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The trend towards in vivo bioprinting

culture, and transportation to in vivo implantation), 2. Current Status of in vivo Bioprinting
can lead to low replication rates and low error toler-
ance rates, which may make in vitro bioprinting-based As the largest and most easily accessible organ in the
therapeutic strategies less attractive to surgeons. body, the skin has logically become the ideal place to
Thirdly, it is possible that the shape/morphology of the start with for the development of in situ bioprinting.
prefabricated construct may not match the actual size Binder et al. demonstrated their in situ inkjet-based
of the defect, which results in not only prolonged 3D skin printer with which they directly repaired the
[6, 7]
surgical time due to further construct-trimming or skin defects on rats . The results indicated that mul-
gap-filling, but also a compromised mechanical anc- tiple skin cells could be directly delivered onto a
horing of the construct to the native tissues. In addi- wound with an acceptable cell survival rate through
tion, the surgical implantation procedure can be des- the in situ printing procedure. The wounded skin also
exhibited faster recovery after being printed with skin
tructive to the prefabricated tissue/organ substitutes, cells. Sofokleous et al. brought up the concept of us-
i.e., the physical impact of the fixation process when ing a portable handheld device to deliver drug, con-
pressing or suturing the in vitro printed construct to struct artificial skin, and apply wound dressing patch
the peripheral native tissues may disrupt both the directly onto the damaged skin . This portable
[8]
micro- and macro-architectures of the substitute, electro-hydrodynamic device demonstrated not only a
resulting in noticeable impairment to the structural co-axial multi-needle design for integral fiber cons-
integrity, cell viability, and initial bridging of the truction with multiple diameters, but is also a good
implant to its surroundings. example of bringing bioprinting techniques out of the
A possible solution to the aforementioned in vitro laboratory and towards practical applications, i.e.,
issues is to directly fabricate and position tissue/organ from in vitro to in vivo.
substitutes at the defective site in the living body, Another branch of pilot studies deal with in vivo
which is the so-called “in vivo” bioprinting, a term repair of osteochondral tissues, i.e., the bone and arti-
occasionally interchangeable with “in situ” bioprinting. cular cartilage. Keriquel et al. applied high-throughput
In a typical in vivo bioprinting scenario following the biological laser bioprinting technologies to repair
real-time surgical schemes, robotic arms with bioprin- mouse calvaria defects of critical size (3 mm in di-
ting units enter the body through minimally invasive ameter, 600 μm in depth) through deposition of nano-
route and automatically reconstruct new tissues/organs hydroxyapatite (n-HA) in vivo as shown in Figure 1.
[9]
with hierarchical and physiological equivalence to the Preliminary results from this study, such as no
originals under the control of surgeons. In this way, detectable deleterious effects of infrared laser light on
the human body functions as the effective “in vivo brain tissues; satisfying morphological, chemical and
bioreactor” to facilitate maturation of the printed con- biological properties of the in vivo printed construct;
structs in a real biological environment right from the and recovery achieved in most cases (29 out of 30
fabrication stage. In vivo bioprinting would be particu- cases, indicated the feasibility of in vivo bioprinting
larly effective in the treatment of tissues/organs that for repairing superficial osseous defects. Cohen et al.
can be safely arrested and immobilized during bio- demonstrated the in situ repair of both chondral and
printing, e.g., the musculoskeletal system. Success in osteochondral defects on ex vivo excised bovine fe-
such a fascinating technology will completely revolu- moral condyles using a built-in-house bioprinter
tionize surgical practice in the future. Rather than be- (Figure 2) [10] . The demineralized bone matrices and
ing a publicity stunt, in vivo bioprinting is now a alginate hydrogels were sequentially printed onto the
promising work in progress. To push this inspiring but osteochondral defect, to rebuild bone and cartilage
tough work forward, it is logical to start with superfi- respectively. A meaningful attempt in this pilot study
cial tissues/organs which can be accessed easily. In was the establishment of a novel geometric feedback
this review, we will give an overview of the state- system, through which the in situ bioprinting system
of-the-art in vivo bioprinting researches carried out boasted a precision of mean surface errors of less than
worldwide, and advances in biofabrication and bioma- 0.1 mm.
terial technologies with a particular focus on the Moreira Teixeira et al. proposed an arthrosco-
potential for the eventual realization of in vivo bio- py-compatible extrusion-based approach to repair
printing in the future. small articular cartilage (AC) defects, by filling the AC

16 International Journal of Bioprinting (2015)–Volume 1, Issue 1