Switching On and Off Macrophages by a “Bridge-Burning” Coating Improves Bone-Implant Integration under Osteoporosis

Osteoporosis poses substantial challenges for biomaterials implantation. New approaches to improve bone-implant integration should resolve the fundamental dilemma of inflammation—proper inflammation is required at early stages but should be suppressed later for better healing, especially under osteoporosis. However, precisely switching on and off inflammation around implants in vivo remains unachieved. To address this challenge, a “bridge-burning” coating material that comprises a macrophage-activating glycan covalently crosslinked by a macrophage-eliminating bisphosphonate to titanium implant surface is designed. Upon implantation, the glycan instructs host macrophages to release pro-osteogenic cytokines (“switch-on”), promoting bone cell differentiation. Later, increasingly mature bone cells secrete alkaline phosphatase to cleave the glycan-bisphosphonate complexes from the implant, which in turn selectively kill the proinflammatory macrophages (“switch-off”) that have completed their contribution—hence in the manner of “burning bridges”—to promote healing. In vivo examination in an osteoporotic rat model demonstrates that this coating significantly enhances bone-implant integration (88.4% higher contact ratio) through modulating local inflammatory niches. In summary, a bioresponsive, endogenously triggered, smart coating material is developed to sequentially harness and abolish the power of inflammation to improve osseointegration under osteoporosis, which represents a new strategy for designing immunomodulatory biomaterials for tissue regeneration.     

Self-Tandem Bio-Heterojunctions Empower Orthopedic Implants with Amplified Chemo-Photodynamic Anti-Pathogenic Therapy and Boosted Diabetic Osseointegration

Hyperglycemic microenvironment in diabetes mellitus inevitably stalls the normal orchestrated course of bone regeneration and encourages pathogenic multiplication. Photodynamic therapy (PDT) and chemo-dynamic therapy (CDT) are extensively harnessed to combat pathogens, yet deep-seated diabetic bone defect has difficulty in supplying sufficient oxygen (O₂) and hydrogen peroxide (H₂O₂) stocks, resulting in inferior therapeutic efficiency. To address the tough plaguing, the self-tandem bio-heterojunctions (bio-HJs) consisting of molybdenum disulfide (MoS₂), graphene oxide (GO), and glucose oxidase (GOx) are constructed on orthopedic polyetheretherketone (PEEK) implants (SP-Mo/G@GOx) for amplified chemo-photodynamic anti-pathogenic therapy and boosted osseointegration in the deep-seated diabetic micromilieu. In this system, GOx exhausts glucose to generate H₂O₂, which provides an abundant stock for CDT. Besides, the bio-HJs produce hyperthermia upon near-infrared light (NIR) to accelerate the dynamic process, which amplifies the antibacterial potency of PDT by promoting the vast yield of singlet oxygen (¹O₂) in a self-tandem manner. More importantly, in vivo and in vitro assays demonstrate that the engineered implants exert a captivated bactericidal ability and significantly boost osseointegration in an infectious diabetic bone defect model. As envisaged, this study furnishes a novel tactic to arm orthopedic implants with self-tandem capability for the remedy of infectious diabetic bone defects.     

Hydrophobic Coating Platforms for High-Efficiency Loading and Direct Transmembrane Delivery of Fat-Soluble Osteogenic Drug for Enhanced Osseointegration of Titanium Implants

Compared with water-soluble osteogenic drugs, fat-soluble osteogenic drugs exhibit higher bioavailability and drug stability, making them valuable for enhancing the osseointegration of implants. However, existing drug-loading coatings are primarily designed for water-soluble drugs, limiting their effectiveness in loading and delivering fat-soluble osteogenic drugs. This study employed alkali treatment, silanization, and oleic acid acylation to sequentially modify the surface of Ti alloy, aiming to fabricate surfaces capable of efficiently loading and delivering fat-soluble osteogenic drugs. Results show that the hydrophilicity and loading capacity of fat-soluble osteogenic drugs strongly depended on the duration of the acylation treatment. Furthermore, the drug release mechanism involved direct diffusion from the coating to the cells in contact, resulting in improved bioavailability, as opposed to diffusion into the surrounding medium and subsequent cellular uptake. In vitro experiments using vitamine D3 (VD₃) as a model drug confirmed that the coating effectively promoted bone formation through the highly efficient delivery of VD₃. Furthermore, in vivo experiments demonstrated that the VD₃-loaded lipophilic surface significantly enhanced osteogenic capability and improved the osseointegration of titanium implants. This study provides a promising strategy for loading fat-soluble drugs onto Ti implants and direct experimental evidence demonstrating the significant value of fat-soluble drugs in promoting implant osseointegration.     

Physico-chemical properties and healing capacity of potentially bioactive titanium surface

The aim of this study was to evaluate physico-chemical properties and the healing capacity of surface treated titanium. Surface treatment combining sand-blasting, acid etching and alkaline etching (BIO surface) was evaluated together with machined titanium as a reference surface. Hydration, wetting angle, surface area and roughness parameters were evaluated for both surfaces. Stability of dental implants with both surfaces implanted in the tibia of dog was measured during the healing of twelve weeks. BIO surface exhibited lower wetting angle, larger surface area, higher degree of hydration and higher average roughness compared to machined titanium. Implants with the BIO surface maintained their stability during the whole healing period in contrast to those with machined titanium surface, which showed a statistically significant decrease in stability three and nine weeks after implantation.     

