Page 318 - v11i4

International Journal of Bioprinting 3D scaffold prevents tendon ossification

reduction in red blood cell count at post-operative day 3, In the prevention of post-traumatic HO by tissue-
suggesting substantial hemorrhage and erythrocyte loss engineered Achilles tendon scaffolds, attenuated
during the early post-operative phase (Figure 9B). inflammatory and immune responses play a critical
role in regulating key pathological mechanisms. Pro-
13
Neutrophil counts and percentages gradually returned inflammatory cytokines upregulate BMP-2 and Wnt
to baseline levels in all groups. The control group showed signaling pathways, driving stem cell differentiation toward
abnormally elevated neutrophil counts and percentages osteoblasts. Suppression of inflammatory responses
68
at day 3, exceeding normal physiological ranges, whereas directly inhibits these pathways, thereby reducing ectopic
the SF and SF–HPC groups maintained neutrophil bone matrix deposition.
parameters within normal limits (Figure 9C and D). These
results further confirm the absence of acute inflammatory Neutrophil-derived reactive oxygen species and
responses following scaffold implantation. matrix metalloproteinases (MMPs) disrupt the local
microenvironment, promoting calcium salt deposition.
Lymphocyte counts and percentages normalized A hypoimmune response inhibits immune cell-mediated
progressively across all groups, with no significant aberrant repair processes. 69,70 A low-inflammatory
intergroup differences observed (Figure 9E and F). This microenvironment downregulates BMP-2/Smad1/5
pattern indicates that tendon transection surgery alone did signaling while upregulating tenogenic markers such as
not elicit chronic inflammatory responses, regardless of Scx, directing stem cell differentiation toward tenocytes
the intervention. rather than osteoblasts. Concurrently, reduced MMP
activity preserves type I collagen integrity by minimizing
Similarly, monocyte counts and percentages returned
to baseline levels across all groups over the observation its degradation, maintaining ordered collagen fiber
70–72
alignment, and enhancing mechanical stability.
period (Figure 9G and H). Collectively, these hematological
profiles demonstrate that neither scaffold implantation nor In summary, reduced inflammatory and immune
surgical injury provoked detectable immune dysregulation. responses play a crucial role in preventing HO of the
Achilles tendon by suppressing osteogenic signaling,
Additionally, serum levels of pro-inflammatory optimizing stem cell differentiation, and blocking aberrant
cytokines (IL-6 and TNF-α) were quantified at post- repair processes.
operative days 3, 7, and 14. IL-6 levels in the control
group significantly surged at post-operative day 3, Collectively, the SF–HPC scaffold demonstrates
exceeding those in both the SF and SF–HPC groups (p < exceptional mechanical properties, tunable degradation
0.05). By post-operative day 14, IL-6 levels in the control kinetics, and favorable biocompatibility, enabling effective
group returned to baseline. In contrast, no statistically tendon repair while preventing HO. Compared to collagen
significant difference was observed between the SF and scaffolds, SF-based scaffolds provide superior degradation
SF–HPC groups, both of which exhibited a gradual resistance and mechanical strength. Although collagen
decline in IL-6 concentrations, returning to near-baseline offers excellent biocompatibility, its low mechanical
levels by post-operative day 7 and fully normalizing integrity and rapid degradation may lead to premature
by post-operative day 14 (Figure 9I). A similar trend loss of structural support post-implantation. In contrast,
maintain
cross-linked
appropriately
SF
scaffolds
was observed for TNF-α (Figure 9J). Collectively, these biocompatibility while enhancing mechanical robustness
findings indicate that neither SF nor SF–HPC scaffolds and controlling degradation rates, thereby providing
induced sustained elevation of inflammatory cytokines sustained tissue support. A distinct advantage over
73
post-implantation, with cytokine levels largely restored PLGA scaffolds lies in SF’s ability to better facilitate cell
within 1–2 weeks. adhesion and proliferation, a finding corroborated by our
74
SF intrinsically possesses immunomodulatory experimental results.
properties. As demonstrated in previous research, SF-
based materials attenuate pro-inflammatory cytokine 4. Conclusion
secretion (e.g., TNF-α, IL-6) through suppression of This study successfully formulated an SF–HPC–
inflammatory pathways such as nuclear factor kappa- TSPC bioink, utilizing SF as the base material, HPC
66
light-chain-enhancer of activated B cell signaling. This as a reinforcing agent, and TSPCs as seed cells. The
reduction in pro-inflammatory cytokines directly impairs developed bioink exhibited excellent cytocompatibility
neutrophil and monocyte recruitment, thereby decreasing and favorable rheological properties. It enabled 3D
WBC infiltration into inflammatory sites—a phenomenon bioprinting of porous tissue-engineered Achilles tendon
reflected by diminished peripheral blood WBC counts. 67 scaffolds with high mechanical strength and controlled

Volume 11 Issue 4 (2025) 310 doi: 10.36922/IJB025210203