Day 2 :
University of the Andes, Chile
Time : 09:00-09:40
Nelson R Pinto is the Founder and Chairman of the Research Center for Tissue Engineering and Regenerative Medicine in Concepcion, Chile, where for the past 30 years he maintained an active private practice specializing in Advance Oral Implantology. Currently, he is a Professor at the Universidad de Los Andes, Chile, Post-Graduate School of and Periodontics and Implantology and a Visiting Professor at the Department of Oral Health Sciences and Periodontology, University Hospitals Catholic University, Belgium. He is a world leading expert in L-PRF, soft and hard tissue regeneration and wound healing.
Leukocyte/platelet-rich fibrin (L-PRF), a second-generation platelet concentrate for topical use, is an autologous blood-derived product, which can be obtained, quickly and at low cost. It is classified as one of the four families of platelet concentrates for surgical use and is, therefore, a different class of products than traditional PRPs. L-PRF is produced from peripheral, which is immediately centrifuged without any anticoagulant. Coagulation starts during the centrifugation according to a specific protocol (FDA approved and CE marking). After centrifugation a red blood cell base at the bottom, acellular plasma as a supernatant (platelet-poor plasma) and the L-PRF clot in-between can be observed. The latter, rich in fibrin, platelets (±95% of initial blood) and leukocytes (±50% of initial blood), can be transformed into a membrane of 1 mm in thickness by careful compression in a surgical box (Expression Box, IntraSpin System, Intra-lock, Boca Raton, USA). L-PRF membranes remain intact for more than 14 days in vitro (even more than 28 days in culture) and over 21 days in vivo. Due to a specific polymerization, architecture of the fibrin matrix and cell content they possess antibacterial effects. L-PRF appeared therefore as a very interesting biomaterial to enhance wound healing. As it was proven in vitro, the Intraspin/LPRF membranes with a special fibrin network, progressively release a significant amount of growth factors (e.g., transforming growth factor β1 (TGFβ-1), platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF), BMPs and insulin-like growth factors (IGF)), matrix glycoproteins (thrombospondin-1 (TSP-1)), fibronectin and vitronectin) and sequences of cytokines (e.g., IL-1β, IL-6, TNF-α and IL-4) for at least 7 days. The effects of L-PRF in vitro on cell cultures are very strong during at least 28 days, with a strong stimulation of proliferation of all tested cell lines (fibroblasts, pre-keratinocytes, preadipocytes, osteoblasts and mesenchymal stem cells) and also a stimulation of differentiation of bone cells. L-PRF membranes behave in vitro like a Human Living Tissue interacting in co-cultures with cells (with the release of the leukocytes from the membrane enhancing the environment to stimulate the M2 macrophage activity and this specific behavior reinforced the idea of using L-PRF membranes like a covering tissue graft in skin wounds. L-PRF can be considered as an autologous blood derivate living tissue graft. In this sense, L-PRF is a very simple treatment without any risk for the patient that could be tried in all cases. The possibility to use L-PRF as a biological scaffold by itself or associate with a biomimetic implant surface as open the opportunity to regenerate soft and hard tissue in such a way that was not possible before. The clinical, immune histochemistry and histological findings (SEM, Confocal Laser and Optical Microscopy) of our animals and humans studies over the last 14 years confirm the potential of L-PRF as a biological scaffold or as a living tissue graft for hard and soft tissue regeneration in acute or chronic wounds. We have been able to probe the potential of L-PRF as a regenerative biomaterial in chronic wounds such as: Diabetic foot, venous ulcers, osteomyelitis, and osteonecrosis by bisphosphonate. In acute wounds: Traumatic wounds and burns. The possibility to use L-PRF in regenerative procedures like bone or skin grafts had led to new treatment concepts affecting a broad spectrum of clinical conditions. What we thought impossible yesterday could be routine tomorrow, through the natural guided regeneration therapy with IntraSpin/L-PRF.
