Osteoinductive Properties Research Articles

Potential of Liposomal FTY720 for Bone Regeneration: Proliferative, Osteoinductive, Chemoattractive, and Angiogenic Properties Compared to Free Bioactive Lipid.

FTY720 bioactive lipid has proliferative, osteoinductive, chemo attractive, and angiogenic properties, being thus a potential exogenous administered agent for promotion of bone regeneration. Herein we developed FTY720-loaded liposomes as a potential delivery system that could retain and prolong the bioactivity of the bioactive lipid and at the same time reduce its cytotoxicity (at high doses). FTY720 liposomes were prepared by thin-lipid hydration and microfluidic flow focusing, and evaluated for their ability to induce proliferation, osteoinduction, and chemoattraction in three cell types: MC3T3-E1 pre-osteoblast cells, L929 fibroblast cells, and ATDC5 chondrogenic cells. The angiogenic activity of free and liposomal FTY720 was investigated using a chick chorioallantoic membrane assay. NBD-FTY720 cellular uptake was quantitated using flow cytometry and morphologically assessed by confocal microscopy. Implicated cellular signaling mechanisms were investigated by quantifying phosphorylated MAPK and CREB proteins. FTY720 liposomes (~80-110 nm) with low polydispersity and ~100% loading were prepared using both methods. FTY720 demonstrated the ability to increase cell proliferation at 10-300nM doses but was cytotoxic at doses>400nM while the corresponding liposomal-FTY720 doses were non-cytotoxic, proving its reduced toxicity. In several cases (cells and doses), FTY720 liposomes demonstrated increased osteogenic differentiation of cells, proliferation, and migration compared to free FTY720, whereas both FTY720 forms demonstrated substantial angiogenic activity. Liposomal FTY720 cellular uptake was substantially higher than that of free FTY720 in some cases, a fact that may be connected to its higher bioactivity. Increased phosphorylated MAPK and CREB protein concentrations provided information about the potential cellular signaling mechanisms involved in FTY720-induced osteogenesis. The current results confirm the high potential of FTY720 bioactive lipid, especially in its liposomal form, that demonstrated substantial reduction of cytotoxicity and prolonged preservation of the lipids bioactivity (compared to the free lipid), for accelerated treatment of bone defects. Interestingly, the current studies prove the potential of FTY720, especially in its liposomal form, to promote reprogramming of L929 fibroblasts into osteoblasts, a novel finding deserving future exploitation.

Modified multilayered porous titanium scaffolds with silicon-doped coating surface-loaded BMP-2 prepared by microarc oxidation for bone defect repair

As is generally known, the lack of osteoinductive properties in titanium scaffolds has been a major barrier to bone defects repair. In our previous studies, we found that silicon-doped porous coatings prepared via micro-arc oxidation (MAO) had the potential application of Si-doped coatings in dental and orthopedic fields. We are currently focused on developing more advanced surface coatings to maximize their osteoinductive efficacy. Bone morphogenetic protein-2 (BMP-2), known for its ability to induce bone and cartilage development, has also been extensively studied. Therefore, in this study, macroporous titanium alloy scaffolds were fabricated using 3D printing technology, silicon ions were introduced onto the surface of customized macroporous titanium alloy scaffolds through MAO to enhance the bioactivity of the scaffolds, and BMP-2 was loaded onto the Si-doped coating to further improve the osseointegration of the titanium alloy scaffolds post-implantation. Results demonstrated that silicon-doped coating-loaded BMP2-modified multi-level porous titanium scaffolds exhibited improved hydrophilicity and biocompatibility. In-vivo and vitro studies further confirmed the superior bone regeneration capabilities of these scaffolds. This study demonstrates an optional strategy to combine two surface modification treatments, offering substantial potential as an advanced bone defect repair material with improved and accelerated bone regeneration.

