Engineering 3D degradable, pliable scaffolds toward adipose tissue regeneration; optimized printability, simulations and surface modification

Abstract

We present a solution to regenerate adipose tissue using degradable, soft, pliable 3D-printed scaffolds made of a medical-grade copolymer coated with polydopamine. The problem today is that while printing, the medical grade copolyesters degrade and the scaffolds become very stiff and brittle, being not optimal for adipose tissue defects. Herein, we have used high molar mass poly(L-lactide-co-trimethylene carbonate) (PLATMC) to engineer scaffolds using a direct extrusion-based 3D printer, the 3D Bioplotter®. Our approach was first focused on how the printing influences the polymer and scaffold’s mechanical properties, then on exploring different printing designs and, in the end, on assessing surface functionalization. Finite element analysis revealed that scaffold’s mechanical properties vary according to the gradual degradation of the polymer as a consequence of the molar mass decrease during printing. Considering this, we defined optimal printing parameters to minimize material’s degradation and printed scaffolds with different designs. We subsequently functionalized one scaffold design with polydopamine coating and conducted in vitro cell studies. Results showed that polydopamine augmented stem cell proliferation and adipogenic differentiation owing to increased surface hydrophilicity. Thus, the present research show that the medical grade PLATMC based scaffolds are a potential candidate towards the development of implantable, resorbable, medical devices for adipose tissue regeneration.

Bone regeneration in rat calvarial defects using dissociated or spheroid mesenchymal stromal cells in scaffold-hydrogel constructs

“…3D-printed PLATMC scaffolds were produced as described elsewhere [ 37 ]. Briefly, a 3D CAD model was designed using the Magics software integrated with a 3D-Bioplotter (both from EnvisionTEC, Gladbeck, Germany).…”

“…Briefly, a 3D CAD model was designed using the Magics software integrated with a 3D-Bioplotter (both from EnvisionTEC, Gladbeck, Germany). Granules of medical-grade PLATMC (RESOMER® LT-706-S 70:30, Evonik GmBh, Essen, Germany) were loaded into the printer cartridge (pre-heated to 220 °C), and rectangular sheets of three layers with an orientation of 0°–90°–0° were printed at 190 °C with an inner nozzle diameter of 400 μm and strand spacing of 0.7 mm [ 37 ]. Disc-shaped scaffolds measuring 5 mm × 1.2 mm were punched out and placed in 48-well plates.…”

“…Trimethylene carbonate (TMC) is a polymer which degrades via surface erosion; when combined with PLA (PLATMC), it stabilizes the PLA resulting in less hydrolysis and thereby less by-products and local pH alterations [ 35 ]. The suitability of PLATMC for producing 3D-printed scaffolds, which support MSC attachment, growth and differentiation, has recently been demonstrated [ 37 ].…”

Recent Advances in 3D Printing of Polyhydroxyalkanoates: A Review

“…The bioplotting gives the possibility to adjust the defined outer and inner structure of scaffolds, which facilitates to create tissues and organs according to particular requirements. This methodology is popular in the medical research for the fabrication of scaffolds based on different medical polymers, such as polylactides ( 63), gelatin ethacryloyl/polyethylene(glycol)diacrylate/alginate (64,65), poly(ε-caprolactone) (66), gelatin/alginate, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)/poly(ε-caprolactone) (62), poly(lactic acid)/poly(3-hydroxybutyrate) (67) and many others (68). The advantage is the possible combination of multiple materials in the same printing process.…”

Three dimensional porous scaffolds derived from collagen, elastin and fibrin proteins orchestrate adipose tissue regeneration

“…It acts as an initial natural scaffold for tissue regeneration and plays a vital role in cell-matrix interaction, inflammation, cell migration and wound healing. 4 , 14 , 15 The properties displayed by these natural polymers present in the ECM can impute its use also in adipose tissue engineering applications.…”