Design and development of 3D printed shape memory triphasic polymer-ceramic bioactive scaffolds for bone tissue engineering.

Scaffolds for bone tissue engineering require considerable mechanical strength to repair damaged bone defects. In this study, we designed and developed mechanically competent composite shape memory triphasic bone scaffolds using fused filament fabrication (FFF) three dimensional (3D) printing. Wollastonite particles (WP) were incorporated into the poly lactic acid (PLA)/polycaprolactone (PCL) matrix as a reinforcing agent (up to 40 wt%) to harness osteoconductive and load-bearing properties from the 3D printed scaffolds. PCL as a minor phase (20 wt%) was added to enhance the toughening effect and induce the shape memory effect in the triphasic composite scaffolds. The 3D-printed composite scaffolds were studied for morphological, thermal, and mechanical properties, in vitro degradation, biocompatibility, and shape memory behaviour. The composite scaffold had interconnected pores of 550 µm, porosity of more than 50%, and appreciable compressive strength (∼50 MPa), which was over 90% greater than that of the pristine PLA scaffolds. The flexural strength was improved by 140% for 40 wt% of WP loading. The inclusion of WP did not affect the thermal property of the scaffolds; however, the inclusion of PCL reduced the thermal stability. An accelerated in vitro degradation was observed for WP incorporated composite scaffolds compared to pristine PLA scaffolds. The inclusion of WP improved the hydrophilic property of the scaffolds, and the result was significant for 40 wt% WP incorporated composite scaffolds having a water contact angle of 49.61°. The triphasic scaffold exhibited excellent shape recovery properties with a shape recovery ratio of ∼84%. These scaffolds were studied for their protein adsorption, cell proliferation, and bone mineralization potential. The incorporation of WP reduced the protein adsorption capacity of the composite scaffolds. The scaffold did not leach any toxic substance and demonstrated good cell viability, indicating its biocompatibility and growth-promoting behavior. The osteogenic potential of the WP incorporated scaffolds was observed in MC3T3-E1 cells, revealing early mineralization in pre-osteoblast cells cultured in different WP incorporated composite scaffolds. These results suggest that 3D-printed WP reinforced PLA/PCL composite bioactive scaffolds are promising for load bearing bone defect repair.

Polycaprolactone-collagen nanofibers loaded with dexamethasone and simvastatin as an osteoinductive and immunocompatible scaffold for bone regeneration applications.

Physiological inflammation has been shown to promote bone regeneration; however, prolonged inflammation impedes the osteogenesis and bone repair process. To overcome the latter we aimed to develop a dual drug delivering nanofibrous scaffold to promote osteogenic differentiation of mesenchymal stromal cells (MSCs) and modulate the pro-inflammatory response of macrophages. The polycaprolactone (PCL)-collagen nanofibrous delivery system incorporating dexamethasone and simvastatin was fabricated by electrospinning process. The morphological analysis and mRNA, as well as protein expression of proinflammatory and anti-inflammatory cytokines in human monocytes (U937 cells), demonstrated the immunocompatibility effect of dual drug-releasing nanofibrous scaffolds. Nitric oxide estimation also demonstrated the anti-inflammatory effect of dual drug releasing scaffolds. The scaffolds demonstrated the osteogenic differentiation of adipose-derived MSCs by enhancing the alkaline phosphatase (ALP) activity and mineral deposition after 17 days of cell culture. The increased expression of Runt-related transcription factor-2 (RUNX-2) and osteocalcin at mRNA and protein levels supported the osteogenic potential of dual drug-loaded fibrous scaffolds. Hence, the results indicate that our fabricated nanofibrous scaffolds exhibit immunomodulatory properties and could be employed for bone regeneration applications after further in-vivo validation.