THE USE OF AUTOLOGOUS DENTIN-GRAFT TO REPLACE PERIODONTAL DEFECTS: CASE REPORT

The purpose of this study was to evaluate the preservation of vertical alveolar ridge parameters in cases of volumetric post-extraction defects in the mandible using a combination of autologous dentin graft and platelet-rich fibrin, assessed at short-term (3 months) and long-term (12 months) follow-ups. Subjects and methods. A clinical case of patient Zh., 45 years old, who sought dental care at the Department of Maxillofacial Surgery, the Lviv Regional Clinical Hospital, is presented. Cone-beam computed tomography, orthopantomogram were performed followed by surgical treatment in accordance with the recommended protocol. Results. Partial or complete tooth loss, regardless of the causes of its occurrence, is accompanied by physiological reduction (atrophy) of the alveolar processes of the jaws in the vertical and horizontal planes, which is an indication for bone-plastic replacement of post-extraction defects. The technology of manufacturing and application of granulated dentin for the replacement of various defects of the alveolar bone has made it possible to consider autologous dentin graft as the “gold standard” of regenerative bone surgery due to its unique osteogenic, osteoinductive, and osteoconductive properties, and its combination with platelet-rich fibrin containing growth factors has an additional positive effect on the healing of soft- and bone-tissue wounds and regenerative processes. A clinical example of replacement of a large post-extraction defect of the lower jaw using a composition of autologous dentin and platelet-rich fibrin with simultaneous implantation is demonstrated. Control radiological examinations performed 3 and 12 months after the operation showed that the newly formed bone tissue in the area of the former defects did not differ in structure and density from the surrounding areas, and most importantly, no vertical loss of height of the reconstructed alveolar ridge was noted. Conclusion. All of the above indicates that the composition of autologous dentin and platelet-rich fibrin may be a promising therapeutic option for the replacement of post-extraction defects, horizontal or vertical augmentation of alveolar ridge.

Exploring the Osteoinductive Potential of Bacterial Pyomelanin Derived from Pseudomonas aeruginosa in a Human Osteoblast Model.

Alkaptonuria (AKU) is a genetically determined disease associated with disorders of tyrosine metabolism. In AKU, the deposition of homogentisic acid polymers contributes to the pathological ossification of cartilage tissue. The controlled use of biomimetics similar to deposits observed in cartilage during AKU potentially may serve the development of new bone regeneration therapy based on the activation of osteoblasts. The proposed biomimetic is pyomelanin (PyoM), a polymeric biomacromolecule synthesized by Pseudomonas aeruginosa. This work presents comprehensive data on the osteoinductive, pro-regenerative, and antibacterial properties, as well as the cytocompatibility, of water-soluble (PyoMsol) or water-insoluble (PyoMinsol) PyoM. Both variants of PyoM support osteoinductive processes as well as the maturation of osteoblasts in cell cultures in vitro due to the upregulation of bone-formation markers, osteocalcin (OC), and alkaline phosphatase (ALP). Furthermore, the cytokines involved in these processes were elevated in cell cultures of osteoblasts exposed to PyoM: tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. The PyoM variants are cytocompatible in a wide concentration range and limit the doxorubicin-induced apoptosis of osteoblasts. This cytoprotective PyoM activity is correlated with an increased migration of osteoblasts. Moreover, PyoMsol and PyoMinsol exhibit antibacterial activity against staphylococci isolated from infected bones. The osteoinductive, pro-regenerative, and antiapoptotic effects achieved through PyoM stimulation prompt the development of new biocomposites modified with this bacterial biopolymer for medical use.

Personalizing β-TCP porous scaffolds to promote osteogenesis: a study of segmental femoral defects in beagle models

The increasing clinical occurrence of segmental bone defects is demanding constant improvements in bone transplantation to overcome issues of limited resources, immune rejection and poor structural complement. This study aimed to develop a personalized bone defect repair modality using 3D-printed tricalcium phosphate (β-TCP) grafts and to assess its osteogenic impacts in a femoral segmental defect model in beagles, as a basis for clinical studies and application. Aβ-TCP scaffold was designed and manufactured using computer-aided design. A 3 cm segmental bone defect model was established in 27 one-year-old male beagles, and were randomly divided into three groups. The control group utilizing only intramedullary fixation, the autograft group with an added autologous bone graft andβ-TCP group using aβ-TCP scaffold. The study animals were monitored for 24 weeks postoperative and assessed for vital signs, imaging, and histological indicators periodically. All of the Beagles underwent successful modeling and experimentation, and were fully ambulatory at four weeks. Postoperative x-rays showed no evidence of loosening or displacement of the intramedullary nails. Micro-CT and histological staining indicated Osteogenesis starting from the fourth week, with the most significant growth seen using autografts (P< 0.05). New bone (NB) formation is seen adhering to the surface and proximal femur after osteotomy. Theβ-TCP group had significantly more evidence of Osteogenesis when compared to the control group (P< 0.05), characterized by NB visible throughout the porous structure and distal residual femur. The control group showed bone formation impeded by fibrosis, showing poor bone growth mainly around the distal end after osteotomy, with poor overall repair outcomes.Conclusion.Growth factor-deficientβ-TCP porous scaffolds demonstrated promising Osteoinductive properties in repairing large segment bone defects in Beagles' femurs. It effectively promoted bone growth and is structurally advantageous for weight bearing long bones.

