The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization

Our plain-English summary of The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization, by Y. Xuan, L. Li, C. Zhang, et al (International Journal of Nanomedicine, 2023).

The study

• Authors: Y. Xuan, L. Li, C. Zhang, M. Zhang, J. Cao, Z. Zhang
• Journal: International Journal of Nanomedicine
• Published: 2023;18:917-932
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Repairing critical-sized bone defects secondary to traumatic or tumorous damage is a complex conundrum in clinical practice; in this case, artificial scaffolds exhibited preferable outcomes. Bredigite (BRT, Ca7MgSi4O16) bioceramic possesses excellent physicochemical properties and biological activity as a promising candidate for bone tissue engineering.

Methods: Structurally ordered BRT (BRT-O) scaffolds were fabricated by a three-dimensional (3D) printing technique, and the random BRT (BRT-R) scaffolds and clinically available β-tricalcium phosphate (β-TCP) scaffolds were compared as control groups. Their physicochemical properties were characterized, and RAW 264.7 cells, bone marrow mesenchymal stem cells (BMSCs), and rat cranial critical-sized bone defect models were utilized for evaluating macrophage polarization and bone regeneration.

Results: The BRT-O scaffolds exhibited regular morphology and homogeneous porosity. In addition, the BRT-O scaffolds released higher concentrations of ionic products based on coordinated biodegradability than the β-TCP scaffolds. In vitro, the BRT-O scaffolds facilitated RWA264.7 cells polarization to pro-healing M2 macrophage phenotype, whereas the BRT-R and β-TCP scaffolds stimulated more pro-inflammatory M1-type macrophages. A conditioned medium derived from macrophages seeding on the BRT-O scaffolds notably promoted the osteogenic lineage differentiation of BMSCs in vitro. The cell migration ability of BMSCs was significantly enhanced under the BRT-O-induced immune microenvironment. Moreover, in rat cranial critical-sized bone defect models, the BRT-O scaffolds group promoted new bone formation with a higher proportion of M2-type macrophage infiltration and expression of osteogenesis-related markers. Therefore, in vivo, BRT-O scaffolds play immunomodulatory roles in promoting critical-sized bone defects by enhancing the polarization of M2 macrophages.

Conclusion: 3D-printed BRT-O scaffolds can be a promising option for bone tissue engineering, at least partly through macrophage polarization and osteoimmunomodulation.

© 2023 Xuan et al.

In plain English

This study is not about asbestos. The authors 3D-printed ordered scaffolds (BRT-O) of bredigite, a calcium magnesium silicate ceramic, and compared them with randomly structured bredigite scaffolds (BRT-R) and β-tricalcium phosphate (β-TCP) scaffolds. BRT-O had the highest compressive strength: more than 30 MPa, against 20 to 25 MPa for BRT-R and about 5 MPa for β-TCP. Mouse macrophages grown on BRT-O shifted toward the M2 type. Mouse bone marrow stem cells showed more bone-forming activity in fluid from macrophages cultured on BRT-O, and migrated more in a two-chamber test with macrophages on BRT-O. The authors then made 5-mm skull defects in 48 male rats. At 12 weeks, both bredigite groups showed well-integrated new bone; the β-TCP group showed limited bone formation. New bone amounts differed significantly between BRT-O and BRT-R at 6 and 12 weeks; at 12 weeks, BRT-O new bone covered the defect center. At one week, more M2 macrophages had gathered around the defect in the BRT-O group. The authors concluded that BRT-O scaffolds can be a promising option for bone tissue engineering and that further studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (cell culture) experiments and an animal experiment in rats
• Who was studied: The study used three sources. The first was a mouse macrophage cell line (RAW 264.7). The second was bone marrow stem cells taken from male C57BL/6N mice. The third was 48 male Sprague-Dawley rats aged 8 to 10 weeks, randomly divided into 4 groups (blank, β-TCP, BRT-R, BRT-O). The animal work was approved by an ethics committee at the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China. The article gives no study dates.
• Exposure: No asbestos was studied. Three materials were tested: 3D-printed ordered bredigite (Ca7MgSi4O16) scaffolds (BRT-O), randomly structured bredigite scaffolds (BRT-R), and β-tricalcium phosphate (β-TCP) scaffolds as a control. In the rats, these were implanted into 5-mm diameter defects in the skull (parietal bone).
• Main results:
  • Compressive strength was more than 30 MPa for the BRT-O scaffold, 20 to 25 MPa for the BRT-R scaffold, and about 5 MPa for the β-TCP scaffold.
  • After soaking in Tris solution for six weeks, BRT-O and BRT-R lost 20% of their weight, compared with less than 5% for β-TCP.
  • In cell culture, BRT-O scaffolds stimulated mouse macrophages to shift toward the M2 phenotype.
  • The stem-cell tests worked through macrophages. Bone marrow stem cells were cultured in medium taken from macrophages grown on each scaffold.
  • In a two-chamber (Transwell) test, macrophages were placed on the scaffolds in the lower chamber. Bone marrow stem cells in the upper chamber migrated through the membrane more in the BRT-O group.
  • In bone marrow stem cells cultured with macrophage-conditioned medium, ALP activity and mineral nodule formation were markedly enhanced in the BRT-O group.
  • In rats at 12 weeks (n=4 per group for imaging and histology), the BRT-R and BRT-O groups showed well-integrated new bone growing into the scaffolds.
  • The quantity of new bone (toluidine blue staining) differed significantly between the BRT-R and BRT-O groups at weeks 6 and 12.
  • At week 12, H&E staining showed a considerable amount of new bone in the BRT-O group, completely covering the defect center, compared with the other three groups.
  • In rats, the β-TCP group showed only limited, scattered bone formation in the defect.
  • At one week after surgery, the BRT-R group had markedly more M1 macrophages and fewer M2 macrophages. The BRT-O group had more M2 macrophages gathering around the defect than the other groups.
• The authors' conclusion: The authors concluded that 3D-printed BRT-O scaffolds can be a promising option for bone tissue engineering, through macrophage polarization and osteoimmunomodulation.
• Limitations the authors state:
  • The authors stated that further experiments and clinical studies are still needed to explore how the material's structure acts and to establish the clinical usability of BRT-O materials.
  • Because macrophages pass through multiple intermediate states, the authors stated that sequencing technology could determine polarization more accurately in further studies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Tremolite.

Medical terms in this study, explained in our Lexicon: Macrophage, STEM.

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