A xonotlite nanofiber bioactive 3D-printed hydrogel scaffold based on osteo-/angiogenesis and osteoimmune microenvironment remodeling accelerates vascularized bone regeneration.

BACKGROUND: Coordination between osteo-/angiogenesis and the osteoimmune microenvironment is essential for effective bone repair with biomaterials. As a highly personalized and precise biomaterial suitable for repairing complex bone defects in clinical practice, it is essential to endow 3D-printed scaffold the above key capabilities. RESULTS: Herein, by introducing xonotlite nanofiber (Ca6(Si6O17) (OH)2, CS) into the 3D-printed silk fibroin/gelatin basal scaffold, a novel bone repair system named SGC was fabricated. It was noted that the incorporation of CS could greatly enhance the chemical and mechanical properties of the scaffold to match the needs of bone regeneration. Besides, benefiting from the addition of CS, SGC scaffolds could accelerate osteo-/angiogenic differentiation of bone mesenchymal stem cells (BMSCs) and meanwhile reprogram macrophages to establish a favorable osteoimmune microenvironment. In vivo experiments further demonstrated that SGC scaffolds could efficiently stimulate bone repair and create a regeneration-friendly osteoimmune microenvironment. Mechanistically, we discovered that SGC scaffolds may achieve immune reprogramming in macrophages through a decrease in the expression of Smad6 and Smad7, both of which participate in the transforming growth factor-ß (TGF-ß) signaling pathway. CONCLUSION: Overall, this study demonstrated the clinical potential of the SGC scaffold due to its favorable pro-osteo-/angiogenic and osteoimmunomodulatory properties. In addition, it is a promising strategy to develop novel bone repair biomaterials by taking osteoinduction and osteoimmune microenvironment remodeling functions into account.

Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway.

BACKGROUND: Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS: In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION: In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.

Aligned electrospun poly(L-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways.

Delayed wound healing remains a challenge, and macrophages play an important role in the inflammatory process of wound healing. Morphological changes in macrophages can affect their phenotype, but little is known about the underlying mechanism. Aligned electrospun nanofibers have natural advantages in modulating cell morphology. Therefore, the current study constructed aligned electrospun nanofibers that could transform macrophages into elongated shapes. Our results demonstrated that aligned nanofibers without exogenous cytokines could downregulate the proinflammatory M1 phenotype and upregulate the prohealing M2 phenotype in an inflammatory environment. Importantly, our study revealed that aligned electrospun nanofibers could inhibit macrophage M1 polarization via the JAK-STAT and NF-κB pathways. Furthermore, the conditioned medium from macrophages cultured on aligned nanofibers could encourage fibroblast migration, proliferation and collagen secretion. In vivo, aligned nanofibers alleviated the inflammatory microenvironment, promoted angiogenesis and accelerated wound healing in mouse skin defects by modulating macrophage phenotypes. Collectively, aligned electrospun nanofibers can influence macrophage polarization via the JAK-STAT and NF-κB pathways and attenuate the local inflammatory response in skin wounds. This study provides a potential strategy to modulate macrophage polarization and promote wound healing by controlling the topology of biomaterials and offers a new perspective for the application of nanotechnology in wound healing.

Degradation and silicon excretion of the calcium silicate bioactive ceramics during bone regeneration using rabbit femur defect model.

The investigation of the bone regeneration ability, degradation and excretion of the grafts is critical for development and application of the newly developed biomaterials. Herein, the in vivo bone-regeneration, biodegradation and silicon (Si) excretion of the new type calcium silicate (CaSiO3, CS) bioactive ceramics were investigated using rabbit femur defect model, and the results were compared with the traditional ß-tricalcium phosphate [ß-Ca3(PO4)2, ß-TCP] bioceramics. After implantation of the scaffolds in rabbit femur defects for 4, 8 and 12 weeks, the bone regenerative capacity and degradation were evaluated by histomorphometric analysis. While urine and some organs such as kidney, liver, lung and spleen were resected for chemical analysis to determine the excretion of the ionic products from CS implants. The histomorphometric analysis showed that the bioresorption rate of CS was similar to that of ß-TCP in femur defect model, while the CS grafts could significantly stimulate bone formation capacity as compared with ß-TCP bioceramics (P < 0.05). The chemical analysis results showed that Si concentration in urinary of the CS group was apparently higher than that in control group of ß-TCP. However, no significant increase of the Si excretion was found in the organs including kidney, which suggests that the resorbed Si element is harmlessly excreted in soluble form via the urine. The present studies show that the CS ceramics can be used as safe, bioactive and biodegradable materials for hard tissue repair and tissue engineering applications.