Biomimetic Mineralized Fiber Bundle-Inspired Scaffolding Surface on Polyetheretherketone Implants Promotes Osseointegration

The stress shielding effect caused by traditional metal implants is circumvented by using polyetheretherketone (PEEK), due to its excellent mechanical properties; however, the biologically inert nature of PEEK limits its application. Endowing PEEK with biological activity to promote osseointegration would increase its applicability for bone replacement implants. A biomimetic study is performed, inspired by mineralized collagen fiber bundles that contact bone marrow mesenchymal stem cells (BMMSCs) on the native trabecular bone surface. The PEEK surface (P) is first sulfonated with sulfuric acid to form a porous network structure (sP). The surface is then encapsulated with amorphous hydroxyapatite (HA) by magnetron sputtering to form a biomimetic scaffold that resembles mineralized collagen fiber bundles (sPHA). Amorphous HA simulates the composition of osteogenic regions in vivo and exhibits strong biological activity. In vitro results show that more favorable cell adhesion and osteogenic differentiation can be attained with the novelsurface of sPHA than with SP. The results of in vivo experiments show that sPHA exhibits osteoinductive and osteoconductive activity and facilitates bone formation and osseointegration. Therefore, the surface modification strategy can significantly improve the biological activity of PEEK, facilitate effective osseointegration, and inspire further bionic modification of other inert polymers similar to PEEK.     

Built‐In Electric Fields Dramatically Induce Enhancement of Osseointegration

Rapid and effective osseointegration is a great challenge in clinical practice. Endogenous electronegative potentials spontaneously appear on bone defect sites and mediate healing. Thus, bone healing can potentially be stimulated using physiologically relevant electrical signals in implants. However, it is difficult to directly introduce physiologically relevant electric fields in bone tissue. In this study, built‐in electric fields are established between electropositive ferroelectric BiFeO₃ (BFO) nanofilms and electronegative bone defect walls to trigger implant osseointegration and biological healing. Epitaxial growth technique is used to organize the crystal panel at an atomic scale, and ferroelectric polarization of BFO nanofilms matching the amplitude and direction of endogenous electric potentials on bone defect walls is achieved. In the presence of built‐in electric fields, implants with BFO nanofilms with downward polarization (BFO+) show rapid and superior osseointegration in the rat femur. The mechanism of this phenotypic osteogenic behavior is further studied by protein adsorption and stem cell behavior in different time points. BFO+ promotes protein adsorption and mesenchymal stem cell (MSC) attachment, spreading, and osteogenic differentiation. Custom‐designed PCR array examination shows sequentially initiated Ca²⁺ signaling, cell adhesion and spreading, and PI3K‐AKT signaling in MSCs. The results of this study provide a novel strategy for the development of implant surface modification technology.     

On the Future Design of Bio‐Inspired Polyetheretherketone Dental Implants

Polyetheretherketone (PEEK) is a promising implant material because of its excellent mechanical characteristics. Although this polymer is a standard material in spinal applications, PEEK is not in use in the manufacturing of dental implants, where titanium is still the most‐used material. This may be caused by its relative bio‐inertness. By the use of various surface modification techniques, efforts have been made to enhance its osseointegrative characteristics to enable the polymer to be used in dentistry. In this feature paper, the state‐of‐the‐art for dental implants is given and different surface modification techniques of PEEK are discussed. The focus will lie on a covalently attached surface layer mimicking natural bone. The usage of such covalently anchored biomimetic composite materials combines many advantageous properties: A biocompatible organic matrix and a mineral component provide the cells with a surrounding close to natural bone. Bone‐related cells may not recognize the implant as a foreign body and therefore, may heal and integrate faster and more firmly. Because neither metal‐based nor ceramics are ideal material candidates for a dental implant, the combination of PEEK and a covalently anchored mineralized biopolymer layer may be the start of the desired evolution in dental surgery.     

The Role of Epigenetic Functionalization of Implants and Biomaterials in Osseointegration and Bone Regeneration—A Review

The contribution of epigenetic mechanisms as a potential treatment model has been observed in cancer and autoimmune/inflammatory diseases. This review aims to put forward the epigenetic mechanisms as a promising strategy in implant surface functionalization and modification of biomaterials, to promote better osseointegration and bone regeneration, and could be applicable for alveolar bone regeneration and osseointegration in the future. Materials and Methods: Electronic and manual searches of the literature in PubMed, MEDLINE, and EMBASE were conducted, using a specific search strategy limited to publications in the last 5 years to identify preclinical studies in order to address the following focused questions: (i) Which, if any, are the epigenetic mechanisms used to functionalize implant surfaces to achieve better osseointegration? (ii) Which, if any, are the epigenetic mechanisms used to functionalize biomaterials to achieve better bone regeneration? Results: Findings from several studies have emphasized the role of miRNAs in functionalizing implants surfaces and biomaterials to promote osseointegration and bone regeneration, respectively. However, there are scarce data on the role of DNA methylation and histone modifications for these specific applications, despite being commonly applied in cancer research. Conclusions: Studies over the past few years have demonstrated that biomaterials are immunomodulatory rather than inert materials. In this context, epigenetics can act as next generation of advanced treatment tools for future regenerative techniques. Yet, there is a need to evaluate the efficacy/cost effectiveness of these techniques in comparison to current standards of care.