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3D Printable PLA/BG Composite In Vitro Evaluation
the PLA control, and 23 in the BG20 approach. In the Fundraising: Johannes Frank, Dirk Henrich, Nicolas
LPS approach (5 µg/mL), the expression of 31 mediators Söhling, Jonas Neijhoft, Andreas Blaeser
could be induced, including primary immune activators
such as TNF-α and chemokines such as CXCL8
(IL-8), CCL2 (MCP-1), CCL3 (MIP-1α), CCL20 References
(MIP-3α), and CXCL5 (ENA-78), which exert potent
chemoattractant and stimulatory effects on monocytes 1. Söhling N, Neijhoft J, Nienhaus V, et al., 2020, 3D-Printing
and/or granulocytes [61-65] . The factors induced in the of Hierarchically Designed and Osteoconductive Bone Tissue
PLA and BG20 approaches are part of cascades such as Engineering Scaffolds. Materials (Basel), 13:1836.
primary inflammatory, anti-inflammatory, chemotaxis, https://doi.org/10.3390/ma13081836
cell activation (growth, proliferation), complement, 2. Grémare A, Guduric V, Bareille R, et al., 2018,
angiogenesis, tissue repair, tissue remodeling, peptide
hormone, surface receptor, and other (transport, Characterization of Printed PLA Scaffolds for Bone Tissue
opsonization, proteolysis, and regulation) and are Engineering. J Biomed Mater Res Part A, 106:887–94.
similarly expressed compared to the medium control. https://doi.org/10.1002/jbm.a.36289
The lack of induction of strongly inflammatory cytokines, 3. Lam CX, Hutmacher DW, Schantz JT, et al., 2009, Evaluation
as observed in the LPS approach, suggests a good of Polycaprolactone Scaffold Degradation for 6 Months In
immunological compatibility of BG20. Whether this Vitro and In Vivo. J Biomed Mater Res A, 90:906–19.
assessment correlates with a low foreign body reaction, https://doi.org/10.1002/jbm.a.32052
in vivo remains to be analyzed in appropriate animal
experiments, for example, implantation of the material in 4. Shrivats AR, McDermott MC, Hollinger JO, 2014, Bone
subcutaneous pockets in the rat . Tissue Engineering: State of the Union. Drug Discov Today,
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5. Conclusion https://doi.org/10.1016/j.drudis.2014.04.010
The present study demonstrated that a 3D printable 5. Mehrpouya M, Vahabi H, Barletta M, et al., 2021,
material made of PLA with 20% BG content exhibits Additive Manufacturing of Polyhydroxyalkanoates
high cytocompatibility for MSC, probably supports OD, (PHAs) Biopolymers: Materials, Printing Techniques, and
and has a low and thus beneficial immunostimulatory Applications. Mater Sci Eng C, 127:112216.
potential. However, whether 3D-printed bone graft
substitutes made from this material support healing of https://doi.org/10.1016/j.msec.2021.112216
large bone defects needs to be determined in appropriate 6. Kalia VC, Singh Patel SK, Shanmugam R, et al., 2021,
in vivo experiments and additionally also depends on Polyhydroxyalkanoates: Trends and Advances Toward
factors such as scaffold design. Biotechnological Applications. Bioresour Technol,

Funding 326:124737.
https://doi.org/10.1016/j.biortech.2021.124737
This research was funded by RMU-Initiativfond 7. Eldesoqi K, Seebach C, Ngoc CN, et al., 2013, High
Forschung (Förderlinie 2). Calcium Bioglass Enhances Differentiation and Survival of

Conflict of interest Endothelial Progenitor Cells, Inducing Early Vascularization
in Critical Size Bone Defects. PLoS One, 8:e79058.
The authors declare no conflicts of interest.
https://doi.org/10.1371/journal.pone.0079058
Author contributions 8. Zhang J, Liu W, Schnitzler V, et al., 2014, Calcium Phosphate
Study Design: Dirk Henrich. Ulrike Ritz Cements for Bone Substitution: Chemistry, Handling and
Experiments: Shahed Al Zooghol, Eva Schätzlein, Mechanical Properties. Acta Biomater, 10:1035–49.
Nicolas Söhling https://doi.org/10.1016/j.actbio.2013.11.001
Analysis and visualization: Dirk Henrich, Shahed Al 9. Henriksen SS, Ding M, Juhl MV, et al., 2011, Mechanical
Zooghol, Nicolas Söhling Strength of Ceramic Scaffolds Reinforced with Biopolymers
Resources: Johannes Frank, Ingo Marzi, Edgar Dörsam, is Comparable to that of Human Bone. J Mater Sci Mater
Andreas Blaeser
Writing – original draft: Nicolas Söhling, Dirk Henrich Med, 22:1111–8.
Writing – review & editing: Eva Schätzlein, Nicolas https://doi.org/10.1007/s10856-011-4290-y
Söhling, Dirk Henrich, Johannes Frank, Ingo Marzi, 10. Wu C, Fan W, Zhou Y, et al., 2012, 3D-Printing of
Edgar Dörsam, Andreas Blaeser, Ulrike Ritz Highly Uniform CaSiO3 Ceramic Scaffolds: Preparation,

78 International Journal of Bioprinting (2022)–Volume 8, Issue 4