Bioprinting: A Further Step to Effective Regenerative Medicine and Tissue Engineering

Abstract

Regenerative medicine is a multidisciplinary field that aims to replace or regenerate human cells, tissues, or organs in order to restore or establish normal function. In this broad sense, this operational definition should include the ultimate goal of tissue (bio) engineering, i.e. ‘the manufacture of living functional tissues and organs suitable for transplantation in reasonable time scales’ [1]. The process of regenerating body parts can occur in vivo or ex vivo, and may require stem cells, natural or synthetic cell-supporting scaffold materials, bioactive molecules such as for example trophic factors, genetic manipulation, or combinations of all of the above [2]. The interest in embryonic stem cells has increasingly faded away when the possibility of obtaining pluripotent cells by reprogramming adult somatic cells was achieved. Induced Pluripotent Stem Cells (iPSCs) represents nowadays the most interesting source to be used in regenerative medicine, as, besides pluripotency, they are obtained from the very same patient whom they will administer to and should thus not give any immune reaction [3]. Regenerative medicine and tissue engineering have broad interest as to the application to different fields of general surgery, among which skin restoration, heart repair, bioengineering of vessels, kidney, gastroenteric and upper respiratory tracts [4]. The medical application in this field started up in 2006 when Atala and colleagues implanted in patients who need cystoplasty bladders engineered ex vivo from the seeding of autologous cells (urothelium and muscle cells) on collagen-polyglycolic acid scaffolds as artificial supporting biomaterial [5]. Another milestone was the manufacture of a trachea from human components. Macchiarini and colleagues transplanted the first tissue-engineered trachea, utilizing the patient’s own stem cells, into a 30-year old woman with end-stage bronchomalacia, with positive results about respiratory functional tests following the transplantation [6]. The trachea was denuded and reseeded with cells from the recipient, i.e. chondrocytes differentiated from hematopoietic stem/progenitor cells on the outer surface and epithelial cells obtained from the right bronchus on the inner surface. A 5-year follow-up reported the safety and efficacy of this procedure highlighting the function of the tissue-engineered trachea and, importantly, the well-being of the patient [7].