Multilevel hierarchically ordered artificial biomineral.

Living organisms are known for creating complex organic-inorganic hybrid materials such as bone, teeth, and shells, which possess outstanding functions as compared to their simple mineral forms. This has inspired many attempts to mimic such structures, but has yielded few practical advances. In this study, a multilevel hierarchically ordered artificial biomineral (a composite of hydroxyapatite and gelatine) with favorable nanomechanical properties is reported. A typical optimized HAp/gelatin hybrid material in the perpendicular direction of the HAp c-axis has a modulus of 25.91 + 1.78 GPa and hardness of 0.90 + 0.10 GPa, which well matches that of human cortical bone (modulus 24.3 + 1.4 GPa, hardness 0.69 + 0.05 GPa). The bottom-up crystal constructions (from nano- to micro- to macroscale) of this material are achieved through a hard template approach by the phase transformation from DCP to HAp. The structural biomimetic material shows another way to mimic the complex hierarchical designs of sclerous tissues which have potential value for application in hard tissue engineering.

Sensory Nerve Regulation via H3K27 Demethylation Revealed in Akermanite Composite Microspheres Repairing Maxillofacial Bone Defect.

Maxillofacial bone defects exhibit intricate anatomy and irregular morphology, presenting challenges for effective treatment. This study aimed to address these challenges by developing an injectable bioactive composite microsphere, termed D-P-Ak (polydopamine-PLGA-akermanite), designed to fit within the defect site while minimizing injury. The D-P-Ak microspheres biodegraded gradually, releasing calcium, magnesium, and silicon ions, which, notably, not only directly stimulated the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) but also activated sensory nerve cells to secrete calcitonin gene-related peptide (CGRP), a key factor in bone repair. Moreover, the released CGRP enhanced the osteogenic differentiation of BMSCs through epigenetic methylation modification. Specifically, inhibition of EZH2 and enhancement of KDM6A reduced the trimethylation level of histone 3 at lysine 27 (H3K27), thereby activating the transcription of osteogenic genes such as Runx2 and Osx. The efficacy of the bioactive microspheres in bone repair is validated in a rat mandibular defect model, demonstrating that peripheral nerve response facilitates bone regeneration through epigenetic modification. These findings illuminated a novel strategy for constructing neuroactive osteo-inductive biomaterials with potential for further clinical applications.

A coaxial electrospun mat coupled with piezoelectric stimulation and atorvastatin for rapid vascularized bone regeneration.

