Bioprinting: A Further Step to Efective Regenerative Medicine and Tissue
Engineering
Massimo Conese
*
Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy
*
Corresponding author: Massimo Conese, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy, Tel.: +39-0881-588019; E-mail:
massimo.conese@unifg.it
Rec date: Aug 11, 2014, Acc date: Aug 12, 2014, Pub date: Aug 16, 2014
Copyright: © 2014 Conese M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Bio-fabrication Cell printing; Composite organ;
Hydrogel; Organ printing; Stem cell therapy; Tree-dimensional
printing
Editorial
Regenerative medicine is a multidisciplinary feld 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
defnition 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]. Te process of
regenerating body parts can occur in vivo or ex vivo, and may require
stem cells, natural or synthetic cell-supporting scafold materials,
bioactive molecules such as for example trophic factors, genetic
manipulation, or combinations of all of the above [2]. Te 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 diferent felds
of general surgery, among which skin restoration, heart repair,
bioengineering of vessels, kidney, gastroenteric and upper respiratory
tracts [4]. Te medical application in this feld 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 scafolds
as artifcial supporting biomaterial [5]. Another milestone was the
manufacture of a trachea from human components. Macchiarini and
colleagues transplanted the frst 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]. Te trachea was denuded and re-
seeded with cells from the recipient, i.e. chondrocytes diferentiated
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 efcacy of this procedure
highlighting the function of the tissue-engineered trachea and,
importantly, the well-being of the patient [7].
In regenerative medicine, however, the engineering of complex
vascularised organs is presently the major challenge to be overcome to
guarantee transplantation of organs which are very limited in supply
from other individuals [8]. Te use of autologous cellular components
with an internal vascular bed will theoretically overcome the two
major hurdles in transplantation, namely the shortage of organs and
the toxicity deriving from lifelong immunosuppression. Tus, major
progress in regenerative therapies will require cell-based products
made of many cell types to recapitulate organ metabolic function, and
structure to support mechanical function. Recently, this has been
partially accomplished by the generation of functional Liver Buds
(LBs) from iPSCs [9]. Hepatic endoderm cells from human iPSCs
(iPSC-HEs) were cultivated with stromal cell populations, Human
Umbilical Vein Endothelial Cells (HUVECs) and human Mesenchymal
Stem Cells (MSCs), self-organizing in three-dimensional clusters in
vitro and forming iPSC-LBs. In vivo studies demonstrated that: i)
transplants became functional by connecting to the host vessels within
48 hours; ii) the formation of functional vasculatures stimulated the
maturation of iPSC-LBs into tissue resembling the adult liver; and iii)
mesenteric transplantation of iPSC-LBs rescued the drug-induced
lethal liver failure model.
Tree-dimensional (3D) cell bio-printing is a relatively new
engineering tool being used to design 3D cell constructs (rather than
cell suspensions) for transplantation therapies. A defnition of bio-
printing has been given by Guillemot, Mironov and Nakamura in 2010:
‘the use of computer-aided transfer processes for patterning and
assembling living and non-living materials with a prescribed 2D or 3D
organization in order to produce bio-engineered structures serving in
regenerative medicine, pharmacokinetic and basic cell biology studies’
[10]. An outline of the steps involved in 3D bio-printing is given in
Figure 1.
Tis technological platform has taken advantage of the one based on
2D inkjet printing. Bio-printing with inkjet technology allows to spray
extracellular matrix proteins for providing a defned substrate for cells,
elaborate complex cell structures, or to deliver gene and enzymes to
cells [11-13]. In its simplest version, 3D bio-printing is aimed at print
one layer of cells atop the layer of other cells or scafold biomaterials.
On the other hand, 3D bio-printing would be a platform that facilitates
construction of complex, multicellular tissues or organs in
architectures appropriate for function, and, in one version, it is based
on 3D cellular building blocks, instead of liquid inks [12].
Since the beginning of the XXI century, in labs around the world,
bioengineers have begun to print frst bacteria, mammalian cells and
then prototype organs: heart valves, ears, artifcial bone joints, menisci,
blood vessels and skin grafs [10,12,14-21]. Tree factors are leading
the evolution of 3D bio-printing: more sophisticated printer, advances
in cell therapy and regenerative medicine, and refned Computer-
Assisted Design/Computer-Assisted Manufacturing (CAD/CAM)
sofware. Moreover, the team may use Computed Tomography (CT) or
Magnetic Resonance Imaging (MRI) scans to create a CAD fle of the
wound or organs like meniscus.
Advancements in Genetic
Engineering
Conese, Adv Genet Eng 2014, 2:3
http://dx.doi.org/10.4172/2169-0111.1000e112
Editorial Open Access
Adv Genet Eng
ISSN:2169-0111 AGE, an open access journal
Volume 2 • Issue 3 • e112