Page 296 - IJB-10-5

International Journal of Bioprinting 3D printing of collagen II-scaffolds

in scaffolds with 500 μm pores compared to scaffolds with and substance transportation. Recent works have
7,57
700 and 900 μm pores, but the level of proliferation was addressed the structural issues above with 3D-printed
lower in the former scaffolds. Similarly, Sun et al. reported mesh scaffolds, but these scaffolds have poor resolution
48
upregulation of chondrogenic markers and reduced level (250–500 μm), resulting in low porosity and surface area
of proliferation in scaffolds with 150 μm pores compared for essential cell activities. 24,30,58–61 Likewise, there are well-
to scaffolds with larger pores. designed 3D-printed mesh scaffolds with high resolution
Most studies correlating smaller pores to reduced cell (~150 μm), interconnectivity, and symmetry, but utilize
proliferation often utilize mesh scaffolds composed of poorly bioactive materials 48,49,62 These biomaterials,
thermoplastic polymers or metals. In contrast, collagen II including metals, ceramics, and thermoplastic polymers
in hydrogel form was used in our study, achieving greater (e.g., polycaprolactone), are stiff and hydrophobic, unlike
63–65
cell proliferation in scaffolds with smaller pores (i.e., hydrogel scaffolds that provide a favorable viscoelastic
<150 μm). Hence, we infer that pore size effects could be and hydrophilic environment 66,67 for cell adhesion and
material-dependent. Small pores are usually unfavorable proliferation. From the biochemical perspective, the use of
for solvent diffusion, which would subsequently hinder cell natural proteins, such as collagen and gelatin, introduces
metabolism and proliferation. Nonetheless, the collagen surface RGD/RGE sequences that could enhance
49
II composition used in this study could have addressed the chondrogenic differentiation and cell adhesion. 68–70
aforementioned issues based on three critical aspects: In comparison to previously reported studies,
(i) the surface RGE groups could bind to cells and our collagen II-containing scaffolds are superior in
organic compounds ; both compositional and structural properties (with a
50
high resolution near 120 μm), and the scaffolds could
(ii) the hydrogel form could have facilitated the synergistically induce chondrogenic differentiation and
adsorption of nutrition substances; and cartilage-specific ECM synthesis, highlighting their
(iii) the higher number of cells and aggregation results in potential for further applications in cartilage tissue
enhanced cell–cell communication. 51 engineering.

Collectively, we demonstrated that collagen II enhances 4.5. Clinical relevance of printing high-resolution
the proliferation and chondrogenic differentiation of natural protein-based hydrogel
MSCs via its biochemical properties and the presence of In this study, we developed collagen II-based scaffolds with
small pores on the scaffolds. a high resolution, i.e., sample d with an average pore size
of 133 ± 17 μm and a rod diameter of 122 ± 18 μm. As
4.4. Prospective applications in cartilage aforementioned, collagen II enhances cell proliferation,
tissue engineering chondrogenic differentiation, and cartilage-specific ECM
Growth factors are essential for cartilage tissue engineering, production, and the effects are augmented by the small
but their inclusion is costly and requires significant efforts pores on the scaffold. Herein, we discuss the future clinical
in preservation, handling, blending, release control, and relevance of producing small-sized pores in tissue scaffolds.
optimization. 52,53 Conversely, the use of collagen II to induce
chondrogenic differentiation could reduce the overall Tissue engineering facilitates tissue defect repairs but
cost and effort required for growth factors. Additionally, has yet to become widely used in clinical routines. One
collagen II can be used synergistically with growth factors of the key hurdles is the inadequate production of ECMs,
to promote chondrogenic differentiation. resulting in diminished mechanical properties of the
regenerated tissue. 71–73 As a consequence, the tissue often
Improving both the compositional and structural
properties of a cartilage scaffold used to be challenging fails to match the load-bearing capacity of the host tissue
and fulfill its function. Inadequate ECM production may
74
primarily due to difficulties in hydrogel processing. also limit the total volume of regenerated tissue, resulting
Some studies have used cartilage-specific biomaterials in voids and a greater probability of tissue fracture.
75
or other natural protein-based hydrogels with excellent Therefore, it is crucial for scaffolds to enhance tissue-
biocompatibility (collagen I, gelatin, etc.), but the specific ECM production. 24,62
developed scaffolds often exhibit undesirable structural
characteristics, such as foam scaffolds produced by In this study, the collagen II-based scaffolds with a high
freeze-drying 21–23,54,55 and nanoscale porous film scaffolds resolution (sample d) significantly improved the level of
produced by electrospinning. These scaffolds lack proliferation, chondrogenic differentiation, and cartilage-
56
uniform, symmetrical, and interconnected macro-micro specific ECM production. Additionally, pore size is essential
pores to sufficiently support cell migration, growth, for increasing total ECM production, and this could be

Volume 10 Issue 5 (2024) 288 doi: 10.36922/ijb.3371