LevaGRAFTM Human Amniotic Membrane Allograft
Material of Choice Augmenting Better Results in Tissue Regeneration and Repair
Photo: Photo: 7 x 15 cm2 Hydrated LevaGRAFTM
LevaGRAFTM is a terminally-sterilized, cryoprotectant and chorion-free human amniotic membrane allograft, that has been cross-linked and bioengineered utilizing a proprietary mechanism to both prolong and sustain the beneficial nutrients and growth factors following transplantation. LevaGRAFTM is offered in hydrated and dehydrated formats that can be stored at room temperature to provide the clinician with more durability and handling flexibility. Data on file
Permeability • Stability • Elasticity • Flexibility • Plasticity • Resorbability
Properties = Benefits
Reduces Pain = Increased blood supply and oxygen 2,3
Accelerates Healing = Effective in tissue regeneration and guided bone regeneration, prevents fibrous tissue invasion 2, 3
Immunoprivileged Tissue = Absence of inducing an immune reaction 3
Reduces Scar Formation = Facilitates migration of epithelial cells 4, 5
Anti-Inflammatory = Modulates Inflammation 5, 6
Anti-bacterial/Anti-microbial = Cleanses and protects, prevents infection 5, 6
Remodels tissue = Mimics function of native Extracellular Matrix, promoting cell migration, replication and angiogenesis 6
Extracellular Matrix Composition (ECM) = Collagen types I, III, IV, VI, fibronectin, nidogen, laminin, proteoglycans 6
Uses Disclaimer: Levana Biologics manufacturer has supplied 4,000+ units of LevaGRAFTM for various applications. This list is not inclusive of all potential applications. Not all uses and applications listed have successfully completed IRB approvals. Some of these applications are currently undergoing clinical trials. It is up to the clinician to determine its’ usefulness or effectiveness.
Photo: Human Amnion Membrane Layers and Composition
Photo: Aseptically Packaged LevaGRAFTM
- Non-Invasive and Safe
- Cryoprotectant-free, chorion-free and gamma-irradiated
- Over 226 growth factors, cytokines, chemokines present post-preservation
- Available in terminally sterilized hydrated or dehydrated formats
- Excess can be folded onto itself for a more customized fit
- Easy to handle and apply
- Guaranteed stability at room temperature for 2 years from date of packaging
- Levana Biologics provides practitioners with a free scientific consultation
- Over 4,000 LevaGRAFTM units have been successfully transplanted
- Some applications may qualify for third party reimbursement
- Terminal Sterilization (gamma-irradiated) processes have been proven to retain maximum biological activity, while ensuring maximum patient safety 7, 8, 9
- LevaGRAFTM qualifies as a human tissue allograft (HCT/P) as outlined in 21 CFR 1271 under Section 361 of the Public Health Service Act.
- LevaGRAFTM is cryoprotectant-free, gamma-irradiated (terminally sterilized), chorion-free human Amniotic Membrane Allograft tissue prepared from birth tissues donated after Cesarean Section delivery from a screened and qualified volunteer donor.
Levana Biologics is partnered with a world-renowned Cell Therapy and Regenerative Medicine Academic Institution and University to manufacture LevaGRAFTM, LevaSOLTM and other biomaterials. These products qualify as a human tissue allograft (HCT/P) as outlined in 21 CFR 1271 under Section 361 of the Public Health Service Act. LevaSOLTM is free of additives or cryoprotectants and each lot has been obtained from a pre-screened, healthy and qualified volunteer donor during full-term Cesarean birth. LevaSOLTM is bioengineered utilizing a cutting-edge sterile filtration technology, to delicately extract dead tissue and debris to ensure maximum patient safety while preserving high quantities of the beneficial “native” properties. Collection, processing, preservation and storage are performed utilizing a proprietary process (patent pending) by an FDA registered, AATB, FACT, CAP accredited, CLIA certified laboratory. Data on file.
Historical Journey of hAM (1)
- The Compendium of Materia Medica was published n 1593 by one of the first and greatest biologists and pharmaceutical experts of China, Li Shi-Zhen. This medical text is a Chinese record of substances with medical properties, and it contains a section entirely devoted to the medical uses of human placenta “zi he chi” as a medicine (Young and Benyshek, 2010). At that time, eating the placenta was thought to be beneficial but since then there has been a shift of paradigms in which scientific rationale supports clinical benefit of placental tissues, or derivatives, for treating patients afflicted by a variety of diseases. As discussed below, the earliest reported applications of the placenta (after Li Shi-Zhen’s) were focused on fetal membranes. The first reports showing that the placenta also harbors cells, which could have stem/progenitor properties, ultimately giving rise to their potential use in regenerative medicine, were published many years later., (Bailo et al., 2004; Fukuchi et al., 2004; Igura et al., 2004; In ‘t Anker et al., 2004; Soncini et al., 2007; Troyer and Weiss, 2008).
- The first documented use of fetal membranes as a surgical material in skin transplantation came more than 3 decades after the placenta was initially reported to possess medicinal properties. In 1910, Davis (1910) showed that the use of amniotic membrane (AM) in skin grafting gave superior results when compared to xenograft or cadaveric coverings. Shortly afterwards in 1913, Stern (1913) and Sabella (1913) reported the use of the AM for treating skin wounds. They applied intact amniotic tissues to skin burns and ulcers and then covered them with dressings. Upon removal of the dressings 2 days later, the authors reported that the amnion had integrated with the patient’s tissues. They also reported lack of infection, a significant decrease in pain, and an increased rate of re-epithelialization of the traumatized skin surface in patients treated with amnion.
