Micro-nanostructured Scaffolds for Bone Regeneration and Drug Delivery

Objectives: In the present study, a three-dimensional (3D) interconnected scaffolds based on the combination of poly(ε-caprolactone) (PCL), nanohydroxyapatite (nHAp), and Humulus lupulus L. extract (hop) for bone regeneration were fabricated. Fused deposition modeling (FDM) and electrospinning were assembled to develop 3D bimodal constructs. Herein, we incorporate hop extract (as antibacterial agent) and nHAp into PCL fibers fabricated by electrospinning. The polymer, ceramic and natural extract combination allowed for the preparation of three-dimensional scaffolds that provide a delivery system to release the antimicrobial compounds from hop extract, improving the osteogenic properties of the nHAp, while at the same time preserved the mechanical strength of PCL.

Methods: For investigating morphology and scaffold compounds, scanning electron microscopy (SEM) and Fourier transform infrared techniques (FTIR) were used. The mechanical and thermogravimetric properties, water absorption and degradability in phosphate buffered saline (PBS) were investigated. Antimicrobial activity against oral pathogens were also evaluated. Furthermore, MC3T3-E1 pre-osteoblasts were used to determine the potential osteogenic properties of the PCL bimodal scaffolds.
Results: The results of the physical and mechanical properties demonstrated that the obtained scaffolds displayed a porous interconnected microstructure. The modulus of tensile strengths were of 20.18±0.7 MPa and compression strength of 5.35 MPa. Contact angle measurement results showed that the developed scaffolds presented hydrophilic properties after nHAp and hop extract addition. Hop loaded samples also presented bacteria growth inhibition ability against P. gingivalis and A. actinomycetemcomitans, proving that its antimicrobial activity was not degraded during the fabrication process.
In vitro biocompatibility evaluation with MC3T3-E1 pre-osteoblastic cell line showed enhanced cell proliferation in the PCL-nHAp-hop extract scaffold by MTT assay.

Conclusions: The combination of different materials and fabrication processes, the antimicrobial activity, mechanical properties, and osteogenic properties of the fabricated PCL-nHAp-hop scaffolds highlight their potential for bone tissue engineering.