The repair of critical bone defects caused by various clinical conditions needs to be addressed urgently, and the regeneration of large bone defects depends on early vascularization. Therefore, enhanced vascularization of artificial bone grafts may be a promising strategy for the regeneration of critical-sized bone defects. Taking into account the importance of rapid angiogenesis during bone repair and the potential of piezoelectric stimulation in promoting bone regeneration, novel coaxial electrospun mats coupled with piezoelectric materials and angiogenic drugs were fabricated in this study using coaxial electrospinning technology, with a shell layer loaded with atorvastatin (AVT) and a core layer loaded with zinc oxide (ZnO). AVT was used as an angiogenesis inducer, and piezoelectric stimulation generated by the zinc oxide was used as an osteogenesis enhancer. The multifunctional mats were characterized in terms of morphology, core-shell structure, piezoelectric properties, drug release, and mechanical properties, and their osteogenic and angiogenic capabilities were validated in vivo and ex vivo. The results revealed that the coaxial electrospun mats exhibit a porous surface morphology and nanofibers with a core-shell structure, and the piezoelectricity of the mats improved with increasing ZnO content. Excellent biocompatibility, hydrophilicity and cell adhesion were observed in the multifunctional mats. Early and rapid release of AVT in the fibrous shell layer of the mat promoted angiogenesis in human umbilical vascular endothelial cells (HUVECs), whereas ZnO in the fibrous core layer harvested bioenergy and converted it into electrical energy to enhance osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs), and both modalities synergistically promoted osteogenesis and angiogenesis. Furthermore, optimal bone regeneration was achieved in a model of critical bone defects in the rat mandible. This osteogenesis-promoting effect was induced by electrical stimulation via activation of the calcium signaling pathway. This multifunctional mat coupling piezoelectric stimulation and atorvastatin promotes angiogenesis and bone regeneration, and shows great potential in the treatment of large bone defects.

ZIF-8-based Nanoparticles for Inflammation Treatment and Oxidative Stress Reduction in Periodontitis.

Periodontitis, an inflammatory bone resorption disease associated with dental plaque, poses significant challenges for effective treatment. In this study, we developed Mino@ZIF-8 nanoparticles inspired by the periodontal microenvironment and the unique properties of zeolitic imidazolate framework 8, aiming to address the complex pathogenesis of periodontitis. Transcriptome analysis revealed the active engagement of Mino@ZIF-8 nanoparticles in innate and adaptive inflammatory host defense and cellular metabolic remodeling. Through sustained release of the anti-inflammatory and antibacterial agent minocycline hydrochloride (Mino) and the generation of Zn2+ with pro-antioxidant effects during degradation, Mino@ZIF-8 nanoparticles synergistically alleviate inflammation and oxidative damage. Notably, our study focuses on the pivotal role of zinc ions in mitochondrial oxidation protection. Under lipopolysaccharide (LPS) stimulation, periodontal ligament cells undergo a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, leading to reduced ATP production and increased reactive oxygen species levels. However, Zn2+ effectively rebalances the glycolysis-OXPHOS imbalance, restoring cellular bioenergetics, mitigating oxidative damage, rescuing impaired mitochondria, and suppressing inflammatory cytokine production through modulation of the AKT/GSK3ß/NRF2 pathway. This research not only presents a promising approach for periodontitis treatment but also offers novel therapeutic opportunities for zinc-containing materials, providing valuable insights into the design of biomaterials targeting cellular energy metabolism regulation.

A five-in-one novel MOF-modified injectable hydrogel with thermo-sensitive and adhesive properties for promoting alveolar bone repair in periodontitis: Antibacterial, hemostasis, immune reprogramming, pro-osteo-/angiogenesis and recruitment.

Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.

Enhancing the osteogenic differentiation of aligned electrospun poly(L-lactic acid) nanofiber scaffolds by incorporation of bioactive calcium silicate nanowires.

Bone defects cause serious psychological and economic burden to patients. Artificially bone repairing materials bring hope to the treatment of bone defects. Electrospun technique has attracted great attention since it can fabricate fibers from nano- to micro- scale continuously. Scaffolds fabricated by electrospun can mimic the structure of extracellular matrix which is beneficial to cell adhesion and migration. Researches have showed that bioactive ions (such as silicon and calcium ions) can promote bone regeneration. In addition, physical cues can affect cellular behavior such as cell adhesion and differentiation. In this study, two kinds of calcium silicate - adopted poly (L-lactic acid) (CS-PLLA) electrospun scaffolds with random/aligned structures were prepared by electrospun to promote bone regeneration. The integration of CS nanowires improved the biological property of PLLA electrospun scaffolds. Furthermore, in vitro results indicated that aligned 1 wt% CS adopted PLLA (PCA1) electrospun scaffolds with better physical properties and facilitated cell adhesion, improved alkaline phosphate (ALP) activity and the expression of osteogenic genes (Osteopontin (OPN), Collagen type 1 (Col-1) and Bone morphogenetic protein-2 (BMP-2)) compared with random 1 wt% CS adopted PLLA (PCR1) electrospun scaffolds. In conclusion, the prepared PCA1 electrospun scaffolds might be a potential candidate for bone regeneration in defect areas.

