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. 2024;14(3):27510.
doi: 10.34172/bi.2023.27510. Epub 2023 Jul 19.

Poly (acrylic acid)/tricalcium phosphate nanoparticles scaffold enriched with exosomes for cell-free therapy in bone tissue engineering: An in vivo evaluation

Nahid Moradi  1 , Mina Soufi-Zomorrod  1 , Simzar Hosseinzadeh  2   3 , Masoud Soleimani  1   3
Affiliations

Poly (acrylic acid)/tricalcium phosphate nanoparticles scaffold enriched with exosomes for cell-free therapy in bone tissue engineering: An in vivo evaluation

Nahid Moradi et al. Bioimpacts. 2024.

Abstract

Introduction: This study aimed to assess the potential of poly (acrylic acid)/tricalcium phosphate nanoparticles (PAA/triCaPNPs) scaffold in terms of biocompatibility and osteoconductivity properties the in-vivo evaluation as well as to investigate the performance of PAA/triCaPNPs scaffold (with or without exosomes derived from UC-MSCs) for bone regeneration of rat critical-sized defect.

Methods: PAA/triCaPNPs scaffold was made from acrylic acid (AA) monomer, N,N'-methylenebisacrylamide (MBAA), sodium bicarbonate (SBC), and ammonium persulfate (APS) through freeze-drying method. For in vivo evaluation, we randomly divided 24 rats into three groups. The rat calvarial bone defects were treated as follows: (1) Control group: defects without any treatment, (2) scaffold group: defects treated with scaffold only, (3) scaffold+exo group: defects treated with scaffold enriched with exosomes (1 μg/μL, 150 μg per rat). Eight- and 12-weeks post-surgery, half of the animals were sacrificed and bone regeneration was examined through micro-computerized tomography (µ-CT), histological staining, and immunohistochemistry (IHC).

Results: Quantitative analysis based on µ-CT scan images at 8 and 12 weeks post-implantation clearly indicated that healing rate for defects that were filled with scaffold enriched with exosome was significantly higher than defects filled with scaffold without exosome. The H&E and Masson staining results revealed that more new bone-like form developed in the scaffold+exo group than that in control and scaffold groups. Further, IHC staining for osteocalcin and CD31 confirmed that more bone healing in the scaffold+exo group at 12 weeks could be associated with osteogenesis and angiogenesis concurrently.

Conclusion: In the present study, we aimed to investigate the therapeutic potential of PAA/triCaPNPs scaffold as a carrier of human UC-MSC-derived exosome to achieve the exosome-controlled release on calvarial bone defect. The in vivo results indicated that the exosome-enriched scaffold could effectively minify the defect area and improve the bone healing in rat model, and as such it could be an option for exosome-based therapy.

Keywords: Cell-free therapy; Critical-sized bone defect; PAA; Preclinical imaging; Tricalcium phosphate nanoparticles; UCMSC-exosome.

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Conflict of interest statement

There is no competing financial interest.

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