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3D printed gene-activated implants for bone regeneration
contraindications, a considerable duration of the capacity required to restore large bone defects that
intervention, and post-surgery rehabilitation . are characterized by “osteogenic insufficiency” .
[9]
[2]
This creates a strong need for acceptable Cells and growth factors are most actively
alternative of bone autografts in clinical practice. employed osteoinducing factors for 3D printed
Biodegradable implants possesing chemical scaffolds . However, cells require oxygenation
[10]
composition, structure, osteoconductive and that limits their possible use in creating
osteoinductive potential corresponding to native personalized tissue engineering constructions or
bone, with shape and sizes exactly conforming bioactive implants of large sizes, whereas growth
to the parameters of substitute for specific bone factors are short-lived and short-distant . Gene-
[9]
defect could become such an alternative. In activated materials are devoid of these drawbacks,
addition, a personalized bone substitute should though the delivery of gene constructs in the
have optimal biomechanical properties allowing safest, a non-viral, variant is “Achilles heel” of the
at least its stable fixation in situ with standard, for approach .
[9]
example, metal constructions. In this study, based on our previous experience
Three-dimensional (3D) printing techniques in 3D printing of OCP bone substitutes [11,12] ,
that facilitate development of custom-made considering the critical role of angiogenesis
medical devices are the most promising approach for reparative osteogenesis, we hypothesized
to solve the problems in personalized bone that deposition of plasmid DNA carrying a
reconstruction. However, in selecting the material gene of vascular endothelial growth factor
for 3D printing, scientists frequently make their (pDNA-VEGFA), as an active substance of the
decision based on technical feasibility of additive “Neovasculgen” drug (developed and certified
manufacturing with a high spatial resolution rather for clinical applications by HSCI, Russia) , into
[13]
than on the potential of a biomaterial to actually custom-made OCP-based 3D printed implants
improve reparative osteogenesis. Therefore, some would make it effective in large bone defect
polymer materials such as polycaprolactone and substitution and guided bone regeneration.
[3]
polylactic-co-glycolic acid , which are greatly
[4]
suitable for 3D printing including that associated 2 Experimental method
with addition of biologically active components
(living cells, growth factors, etc.), but less effective 2.1 Materials
for bone grafting are taken often. On the other
[5]
hand, natural and synthetic analogues of bone Initial tricalcium phosphate (TCP) powder was
matrix components with optimal biomechanical produced in an aqueous medium by slowly
properties show that osteoconduction and adding diammonium phosphate ((NH ) HPO )
4
4 2
biodegradable property through the release of solution into calcium nitrate (Ca(NO ) 4H O)
3 2
2
components that cells can utilize to produce solution, containing NH OH. Fraction of TCP
4
and mineralize the intercellular matrix are more agglomerated particles with mean size in diameter
appropriate for bone regeneration . For instance, 40 – 80 μm was selected as a row material for all
[6]
octacalcium phosphate (OCP) has optimal further experiments. 1.0% aqueous solution of
osteoconductive properties and biodegradation salts of phosphoric acid (pH value equals 4.75)
[11]
rate. It is a precursor of natural mineral component was utilized as “ink” for 3D printing . All used
of the bone matrix , and it stimulates differentiation reagents were ordered and received from Sigma-
[7]
of multipotent mesenchymal stromal cells to Aldrich (USA).
osteogenic lineage . However, it is very difficult 2.2 3D printing
[8]
to achieve a high spatial resolution in 3D printing
of ceramic implants, and the problem becomes 3D printed samples were made under a previously
even more irresistible if some biologically active modified printing algorithm of ceramic
components are needed to enhance osteoinductive constructions described elsewhere in details .
[12]
94 International Journal of Bioprinting (2020)–Volume 6, Issue 3