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International Journal of Bioprinting Sr-doped printed scaffolds for bone repair

1. Introduction its excellent biocompatibility, degradability, and bone-
enhancing properties. Research has demonstrated that
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Bone defects refer to the destruction of bone tissue caused mesoporous BG (MBG) effectively enhances apatite
by trauma, infection, tumors, or other pathological production rate. Zhao et al. used an MBG composite
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conditions. Tissue engineering is a promising strategy fibrin hydrogel for maxillofacial bone defect implantation,
1
for reconstructing bone defects, and it has received much and MBG enhanced the mechanical strength, bioactivity,
attention recently. To enhance repair effectiveness, many and osteogenic properties of the hydrogel. In addition,
past studies have explored the composition, degradation BG exhibits excellent cytocompatibility and antimicrobial
properties, and bone-regenerative properties of composite effects as a coating material for metal implants. 28,29 In
2–4
scaffolds. Although the mechanical properties and contrast, recent studies have reported that exosomes
degradation characteristics of scaffolds have significantly generated from MBG-stimulated mesenchymal stem
improved, bone repair results remain unsatisfactory, cells (MSCs) are significantly more productive and
limiting their clinical application. In addition, scaffold– exhibit enhanced immunomodulatory and bone repair
5,6
tissue interactions play a central role in tissue repair. capabilities. In recent years, strontium-doped BG
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Therefore, elucidating and modulating scaffold–tissue (SrBG) has received attention for its ability to promote
interactions is essential to improve repair outcomes. osteoblast proliferation, osteogenic differentiation, and
Recent studies have found that bone filler materials angiogenesis. Sr² inhibits the expression of inflammatory
+
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trigger innate and adaptive immune responses after genes and provides a favorable environment for tissue
implantation. Excessive immune responses may lead repair. In addition, Sr² has immunomodulatory effects
8,9
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+
to chronic inflammation, fibrosis, and implant failure, and is concentration-dependent. Ding et al. found that
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increasing the risk of secondary surgery. 10–12 Therefore, SrBG was able to mobilize monocytes from the spleen to
reducing inappropriate immune responses triggered reach the bone defect site and convert them into M2 MPs
during early implant stages is particularly important. to promote bone tissue regeneration. SrBG promotes bone
Macrophages (MPs) play a key immunoregulatory role repair by activating the Akt signaling pathway to promote
in bone defect repair, with M1 (pro-inflammatory) and M2 MP polarization and release osteogenesis-related
M2 (anti-inflammatory) MPs regulating bone formation, cytokines. Although PCL/SrBG composite scaffolds
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remodeling, and repair by secreting different cytokines. 13,14 displayed better bioactivity and osteogenic induction
Biodegradable polymers create favorable conditions for compared to PCL scaffolds, PCL/SrBG scaffolds alone
regenerating new bone tissue and defect repair compared were still insufficient to induce significant osteogenic
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to permanent implants. In comparison with inorganic differentiation. 36,37 Poh et al. cultured PCL and PCL/SrBG
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materials, polymer materials have better degradability, scaffolds under non-osteoinductive conditions to evaluate
higher biocompatibility, and more stable mechanical their positive effect on osteoinductive differentiation;
properties. 16,17 Among various degradable materials, the PCL/SrBG scaffolds did not exhibit any significant
synthetic polyesters have controlled biodegradability osteoinductive differentiation ability, which may be related
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in vivo and are non-toxic. Synthetic polyester-based to the concentration of Sr² released by the scaffolds.
materials have better mechanical properties than natural Polydopamine (PDA) is an implant surface modification
polymers and are more suitable for bone repair. Among material with good hydrophilicity, biocompatibility,
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them, polycaprolactone (PCL) has good biocompatibility antimicrobial properties, and bone-enhancing properties.
and can be effectively combined with biological tissues. 20,21 More importantly, the PDA coating has a large number
However, PCL has low bioactivity, poor cell adhesion, of catecholamine groups for scavenging reactive oxygen
and lacks osteogenic activity. 22,23 In addition, Tang species (ROS) and anti-inflammatory properties that inhibit
et al. prepared Panax notoginseng saponin (PNS)-PCL M1 MP polarization and activate MP polarization toward
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scaffolds via 3D printing to evaluate their reparative the M2 phenotype, thereby promoting the expression of
osteogenesis-related cytokines. Jin et al. demonstrated
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effect on vascular injury in rabbit carotid arteries, and that PDA inhibits pro-inflammatory cytokine expression
the inflammation scoring results indicated that pure PCL in MPs by downregulating the TLR-4-MYD88-NF-κB
scaffolds exhibited poor anti-inflammatory performance. pathway. Moreover, PDA can regulate ROS production and
Therefore, PCL needs to be compounded with other upregulate heme oxygenase 1 (HO-1) expression, thereby
biomaterials to enhance its osteogenic activity and influencing MP phenotypic differentiation and suppressing
immunomodulatory ability.
the inflammatory response. In this study, we innovatively
Bioactive glass (BG) is an inorganic bioactive material and synergistically used PDA and SrBG to modify the
that can form strong bonds with hard and soft tissues, surface and interior of PCL scaffolds to enhance the cell
and it is widely used in bone tissue engineering due to adhesion and proliferation of the scaffolds. PDA coating
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Volume 11 Issue 4 (2025) 351 doi: 10.36922/IJB025210211