Metal-Organic Framework-Based Nanomaterials for Regulation of the Osteogenic Microenvironment.

As the global population ages, bone diseases have become increasingly prevalent in clinical settings. These conditions often involve detrimental factors such as infection, inflammation, and oxidative stress that disrupt bone homeostasis. Addressing these disorders requires exogenous strategies to regulate the osteogenic microenvironment (OME). The exogenous regulation of OME can be divided into four processes: induction, modulation, protection, and support, each serving a specific purpose. To this end, metal-organic frameworks (MOFs) are an emerging focus in nanomedicine, which show tremendous potential due to their superior delivery capability. MOFs play numerous roles in OME regulation such as metal ion donors, drug carriers, nanozymes, and photosensitizers, which have been extensively explored in recent studies. This review presents a comprehensive introduction to the exogenous regulation of OME by MOF-based nanomaterials. By discussing various functional MOF composites, this work aims to inspire and guide the creation of sophisticated and efficient nanomaterials for bone disease management.

Apoptotic Extracellular Vesicles Derived from Human Umbilical Vein Endothelial Cells Promote Skin Repair by Enhancing Angiogenesis: From Death to Regeneration.

Purpose: The promotion of angiogenesis is an effective strategy for skin wound repair. While the transplantation of endothelial cells has shown promise in vascularization, the underlying mechanism remains unclear. Recent studies have suggested that transplanted cells undergo apoptosis in a short period and release apoptotic extracellular vesicles (ApoEVs) that may have therapeutic potential. Methods: In this study, we isolated ApoEVs from human umbilical vein endothelial cells (HUVECs) and characterized their properties. In vitro, we assessed the effects of ApoEVs on the proliferation, migration, and differentiation of endothelial cells and fibroblasts. In vivo, we investigated the therapeutic role of ApoEVs-AT in full-thickness skin wounds, evaluating wound closure rate, re-epithelialization, granulation tissue formation, vascularization, scar area, and collagen 3(Col3)/collagen 1(Col 1) ratio. Results: ApoEVs derived from HUVECs displayed typical characteristics. In vitro, ApoEVs significantly enhanced the proliferation, migration, tube formation, and expression of angiogenic-related genes in endothelial cells and slightly promoted the proliferation and migration of fibroblasts. In vivo, ApoEVs improved the wound closure rate, re-epithelialization, the formation of granulation tissue, and vascularization. Besides, ApoEVs reduced scar formation, accompanied by an increase in the Col 3/ Col 1 ratio. Conclusion: Given their abundant source and effectiveness, this study provided a novel approach for angiogenesis in tissue regeneration and deepened the understanding of from death to regeneration.

Recent advances of hydrogels as smart dressings for diabetic wounds.

Chronic diabetic wounds have been an urgent clinical problem, and wound dressings play an important role in their management. Due to the design of traditional dressings, it is difficult to achieve adaptive adhesion and on-demand removal of complex diabetic wounds, real-time monitoring of wound status, and dynamic adjustment of drug release behavior according to the wound microenvironment. Smart hydrogels, as smart dressings, can respond to environmental stimuli and achieve more precise local treatment. Here, we review the latest progress of smart hydrogels in wound bandaging, dynamic monitoring, and drug delivery for treatment of diabetic wounds. It is worth noting that we have summarized the most important properties of smart hydrogels for diabetic wound healing. In addition, we discuss the unresolved challenges and future prospects in this field. We hope that this review will contribute to furthering progress on smart hydrogels as improved dressing for diabetic wound healing and practical clinical application.

The development of magnesium-based biomaterials in bone tissue engineering: A review.

