Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model

Abstract

We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 μm and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, β-tricalcium phosphate (β-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the biocompatibility, bone repairing capacity and degradation in three different bone substitute materials were estimated using a critical-size rat calvarial defect model in vivo. The defects were evaluated by micro-computed tomography and histological analysis at four and eight weeks after surgery, respectively. The results showed that each of the studied scaffolds had its own specific merits and drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good biocompatibility and stimulated BMSC cell proliferation and differentiation to osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds had good osteogenic capability and biodegradation activity with no difference in inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential applications in bone tissue engineering and may be used as graft substitutes in reconstructive surgery.

Characterization of printed PLA scaffolds for bone tissue engineering

“…Possible changes of PLA properties after gamma‐radiation sterilization were not studied here but the biocompatibility of sterilized PLA printed scaffolds was evaluated. Previous studies showed that PLA degradation releases acidic monomers (lactic acid) that cause inflammation and this property could affect cell attachment and behavior . However, lactic acid is present in the human body and is removed by natural metabolic pathways .…”

“…Several techniques have been developed for AM such as stereolithography (SLA), selective laser sintering (SLS), three‐dimensional printing (3DP), fused deposition modeling (FDM) for the production of custom, defect‐matched constructs for bone repair . FDM is the most commonly used technique in which the material, a filament, is melted, extruded and deposited to generate a three‐dimensional structure in a layer‐by‐layer fashion with the benefit of controlling both the porosity and the pore size . Another advantage of FDM technology is the ease to associate cells with these thin polymeric scaffolds resulting in a better cell colonization, proliferation and differentiation compared with a larger 3D structure which often includes an inner hypoxic central area, which prevents deep cell colonization.…”

3D printed polymer–mineral composite biomaterials for bone tissue engineering: Fabrication and characterization

“…PCL was the most used polymer as it was found in 29 articles . PLA was used in 13 studies and PLGA in 14 studies . Polyethylene glycol (PEG) was also used in six studies but not as major polymer: it was mixed with PLA, PCL, or with polyoxyethylene terephthalate and polybutylene terephthalate (PEOT/PBT) .…”

Concise Review: Bioprinting of Stem Cells for Transplantable Tissue Fabrication

“…In vivo study of 3D‐printed polylactic acid/HA scaffolds seeded with BMSCs showed they have good osteogenic capability with no difference in inflammation (Fig. B) .…”