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The decreased reconstruction potential of aging bone marrow mesenchymal stem cells (BMMSCs) fails to resist compromised bone healing, and strategies to remodel the regeneration capacity of senescent BMMSCs are urgently needed. A depletion of ARG1+ macrophages in aging murine exacerbates the impaired reconstructive functionality of BMMSCs, eventually becomes a critical obstacle for aged osteointegration. Herein, we fabricated a niche-like multiscale porous Titanium (p-Ti) implant using a vapor-phase-assisted alloying-dealloying strategy for in-situ manipulating the regenerative repair potential of BMMSCs while alleviating immunosenescence during bone reconstruction. This versatile method can be used to fabricate a porous surface layer on commercial implants with complex geometries. As benchmarked with commercial Ti, the in vitro and in vivo results of rabbits and rats show our niche-like p-Ti efficiently promotes BMMSCs to engender an osteogenic phenotype and attune the areas of bone defect. Moreover, niche-like multiscale porous structure yields rejuvenated ARG1+ macrophages in tandem with BMMSCs osteogenic differentiation at the bone-implant interface, modulating the immunosenescence, and synergistically promoting the osteointegration. Our findings establish that the macrophage can be re-engineered to be youthful for maintaining immune homeostasis, thereby providing a reversible treatment strategy for bone reconstruction of old people with broad applications in other senescence-related diseases. The declined reconstruction potential of aging BMMSCs fails to antagonize compromised bone healing. Our vapor-phase-assisted alloying-dealloying-customized niche-like multiscale porous p-Ti efficiently manipulates the regenerative repair potential of BMMSCs to engender an osteogenic phenotypic and attune the balance of immunosenecence. Moreover, multiscale structure with niche-like pores yields rejuvenated ARG1+ macrophages enlists the regenerative capacity of resident BMMSCs and restoration youthful structure and functional features to the aged bone. [Display omitted] •Niche-like porous Ti (p-Ti) can be fabricated through vapor phase dealloying.•P-Ti manipulates BMMSCs osteogenesis in tandem with macrophages rejuvenation.•P-Ti revolutionizes the treatment in senescence-related diseases.

Background Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) can directly increase cancellous bone formation and play an essential role in bone modeling and remodeling. However, whether an increased HIF-1α expression in adipose-derived stem cells (ADSCs) increases osteogenic capacity and promotes bone regeneration is not known. Results In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression plasmid were established to investigate the proliferation, migration, adhesion, and osteogenic capacity of ADSCs and the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Overexpression of HIF-1α could promote the biological functions of ADSCs, and the angiogenic ability of HUVECs. Western blotting showed that the protein levels of osteogenesis-related factors were increased when HIF-1α was overexpressed. Furthermore, the influence of upregulation of HIF-1α in ADSC sheets on osseointegration was evaluated using a Sprague–Dawley (SD) rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The overexpression of HIF-1α in ADSCs enhanced bone remodeling and osseointegration around titanium implants. However, transfecting the small interfering RNA (siRNA) of HIF-1α in ADSCs attenuated their osteogenic and angiogenic capacity. Finally, it was confirmed in vitro that HIF-1α promotes osteogenic differentiation and the biological functions in ADSCs via the VEGF/AKT/mTOR pathway. Conclusions This study demonstrates that HIF-1α has a critical ability to promote osteogenic differentiation in ADSCs by coupling osteogenesis and angiogenesis via the VEGF/AKT/mTOR signaling pathway, which in turn increases osteointegration and bone formation around titanium implants. Graphical Abstract

Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants.

Chitin-derived hydrogels are commonly used in bone regeneration because of their high cell compatibility; however, their poor mechanical properties and little knowledge of the interaction between the materials and host cells have limited their practical application. To evaluate osteoinductivity and enhance the mechanical properties of a newly synthesized thermosensitive hydroxypropyl chitin hydrogel (HPCH), a mesenchymal stem cell (MSC)-encapsulated HPCH was infused into a three-dimensional-printed poly (ε-caprolactone) (PCL)/ nano-hydroxyapatite (nHA) scaffold to form a hybrid scaffold. The mechanical properties and cell compatibility of the scaffold were tested. The interaction between macrophages and scaffold for angiogenesis and osteogenesis were explored and . The hybrid scaffold showed improved mechanical properties and high cell viability. When MSCs were encapsulated in HPCH, osteo-differentiation was promoted properly via endochondral ossification. The co-culture experiments showed that the hybrid scaffold facilitated growth factor secretion from macrophages, thus promoting vascularization and osteoinduction. The Transwell culture proved that MSCs modulated the inflammatory response of HPCH. Additionally, subcutaneous implantation of MSC-encapsulated HPCH confirmed M2 activation. evaluation of calvarial defects confirmed that the repair was optimal in the MSC-loaded HPCH + PCL/nHA group. PCL/nHA + HPCH hybrid scaffolds effectively promoted vascularization and osteoinduction via osteogenesis promotion and immunomodulation, which suggests promising applications for bone regeneration.

