are protein scaffold organs a viable transplant optino

By combining the best of current scaffolding technology reproducible polymeric scaffolds and efficiently decellularized human donor liver we have created a niche bioinfluential microenvironment which influences the function of cultured human hepatocytes. With this work in mind we created a new scaffold for liver tissue engineering for the first time incorporating human liver ECM (hLECM) directly into the fibres of electrospun polymer scaffolds. However each protein individually represents a small fraction of the bioactive molecules present in the ECM and when used in isolation cannot recapitulate the healthy hepatic matrix 24, 29, 30. Individual ECM components in the form of gelatin 18, 19, collagen 20, 21, 22, laminin 23, 24, 25 and fibronectin 26, 27, 28 have all been employed each influencing the hepatocytes survival and function and providing insight into the complex cell-matrix interactions present in the hepatic microenvironment. Obstacles such as necrosis, immune reaction and residual decellularization agents are all yet to be fully addressed for decellularized whole organs to be a truly viable option 14, 15, 16, 17. Decellularized extracellular matrix is the obvious avenue for such research 13, 14, and while results are promising a decellularized liver still requires a donor liver and recellularization. In an effort to address this, researchers have been incorporating bioactivity into scaffold environments for hepatocytes 6, 7, 11. While research to date is making inroads into this dilemma, we are yet to see a lab created environment which accurately recapitulates the complex, finely tuned and responsive extracellular matrix (ECM) of the liver 11, 12. Such an environment would also allow for the study of new pharmaceuticals to treat human disease more effectively 10. However, a chronic and ongoing shortage of suitable organs for transplant means many die before a donor liver can be found, and countless others live with severe, debilitating symptoms at a high cost to both the patient and the healthcare system 2.Īs part of the push for a solution to this problem, tissue engineers are focussing on creating niche microenvironments for main cell type of the liver, the hepatocyte, which support cell survival and function and could be used to treat patients in the future 5, 6, 7, 8, 9. Liver disease’s hallmark pathology of late diagnosis and rapid acute disease progression leads to an urgent need for donor organs the only curative treatment for end stage liver disease 4. While liver disease incidence is rising, other top healthcare burdens, such as stroke, cancer, heart disease and lung disease mortality rates continue to fall 2, 3. Blended protein:polymer scaffolds provide a viable, translatable niche for hepatocytes and offers a solution to current obstacles in disease modelling and liver tissue engineering.Īccording to the NHS, liver disease is one of the top five causes of premature death in the UK, with incidence rising sharply by 20% over the last decade 1. Each scaffold maintained hepatocyte growth, albumin production and influenced expression of key hepatic genes, with the decellularized ECM scaffolds exerting an influence which is not recapitulated by individual ECM components. Mechanical testing demonstrated significant increases in the Young’s Modulus of the decellularized ECM scaffold providing significantly stiffer environments for hepatocytes. Immunohistochemistry confirmed retention of proteins in the scaffolds. The resulting scaffolds were validated using THLE-3 hepatocytes. We combined decellularized human liver tissue with electrospun polymers to produce a niche for hepatocytes and compared the human liver ECM to its individual components Collagen I, Laminin-521 and Fibronectin. Enhancing microenvironments using bioactive molecules allows researchers to create more appropriate niches for hepatocytes. Polymers and decellularized tissue scaffolds each provide some of the necessary biological cues for hepatocytes, however, neither alone has proved sufficient. One of the challenges for tissue engineers is the extracellular matrix (ECM) a finely controlled in vivo niche which supports hepatocytes. Tissue engineering of a transplantable liver could provide an alternative to donor livers for transplant, solving the problem of escalating donor shortages.

Are protein scaffold organs a viable transplant optino