Osteogenic differentiation of 3D-printed porous tantalum with nano-topographic modification for repairing craniofacial bone defects.

Introduction: Congenital or acquired bone defects in the oral and cranio-maxillofacial (OCMF) regions can seriously affect the normal function and facial appearance of patients, and cause great harm to their physical and mental health. To achieve good bone defect repair results, the prosthesis requires good osteogenic ability, appropriate porosity, and precise three-dimensional shape. Tantalum (Ta) has better mechanical properties, osteogenic ability, and microstructure compared to Ti6Al4V, and has become a potential alternative material for bone repair. The bones in the OCMF region have unique shapes, and 3D printing technology is the preferred method for manufacturing personalized prosthesis with complex shapes and structures. The surface characteristics of materials, such as surface morphology, can affect the biological behavior of cells. Among them, nano-topographic surface modification can endow materials with unique surface properties such as wettability and large surface area, enhancing the adhesion of osteoblasts and thereby enhancing their osteogenic ability. Methods: This study used 3D-printed porous tantalum scaffolds, and constructed nano-topographic surface through hydrothermal treatment. Its osteogenic ability was verified through a series of in vitro and in vivo experiments. Results: The porous tantalum modified by nano-topographic surface can promote the proliferation and osteogenic differentiation of BMSCs, and accelerate the formation of new bone in the Angle of the mandible bone defect of rabbits. Discussion: It can be seen that 3D-printed nano-topographic surface modified porous tantalum has broad application prospects in the repair of OCMF bone defects.

A sustained-release PDGF-BB nanocomposite hydrogel for DM-associated bone regeneration.

Regeneration of bone tissue in the environment of diabetes mellitus (DM) remains one of the clinical challenges, with malfunction of stem cells in a high-glucose microenvironment being the primary obstacle. We designed an injectable sustained-release PDGF-BB nanocomposite hydrogel. PDGF-BB, a star molecule for treating various complications of DM, was used for the first time for DM-associated bone regeneration, and we showed that it restored stem cell proliferation and migration and facilitated osteogenesis inhibition under high glucose stimulation by activating ERK and AKT pathways. To address the requirements for continuous PDGF-BB release in GelMA while also increasing mechanical strength, nanoclay LAPONITE® was added, which may still exhibit pro-osteogenic activity in diabetic environments by releasing bioactive ions (Si4+, Mg2+, and Li+). This injectable hydrogel heals calvarial lesions successfully in diabetic rats and has the potential to be used as a direct and effective tool for treating diabetic patients.

Melatonin Engineering M2 Macrophage-Derived Exosomes Mediate Endoplasmic Reticulum Stress and Immune Reprogramming for Periodontitis Therapy.

Periodontitis is a chronic infectious disease caused by bacterial irritation. As an essential component of the host immunity, macrophages are highly plastic and play a crucial role in inflammatory response. An appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) macrophages is indispensable for treating periodontitis. As M2 macrophage-derived exosomes (M2-exos) can actively target inflammatory sites and modulate immune microenvironments, M2-exos can effectively treat periodontitis. Excessive endoplasmic reticulum stress (ER stress) and unfolded protein response (UPR) are highly destructive pathological characteristics during inflammatory periodontal bone loss. Although melatonin has antioxidant and anti-inflammatory effects, studies focusing on melatonin ER stress modulation remain limited. This study fabricates engineered M2-exos loading with melatonin (Mel@M2-exos) for treating periodontitis. As a result, M2-exos drive an appropriate and timely macrophage reprogramming from M1 to M2 type, which resolves chronic inflammation and accelerated periodontal healing. Melatonin released from Mel@M2-exos rescues the osteogenic and cementogenic differentiation capacity in inflammatory human periodontal ligament cells (hPDLCs) by reducing excessive ER stress and UPR. Injectable gelatin methacryloyl (GelMA) hydrogels with sustained-release Mel@M2-exos accelerate periodontal bone regeneration in rats with ligation-induced periodontitis. Taken together, melatonin engineering M2 macrophage-derived exosomes are promising candidates for inflammatory periodontal tissue regeneration.

