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Instructive Surfaces and Scaffolds for Tissue Engineering Using Radiation Technology (F23030 and E31007)


Summary


Tissue engineering is poised to revolutionize medicine by shifting the focus of treatment from addressing the symptoms, roots and causes of diseases to repair and regeneration. Regenerative medicine involving cell therapy is an emerging field that seeks to combine the knowledge and expertise of diverse disciplines towards the aim of restoring impaired tissue/organ functions in the body. This paradigm shift will have huge impact in both developed and developing countries. Radiation technologies plays a role in facilitating and speeding up the development of tissue engineering by addressing some of its challenges and opportunities, such as preparation/optimization of instructive scaffolds and their sterilization.

This CRP will provide a forum for knowledge and technology transfer among participating institutions and facilitate the formation of a network between diverse disciplines, as well as promote the early involvement of developing MS, thus enhancing their level of competence. It was formulated based on the recommendations made by  a Consultants’ meetings organized jointly by the ARBR (NAHU) and RPRT (NAPC) sections (held on 23-25 August 2010; and on 12-16 March 2012), and aims to support MS in developing and testing  instructive scaffolds and surfaces using radiation technology to create tissue grafts and help decrease the need for human donors. This is a collaborative CRP between NAPC and NAHU. NAPC will implement the part related to the development and testing of the instructive surfaces and scaffolds, while NAHU will implement the biomedical application part related to the intended end-uses.


Background Situation Analysis


Human tissue is an important resource for medical treatment. For example, it is used in burns treatment, reconstructive surgery, cancer care, and heart tissue replacement. Tissue Banking exists primarily because of the generosity and goodwill of tissue donors and their families. Many countries face a shortage of donor tissues/organs due to several reasons including religious beliefs, lack of donor registration programs etc. Shortage of donor tissue limits the successful application of tissue reconstruction. Tissue engineering is a promising, relatively new area focused on the development of new tissue created either from “cultured” cells (including stem cells and/or by synthetically produced biomaterials (including the use of nanotechnology). Tissue engineering, whether or not combined with traditional tissue banking techniques will improve the outcome of medical treatment and decrease the need for (sterilized) donor material in the future.

New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small building blocks, artificial ECM networks from protein polymers or peptide-conjugated synthetic polymers that present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodelling. These materials have already found application in maintaining functional stem cells and in differentiating stem cells into neurons, repairing bone and inducing angiogenesis.

A number of methods can be used to generate instructive matrices to be employed in tissue engineering. Among them, the application of radiation technology for formation and modification of surfaces and matrices has remarkable advantages such as: initiation of low temperature reactions, absence of harmful initiators, high penetration through the bulk materials and curing of different types polymeric materials (by polymerization, grafting and crosslinking). Additionally, radiation synthesized surfaces and scaffolds might simultaneously be modified and sterilized. Radiation sterilization is a well-established technology, it is a reliable and effective process used industrially for nearly 60 years. Medical devices, raw materials for pharmaceuticals, biomaterials, tissue allografts, and cosmetics among other products are routinely sterilized by ionizing radiation.


Nuclear Component


The CRP has a strong nuclear radiation component: the synthesis of polymer-based scaffolds will be done by radiation induced crosslinking (gamma or electron beam irradiation) and the surface modification will be done by radiation grafting. Additionally, radiation will be used for sterilization of the non-cellular end products.


CRP Overall Objective


The goal of the CRP is to engineer instructive scaffolds and surfaces using radiation technology to create tissues from autologous and allogeneic human somatic cells to provide tissue grafts and decrease the need for human donors.


Specific Research Objective


Specifically, participating institutions will investigate and optimize the preparation on instructive surfaces and scaffolds and their sterilization byradiation, to study the cell- scaffold-matrix interactions, as well as the effectiveness of combining biological and non-biological materials on regeneration/repair.


Expected Research Outputs


Technical guidelines, methods and protocols for synthesizing instructive surfaces and scaffolds by radiation methods and their sterilization, data on the cell-cell-matrix-scaffold interaction, as well as on the effectiveness of combined biological and non-biological materials on regeneration-repair are expected. Moreover, a multidisciplinary network of researchers and end-users is expected to be established.


Expected Research Outcomes


MS will have enhanced capability to engineer and use instructive scaffolds and surfaces for improved wound healing/repair/regeneration and reconstruction.