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Abstract One of the most fundamental characteristics of a biomaterial tailored for bone repair and regeneration is its ability to promote bone regeneration and healing of large defects. This work reports producing a functionalized and hieratically porous bone scaffold that significantly supports cell adhesion and proliferation by providing bone mimicry structure and controlled release of protein. The Slit Guidance Ligand 3 (SLIT3) protein was previously tested to promote bone formation and control the resorption process in natural bone healing. In this study, our goal was to design a nanocomposite bone scaffold to be functionalized with SLIT3 protein and then evaluate the uptake and release profile from surface into culture media to support bone marrow-derived mesenchymal stem cells (MSC) 3D culture. Indirect 3D printing of a polylactic-co-glycolic acid (PLGA), hydroxyapatite nanoparticles, and polydopamine coated (PLGA-HANPs-PDA) was utilized to obtain a hierarchically porous and SLIT3 protein-releasing scaffold. The produced scaffold was evaluated and optimized using chemical, architectural, mechanical, and biological characterization techniques. Optimal physicochemical properties resulted in a unique microstructure with an average pore size of 178.06 ± 45 µm, 63% porosity, and stable and homogenous chemical composition. Mechanical testing demonstrated a compression strength up to 1.5 MPa at 75% strain, with a compression modulus of 0.58 ± 0.05 MPa. Preliminary biological experiments showed that the scaffold exhibited gradual SLIT3 protein release, biodegradability, and reliable biocompatibility for MSC cell culture. Finally, we showed for first time the bioactivity of SLIT3 protein within PLGA-HANPs-PDA scaffold to promote attachment and growth of mesenchymal stem cell (MSCs) seeded in bone mimicry scaffold matrix. The collected findings will serve as a bedrock for thorough and targeted in vitro studies to evaluate anticipated osteogenesis the MSCs.
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This content will become publicly available on June 1, 2026
Doping of Hollow Urchin-like MnO2 Nanoparticles in Beta-Tricalcium Phosphate Scaffold Promotes Stem Cell Osteogenic Differentiation
Effective osteogenesis for bone regeneration is still considerably challenging for a porous β-tricalcium phosphate (β-TCP) scaffold to achieve. To overcome this challenge, hollow manganese dioxide (H-MnO2) nanoparticles with an urchin-like shell structure were prepared and added in the porous β-TCP scaffold. A template-casting method was used to prepare the porous H-MnO2/β-TCP scaffolds. As a control, solid manganese dioxide (S-MnO2) nanoparticles were also added into β-TCP scaffolds. Human bone mesenchymal stem cells (hBMSC) were seeded in the porous scaffolds and characterized through cell viability assay and alkaline phosphatase (ALP) assay. Results from in vitro protein loading and releasing experiments showed that H-MnO2 can load significantly higher proteins and release more proteins compared to S-MnO2 nanoparticles. When they were doped into β-TCP, MnO2 nanoparticles did not significantly change the surface wettability and mechanical properties of porous β-TCP scaffolds. In vitro cell viability results showed that MnO2 nanoparticles promoted cell proliferation in a low dose, but inhibited cell growth when the added concentration went beyond 0.5%. At a range of lower than 0.5%, H-MnO2 doped β-TCP scaffolds promoted the early osteogenesis of hBMSCs. These results suggested that H-MnO2 in the porous β-TCP scaffold has promising potential to stimulate osteogenesis. More studies would be performed to demonstrate the other functions of urchin-like H-MnO2 nanoparticles in the porous β-TCP.
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- Award ID(s):
- 2223702
- PAR ID:
- 10609958
- Publisher / Repository:
- MDPI
- Date Published:
- Journal Name:
- International Journal of Molecular Sciences
- Volume:
- 26
- Issue:
- 11
- ISSN:
- 1422-0067
- Page Range / eLocation ID:
- 5092
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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