Bone regeneration is a vital clinical challenge in massive or complicated bone defects. Recently, bone tissue engineering has come to the fore to meet the demand for bone repair with various innovative materials. However, the reported materials usually cannot satisfy the requirements, such as ideal mechanical and osteogenic properties, as well as biocompatibility at the same time. Mg-based biomaterials have considerable potential in bone tissue engineering owing to their excellent mechanical strength and biosafety. Moreover, the biocompatibility and osteogenic activity of Mg-based biomaterials have been the research focuses in recent years. The main limitation faced in the applications of Mg-based biomaterials is rapid degradation, which can produce excessive Mg2+ and hydrogen, affecting the healing of the bone defect. In order to overcome the limitations, researchers have explored several ways to improve the properties of Mg-based biomaterials, including alloying, surface modification with coatings, and synthesizing other composite materials to control the degradation rate upon implantation. This article reviewed the osteogenic mechanism and requirement for appropriate degradation rate and focused on current progress in the biomedical use of Mg-based biomaterials to inspire more clinical applications of Mg in bone regeneration in the future.

Zinc-based biomaterials for bone repair and regeneration: mechanism and applications.

Zinc (Zn) is one of the most important trace elements in the human body and plays a key role in various physiological processes, especially in bone metabolism. Zn-containing materials have been reported to enhance bone repair through promoting cell proliferation, osteogenic activity, angiogenesis, and inhibiting osteoclast differentiation. Therefore, Zn-based biomaterials are potential substitutes for traditional bone grafts. In this review, the specific mechanisms of bone formation promotion by Zn-based biomaterials were discussed, and recent developments in their application in bone tissue engineering were summarized. Moreover, the challenges and perspectives of Zn-based biomaterials were concluded, revealing their attractive potential and development directions in the future.

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention.

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention.

Osteoimmunity-regulating nanosilicate-reinforced hydrogels for enhancing osseointegration.

Following the introduction of osteo-immunomodulation as a new and important strategy to enhance material osseointegration, achieving an appropriate immune response after biomaterial implantation has become a significant challenge for efficient bone repair. In this study, a nanosilicate-reinforced sodium alginate (SA) hydrogel was fabricated by introducing montmorillonite (MMT) nanoparticles. Meanwhile, an immunogenically bioactive agent, harmine (HM), was loaded and released to induce macrophage differentiation into the M2 type. The fabricated SA/MMT/HM (SMH) hydrogel exhibited improved mechanical stiffness and stability, which also efficiently promoted macrophage anti-inflammatory M2 phenotype polarization and enhanced the secretion of pro-tissue healing cytokines for inducing a favorable immunomodulatory microenvironment for the osteogenic differentiation of bone marrow stromal cells (BMSCs). Furthermore, a rat air-pouch model and a critical-size bone defect model were used and the results showed that the SMH hydrogel increased the proportion of M2 macrophages and markedly reduced local inflammation, while enhancing desirable new bone formation. Transcriptomic analysis revealed that the SMH hydrogel accelerated the M1-to-M2 transition of macrophages by inhibiting relevant inflammatory signaling pathways and activating the PI3K-AKT1 signaling pathway. Taken together, this high-intensity immunomodulatory hydrogel may be a promising biomaterial for bone regeneration and provide a valuable base and positive enlightenment for massive bone defect repair.

Vascular and lymphatic heterogeneity and age-related variations of dental pulps.

OBJECTIVES: Dental pulp tissue is highly vascularized. However, age-related vascular changes of the dental pulp in mice and humans remain poorly understood. We modified a novel tissue clearing method, mapped the vasculature, pericytes, and perivascular matrix in the dental pulp via high-resolution 3D imaging. METHODS: We isolated young and aged pulps from mouse teeth, and mapped vasculature through a high-resolution thick frozen sections imaging method and a modified tissue clearing method. Human dental pulps were also mapped for vasculature studying. Furthermore, young and aged human dental pulps were collected and were compared with mouse pulps through RNA- sequencing. RESULTS: Five vascular subtypes of blood vessels were found in the mouse dental pulp, which constituted the arterioles-capillaries-venules network. The density of capillaries and venules of molars declined obviously in aged mice. Among the age-dependent changes in the perivascular pulp matrix, the perivascular macrophages remarkably increased, lymphatic capillaries increased, while the nerves and extracellular matrix remained unchanged. Furthermore, the vascular patterns of human formed a complex vascular network. Both mouse and human dental pulps exhibited an inflammaging state. TNF pathway and Rap1 pathway might become promising targets for combating inflammaging and promoting angiogenesis. CONCLUSIONS: Five subtypes of blood vessels were identified within the dental pulp of mice. Notably, the density of capillaries and venules in pulps of aged mice was reduced. Furthermore, partial similarities were observed in the vascular patterns between the dental pulps of humans and mice. RNA-sequencing analysis revealed that both mouse and human dental pulps exhibit indications of an inflammaging state. CLINICAL SIGNIFICANCE: This study may contribute to unraveling potential therapeutic targets in the pulp regeneration and treatment of relevant diseases in the elderly.

