The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine

Abstract

Background Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scaffolds to promote bone regeneration. Methods In this study, a porous piezoelectric hydrogel bone scaffold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO3, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scaffold with 0–10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scaffold in vitro and in vivo. Results The incorporation of BaTiO3 into the scaffold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the as-prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization. Conclusion The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat effectiveness in grassroots troops.

A parathyroid hormone related supramolecular peptide for multi-functionalized osteoregeneration

“…Angiogenesis is important for bone regeneration because of oxygen and nutrient transportation by neoformative blood vessels [ [59] , [60] , [61] ]. It has been reported that the administration of intermittent PTH1-34 promoted vascularization in fracture callus [ 62 ].…”

Can self-powered piezoelectric materials be used to treat disc degeneration by means of electrical stimulation?

“…Piezoelectric ceramics such as lead zirconate titanate, barium titanate (BT), zinc oxide, potassium potassium niobate, hydroxyapatite (HA), sodium lithium niobate, and boron nitride nanotubes have significant advantages in terms of piezoelectric coefficients, but what deserves the attention of all researchers is that piezoelectric ceramics continue to release various types of ions within biological fluids, and these ions can produce varying degrees of cytotoxicity ( Rajabi et al, 2015 ; Tandon et al, 2018 ). After doping with 10% BT and 10% HA, an output voltage of 0.8 V can be detected on the hydrogel film ( Wu et al, 2023 ). Moreover, due to the non-degradability and high elastic modulus of piezoelectric ceramic-based tissue engineering scaffolds, most of these materials are doped into various types of polymers or ceramics in the form of piezoelectric particles in order to utilize their excellent piezoelectric properties ( Baxter et al, 2009 ; Bagchi et al, 2014 ).…”

Electrical Stimulation for Immunomodulation

“…Results from in vivo subcutaneous and femoral condyle implantation models revealed reduced expression of iNOS and increased expression of CD206 cells, thus confirming the piezoelectric generated electric field mediated macrophage polarization from M1 to M2. Similarly, Wu et al in 2023 prepared the self-powered piezoelectric nanogenerator (PENG) based on PDA-modified BaTiO 3 nanoparticles into a chitosan/gelatin (Cs/Gel) matrix which generated 0.8 V under 1 kPa pressure and resulted in M2 polarization for enhancing bone regeneration …”