Cardinal Health Regulatory Sciences, USA
Time : 09:40-10:20
Debra Aub Webster has over 20 years of experience in pharmaceutical research and the regulatory environment. She has started her regulatory career with the US FDA as Reviewing Toxicologist/Pharmacologist. As a Principal Scientist in Regulatory Affairs and Product Development with Cardinal Health Regulatory Sciences, she leads projects for biologic and regenerative medicine product development programs. In this capacity, she provides guidance on clinical, nonclinical and regulatory aspects of strategic product development, author’s regulatory documents and acts as the Regulatory Representative for sponsors in interactions with the FDA.
The regulation of human cells and tissues by the United States Food and Drug Administration (FDA) originated with the 1902 Biologics Control Act and the 1944 Public Health Service (PHS) Act. These initial acts were put into place to ensure purity of serum and vaccines and to control the spread of communicable diseases, respectively. As the use of human cells and tissues has expanded, FDA was faced with the dilemma of differentiating between their uses in the practice of medicine versus in the manufacture of a product. Under the authority of Section 361 of the PHS Act, FDA introduced a comprehensive regulatory program in 1997 for human cells, tissues and cellular and tissue-based products (HCT/Ps). This consolidated regulatory approach covered all cells and tissues and was tiered and risk-based to allow for less regulatory evaluation of products determined to present a minimal risk to patient safety. In 2005, this regulatory program was implemented in rules codified under 21 CFR Section 1271. These rules defined the conditions that must be met for an HCT/P to be regulated solely under the PHS Act (called 361 HCT/Ps) and those that would be defined as biological products that would also be regulated under the Food, Drug and Cosmetic Act requiring market clearance (called 351 HCT/Ps). This determination and the potential regulatory pathways for these cutting edge technologies is often complex and understanding these regulatory pathways and the definitions surrounding them is critical to successful product development in the United States. Beyond the challenges of navigating the regulatory maze for new regenerative therapeutics, sponsors must also adopt new approaches to evaluate safety and efficacy, and to identify measurable quality attributes regarding product safety, quality and potency. FDA is actively engaged in providing guidance and expedited approval pathways in order to bring these discoveries safely forward to benefit patients.
Agency for Science, Technology and Research, Singapore
Time : 10:20-11:00
Leah A Vardy is a Principal Investigator at the Institute of Medical Biology, A*STAR and an Adjunct Assistant Professor at the Nanyang Technological University in Singapore. She has received her PhD at the Imperial Cancer Research Fund in London and has completed her Postdoctoral work at the Whitehead Institute in Cambridge at the MIT, USA. She has authored over 35 peer reviewed scientific articles in a diverse array of systems including yeast, fruit flies, embryonic stem cells and epidermal cells. Her recent lab studies on embryonic stem cells were published in a series of papers. Currently she has been focusing her research on the epidermis and has been addressing the role of the polyamines in skin barrier function, wound healing and tissue repair.
The primary function of the epidermis is to serve as a protective barrier against the environment. Loss of skin integrity due to injuries or illness results in wounding. Wound healing is a dynamic process involving changes in gene expression on multiple levels. Here, we describe a role for AMD1 (Adenosylmethionine Decarboxylase 1), the rate limiting enzyme in the polyamine biosynthesis pathway, in wound healing. The polyamines, spermine, spermidine and putrescine are ubiquitously expressed cations that are essential for cellular function and play a role in a wide array of cellular processes. We show that AMD1 is expressed in the more differentiated layers of the epidermis and is transiently up-regulated at the wound edge in ex vivo wounded human skin biopsies. Cultured keratinocytes also showed an up-regulation of AMD1 at the wound edge in a scratch assay. Knock-down of AMD1 delayed cell migration and closure of the scratch wound suggesting that high polyamine levels are required for cell migration. We have been working to determine the downstream targets of the polyamine pathway in the wound healing response and these findings will be presented. We propose that AMD1 is an important regulator of cell migration and targets multiple pathways to promote wound healing.