Development of a Stretchable and Water-Resistant Hydrogel with Antibacterial and Antioxidant Dual Functions for Wound Healing in Movable Parts.

The treatment of wounds that develop on moving parts of the body, such as joints, is considered a challenge due to poor mechanical matching and secondary injury caused by continuous motion and inflammation. Herein, a stretchable, multifunctional hydrogel dressing utilizing the dual cross-linking of chitosan (CS) and acrylic acid (AA) and modified with caffeic acid (CA) and aloin (Alo) was developed. Mechanical testing demonstrated that the hydrogel possessed excellent stretching capability (of approximately 869%) combined with outstanding adhesion (about 56 kPa), contributing to its compatibility with moving parts and allowing complete coverage of wound sites without limiting joint and organ motion. Bioinformatics analysis confirmed that use of the hydrogel resulted in upregulated expression of multiple genes related to angiogenesis and cell proliferation. Furthermore, antibacterial testing indicated that the dressing suppressed the growth of Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), providing a better microenvironment for wound healing. An in vivo wound defect model on movable skin verified that the wound healing observed with the hydrogel dressing was superior to that observed with a commercially available dressing. Taken together, the results suggest that a stretchable multifunctional hydrogel dressing represents a promising alternative wound dressing with therapeutic potential for superior healing, especially for moving parts of the body.

Blue-ringed octopus-inspired microneedle patch for robust tissue surface adhesion and active injection drug delivery.

Intratissue topical medication is important for the treatment of cutaneous, mucosal or splanchnic diseases. However, penetrating surface barriers to providing adequate and controllable drug delivery while guaranteeing adhesion in bodily fluids remains challenging. Here, the predatory behavior of the blue-ringed octopus inspired us with a strategy to improve topical medication. For effective intratissue drug delivery, the active injection microneedles were prepared in a manner inspired by the teeth and venom secretion of blue-ringed octopus. With on demand release function guided by temperature-sensitive hydrophobic and shrinkage variations, these microneedles can supply adequate drug delivery at an early stage and then achieve the long-term release stage. Meanwhile, the bionic suction cups were developed to facilitate microneedles to stay firmly in place (>10 kilopascal) when wet. With wet bonding ability and multiple delivery mode, this microneedle patch achieved satisfactory efficacy, such as accelerating the ulcers' healing speed or halting early tumor progression.

Surface Modification of Titanium Implants by Metal Ions and Nanoparticles for Biomedical Application.

Implant surface modification can improve osseointegration and reduce peri-implant inflammation. Implant surfaces are modified with metals because of their excellent mechanical properties and significant functions. Metal surface modification is divided into metal ions and nanoparticle surface modification. These two methods function by adding a finishing metal to the surface of the implant, and both play a role in promoting osteogenic, angiogenic, and antibacterial properties. Based on this, the nanostructural surface changes confer stronger antibacterial and cellular affinity to the implant surface. The current paper reviews the forms, mechanisms, and applications of nanoparticles and metal ion modifications to provide a foundation for the surface modification of implants.

Drug-Delivery Nanoplatform with Synergistic Regulation of Angiogenesis-Osteogenesis Coupling for Promoting Vascularized Bone Regeneration.