- More than 20 years passed before another study would report the use of amniotic tissues for wound repair or surgery. Around 1940, the AM was increasingly being used successfully in different applications. In the late 1930s, Brindeau (1934) and Burger (1937) reported the successful use of amnion for vaginal reconstruction surgery in a patient with Mullerian agenesis.
- Shortly afterwards, the AM was first applied in ophthalmology to repair conjunctival defects (De Rotth, 1940) and burns (Sorsby and Symons, 1946; Sorsby et al., 1947). Ophthalmology would later go on to be one of the most popular applications of the AM to date.
- In 1940, the first paper was published describing the use of amnion for the prevention of meningocerebral adhesions following head injury. The authors reported lack of adhesions and lack of rejection 60 days after surgery, and “disappearance” of the amnion after 30 days (Chao et al., 1940).
- Later that decade, and following Burger’s work on vaginal reconstruction, Kubanyi (1947) used amnion in patients undergoing abdominal surgery with an enterocutaneus fistula secondary to surgery for lysis of adhesions. After closing the small bowel fistula, the small area of the bowel was wrapped with amnion, and notably, patients were discharged on a regular diet only 12 days after surgery.
- Importantly, Dino et al. (1965) showed that AM from routine deliveries could be sterilized and kept for 6 weeks at 4°C and safely used on acute second degree burns and on skin donor sites (Dino et al., 1965). This was one of the first reports which suggested handling procedures for the AM, which in turn fueled even more interest among clinicians in using the AM for treating skin lesions.
- In 1972, Trelford et al. (1972) used human amnion in sheep, and confirmed previous findings that as a surface graft, amnion was able to reduce pain, decrease infection, and reduce the loss of fluids. Also in 1972, Robson and his colleagues began to study the use of AM for severe burns and skin injuries. Similar to Trelford, they reported notable pain relief and immediate adherence of the AM dressing to the wound. Interestingly, the membranes were easily peeled off 1 week after application and, according to Robson, spontaneous re-epithelialization had occurred underneath the membranes.
- Later that decade, in 1977, Trelford-Sauder et al. (1977) reported the successful use of amnion to replace pelvic peritoneum in patients who had exenterative procedures.
- Following these and other observations, there was an exponential increase of published clinical studies, which reconfirmed the successful application of fetal membranes in diverse clinical indications, including burns (Gruss and Jirsch, 1978; Bose, 1979), ulcers (Troensagaard-Hansen, 1950; Bennett et al., 1980; Subrahmanyam, 1995), surgical reconstruction of the vagina (Dhall, 1984; Nisolle and Donnez, 1992; Georgy and Aziz, 1996), abdominal surgery (Trelford-Sauder et al., 1978; Silverton et al., 1979; Gharib et al., 1996), and other surgical procedures for the prevention of adhesions (Trelford-Sauder et al., 1978; Muralidharan et al., 1991; Young et al., 1991; Arora et al., 1994; Rennekampff et al., 1994).
- The 1990s can be considered the beginning of modern history on the use of AM in ophthalmology (Dua et al., 2004). In this decade, Dr. Tseng, an ophthalmologist from Miami, applied for Human Cell Tissue Products (HCT/P) regulatory status for the use of amniotic tissues in ocular repair. In 1999, Dr. Tseng’s proposal was rejected by the US Food and Drug Administration’s (FDA) tissue reference group stating “Amniotic membrane for ocular surface reconstruction is considered a tissue under the current code of federal regulations (CFR) at 21 CFR Part 1270, but the intended use would be non-homologous when 21 CFR Part 1271 becomes effective” (Lee and Tseng, 1997; Tseng et al., 1997). Dr. Tseng appealed the ruling and 1 year later, the FDA reversed the prior ruling stating that “Allogeneic amniotic membrane for ocular repair is considered to be a section 361 HCT/P if the product’s advertising is restricted to homologous use for wound covering.” The two main points made by the FDA were that it had to be used as a covering and must be acellular, whereas “Amniotic membrane cultured with stem cells for ocular repair is considered to be a biologic product subject to Investigational New Drug and Biologic License Application.” From that point on, the use of AM in ophthalmic surgery catapulted. Nowadays, there are over 45,000 applications used by the ophthalmologists, including conjunctival reconstruction, burn treatment, glaucoma surgery, and wound healing (Fetterolf and Snyder, 2012).
References: (1) The long path of human placenta, and its derivatives, in regenerative medicine Antonietta R. Silini , Anna Cargnoni , Marta Magatti , Stefano Pianta and Ornella Parolini* Centro di Ricerca “E. Menni”, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy Review published: 19 October 2015 doi: 10.3389/fbioe.2015.00162 (2) Amnion and Chorion Membranes: Potential Stem Cell Reservoir with Wide Applications in Periodontics Akanksha Gupta,1 Suresh D. Kedige,1 and Kanu Jain2 1Department of Periodontics, Maharishi Markandeshwar College of Dental Sciences and Research, Mullana, Ambala, Haryana 133207, India 2 Department of Oral Pathology, Jaipur Dental College, Jaipur, Rajasthan 303805, India.
LevaGRAFTM Sizes and Ordering Information
LG- 1100 1 x 1 cm2
LG 2200 2 x 2 cm2
LG 2400 2 x 4 cm2
LG 4400 4 x 4 cm2
LG- 4600 4 x 6 cm2
LG- 4800 4 x 8 cm2
LG- 7150 7 x 15 cm2
All sizes are available in hydrated and dehydrated formats, with the exception of the 7 x 15-cm2 which is only offered in a hydrated format. Both formats can be stored at room temperature.