Lingzhou Zhao

Conventional titanium implants often exhibit limited bioactivity, failing to adequately modulate the immune response and promote endogenous regeneration, which leads to suboptimal osseointegration. To address this, we developed a multifunctional implant (NTP/Apt-VPA) by conjugating Apt19s—an mesenchymal stem cell (MSC)-specific aptamer—with valproic acid (VPA), anchored onto a polydopamine-coated TiO₂ nanotubular surface. The NTP/Apt-VPA implant demonstrated exceptional capabilities in scavenging reactive oxygen species, programming macrophages toward the regenerative M2 phenotype, and enhancing the recruitment and osteogenic differentiation of MSCs. Through comprehensive in vitro and in vivo assessments, as well as RNA sequencing analysis, we observed that the modified implant was associated with accelerated early inflammation resolution, enhanced stem cell homing, and activation of key osteogenic pathways, including PI3K/AKT and MAPK signaling. This study presents a bioengineering strategy that aims to synchronize immunomodulation with osteogenesis through an Apt19s-VPA conjugate, which may offer a promising platform for enhancing implant osseointegration.

Oral bone defects are frequently complicated by concurrent soft tissue loss, posing significant challenges for their simultaneous regeneration during guided bone regeneration (GBR). In this study, a biomimetic bilayer GBR membrane repaired both hard and soft tissues was developed by integrating an acellular dermal matrix (ADM) with an electrospun piezoelectric layer composed of poly-(L-lactic acid)-chitosan-polydopamine (PLLA-CS-PDA). The ADM component was prepared through detergent-nuclease decellularization with its dense epidermal surface oriented toward the soft tissue to provide barrier protection, while the porous PLLA-CS-PDA layer faced the bone defect to support osteogenesis. The PLLA-CS-PDA-ADM (PCPA) membrane exhibited distinct microstructural features on each side, along with favorable hydrophilicity and stable piezoelectric characteristics. In vitro, the PCPA membrane exhibited good cytocompatibility, which under ultrasound-triggered piezoelectric stimulation significantly enhanced bone marrow mesenchymal stem cells adhesion, migration, and osteogenic differentiation, as well as vascular endothelial cells migration and tube formation. In vivo, PCPA membrane facilitated concurrent regeneration of both bone and overlying soft tissue in a rat maxillary defect model. The PCPA bilayer membrane supports bone‑soft‑tissue repair through native‑structure biomimicry, providing an innovative solution for the simultaneous repair of oral bone and soft tissue defects and highlighting its potential a highly promising new composite material.

Conventional titanium implants often exhibit limited bioactivity, failing to adequately modulate the immune response and promote endogenous regeneration, which leads to suboptimal osseointegration. To address this, we developed a multifunctional implant (NTP/Apt-VPA) by conjugating Apt19s - an MSC-specific aptamer - with valproic acid (VPA), anchored onto a polydopamine-coated TiO2 nanotubular surface. The NTP/Apt-VPA implant demonstrated exceptional capabilities in scavenging reactive oxygen species, programming macrophages toward the regenerative M2 phenotype, and enhancing the recruitment and osteogenic differentiation of mesenchymal stem cells. Through comprehensive in vitro and in vivo assessments, as well as RNA sequencing analysis, we confirmed that the modified implant significantly accelerates early inflammation resolution, promotes stem cell homing, and activates key osteogenic pathways, including PI3K/Akt and MAPK signaling. This study presents a bioengineering strategy that synchronizes immunomodulation with osteogenesis, offering a promising platform for enhancing implant integration.

With the increasing aging population, more implants are being used in the body. However, these implants often fail, and they suffer from a lack of integration or proper function. Efforts have been made to generate implants by employing bioactive materials, adding cellular components, and integrating smart characteristics such as self‐healing properties. The vision is, however, to develop an implant that can mimic native tissues in their way of doing things, responding to challenges and remodeling. Such automated implants require the integration of advances made in various fields of science. Although early, there are good steps taken in this way, e.g., the development of stimuli‐responsive, self‐powering, self‐actuating, self‐healing, self‐regenerating, self‐aware implants. Attempts to combine more than one smart property into these implants are still at the beginning, e.g., the integration of such special characteristics requires a new set of skills and thinking, which presents new challenges that warrant exploration and investment. Such an implant evolution is expected to be in stages, where the first implant will be able to communicate with doctors and hospitals; then, in the next stage, with patients, and later, they will be independent, sense any disturbances and aberrations from normal early on, and correct themselves before damage becomes irreversible. This forward‐looking review looks at the research done thus far in this direction and efforts to assemble individual aspects of smart implants into multifunctional implants in the future. The stages of material, in vitro, and in vivo testing and clinical application, if any, are critically reviewed. In addition, the challenges facing the development of autonomous smart implants are discussed, and research directions and ideas are suggested.

Rationale: Spinal cord injury (SCI) leads to limited regenerative capacity and severe energy deficiency in the injury microenvironment. This study aimed to develop a biomimetic piezoelectric hydrogel system that could recapitulate the native tissue microenvironment while enabling wireless physical regulation for SCI repair.

Repairing large bone defects remains a significant clinical challenge. Stem cell is of great importance in bone regeneration, and periosteum is rich in periosteal stem cell, which has a great influence on repairing bone defects. Bioengineered periosteum with excellent biocompatibility and stem cell homing capabilities to promote bone regeneration is of great clinical significance. The E7 peptide (EPLQLKM), which exhibits a specific affinity for mesenchymal stem cells (MSCs), is beneficial for modulating cellular functions. In this study, a unique microporous structured carboxymethyl chitosan/sodium alginate membrane with a proper mass ratio is developed by the addition of Poloxam 407 （P407）, which is then functionalized with the E7 affinitive peptide. This membrane, characterized by its microporous structure and E7 peptide functionalization (CSSA/P/E), not only demonstrated favorable mechanical properties, enhanced hydrophilicity, satisfactory biodegradation profile, and excellent biocompatibility, but also synergistically enhanced MSCs recruitment. It is found to promote the proliferation, spreading, and osteogenic differentiation of MSCs in vitro and to accelerate early periosteal regeneration, bone matrix deposition, and vascularization in vivo, leading to effective regeneration of critical‐sized bone defects. Overall, this study presents a robust, cell and growth factor‐free strategy for bioengineering periosteum, offering a potential solution for the challenging large size bone defects.

In recent years, porous titanium (Ti) scaffolds with BaTiO₃ coatings have been designed to promote bone regeneration. However, the phase transitions of BaTiO₃ have been understudied, and their coatings have yielded low effective piezoelectric coefficients (EPCs < 1 pm/V). In addition, piezoelectric nanomaterials bring many advantages in eliciting cell-specific responses. However, no study has attempted to design a nanostructured BaTiO₃ coating with high EPCs. Herein, nanoparticulate tetragonal phase BaTiO₃ coatings with cube-like nanoparticles but different effective piezoelectric coefficients were fabricated via anodization combining two hydrothermal processes. The effects of nanostructure-mediated piezoelectricity on the spreading, proliferation, and osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (hJBMSCs) were explored. We found that the nanostructured tetragonal BaTiO₃ coatings exhibited good biocompatibility and an EPC-dependent inhibitory effect on hJBMSC proliferation. The nanostructured tetragonal BaTiO₃ coatings of relatively smaller EPCs (3 coatings promising for application on implant surfaces to promote osseointegration.