The concept of regenerating tissues, with properties and functions that mimic natural
tissues, has attracted significant attention in recent years. It provides potential
solutions for many diseases treatment and other healthcare problems. To fully realize
the potential of the approach, it is crucial to have a rational biomaterial design
to create novel scaffolds and other material systems suitable for tissue engineering,
repair, and regeneration. Research advances in the topic include the design of new
biomaterials and their composites, the scaffold fabrication via subtractive and additive
manufacturing approaches, the development of implantable scaffolds for disease monitoring,
diagnostics, and treatment, as well as the understanding of cell–biomaterial scaffolds
interaction.
In the Special Issue “Novel Biomaterials for Tissue Engineering 2018”, promising findings
on different approaches to designing and developing new biomaterials, biomaterial
systems, and methods for tissue engineering, are presented and discussed.
In particular, Rahali et al. report on the synthesis and characterization of novel
gelatin methacrylate hydrogels functionalized with nanoliposomes and nanodroplets
[1]. This nanofunctionalization approach enables control over the design of the biomaterial,
via tailoring the type of incorporated nanoparticle for the specific application.
Furthermore, hydroxyapatite (HA) films with minute amounts (ca. 1 weight %) of (rhenium-doped)
fullerene-like MoS2 nanoparticles (IF) were deposited through an electrophoretic process
[2]. Tribological tests revealed that the nanoparticles endow the HA film very low
friction and wear characteristics. As a consequence, HA-IF films could be of interest
for various medical technologies. Al-Kattan et al. [3] reviewed the application of
bare, ligand-free, laser-synthesized nanoparticles of Au and Si as functional modules
(additives) in scaffold platforms intended for tissue engineering purposes. In addition,
a new biodegradable medical adhesive material was recently developed by blending Poly(lactic
acid) (PLA) with Poly(trimethylene carbonate) (PTMC) in ethyl acetate [4]. It is shown
that in addition to having a positive effect on hemostasis and no sensibility to wounds,
PLA-PTMC can efficiently prevent infections. Moreover, Babaliari et al., demonstrated
the use of ultrafast laser-fabricated microstructured culture substrates on different
materials, including Si, Polyethylene terephthalate (PET), and Poly(lactide-co-glycolide)
(PLGA), as a mean to control cellular adhesion and orientation [5]. This property
is potentially useful in the field of neural tissue engineering and for microenvironment
systems that simulate in vivo conditions. The recent achievements in the field of
non-apatitic calcium phosphate materials (CaPs) substituted with various ions were
reviewed by Laskus and Kolmas [6]. The authors focused particularly on tricalcium
phosphates (TCP) and “additives” such as magnesium, zinc, strontium, and silicate
ions, all of which have been widely investigated thanks to their important biological
role. The review also highlights some of the potential biomedical applications of
non-apatitic substituted CaPs. Besides this, Khan and Tanaka [7] discussed the prospect
of using functional biomaterials, which respond to external stimulus, for the development
of smart 3D biomimetic scaffolds. The authors elaborated on how smart biomaterials
are designed to interact with biological systems, for a wide range of biomedical applications,
including the delivery of bioactive molecules, cell adhesion mediators, and cellular
functioning for the engineering of functional tissues to treat diseases.
Human mesenchymal stem cells (MSCs) have been widely studied for therapeutic development
in tissue engineering and regenerative medicine. However, directing the differentiation
of MSCs still remains challenging for tissue engineering applications. To address
this issue, Balikov et al. [8] developed a low-cost, scalable, and effective copolymer
film to direct angiogenic differentiation of MSCs. hMSCs were cultured over several
passages without the loss of reactive oxygen species handling or differentiation capacity.
In another approach, Lee et al. [9] developed in situ cross-linkable gelatin−hydroxyphenyl
propionic acid hydrogels that can direct endothelial differentiation of MSCs, thereby
promoting vascularization of scaffolds towards tissue engineering and regenerative
medicine applications in humans. Besides this, the development of techniques and devices
for the development of new cellular microenvironments (i.e, niche), which is poorly
represented by the typical plastic substrate used for the two-dimensional growth of
MSCs in a tissue culture flask, is of critical importance. Aubert et al. [10] presented
a collagen-based medical device as a mimetic niche for MSCs with the ability to preserve
human MSC stemness in vitro. Nativel et al. [11] reported on the application of droplet
millifluidics to encapsulate and support viable hMSCs in a polysaccharide hydrogel.
This Special Issue also presents recent advances in bone tissue engineering and regeneration
as well as in osteogenic differentiation. Specifically, resorbable bacterial cellulose
membranes, treated by electron beam irradiation, have been reported to be excellent
biomaterials for guided bone regeneration [12]. Moreover, Hum et al. [13] developed
highly porous bioactive glass-based scaffolds, fabricated by the foam replica technique
and coated with collagen. The combination of bioactivity, mechanical competence, and
cellular response makes this novel scaffold system attractive for bone tissue engineering.