Growth of highly oriented hydroxyapatite arrays tuned by quercetin.

Crystal calls: the remarkable crystal modulation ability of quercetin (QUE) in highly oriented hydroxyapatite (HAp) array crystallization is reported. Organized HAp crystals were obtained by hydrothermal exchange of α-tricalcium phosphate (α-TCP) precursor in solution with a progressive increase in QUE concentration. Experimental results revealed that QUE would be a potentially effective crystal modulation assistant.

Construction of a Hierarchical Micro-/Submicro-/Nanostructured 3D-Printed Ti6Al4V Surface Feature to Promote Osteogenesis: Involvement of Sema7A through the ITGB1/FAK/ERK Signaling Pathway.

Constructing hierarchical hybrid structures is considered a facile method to improve the osseointegration of implants. Herein, a hierarchical micro-/submicro-/nanostructured surface feature of Ti6Al4V implants (3DAT group) was successfully constructed by combining the inherently formed three-dimensional (3D)-printed microscale topography, acid-etched sub-micropits, and anodized nanotubes. Compared with the classical SLA surface, the microscale topography and sub-micropits increased the three-dimensional space for the cell growth and mechanical stability of implants, while the modification of nanotubes dramatically improved the surface hydrophilicity, protein adsorption, and biomineralization. Most importantly, the 3DAT surface feature possessed excellent osteogenic performance in vitro and in vivo, with the involvement of semaphorin 7A (Sema7A) as revealed by RNA-seq through the ITGB1/FAK/ERK signaling pathway. The present study suggested that the hierarchically structured surface design strategy could accelerate the osseointegration rate of 3D-printed Ti6Al4V implants, promising personalized reconstruction of bone defects.

In situ construction of a nano-structured akermanite coating for promoting bone formation and osseointegration of Ti-6Al-4V implants in a rabbit osteoporosis model.

With the aging population worldwide, osteoporosis, as an age-related bone metabolic disease, is becoming a hot issue in public health. However, it is still a great challenge to realize osteoporotic bone healing due to the alteration of the bone microenvironment in osteoporosis patients. In this study, a nano-structured akermanite (nAK) coating was in situ constructed on Ti-6Al-4V implants to improve osteoporotic bone repair. In vitro studies indicated that both the surface nano-topography and bioactive ions released from the nAK coatings promoted the proliferation, osteogenesis, angiogenesis and inhibited osteoclastogenesis of ovariectomy rabbit-derived bone marrow mesenchymal stem cells (OVX-rBMSCs). Furthermore, the nAK-coated Ti-6Al-4V implants improved new bone formation and osseointegration in an osteoporosis rabbit model in vivo. These results indicated that the AK coating with a nano-structured surface on the Ti-6Al-4V implant could synergistically promote bone formation and osseointegration for osteoporosis patients. This may be a promising strategy to improve the bone regeneration and osseointegration capability of orthopedic implants under osteoporosis conditions.

Modifying a 3D-Printed Ti6Al4V Implant with Polydopamine Coating to Improve BMSCs Growth, Osteogenic Differentiation, and In Situ Osseointegration In Vivo.

Nowadays, 3D printing technology has been applied in dentistry to fabricate customized implants. However, the biological performance is unsatisfactory. Polydopamine (PDA) has been used to immobilize bioactive agents on implant surfaces to endow them with multiple properties, such as anti-infection and pro-osteogenesis, benefiting rapid osseointegration. Herein, we fabricated a PDA coating on a 3D-printed implant surface (3D-PDA) via the in situ polymerization method. Then the 3D-PDA implants' pro-osteogenesis capacity and the osseointegration performance were evaluated in comparison with the 3D group. The in vitro results revealed that the PDA coating modification increased the hydrophilicity of the implants, promoting the improvement of the adhesion, propagation, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. Additionally, the 3D-PDA implant improved osteointegration performance in vivo. The present study suggested that PDA coating might be a feasible strategy to optimize 3D-printed implant surfaces, making a preliminary research basis for the subsequent work to immobilize bioactive factors on the 3D-printed implant surface.