Bone tissue has an astonishing self-healing capacity yet only for non-critical size defects (<6 mm) and clinical intervention is needed for critical-size defects and beyond that along with non-union bone fractures and bone defects larger than critical size represent a major healthcare problem. Autografts are, still, being used as preferred to treat large bone defects. Mostly, due to the presence of living differentiated and progenitor cells, its osteogenic, osteoinductive and osteoconductive properties that allow osteogenesis, vascularization, and provide structural support. Bone tissue engineering strategies have been proposed to overcome the limited supply of grafts. Complete and successful bone regeneration can be influenced by several factors namely: the age of the patient, health, gender and is expected that the ideal scaffold for bone regeneration combines factors such as bioactivity and osteoinductivity. The commercially available products have as their main function the replacement of bone. Moreover, scaffolds still present limitations including poor osteointegration and limited vascularization. The introduction of pores in scaffolds are being used to promote the osteointegration as it allows cell and vessel infiltration. Moreover, combinations with growth factors or coatings have been explored as they can improve the osteoconductive and osteoinductive properties of the scaffold. This review focuses on the bone defects treatments and on the research of scaffolds for bone regeneration. Moreover, it summarizes the latest progress in the development of coatings used in bone tissue engineering. Despite the interesting advances which include the development of hybrid scaffolds, there are still important challenges that need to be addressed in order to fasten translation of scaffolds into the clinical scenario. Finally, we must reflect on the main challenges for bone tissue regeneration. There is a need to achieve a proper mechanical properties to bear the load of movements; have a scaffolds with a structure that fit the bone anatomy.

Titanium is commonly and successfully used in dental and orthopedic implants. However, patients still have to face the risk of implant failure due to various reasons, such as implant loosening or infection. The risk of implant loosening can be countered by optimizing the osteointegration capacity of implant materials. Implant surface modifications for structuring, roughening and biological activation in favor for osteogenic differentiation have been vastly studied. A key factor for a successful stable long‐term integration is the initial cellular response to the implant material. Hence, cell–material interactions, which are dependent on the surface parameters, need to be considered in the implant design. Therefore, this review starts with an introduction to the basics of cell–material interactions as well as common surface modification techniques. Afterwards, recent research on the impact of osteogenic processes in vitro and vivo provoked by various surface modifications is reviewed and discussed, in order to give an update on currently applied and developing implant modification techniques for enhancing osteointegration.

Bioactive glass and glass ceramic materials are widely used as substitutes for bone augmentation and restoration, in orthopaedic, dental and maxillofacial surgery and in the tissue engineering field. Indeed, these materials are bioactive, biocompatible, mechanically stable, biodegradable and favour osteointegration, being able to promote bone tissue formation at their surface and to bond to surrounding living tissues when implanted in the human body. It has been demonstrated that bioglass (BG) ionic dissolution products (e.g. Si, Ca, P and Na) are able to induce and stimulate the expressions of genes related to the osteoblastic differentiation and bone formation, to stimulate angiogenesis in vitro and in vivo, as well as to play possible antibacterial and anti-inflammatory actions. Thus, it is possible to tailor BGs properties properly formulating their chemical composition and adding selected ions with specific functional and biological role. In this perspective, Hench proposed a new generation of genetically designed glasses, on the basis of their ability to activate specific genes involved in in situ tissue regeneration, by doping silicate and phosphate glasses with several active ions, particularly metallic ions with therapeutic effects. In this framework, the present review is aimed to provide an overview about the effect of selected cationic substitutions (i.e. magnesium, zinc, strontium and copper), incorporated within the bioglasses structure, on the physical and biological properties of these materials, since the comprehension of the influence of the most employed metallic ions has to be considered pivotal to address the formulation of more promising and performing glasses.