Antisolvent 3D Printing of Gene-Activated Scaffolds for Bone Regeneration.

The use of 3D-printed gene-activated bone grafts represents a highly promising approach in the fields of dentistry and orthopedics. Bioresorbable poly-lactic-co-glycolic acid (PLGA) scaffolds, infused with adenoviral constructs that carry osteoinductive factor genes, may provide an effective alternative to existing bone grafts for the reconstruction of extensive bone defects. This study aims to develop and investigate the properties of 3D scaffolds composed of PLGA and adenoviral constructs carrying the BMP2 gene (Ad-BMP2), both in vitro and in vivo. The elastic modulus of the disk-shaped PLGA scaffolds created using a specialized 3D printer was determined by compressive testing in both axial and radial directions. In vitro cytocompatibility was assessed using adipose-derived stem cells (ADSCs). The ability of Ad-BMP2 to transduce cells was evaluated. The osteoinductive and biocompatible properties of the scaffolds were also assessed in vivo. The Young's modulus of the 3D-printed PLGA scaffolds exhibited comparable values in both axial and radial compression directions, measuring 3.4 ± 0.7 MPa for axial and 3.17 ± 1.4 MPa for radial compression. The scaffolds promoted cell adhesion and had no cytotoxic effect on ADSCs. Ad-BMP2 successfully transduced the cells and induced osteogenic differentiation in vitro. In vivo studies demonstrated that the 3D-printed PLGA scaffolds had osteoinductive properties, promoting bone formation within the scaffold filaments as well as at the center of a critical calvarial bone defect.

Injectable MXene/Ag-HA composite hydrogel for enhanced alveolar bone healing and mechanistic study.

Alveolar bone defects pose significant challenges in dentistry. Due to the complexity of alveolar bone anatomy and insufficient repair mechanisms, large bone defects are difficult for the body to heal naturally. Clinical treatment typically involves the use of bone substitute materials. However, current substitutes often suffer from limitations such as insufficient osteoinductivity, rapid degradation, inflammatory responses, and poor mechanical properties. Additionally, the irregular morphology of alveolar bone defects complicates the application of solid bone substitutes, potentially leading to secondary damage at the repair site. To address these challenges, this study introduces an innovative approach by integrating MXene nanomaterials into Ag-HA/GelMA hydrogels to create an injectable MXene/Ag-HA composite hydrogel. MXene nanomaterials are renowned for their excellent biocompatibility, antibacterial properties, and mechanical strength. The results indicate that the MXene/Ag-HA composite hydrogel exhibits satisfactory mechanical and biological properties. Specifically, it demonstrates excellent antibacterial, antioxidant, and osteogenic activities. Gene expression analysis further reveals that the MXene composite hydrogel promotes osteogenesis by regulating the expression of Dmp1 and Dusp1. The findings of this study suggest that the MXene/Ag-HA composite hydrogel is a promising candidate for alveolar bone repair and regeneration. The integration of MXene nanomaterials into the hydrogel enhances its mechanical and biological properties, making it well-suited for the treatment of irregular alveolar bone defects. Furthermore, the study underscores the vast potential of MXene nanomaterials in the biomedical field, hinting at potential applications beyond alveolar bone repair.

