Enhanced Cell Osteogenesis and Osteoimmunology Regulated by Piezoelectric Biomaterials with Controllable Surface Potential and Charges

Abstract

Bone regeneration is a well-orchestrated process involving electrical, biochemical, and mechanical multiple physiological cues. Electrical signals play a vital role in the process of bone repair. The endogenous potential will spontaneously form on defect sites, guide the cell behaviors, and mediate bone healing when the bone fracture occurs. However, the mechanism on how the surface charges of implant potentially guides osteogenesis and osteoimmunology has not been clearly revealed yet. In this study, piezoelectric BaTiO3/β-TCP (BTCP) ceramics are prepared by two-step sintering, and different surface charges are established by polarization. In addition, the cell osteogenesis and osteoimmunology of BMSCs and RAW264.7 on different surface charges were explored. The results showed that the piezoelectric constant d33 of BTCP was controllable by adjusting the sintering temperature and rate. The polarized BTCP with a negative surface charge (BTCP−) promoted protein adsorption and BMSC extracellular Ca2+ influx. The attachment, spreading, migration, and osteogenic differentiation of BMSCs were enhanced on BTCP–. Additionally, the polarized BTCP ceramics with a positive surface charge (BTCP+) significantly inhibited M1 polarization of macrophages, affecting the expression of the M1 marker in macrophages and changing secretion of proinflammatory cytokines. It in turn enhanced osteogenic differentiation of BMSCs, suggesting that positive surface charges could modulate the bone immunoregulatory properties and shift the immune microenvironment to one that favored osteogenesis. The result provides an alternative method of synergistically modulating cellular immunity and the osteogenesis function and enhancing the bone regeneration by fabricating piezoelectric biomaterials with electrical signals.

Biomaterial scaffolds regulate macrophage activity to accelerate bone regeneration

“…In a previous study, the surface of titanium implants was modified with divalent cations and macrophage polarization toward the M2 phenotype was significantly enhanced ( Lee et al, 2016 ). Mao et al (2022) further evaluated the effect of material surface charge on macrophages and bone regeneration. Scaffold with positive surface charges significantly inhibited M1 polarization of macrophages and enhanced osteogenic differentiation of MSCs.…”

Electrical Stimulation for Immunomodulation

“…Among all energy sources, mechanical energy is widely available in our daily lives either from human motions such as walking and running or from nature such as water flow, vibrations, and so on. To harvest these mechanical energies, self-powered systems based on piezoelectric materials have been developed, which can generate electric fields in response to small mechanical deformations such as cell movements, body motions, or external stimulation, to regulate the membrane voltage and ion channel activity of immune cells. − Piezoelectric materials are noncentrosymmetric in nature, which undergo deformation when subjected to external force and lead to piezoelectric polarization, resulting in electric charge generation across the edges. Electrical stimulation based on piezoelectric materials such as poly- l -lactic acid (PLLA), barium titanate (BaTiO 3 ), polyvinylidene fluoride (PVDF), etc.…”

“…Moreover, an enhanced immunomodulatory effect was observed with positively charged piezoelectric materials compared to their negative counterparts. Mao et al in 2022 showed that positive charges on BaTiO 3 /β-TCP (BTCP) favored the transition of macrophages toward the M2 phenotype which reduced the local inflammatory response and facilitated osteogenesis. BTCP+ and BTCP– were developed by orienting the polarization in the opposite direction, and their surface potentials were measured to be +107 and −175 mV, respectively .…”

“…Mao et al in 2022 showed that positive charges on BaTiO 3 /β-TCP (BTCP) favored the transition of macrophages toward the M2 phenotype which reduced the local inflammatory response and facilitated osteogenesis. BTCP+ and BTCP– were developed by orienting the polarization in the opposite direction, and their surface potentials were measured to be +107 and −175 mV, respectively . The output current and voltage of the as-prepared BTCP films were 300 nA and 590 mV, respectively, which were like the endogenous electric fields.…”

Electroactive Materials Surface Charge Impacts Neuron Viability and Maturation in 2D Cultures

“…The use of electroactive materials and, in particular piezoelectric ones, for the electrical stimulation of cell cultures and tissues has been proposed. − Among them, poly­(vinylidene fluoride) (PVDF) and its co-polymers stand out due to their highest piezoelectric coefficient (d 33 ) and their possibility to be processed in a large variety of tailored morphologies and microstructures. , Depending on the processing conditions, semicrystalline PVDF can be obtained in five different crystalline phases, known as α, β, γ, ε, and δ, , being the β-phase the most electroactive one. In addition, the dipole moments of the β-phase PVDF can be aligned by the application of an electric field.…”