In another approach, Hsieh et al. [14] explored the development of solid biomimetic
scaffolds of Poly(ε-Caprolactone)/Hydroxyapatite and Glycidyl-Methacrylate-Modified
Hyaluronic Acid. In vivo experiments on the healing of osteochondral defects, performed
on the knees of miniature pigs, concluded that the structural design of the scaffold
should be reconsidered to match the regeneration process of both cartilage and subchondral
bone. Besides this, different approaches to osteogenic differentiation are reported.
In particular, the osteogenic differentiation effect of the FN Type 10-Peptide Amphiphile
(FNIII10-PA) on Polycaprolactone fibers has been investigated [15]. It is shown that
the FNIII10-PA-induced the osteogenic differentiation of MC3T3-E1 cells, indicating
its potential as a new biomaterial for bone tissue engineering applications. Sobreiro-Almeida
et al. investigated the hMSCs osteogenic differentiation on piezoelectric Poly(vinylidene
fluoride) microsphere substrates [16]. It is concluded that such microspheres are
a suitable support for bone tissue engineering purposes, as hMSCs can proliferate,
be viable, and undergo osteogenic differentiation when chemically stimulated. Finally,
Paun et al. developed 3D magnetic structures, fabricated by direct laser writing via
two-photon polymerization and coated with a thin layer of collagen-chitosan-hydroxyapatite-magnetic
nanoparticles composite [17]. In vitro experiments showed that such scaffolds stimulate
the osteogenesis in the static magnetic field, via promotion of the MG-63 osteoblast-like
cells proliferation and differentiation.
Tissue engineering methods to address skin regeneration and fertility restoration
have been additionally reported. Specifically, Pang et al. [18] evaluated the effects
of total flavonoids from Blumea balsamifera (L.) DC. on skin excisional wounds on
the backs of Sprague-Dawley rats and revealed its chemical constitution, as well as
its action mechanism. The study concluded that flavonoids were the main active constituents
that contribute to excisional wound healing. Del Vento et al., reviewed the tissue
engineering approaches to the improvement of immature testicular tissue and cell transplantation
outcomes [19]. It is concluded that such bioengineering techniques may be a step closer
to fertility restoration for prepubertal boys exposed to gonadotoxic treatments.
Finally, this Special Issue includes recent advances in biofabrication techniques
for tissue engineering purposes. In particular, Zhang et al., provided an overview
of the application of the layer-by-layer (LbL) self-assembly technology for the surface
design and control of biomaterial scaffolds to mimic the unique features of native
extracellular matrices [20]. It is concluded that LbL self-assembly not only provides
advances for molecular deposition but also opens avenues for the design and development
of innovative biomaterials for tissue engineering. Another emerging biofabrication
tool is 3D printing, which has been recently applied for the development of an artificial
trachea [21]. It is shown that epithelial cells in the 3D bioprinted artificial trachea
were effective in respiratory epithelium regeneration. Furthermore, chondrogenic-differentiated
bone marrow-derived MSCs had more neo-cartilage formation potential in a short period,
although in a localized area. Furthermore, Park et al. [22] demonstrated the generation
of oriented ligamentous architectures, driven by a 3D-printed microgroove pattern.
The results of this study demonstrate that 3D-printed topographical approaches can
regulate spatiotemporal cell organizations that offer strong potential for adaptation
to complex tissue defects to regenerate ligament-bone complexes. In another study,
a new bone substitute developed from 3D-printed structures of Polylactide (PLA) loaded
with collagen I, have been demonstrated [23]. The results obtained from in vitro cultures
of various cell types, including osteoblasts, osteoblast-like, fibroblasts, and endothelial,
indicate the potential use of 3D-printed PLA scaffolds in bone tissue engineering.
Being a promising biofabrication technique, electrospinning has been widely used for
the fabrication of extracellular matrix (ECM)-mimicking fibrous scaffolds for several
decades. In this context, Jun et al. [24] summarized the fundamental principles of
electrospinning processes for generating complex fibrous scaffold geometries that
are similar in structural complexity to the ECM of living tissues. Qasim et al. [25]
reviewed the research progress on the electrospinning of chitosan and its composite
formulations for creating fibers in combination with other natural polymers to be
employed in tissue engineering. The review shows that evidence exists in support of
the favorable properties and biocompatibility of chitosan electrospun composite biomaterials
for a range of applications. It is concluded, however, that further research and in
vivo studies are required to translate these materials from the laboratory to clinical
applications.