Biological and Synthetic Materials in Mandibular Reconstruction

Mandibular reconstruction is a critical surgical procedure necessary for restoring both function and aesthetics following trauma, tumor resection, or congenital defects. Over time, a variety of biological and synthetic materials have been developed to address the challenges of reconstructing the complex anatomy of the mandible. Biological materials, such as autografts, offer superior biocompatibility and osteogenic potential, but are limited by donor site morbidity and graft availability. Allografts and xenografts provide more accessible alternatives but are associated with higher risks of immune rejection and slower integration. In contrast, synthetic materials like titanium, PEEK (polyether ether ketone), and hydroxyapatite provide excellent mechanical strength and durability but often lack osteoinductive properties, requiring surface modifications to improve tissue integration.This review aims to provide a comprehensive analysis of the current materials used in mandibular reconstruction, comparing their biocompatibility, mechanical properties, osteoinductive potential, and clinical outcomes. Additionally, the review explores the growing role of composite materials that combine the strength of synthetics with the biological activity of natural tissues, as well as the advent of tissue engineering approaches that incorporate stem cell therapies and biomaterial scaffolds to promote bone regeneration. Emerging technologies such as 3D printing of custom-made implants and the application of nanotechnology for enhanced integration and infection control are also discussed as promising directions for future clinical applications. The findings highlight the need for continued research into optimizing biomaterial design and improving regenerative therapies to enhance patient-specific outcomes, reduce complications, and foster successful long-term integration of reconstructed mandibular structures. This review provides a roadmap for advancing both material science and clinical practice in the field of mandibular reconstruction.

Advancements for artificial ligaments: enhancing biological activity and antibacterial performance

Anterior cruciate ligament (ACL) reconstruction is one of the most frequently performed orthopedic procedures, particularly for athletes seeking to restore knee stability and function. Polyethylene terephthalate (PET) is widely used for artificial ligaments due to its durability and chemical stability. However, PETs inherent limitations, including poor osteoconductivity and biocompatibility, contribute to graft failure and postoperative infections. Recent advancements in surface functionalization, including the incorporation of hydroxyapatite (HAp) and bioactive glass, have significantly improved PET's osteoconductive and osteoinductive properties, promoting enhanced bone integration and healing. Additionally, innovations in antibacterial coatings, such as silver nanoparticles and polydopamine, have demonstrated potential in reducing infection rates and improving the longevity of implants. This review highlights these technological advances, emphasizing how biomaterials and surface modifications are transforming the performance of PET-based artificial ligaments, leading to more successful ACL reconstructions and improved patient outcomes.

Injectable Polyhydroxyalkanoate-Nano-Clay Microcarriers Loaded with r-BMSCs Enhance the Repair of Cranial Defects in Rats.

Successful regeneration of cranial defects necessitates the use of porous bone fillers to facilitate cell proliferation and nutrient diffusion. Open porous microspheres, characterized by their high specific surface area and osteo-inductive properties, offer an optimal microenvironment for cell ingrowth and efficient ossification, potentially accelerating bone regeneration. An in vitro investigation was conducted to assess the physicochemical properties, porosity, and biocompatibility of PHA-nano-clay open porous microspheres. Subsequently, PHA-nano-clay microspheres loaded with rat bone marrow mesenchymal stem cells were implanted into 5 mm cranial defects in rats for a duration of 12weeks and were evaluated through histological and immunohistochemical analyses. The incorporation of nano-clay into PHA resulted in improved mechanical properties of the porous scaffolds. Furthermore, cell adhesion, viability, and morphology on the scaffolds were maintained. The PHA-3% nano-clay open porous microspheres effectively enhanced the repair of cranial defects compared to the control group, without recurrence or complications. Porous PHA-nano-clay microspheres, with their high specific surface area, biodegradability, and osteo-inductive properties, can be utilized as a bone-filling material for improved bone defect repair through cell delivery. In particular, PHA-3% nano-clay open porous microspheres exhibit promising therapeutic potential in the repair of cranial defects.

Design of patient-specific mandibular reconstruction plates and a hybrid scaffold

Background:Managing segmental mandibular defects remains challenging, requiring a multidisciplinary approach despite the remarkable progress in mandibular reconstruction plates, finite element methods, computer-aided design and manufacturing techniques, and novel surgical procedures. Complex surgeries require a comprehensive approach, as using only reconstruction plates or tissue scaffolds may not be adequate for optimal results. The limitations of the treatment options should be investigated towards a patient-specific trend to provide shorter surgery time, better healing, and lower costs. Integrated hybrid scaffold systems are promising in improving mechanical properties and facilitating healing. By combining different materials and structures, hybrid scaffolds can provide enhanced support and stability to the tissue regeneration process, leading to better patient outcomes. The use of such systems represents a significant advancement in tissue engineering and a wide range of medical procedures. Materials and Methods:A head and neck computed tomography (CT) data of a patient with odontogenic myxoma was used for creating a three-dimensional (3D) mandible model. Virtual osteotomies were performed to create a segmental defect model, including the angulus mandibulae region. The first mandibular reconstruction plate was designed. Finite elemental analyses (FEA) and topology optimizations were performed to create two different reconstruction plates for different treatment scenarios. The FEA were performed for the resulting two plates to assess their biomechanical performance. To provide osteoconductive and osteoinductive properties a scaffold was designed using the defect area. A biomimetic Tricalcium phosphate-Polycaprolactone (TCP-PCL) hybrid bone scaffold enhanced with Hyaluronic acid dipping was manufactured. Results:The results of the in-silico analysis indicate that the designed reconstruction plates possess robust biomechanical performance and demonstrate remarkable stability under the most rigorous masticatory activities. Using the Voronoi pattern decreased the mass by %37 without losing endurance. Using reconstruction plates and hybrid scaffolds exhibits promising potential for clinical applications, subject to further in vivo and clinical studies.

