Page 486 - IJB-9-6

International Journal of Bioprinting Bioprinting cell-laden protein-based hydrogel

the comparison of samples with and without GFs in a Interestingly, chondroblasts could form tiny isogenic
subcutaneously implantation BALB/c OlaHsd-Foxn1nu groups with an ECM having a pronounced perichondrium,
nude mice models showed that the groups treated with and the produced ECM accumulated a great content of
GF-loaded constructs had higher levels of sulfated GAGs GAG. Moreover, an intense reaction to collagen type II by
(sGAGs) and collagen type II, as well as greater accumulation the tissue and signs of reduced proliferative activity were
of matrix, indicating the formation of hyaline-like cartilage found (Figure 3D(v–viii)).
tissue [151] . Since exosomes act as media for communication
between cells [152,153] , a composite scaffold made up of 3.2.3. Cell signaling
decellularized cartilage ECM/GelMA (2% wt for ECM and The behaviors of cells within the bioprinted constructs
10% w/v for GelMA) containing BMSCs-derived exosomes are influenced not only by the bioinks cues but also by
bioinks was fabricated utilizing stereolithography 3D the signals from other cells as well as various types of
printing (crosslinking approach: photo-crosslinking with intercellular signals, including autocrine, intracrine,
0.25% w/v LAP at 405 nm wavelength, visible light, and endocrine, paracrine, and juxtacrine signals, categorized
exposure time of 30 s) for osteochondral repair by Chen based on the distance between responder cells and
et al. [139] , and the therapeutic effects of MSCs-derived signaling. Of note, paracrine and juxtacrine signaling
exosomes on osteoarthritis was examined using New pathways are of higher significance in bioprinting of stem
Zealand White rabbit models. Interestingly, ECM/GelMA/ cells owing to the size of printed structures. In juxtacrine
exosome constructs could efficiently retain exosomes signaling and via molecule transfer through gap junction
for at least 7 days, restore chondrocytes’ mitochondrial channels that are along the surface of contact, intercellular
[155]
dysfunction, improve cells migration, and polarize the communication is realized . Stem cells, tending to form
synovial macrophage response toward an M2 phenotype. aggregates, are deeply affected by cluster situation under
Comparing animals implanted with scaffolds with or the mentioned mechanism. Specifically, the degree of MSCs
without exosomes, it was demonstrated that ECM/ differentiation into osteogenic lineage is revealed much
[46]
GelMA/exosome-treated groups showed the formation greater in aggregated cells compared with isolated ones .
of smooth tissues, regenerated fibrocartilage and hyaline- Furthermore, the stem cell aggregates’ size is capable
[156]
like cartilage, and more ossified tissues at 6 weeks post- of regulating the differentiation fate . By controlling
implantation. The International Cartilage Repair Society the bioprinting volume, initial seeding density of cells,
(ICRS) scoring indicated a higher score for animals treated and cultivation time, stem cell aggregates with regular
with exosome-embedded structures (14.1 ± 0.71) than shapes and uniform sizes can be created through cellular
[157]
the ECM/GelMA-and GelMA-treated groups (12.2 ± 0.61 proliferation post-bioprinting . Signaling cells release
and 7.8 ± 0.39, respectively) at 6 weeks after implantation. paracrine signals, and they target the nearby cells. In this
Each tissue’s ECM generates a very unique tissue-specific regard, one of the most essential uses is the co-culture of
[9,69]
microenvironment for the resident cells, which can several cells in order to enhance cellular functions ,
provide them with the biochemical signals required for and another approach to control the migration of cells
[158]
their functioning. Within an innovative evaluation, Isaeva is the co-printing of different cell types . Additionally,
et al. [154] assessed two compositions of collagen-based multiple cells’ deposition in arranged positions facilitates
bioinks (4% w/v for pig atelocollagen type I) printed via the complex tissues’ construction, and regulation of
extrusion printing: (i) with hMSCs (isolated from human cellular survival and density can influence the bioactive
adipose tissue) and (ii) with decellularized ECM granules proteins’ local concentration, further affecting the stem cell
[159]
(2.5% w/v with a particle size of 280 µm) and hMSCs (cell differentiation . Table 3 recapitulates the biochemical
density: 5 × 10 cells/mL) for cartilage TE. After bioprinted parameters influencing PBHs’ bioprinting in the cartilage
6
constructs’ subcutaneous implantation in white male rats, and bone TE.
two groups were compared from various perspectives. In a nutshell, the behaviors of cells encapsulated in
In the first group (MSCs only), scholars observed the the PBHs are affected by biophysical cues, including
formation of a connective tissue capsule with multiple composition, biodegradation, porosity-related parameters,
blood vessels and detected cells with cytoplasm including and crosslinking process. In this regard, elastic stiffness,
collagen type II 2 weeks post-implantation. The only degradation rate, pore size, porogen concentration, as
evidence of the formed cartilage was the small islands well as time and concentration of the used crosslinker,
of cartilaginous tissue with irregular shapes adjacent to which exert various effects on cell viability, proliferation,
the construct (Figure 3D(i–iv)). In the second group differentiation, and tissue regeneration, should be
(decellularized ECM granules + MSCs), generation of a considered and optimized with respect to the PBHs.
cartilage tissue was shown 2 weeks after implantation. Furthermore, biochemical cues, such as chemical

Volume 9 Issue 6 (2023) 478 https://doi.org/10.36922/ijb.1089