Rationale: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are effective interventions for end-stage osteoarthritis; however, periprosthetic infection is a devastating complication of arthroplasty. To safely prevent periprosthetic infection and enhance osteointegration, the surface modification strategy was utilized to kill bacteria, modulate the osteoimmune microenvironment, and improve new bone formation. Methods: We used the hydrothermal method to fabricate a bionic insect wing with the disordered titanium dioxide nanoneedle (TNN) coating. The mussel-inspired poly-dopamine (PDA) and antibacterial silver nanoparticles (AgNPs) were coated on TNN, named AgNPs-PDA@TNN, to improve the biocompatibility and long-lasting bactericidal capacity. The physicochemical properties of the engineered specimen were evaluated with SEM, AFM, XPS spectrum, and water contact assay. The biocompatibility, bactericidal ability, and the effects on macrophages and osteogenic differentiation were assessed with RT-qPCR, Western blotting, live/dead staining, immunofluorescent staining, etc. Results: The AgNPs-PDA@TNN were biocompatible with macrophages and exhibited immunomodulatory ability to promote M2 macrophage polarization. In addition, AgNPs-PDA@TNN ameliorated the cytotoxicity caused by AgNPs, promoted cell spreading, and increased osteogenesis and matrix deposition of BMSCs. Furthermore, AgNPs-PDA@TNN exhibited bactericidal ability against E. coli and S. aureus by the bionic nanostructure and coated AgNPs. Various imaging analyses indicated the enhanced bactericidal ability and improved new bone formation by AgNPs-PDA@TNN in vivo. H&E, Gram, and Masson staining, verified the improved bone formation, less inflammation, infection, and fibrosis encapsulation. The immunofluorescence staining confirmed the immunomodulatory ability of AgNPs-PDA@TNN in vivo. Conclusion: The bionic insect wing AgNPs-PDA@TNN coating exhibited bactericidal property, immunomodulatory ability, and enhanced osteointegration. Thus, this multidimensional bionic implant surface holds promise as a novel strategy to prevent periprosthetic infection.Rationale: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are effective interventions for end-stage osteoarthritis; however, periprosthetic infection is a devastating complication of arthroplasty. To safely prevent periprosthetic infection and enhance osteointegration, the surface modification strategy was utilized to kill bacteria, modulate the osteoimmune microenvironment, and improve new bone formation. Methods: We used the hydrothermal method to fabricate a bionic insect wing with the disordered titanium dioxide nanoneedle (TNN) coating. The mussel-inspired poly-dopamine (PDA) and antibacterial silver nanoparticles (AgNPs) were coated on TNN, named AgNPs-PDA@TNN, to improve the biocompatibility and long-lasting bactericidal capacity. The physicochemical properties of the engineered specimen were evaluated with SEM, AFM, XPS spectrum, and water contact assay. The biocompatibility, bactericidal ability, and the effects on macrophages and osteogenic differentiation were assessed with RT-qPCR, Western blotting, live/dead staining, immunofluorescent staining, etc. Results: The AgNPs-PDA@TNN were biocompatible with macrophages and exhibited immunomodulatory ability to promote M2 macrophage polarization. In addition, AgNPs-PDA@TNN ameliorated the cytotoxicity caused by AgNPs, promoted cell spreading, and increased osteogenesis and matrix deposition of BMSCs. Furthermore, AgNPs-PDA@TNN exhibited bactericidal ability against E. coli and S. aureus by the bionic nanostructure and coated AgNPs. Various imaging analyses indicated the enhanced bactericidal ability and improved new bone formation by AgNPs-PDA@TNN in vivo. H&E, Gram, and Masson staining, verified the improved bone formation, less inflammation, infection, and fibrosis encapsulation. The immunofluorescence staining confirmed the immunomodulatory ability of AgNPs-PDA@TNN in vivo. Conclusion: The bionic insect wing AgNPs-PDA@TNN coating exhibited bactericidal property, immunomodulatory ability, and enhanced osteointegration. Thus, this multidimensional bionic implant surface holds promise as a novel strategy to prevent periprosthetic infection.

The prospect of improved quality of life and the increasingly younger age of patients benefiting from Total Hip Arthroplasty will soon lead to the landmark of 10 million interventions per year worldwide. More than 10% of these procedures lead to significant bone resorption, increasing the need for revision surgeries. Current research focuses on the development of hip implant designs to achieve a stiffness profile closer to the natural bone. Additive Manufacturing has emerged as a viable solution by offering promising results in the fabrication of implant architectures based on metallic cellular structures that have demonstrated their capacity to replicate bone behavior mechanically and biologically. Aiming to offer an up-to-date overview of titanium cellular structures in hip implants, for both acetabular and femoral components, produced by Additive Manufacturing, including its design intricacies and performance, this comprehensive review meticulously examines the historical development of hip implants, encompassing commercial solutions and innovative attempts. A broad view of the practical applications and transformative potential of hip implants incorporating cellular structures is presented, aiming to outline opportunities for innovation.

[This corrects the article DOI: 10.3389/fbioe.2025.1549439.].[This corrects the article DOI: 10.3389/fbioe.2025.1549439.].