Biocompatibility Analysis of the Silver-Coated Microporous Titanium Implants Manufactured with 3D-Printing Technology.

3D-printed microporous titanium scaffolds enjoy good biointegration with the residuum's soft and bone tissues, and they promote excellent biomechanical properties in attached prostheses. Implant-associated infection, however, remains a major clinical challenge. Silver-based implant coatings can potentially reduce bacterial growth and inhibit biofilm formation, thereby reducing the risk of periprosthetic infections. In the current study, a 1-µm thick silver coating was prepared on the surface of a 3D-printed microporous titanium alloy with physical vapor deposition (PVD), with a final silver content of 1.00 ± 02 mg/cm2. Cell viability was evaluated with an MTT assay of MC3T3-E1 osteoblasts and human dermal fibroblasts cultured on the surface of the implants, and showed low cytotoxicity for cells during the 14-day follow-up period. Quantitative real-time polymerase chain reaction (RT-PCR) analysis of the relative gene expression of the extracellular matrix components (fibronectin, vitronectin, type I collagen) and cell adhesion markers (α2, α5, αV, β1 integrins) in dermal fibroblasts showed that cell adhesion was not reduced by the silver coating of the microporous implants. An RT-PCR analysis of gene expression related to osteogenic differentiation, including TGF-β1, SMAD4, osteocalcin, osteopontin, and osteonectin in MC3T3-E1 osteoblasts, demonstrated that silver coating did not reduce the osteogenic activity of cells and, to the contrary, enhanced the activity of the TGF-β signaling pathway. For representative sample S5 on day 14, the gene expression levels were 7.15 ± 0.29 (osteonectin), 6.08 ± 0.12 (osteocalcin), and 11.19 ± 0.77 (osteopontin). In conclusion, the data indicate that the silver coating of the microporous titanium implants did not reduce the biointegrative or osteoinductive properties of the titanium scaffold, a finding that argues in favor of applying this coating in designing personalized osseointegrated implants.

Impact of Hyaluronic Acid and Other Re-Epithelializing Agents in Periodontal Regeneration: A Molecular Perspective.

This narrative review delves into the molecular mechanisms of hyaluronic acid (HA) and re-epithelializing agents in the context of periodontal regeneration. Periodontitis, characterized by chronic inflammation and the destruction of tooth-supporting tissues, presents a significant challenge in restorative dentistry. Traditional non-surgical therapies (NSPTs) sometimes fail to fully manage subgingival biofilms and could benefit from adjunctive treatments. HA, with its antibacterial, antifungal, anti-inflammatory, angiogenic, and osteoinductive properties, offers promising therapeutic potential. This review synthesizes the current literature on the bioactive effects of HA and re-epithelializing agents, such as growth factors and biomaterials, in promoting cell migration, proliferation, and extracellular matrix (ECM) synthesis. By modulating signaling pathways like the Wnt/β-catenin, TGF-β, and CD44 interaction pathways, HA enhances wound healing processes and tissue regeneration. Additionally, the role of HA in facilitating cellular crosstalk between epithelial and connective tissues is highlighted, as it impacts the inflammatory response and ECM remodeling. This review also explores the combined use of HA with growth factors and cytokines in wound healing, revealing how these agents interact synergistically to optimize periodontal regeneration. Future perspectives emphasize the need for further clinical trials to evaluate the long-term outcomes of these therapies and their potential integration into periodontal treatment paradigms.

A Review on Advances and Challenges in Core-Shell Scaffolds for Bone Tissue Engineering: Design, Fabrication, and Clinical Translation.