It has been confirmed that substantial vascularization is an effective strategy to heal large-scale bone defects in the field of bone tissue engineering. The local application of deferoxamine (DFO) is among the most common and effective methods for promoting the formation of blood vessels, although its short half-life in plasma, rapid clearance, and poor biocompatibility limit its therapeutic suitability. Herein, zeolitic imidazolate framework-8 (ZIF-8) was selected as a vehicle to extend the half-life of DFO. In the present study, a nano DFO-loaded ZIF-8 (DFO@ZIF-8) drug delivery system was established to promote angiogenesis-osteogenesis coupling. The nanoparticles were characterized, and their drug loading efficiency was examined to confirm the successful synthesis of nano DFO@ZIF-8. Additionally, due to the sustained release of DFO and Zn2+, DFO@ZIF-8 NPs were able to promote angiogenesis in human umbilical vein endothelial cells (HUVECs) culture and osteogenesis in bone marrow stem cells (BMSCs) in vitro. Furthermore, the DFO@ZIF-8 NPs promoted vascularization by enhancing the expression of type H vessels and a vascular network. The DFO@ZIF-8 NPs promoted bone regeneration in vivo by increasing the expression of OCN and BMP-2. RNA sequencing analysis revealed that the PI3K-AKT-MMP-2/9 and HIF-1α pathways were upregulated by DFO@ZIF-8 NPs in HUVECs, ultimately leading to the formation of new blood vessels. In addition, the mechanism by which DFO@ZIF-8 NPs promoted bone regeneration was potentially related to the synergistic effect of angiogenesis-osteogenesis coupling and Zn2+-mediation of the MAPK pathway. Taken together, DFO@ZIF-8 NPs, which were demonstrated to have low cytotoxicity and excellent coupling of angiogenesis and osteogenesis, represent a promising strategy for the reconstruction of critical-sized bone defects.

Alkaline earth metals for osteogenic scaffolds: From mechanisms to applications.

Regeneration of bone defects is a significant challenge today. As alternative approaches to the autologous bone, scaffold materials have remarkable features in treating bone defects; however, the various properties of current scaffold materials still fall short of expectations. Due to the osteogenic capability of alkaline earth metals, their application in scaffold materials has become an effective approach to improving their properties. Furthermore, numerous studies have shown that combining alkaline earth metals leads to better osteogenic properties than applying them alone. In this review, the physicochemical and physiological characteristics of alkaline earth metals are introduced, mainly focusing on their mechanisms and applications in osteogenesis, especially magnesium (Mg), calcium (Ca), strontium (Sr), and barium (Ba). Furthermore, this review highlights the possible cross-talk between pathways when alkaline earth metals are combined. Finally, some of the current drawbacks of scaffold materials are enumerated, such as the high corrosion rate of Mg scaffolds and defects in the mechanical properties of Ca scaffolds. Moreover, a brief perspective is also provided regarding future directions in this field. It is worth exploring that whether the levels of alkaline earth metals in newly regenerated bone differs from those in normal bone. The ideal ratio of each element in the bone tissue engineering scaffolds or the optimal concentration of each elemental ion in the created osteogenic environment still needs further exploration. The review not only summarizes the research developments in osteogenesis but also offers a direction for developing new scaffold materials.

Biomechanical behavior analysis of four types of short implants with different placement depths using the finite element method.

STATEMENT OF PROBLEM: The clinical application of short implants has been increasing. However, studies on the marginal bone loss of short implants are sparse, and clinicians often choose short implants based on their own experience rather than on scientific information. PURPOSE: The purpose of this finite element analysis study was to evaluate the microstrain-stress distribution in the peri-implant bone and implant components for 4 types of short implants at different placement depths of platform switching. MATERIAL AND METHODS: By using short implants as prototypes, 4 short implant models were 1:1 modeled. The diameter and length of the implants were 5×5, 5×6, 6×5, and 6×6 mm. The restoration was identical for all implants. Three different depths of implant platform switching were set: equicrestal, 0.5-mm subcrestal, and 1-mm subcrestal. The models were then assembled and assigned an occlusal force of 200 N (vertical or 30-degree oblique). A finite element analysis was carried out to evaluate the maximum equivalent elastic strain and von Mises stress in the bone and the stress distribution in the implant components. RESULTS: The 5×5 implant group showed the largest intraosseous strain (21.921×103 µÎµ). A 1-mm increase in implant diameter resulted in a 17.1% to 37.4% reduction in maximum intraosseous strain when loaded with oblique forces. The strain in the bone tended to be much smaller than the placement depth at the equicrestal and 0.5-mm subcrestal positions than that at the 1-mm subcrestal position, especially under oblique force loading, with an increase of approximately 37.4% to 81.8%. In addition, when the cortical bone thickness was less than 4 mm, 5×6 implants caused significantly higher intraosseous stresses than 6×6 implants. CONCLUSIONS: Large implant diameters, rather than long implants, led to reduced intraosseous strain, especially under oblique loading. Regarding the implant platform switching depth, the short implant showed small intraosseous strains when the platform switching depth was equicrestal or 0.5-mm subcrestal.

