombofibrin clot of plateletrich plasma in ulcerative lesions of the cornea

Purpose: to study the effectiveness of the use of thrombofibrin clot of platelet-rich plasma (PRP) in patients with corneal ulcers. Material and methods. A clinical study, conducted by the Department of Traumatology and Reconstructive Surgery of Helmholtz National Medical Research Center of Eye Diseases, involved 20 patients, aged from 22 to 82, with corneal ulcers of inflammatory and burn genesis more than 100 microns deep. All patients got coated with a thrombofibrin PRP clot from autologous blood. Prior to the study, all patients received standard treatment for 2 weeks to 3 months, including multiple amniotic membrane coating, with no effect. The thrombofibrin clot was produced by the Scientific Department of Biotechnology and Transfusiology of the N.V. Sklifosovsky Research Institute for Emergency Medicine. The ready clot was placed on the surface of the cornea and covered with an amniotic membrane. The membrane was fixed to the episclera along the border of the limb with a circular suture, whereupon autologous serum was injected along the limb in 4 quadrants, to be followed by temporary lateral blepharography. Results. On the 2nd day following the procedure, the patients noted a decrease in lacrimation and pain in the operated eye. As shown by optical coherence tomography, the average depth of the corneal ulcer at the beginning of the study in all patients was 129 ± 28.5 microns. On the 5th day, the depth lowered to an average of 71 ± 32.6 microns, and on the 10th day, to 23.3 ± 15.1 microns. In 7 patients (35%), complete healing of the defect was observed on the 15th day, while in 9 patients (45%) it was stated between the 16th and the 20th day. Thus, the average time of healing of the ulcer with complete epithelization occurred was 15 days. In four patients with the consequences of severe burns (20%), the ulcer did not heal due to extensive damage to the limbal zone. Conclusion. The use of a thrombofibrin PRP clot in combination with amniotic membrane transplantation allows achieving a stable and fairly rapid healing of corneal ulcers of various origins. However, this method is ineffective in patients with limbal cell insufficiency, severe burns and extensive damage to the limbal zone. In such cases, it is advisable to use more radical surgical methods, such as buccal or limbal cell transplantation, or allolimbal transplantation.

Outcome of Amniotic Membrane Transplant in Persistent Corneal Epithelial Defects

Purpose: To determine the outcome of amniotic membrane transplant in patients with ocular surface disease. Study Design: Interventional Case series study Place and Duration of Study: Layton Rahmatullah Benevolent Trust Eye Hospital, Korangi 2½, Karachi, from January, 2019 to July 2019. Methods: Patients with an age range of 20–45 years, either gender and who had persistent corneal epithelial defects as a consequence of keratitis, chemical injuries, bullous keratopathy and Mooren’s ulcers were included. Informed consent was obtained. Preserved amniotic membrane was used in all patients and they were followed at 1 week, 1, 3 and finally at 6 months and results were evaluated in terms of stable, healed and pain-free cornea. Results: Mean age of the patients was 37.94 ± 6.78 years. Majority of the patients (60.0%) were less than 40 years of age. Out of 58 patients, 45 (77.6%) were males and 13 (22.4%) were females. Mean duration of injury was 7.67 ± 2.28 weeks with majority of patients i.e. 62% were with less than 8 weeks of duration. Most common cause of persistent corneal epithelial defect was bacterial keratitis (17.2%) followed by vegetative trauma (13.8%). Successful surgical outcome as healed cornea was observed in 53 (91.4%) patients. Conclusion: Amniotic membrane transplant is an effective treatment for persistent corneal epithelial defects unresponsive to standard medical treatment. This surgical technique is effective in terms of healing and resolving the inflammation and preserving the useful vision. Key Words: Persistant corneal epithelial defect, Amniotic Membrane, Bullous keratopathy.