The effects of alignment and diameter of electrospun fibers on the cellular behaviors and osteogenesis of BMSCs.

Electrospun fiber scaffolds, due to their mimicry of bone extracellular matrix (ECM), have become an important biomaterial widely applied in bone tissue engineering in recent years. While topographic cues of electrospun membranes such as alignment and diameter played vital roles in determining cellular behaviors. Yet few researches about the effects of these two significant parameters on osteogenesis have been reported. Thus, the present work explored the influence of aligned and random poly (L-lactic acid) (PLLA) fiber matrices with diameters of nanoscale (0.6 µm) and microscale (1.2 µm), respectively, on cellular responses of bone marrow mesenchymal stem cells (BMSCs), such as cell adhesion, migration, proliferation and osteogenesis. Our results revealed that aligned nanofibers (AN) could affect cell morphology and promote the migration of BMSCs after 24 h of cell culturing. Besides, AN group was observed to possess excellent biocompatibility and have significantly improved cell growth comparing with random nanofibers. More importantly, in vitro osteogenesis researches including ALP and Alizarin Red S staining, qRT-PCR and immunofluorescence staining demonstrated that BMSCs culturing on AN group exhibited higher osteogenic induction proficiency than that on aligned microfibers (AM) and random fiber substrates (RN and RM). Accordingly, aligned nanofiber scaffolds have greater application potential in bone tissue engineering.

A polydopamine-assisted strontium-substituted apatite coating for titanium promotes osteogenesis and angiogenesis via FAK/MAPK and PI3K/AKT signaling pathways.

Early osteointegration is essential for biomedical implants. Surface modifications can significantly compensate for an implant's lack of biocompatibility and osteo-differentiation. They can also be designed to promote angiogenesis in order to assist osteogenesis and ultimately facilitate bone regeneration. In this study, a polydopamine-assisted strontium-substituted apatite coating (Ti@PDA + SrHA) was fabricated on a multifunctional titanium implant to induce both angiogenic and osteogenic abilities for rapid osseointegration. Polydopamine and Sr-substituted hydroxyapatite were coated on the implant through biomineralization. The in vitro results showed that Ti@PDA + SrHA improved cell adhesion and increased the proliferation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs). Ti@PDA + SrHA upregulated the expression of ALP activity and osteogenic genes in rBMSCs and elevated angiogenic genes in both rBMSCs and HUVECs. Mechanically, the FAK/MAPK signaling pathway was activated in rBMSCs, and the PI3K/AKT signaling pathway was activated in both rBMSCs and HUVECs. Consistent with these findings, Ti@PDA + SrHA accelerated new bone formation and rapid osseointegration in the femoral condyle implantation study with good stability. Overall, we fabricated a multifunctional biocompatible implant with better angiogenic and osteogenic performance compared to the non-coated implant.

Dental Implants Loaded With Bioactive Agents Promote Osseointegration in Osteoporosis: A Review.

Implant-supported dentures are widely used in patients with defect or loss of dentition because these have higher chewing efficiency and do not damage the adjacent teeth compared with fixed or removable denture. An implant-supported denture carries the risk of failure in some systemic diseases, including osteoporosis, because of a non-ideal local microenvironment. Clinically common physical and chemical modifications are used to change the roughness of the implant surface to promote osseointegration, but they have limitations in promoting osteoinduction and inhibiting bone resorption. Recently, many researchers have focused on the study of bioactive modification of implants and have achieved promising results. Herein we have summarized the progress in bioactive modification strategy to promote osseointegration by regulating the local osteoporotic microenvironment.