Alginate-based biomaterial-mediated regulation of macrophages in bone tissue engineering.

Many studies in the bone tissue engineering field have focused on the interactions between materials and bone marrow stem cells. With the development of osteoimmunology, the immune cells' essential role in biomaterial-mediated osteogenesis has increasingly been recognized. As a promising therapeutic candidate for bone defects due to their prominent biocompatibility, tuneability, and versatility, it is necessary to develop alginate-based biomaterials that can regulate immune cells, especially macrophages. Moreover, modified alginate-based biomaterials may facilitate better regulation of macrophage phenotypes by the newly endowed physicochemical properties, including stiffness, porosity, hydrophilicity, and electrical properties. This review summarizes the role of macrophages in bone regeneration and the recent research progress related to the effects of alginate-based biomaterials on macrophages applied in bone tissue engineering. This review also emphasizes the strategies adopted by material design to regulate macrophage phenotypes, the corresponding macrophage responses, and their contribution to osteogenesis.

Multi-Mechanism Antibacterial Strategies Enabled by Synergistic Activity of Metal-Organic Framework-Based Nanosystem for Infected Tissue Regeneration.

Drug-resistant bacterial infection impairs tissue regeneration and is a challenging clinical problem. Metal-organic frameworks (MOFs)-based photodynamic therapy (PDT) opens up a new era for antibiotic-free infection treatment. However, the MOF-based PDT normally encounters limited photon absorbance under visible light and notorious recombination of photogenerated holes and electrons, which significantly impede their applications. Herein, a MOFs-based nanosystem (AgNPs@MOFs) with enhanced visible light response and charge carrier separation is developed by modifying MOFs with silver nanoparticles (AgNPs) to improve PDT efficiency. The AgNPs@MOFs with enhanced photodynamic performance under visible light irradiation mainly disrupt bacteria translation process and the metabolism of purine and pyrimidine. In addition, the introduction of AgNPs endows nanosystems with chemotherapy ability, which causes destructive effect on bacterial cell membrane, including membrane ATPase protein and fatty acids. AgNPs@MOFs show excellent synergistic drug-resistant bacterial killing efficiency through multiple mechanisms, which further restrain bacterial resistance. In addition, biocompatible AgNPs@MOFs pose potential tissue regeneration ability in both Methicillin-resistant Staphylococcus aureus (MRSA)-related soft and hard tissue infection. Overall, this study provides a promising perspective in the exploration of AgNPs@MOFs as nano antibacterial medicine against drug-resistant bacteria for infected tissue regeneration in the future.

One-Pot Facile Encapsulation of Dimethyloxallyl Glycine by Nanoscale Zeolitic Imidazolate Frameworks-8 for Enhancing Vascularized Bone Regeneration.

