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Introduction: Scaffolds loaded with antibacterial agents and osteogenic drugs are considered essential tools for repairing bone defects caused by osteomyelitis. However, the simultaneous release of two drugs leads to premature osteogenesis and subsequent sequestrum formation in the pathological situation of unthorough antibiosis. Objectives: In this study, a spatiotemporal drug-release polydopamine-functionalized mesoporous silicon nanoparticle (MSN) core/shell drug delivery system loaded with antibacterial silver (Ag) nanoparticles and osteogenic dexamethasone (Dex) was constructed and introduced into a poly-l-lactic acid (PLLA) scaffold for osteomyelitis therapy. Methods: MSNs formed the inner core and were loaded with Dex through electrostatic adsorption (MSNs@Dex), and then polydopamine was used to seal the core through the self-assembly of dopamine as the outer shell (pMSNs@Dex). Ag nanoparticles were embedded in the polydopamine shell via an in situ growth technique. Finally, the Ag-pMSNs@Dex nanoparticles were introduced into PLLA scaffolds (Ag-pMSNs@Dex/PLLA) constructed by selective laser sintering (SLS). Results: The Ag-pMSNs@Dex/PLLA scaffold released Ag+ at the 12th hour, followed by the release of Dex starting on the fifth day. The experiments verified that the scaffold had excellent antibacterial performance against Escherichia coli and Staphylococcus aureus. Moreover, the scaffold significantly enhanced the osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Conclusion: The findings suggested that this spatiotemporal drug release scaffold had promising potential for osteomyelitis therapy.

Abstract Background Fe3O4 nanoparticles are highly desired for constructing endogenous magnetic microenvironment in scaffold to accelerate bone regeneration due to their superior magnetism. However, their random arrangement easily leads to mutual consumption of magnetic poles, thereby weakening the magnetic stimulation effect. Methods In this study, magnetic nanochains are synthesized by magnetic-field-guided interface co-assembly of Fe3O4 nanoparticles. In detail, multiple Fe3O4 nanoparticles are aligned along the direction of magnetic force lines and are connected in series to form nanochain structures under an external magnetic field. Subsequently, the nanochain structures are covered and fixed by depositing a thin layer of silica (SiO2), and consequently forming linear magnetic nanochains (Fe3O4@SiO2). The Fe3O4@SiO2 nanochains are then incorporated into poly l-lactic acid (PLLA) scaffold prepared by selective laser sintering technology. Results The results show that the Fe3O4@SiO2 nanochains with unique core–shell structure are successfully constructed. Meanwhile, the orderly assembly of nanoparticles in the Fe3O4@SiO2 nanochains enable to form magnetic energy coupling and obtain a highly magnetic micro-field. The in vitro tests indicate that the PLLA/Fe3O4@SiO2 scaffolds exhibit superior capacity in enhancing cell activity, improving osteogenesis-related gene expressions, and inducing cell mineralization compared with PLLA and PLLA/Fe3O4 scaffolds. Conclusion In short, the Fe3O4@SiO2 nanochains endow scaffolds with good magnetism and cytocompatibility, which have great potential in accelerating bone repair.

The repair of segmental bone defects caused by traumatic injury or pathological diseases remains a substantial challenge in clinic. Poly-l-lactic acid (PLLA) is recognized as one potential bone substitute material due to its natural biodegradability and excellent biocompatibility. Nevertheless, it still faces several fundamental puzzles including insufficient mechanical properties, slow degradation and poor osteogenic activity. To address these issues, the corresponding strategies were thoroughly explored in this review. Regulation of molecular weight and crystallization, as well as the control of crack propagation were the mainstream methods to improve the mechanical properties of PLLA, whereas surface medication and polymer blending was commonly adopted to regulate the degradation behavior. To achieve desirable tissue regeneration ability, the combination of physical stimulation (electric and magnetic) brings about a new and attractive solution, since it is able to mimic the electro-magnetic microenvironment of human body. Furthermore, future research directions are proposed from the prospects of fabrication process, dynamic degradation and multifunctional application. This review aims to offer deep insights and meaningful guidelines for future study of PLLA as implants.

Poly l-lactic acid (PLLA) was limited in the further orthopaedic application due to its insufficient mechanical property and poor bioactivity. Graphene oxide (GO) is an effective reinforcement, whereas silicon-doped hydroxyapatite (Si-HA) possesses excellent bioactivity, but either GO or Si-HA tends to aggregate in PLLA matrix. In this study, a GO@Si-HA nanosystem was achieved by in-situ growth of Si-HA on GO, and then incorporated into PLLA scaffold fabricated by laser sintering technology. On one hand, Si-HA on the surface of GO effectively prevented the aggregation of GO by acting as a barrier between GO nanosheets. On the other hand, GO hindered the aggregation of Si-HA by means of anchoring Si-HA. Results displayed that the compressive strength and modulus of the PLLA/GO@Si-HA composite scaffold were enhanced by 85% and 120%, respectively. Meanwhile, the scaffold exhibited significantly improved bioactivity, and consequently promoted cell adhesion, proliferation and differentiation. The developed PLLA/GO@Si-HA composite scaffold with excellent mechanical properties and superior bioactivity could serve as a promising substitute for bone repairing.

Polyvinylidene fluoride (PVDF), as a typical piezoelectric polymer, has a great potential in reconstructing the electrical microenvironment of bone tissue. In present study, graphene oxide (GO) was introduced into PVDF scaffold manufactured via selective laser sintering, aiming to enhance piezoelectric effect of PVDF by increasing β phase content. In detail, the oxygen-containing functional groups of GO could form strong hydrogen bonding with fluorine groups of PVDF. The interaction would force the fluorine groups to be arranged in parallel and perpendicular to the polymer chain, thereby inducing the transformation from α phase to β phase. Results demonstrated that the PVDF/0.3GO scaffold with improved β phase exhibited the maximal output voltage (~8.2 V) and current (~101.6 nA), which were improved by 82.2% and 68.2%, respectively, in comparison with pure PVDF. In vitro cell culture confirmed that enhanced electrical charges could significantly improve cell behavior. Moreover, the scaffold presented a 97.9% increase in compressive strength and 24.5% increase in tensile strength, which was attributed to GO reinforcements forming strong interaction with PVDF chains. These positive results suggested that the scaffold might have possible application in bone tissue engineering. Keywords: Bone regeneration, Piezoelectric, Polyvinylidene fluoride, Graphene oxide, Selective laser sintering