This review explores core-shell scaffolds in bone tissue engineering, highlighting their osteoconductive and osteoinductive properties critical for bone growth and regeneration. Key design factors include material selection, porosity, mechanical strength, biodegradation kinetics, and bioactivity. Electrospun core-shell nanofibrous scaffolds demonstrate potential in delivering therapeutic agents and enhancing bone regeneration. Critical characterization techniques include structural, surface, chemical composition, mechanical, and degradation analyses. Scaling up production poses challenges, addressed by innovative electrospinning techniques. Future research focuses on regulatory and commercial considerations, while exploring advanced materials and fabrication methods to optimize scaffold performance for improved clinical outcomes.

Green Synthesis of Silver Nanoparticles with Roasted Green Tea: Applications in Alginate-Gelatin Hydrogels for Bone Regeneration.

The incorporation of silver nanoparticles (AgNPs) into alginate-gelatin (Alg-Gel) hydrogels can enhance the properties of these materials for bone regeneration applications, due to the antimicrobial properties of AgNPs and non-cytotoxic concentrations, osteoinductive properties, and regulation of stem cell proliferation and differentiation. Here, the hydrogel formulation included 2% (w/v) sodium alginate, 4 µg/mL AgNPs, and 2.5% (w/v) gelatin. AgNPs were synthesized using a 2% (w/v) aqueous extract of roasted green tea with silver nitrate. The aqueous extract of roasted green tea for AgNP synthesis was characterized using HPLC and UHPLC-ESI-QTOF-MS/MS, and antioxidant capacity was measured in Trolox equivalents (TE) from 4 to 20 nmol/well concentrations. Stem cells from human exfoliated deciduous tooth cells were used for differentiation assays including positive (SHEDs/hydrogel with AgNPs) and negative controls (hydrogel without AgNPs). FTIR was used for hydrogel chemical characterization. Statistical analysis (p < 0.05, ANOVA) confirmed significant findings. Roasted green tea extract contained caffeine (most abundant), (-)-Gallocatechin, gallic acid, and various catechins. XRD analysis revealed FCC structure, TEM showed quasispheroidal AgNPs (19.85 ± 3 nm), and UV-Vis indicated a plasmon surface of 418 nm. This integration of nanotechnology and biomaterials shows promise for addressing bone tissue loss in clinical and surgical settings.

3D Bioprinting Strategies for Melatonin‐Loaded Polymers in Bone Tissue Engineering

AbstractBone pathologies are still among the most challenging issues for orthopedics. Over the past decade, different methods are developed for bone repair. In addition to advanced surgical and graft techniques, polymer‐based biomaterials, bioactive glass, chitosan, hydrogels, nanoparticles, and cell‐derived exosomes are used for bone healing strategies. Owing to their variation and promising advantages, most of these methods are not translated into clinical practice. Three dimensonal (3D) bioprinting is an additive manufacturing technique that has become a next‐generation biomaterial technique adapted for anatomic modeling, artificial tissue or organs, grafting, and bridging tissues. Polymer‐based biomaterials are mostly used for the controlled release of various drugs, therapeutic agents, mesenchymal stem cells, ions, and growth factors. Polymers are now among the most preferable materials for 3D bioprinting. Melatonin is a well‐known antioxidant with many osteoinductive properties and is one of the key hormones in the brain–bone axis. 3D bioprinted melatonin‐loaded polymers with unique lipophilic, anti‐inflammatory, antioxidant, and osteoinductive properties for filling large bone gaps following fractures or congenital bone deformities may be developed in the future. This study summarized the benefits of 3D bioprinted and polymeric materials integrated with melatonin for sustained release in bone regeneration approaches.

Preparation of zirconium hydrogen phosphate coatings on alkali thermal titanium via a one-step sol–gel method to improve the friction resistance, bioactivity, and osteogenic potential

Titanium implants are widely used in dental restorations for patients suffering from dentition defects. However, the biologically inert of Ti, poor osteoinduction properties and the release of Ti particles due to friction between the bone and the implants can inhibit osseointegration and adversely affect the success rate of implantation. In this study, a zirconium phosphate (ZrP) coating was constructed on the surface of alkali thermal titanium (AT-Ti) via a one-step sol–gel approach. Subsequently, the friction resistance, bioactivity, and osteogenesis properties of the prepared coating were studied. The surface characterization results confirmed that AT-Ti was successfully coated with amorphous ZrP, and ZrP modification was found to effectively reduce the friction rate. In addition, the surface morphology after friction test was smoother. In terms of the bioactivity, the presence of a phosphate group in the ZrP coating led to the effective enrichment of Ca2+ to promote the formation of hydroxyapatite (HAp). It was also discovered that ZrP exhibited an excellent performance in cell viability and mineralization experiments, in addition to up-regulating the expression of osteogenesis related genes. Overall, ZrP modification of AT-Ti leads to an excellent friction resistance, bioactivity, and osteoinductive properties, thereby indicating its broad application prospects in implant therapy.