In the process of bone tissue regeneration, regulation of osteogenesis-angiogenesis coupling is of great importance. Therefore, dimethyloxallyl glycine (DMOG) is loaded by nanoscale zeolitic imidazolate frameworks-8 (ZIF-8) to obtain a drug-loading system that can promote osteogenesis-angiogenesis coupling. Characterization of the drug-loading nanoparticles (DMOG@ZIF-8) reveals that DMOG is successfully loaded into ZIF-8 by two different methods, and the DMOG@ZIF-8 is prepared using the one-pot method (OD@ZIF-8) achieves higher loading efficiency and longer release time than those prepared using the post-loading method (PD@ZIF-8). In vitro studies found that DMOG@ZIF-8 significantly enhances the migration, tube formation, and angiogenesis-related protein secretion of human umbilical vein endothelial cells as well as the extracellular matrix mineralization, alkaline phosphatase activity, and osteogenesis-related protein secretion of bone marrow mesenchymal stem cells. Moreover, OD@ZIF-8 nanoparticles are more efficient than PD@ZIF-8 nanoparticles in induction of osteogenesis-angiogenesis coupling. Then, in vivo cranial critical defect model shows that the addition of OD@ZIF-8 significantly promotes vascularized bone formation as indicated by the results including microcomputed tomographic, histological and immunofluorescence staining, and so on. Taken together, loading ZIF-8 with DMOG may be a promising solution for critical-sized bone defect reconstruction and the one-pot method is preferred in the preparation of such drug-loading system.

Low-Swelling Adhesive Hydrogel with Rapid Hemostasis and Potent Anti-Inflammatory Capability for Full-Thickness Oral Mucosal Defect Repair.

Full-thickness oral mucosal defects are accompanied by significant blood loss and frequent infections. Instead of conventional therapies that separate hemostasis and anti-inflammation in steps, emerging hydrogels can integrate multiple functions for the successive process after defect including hemostasis/inflammatory phase, proliferative phase, and remodeling phase. However, these functions can be easily compromised by rapid swelling and degradation of hydrogels in wet oral environment. Herein, a low-swelling adhesive hydrogel with rapid hemostasis and potent anti-inflammatory capability was developed using a dual cross-linking strategy as well as a safe and facile fabrication method. It was double cross-linked hydrogel consisting of gelatin methacrylate (GelMA), nanoclay, and tannic acid (TA) (referred to as GNT). GNT hydrogel exhibited low-swelling (one-eighth of that of GelMA), excellent stretchability (211.86%), and good adhesive properties (5 times the adhesive strength of GelMA). Physicochemical characterization illuminated the close interactions among the three components. A systematic investigation of the therapeutic effects of GNT hydrogels was performed. In vitro and in vivo experimental results demonstrated the potent hemostatic property and excellent antibacterial and anti-inflammatory effects of GNT hydrogels. The RNA sequencing analysis results for rat full-thickness oral mucosal samples showed that GNT reduced inflammation levels by down-regulating the expression of multiple inflammation-related pathways, including TNF and IL-17 pathways. It also enhanced the expression levels of tissue regeneration-related genes and thus accelerated defective mucosal repair. More importantly, the therapeutic effects of GNT were superior to those of a commercial oral tissue repair membrane when applied for full-thickness oral mucosal defect repair in rabbits. In summary, the prepared low-swelling adhesive GNT hydrogel with rapid hemostasis and potent anti-inflammatory is a promising therapy for full-thickness mucosal defect in the moist and dynamic oral environment.

Surface modification of the Ti surface with nanoscale bio-MOF-1 for improving biocompatibility and osteointegration in vitro and in vivo.

Biocompatibility and osteointegration of implants are highly desired in orthopedic and dentistry applications. The synthesis of a coating with ideal biocompatibility and osteogenic effect carries practical significance for improving the bio-inertness of pure Ti implants. Metal-organic frameworks (MOFs) are effective surface modification agents in bone regeneration applications. Bio-MOF-1, a classic type of biofriendly MOF with a bio-derived constitution, possesses biocompatibility and osteogenic potential resulting from its Zn core and adenine ligand. In this study, bio-MOF-1 coatings at multiple concentrations were synthesized on alkali-heat treated Ti, and their cytocompatibility and osteogenic properties were systematically examined both in vitro and in vivo. Coatings were characterized to confirm the successful synthesis of bio-MOF-1 coatings. These coatings exhibited advanced thermostability, excellent biocompatibility, and stable Zn2+ release, which up-regulated the expression of osteogenesis-related genes and proteins. Furthermore, bio-MOF-1 coating of Ti implants enhanced early osseointegration at the bone-implant interface. This study demonstrates the promising potential of bio-MOF-1 coatings with the osteogenic effect for surface modification in bone tissue engineering.