Ideal periosteum materials are required to participate
in a sequence
of bone repair-related physiological events, including the initial
immune response, endogenous stem cell recruitment, angiogenesis, and
osteogenesis. However, conventional tissue-engineered periosteal materials
have difficulty achieving these functions by simply mimicking the
periosteum via structural design or by loading exogenous stem cells,
cytokines, or growth factors. Herein, we present a novel biomimetic
periosteum preparation strategy to comprehensively enhance the bone
regeneration effect using functionalized piezoelectric materials.
The resulting biomimetic periosteum possessing an excellent piezoelectric
effect and improved physicochemical properties was prepared using
a biocompatible and biodegradable poly(3-hydroxybutyric acid-co-3-hydrovaleric acid) (PHBV) polymer matrix, antioxidized
polydopamine-modified hydroxyapatite (PHA), and barium titanate (PBT),
which were further incorporated into the polymer matrix to fabricate
a multifunctional piezoelectric periosteum by a simple one-step spin-coating
method. The addition of PHA and PBT dramatically enhanced the physicochemical
properties and biological functions of the piezoelectric periosteum,
resulting in improved surface hydrophilicity and roughness, enhanced
mechanical performance, tunable degradation behavior, and stable and
desired endogenous electrical stimulations, which is conducive to
accelerating bone regeneration. Benefiting from endogenous piezoelectric
stimulation and bioactive components, the as-fabricated biomimetic
periosteum demonstrated favorable biocompatibility, osteogenic activity,
and immunomodulatory functions in vitro, which not only promoted adhesion,
proliferation, and spreading as well as osteogenesis of mesenchymal
stem cells (MSCs) but also effectively induced M2 macrophage polarization,
thereby suppressing reactive oxygen species (ROS)-induced inflammatory
reactions. Through in vivo experiments, the biomimetic periosteum
with endogenous piezoelectric stimulation synergistically accelerated
the formation of new bone in a rat critical-sized cranial defect model.
The whole defect was almost completely covered by new bone at 8 weeks
post treatment, with a thickness close to that of the host bone. Collectively,
with its favorable immunomodulatory and osteogenic properties, the
biomimetic periosteum developed here represents a novel method to
rapidly regenerate bone tissue using piezoelectric stimulation.