Porous titanium/hydroxyapatite interpenetrating phase composites with optimal mechanical and biological properties for personalized bone repair

This study introduces the first fabrication of porous titanium/hydroxyapatite interpenetrating phase composites through an innovative processing method. The approach combines additive manufacturing of a customized titanium skeleton with the infiltration of an injectable hydroxyapatite foam, followed by in situ foam hardening at physiological temperature. This biomimetic process circumvents ceramic sintering and metal casting, effectively avoiding the formation of secondary phases that can impair mechanical performance. Hydroxyapatite foams, prepared using two foaming agents (polysorbate 80 and gelatine), significantly reinforce the titanium skeleton while preserving the microstructural characteristics essential for osteoinductive properties. The strengthening mechanisms rely on the conformation of the foams to the titanium surface, thereby enabling stable mechanical interlocking and effective interfacial stress transfer. This, combined with the mechanical constriction of phases, enhances damage tolerance and mechanical reliability of the interpenetrating phase composites. In addition, the interpenetrating phase composites feature a network of concave pores with an optimal size for bone repair, support human osteoblast proliferation, and exhibit mechanical properties compatible with bone, offering a promising solution for the efficient and personalized reconstruction of large bone defects. The results demonstrate a significant advancement in composite fabrication, integrating the benefits of additive manufacturing for bone repair with the osteogenic capacity of calcium phosphate ceramics.

Exploring the Impact of Catechins on Bone Metabolism: A Comprehensive Review of Current Research and Future Directions.

Background/Objectives: Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. Methods: The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. Results: EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. Conclusions: EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures.

A multifunctional self-reinforced injectable hydrogel for enhancing repair of infected bone defects by simultaneously targeting macrophages, bacteria, and bone marrow stromal cells

Injectable hydrogels (IHs) have demonstrated huge potential in promoting repair of infected bone defects (IBDs), but how to endow them with desired anti-bacterial, immunoregulatory, and osteo-inductive properties as well as avoid mechanical failure during their manipulation are challenging. In this regard, we developed a multifunctional AOHA-RA/Lap nanocomposite IH for IBDs repair, which was constructed mainly through two kinds of reversible cross-links: (i) the laponite (Lap) crystals mediated electrostatic interactions; (ii) the phenylboronic acid easter bonds between the 4-aminobenzeneboronic acid grafted oxidized hyaluronic acid (AOHA) and rosmarinic acid (RA). Due to the specific structural composition, the AOHA-RA/Lap IH demonstrated superior injectability, self-recoverability, spatial adaptation, and self-reinforced mechanical properties after being injected to the bone defect site. In addition, the RA molecules could be locally released from the hydrogel following a Weibull model for over 10 days. Systematic in vitro/vivo assays proved the strong anti-bacterial activity of the hydrogel against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Moreover, its capability of inducing M2 polarization of macrophages (Mφ) and osteogenic differentiation of bone marrow stromal cells (BMSCs) was verified either, and the mechanism of the former was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways and that of the latter was identified to be related to the calcium signaling pathway, extracellular matrix (ECM) receptor interaction and TGF-β signaling pathway. After being implanted to a S. aureus infected rat skull defect model, the AOHA-RA/Lap IH significantly accelerated repair of IBDs without causing significant systemic toxicity. Statement of significanceRosmarinic acid and laponite were utilized to develop an injectable hydrogel, promising for accelerating repair of infected bone defects in clinic. The gelation of the hydrogel was completely driven by two kinds of reversible cross-links, which endow the hydrogel superior spatial adaption, self-recoverability, and structural stability. The as-prepared hydrogel demonstrated superior anti-bacterial/anti-biofilm activity and could induce M2 polarization of macrophages and osteogenic differentiation of BMSCs. The mechanism behind macrophages polarization was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways. The mechanism behind osteogenic differentiation of BMSCs was identified to be related to the ECM receptor interaction and calcium signaling/TGF-β signaling pathways.