Accelerate Bone Regeneration Research Articles

Dual-Functionalized Injectable pH-Responsive Hydrogels Loaded with Magnesium Peroxide for the Treatment of Implant-Associated Infection.

Implant-associated infections frequently complicate orthopedic surgeries, resulting in challenging issues. The current therapy of antibiotic treatment and surgical debridement often leads to drug resistance and bone defect. The development of pH-responsive antimicrobial and pro-osteogenic materials is a promising approach to controlling infections and repairing infected bone defects, especially given the weakly acidic pH of the bacterial infection area. Solid peroxides have the potential to provide a sustained release of hydrogen peroxide (H2O2), rendering them applicable for antimicrobial purposes. Additionally, their chemical properties render them inherently responsive to pH. Here, we propose a novel GelBA/PVA/MgO2 hydrogel composed of gelatin (Gel), benzeneboronic acid (BA), poly(vinyl alcohol) (PVA), and magnesium peroxide (MgO2) with self-healing ability and pH-responsiveness. The borate ester bond formed between PVA and BA is a dynamic chemical bond with properties of dynamic formation and dissociation, making the hydrogel both self-healable and pH-responsive. Meanwhile, the addition of MgO2 improves the network structure of the hydrogel and gives the hydrogel the ability to perform sustained release of H2O2 and Mg2+. Experimentally, the GelBA/PVA/MgO2 hydrogel exhibits controlled and pH-dependent H2O2 and Mg2+ release, sustained over time at physiological pH (7.4) and significantly increased at infection pH (5.5). In vitro and in vivo outcomes revealed that this hydrogel is able to inhibit Staphylococcus aureus growth and accelerate bone regeneration, improving bone healing without cytotoxic effects on normal tissues. These findings suggest that the GelBA/PVA/MgO2 hydrogel is a unique and efficient approach for anti-infection and therapeutic implant-associated infections.

Framework Nucleic Acid-Based Selective Cell Catcher for Endogenous Stem Cell Recruitment.

Cell-surface engineering holds great promise in boosting endogenous stem cell attraction for tissue regeneration. However, challenges such as cellular internalization of ligand and the dynamic nature of cell membranes often complicate ligand-receptor interactions. The aim of this study is to harness the innovative potential of programmable tetrahedral framework nucleic acid (tFNA) to enable precise, tunable ligand-receptor interactions, thereby improving stem cell recruitment efficiency. This approach involves experimental screening and theoretical analysis using dissipative particle dynamics. The results demonstrate that altering the flexibility and topology of ligands on tFNA changes their cellular internalization and membrane binding efficiency. Furthermore, optimizing the distribution of the mesenchymal stem cell (MSC)-binding aptamer 19S (Apt19S) on the tFNA enhances the stem cell capture efficiency. Following successful in vitro MSC capture, Apt19S-modified tFNA is chemically linked to a hyaluronic acid hydrogel, forming an efficient "stem cell catcher" system. Subsequent in vivo experiments demonstrate that this system effectively promotes early stem cell recruitment and accelerates bone regeneration in different bone healing scenarios, including cranial and maxillary defects.

Synergy of engineered gelatin methacrylate-based porous microspheres and multicellular assembly to promote osteogenesis and angiogenesis in bone tissue reconstruction

One of the key challenges in bone defects treatment is providing adequate and stable blood supply during new tissue regeneration. Mesenchymal stem cells (MSCs) and endothelial cells (ECs) have great potential to promote osteogenesis and angiogenesis during bone defect repair through paracrine effects, but their therapeutic efficacy depends on effective cellular assembly and delivery. In this work, we developed various microspheres with different pore sizes for multi-cellular delivery to enhance the angiogenic and osteogenic capability via combining microfluidic and gradient freeze-drying techniques. The particle and pore size of fabricated porous gelatin methacrylate (GelMA)-based hydrogel microspheres (PGMS) could be controllable through adjusting the freezing time of hydrogel microspheres, the range of particles and pores size are 150–250 μm and 10–100 μm with different freezing time from 0 min to 30 min. The optimized particle size (200.8 ± 14.2 μm) and pore size (11.2 ± 1.9 μm) were explored to promote cell assemble, adhesion, growth, and proliferation in the PGMS. Furthermore, the co-assembly and delivery of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) on the PGMS was achieved and an optimal cellular ratio of BMSCs to HUVECs (20:2) was established for co-culturing of them to achieve optimal paracrine effects, further promoting osteogenic differentiation and angiogenesis. Finally, results from both in vitro and in vivo experiments showed that the developed PGMS with co-assembly of BMSCs to HUVECs contributed to accelerate bone regeneration and vascularization process daringly, exhibited great potential in vascularized bone tissue reconstruction.

Enhanced bone tissue regeneration via mesenchymal stem cells-laden Alginate/GelMa 3D-Bioprinted scaffold treated with Haplophyllum tuberculatum extract

Background and aimRegeneration of critical-sized bone defects is challenging due to avascular necrosis, inflammation, and disrupted osteogenesis. This study explores the synergistic effects of Haplophyllum tuberculatum (HT) extract and mesenchymal stem cells (MSCs) in an Alg/GelMa 3D-bioprinted scaffold to enhance bone regeneration. MethodsEthanolic extracts of stems (HTS), flowers (HTF), and a mixture (HTM) were obtained via Soxhlet extraction and subsequently characterized. Further investigations into their cytotoxicity, osteogenic and bone tissue regeneration potential were conducted, in vitro and in vivo. ResultsAlongside GC-MS analysis, vitamin and elemental analyses of HTS, HTF, and HTM revealed varying concentrations of key elements essential for bone regeneration. All extracts exhibited moderate antioxidant activity, with more potency in the HTF group. Cytotoxicity assays indicated the lack of cytotoxic effects from HTS and HTF on MSCs. The calcium secretion and deposition on MSCs revealed the osteogenic potential of HTF and HTM. Gene and protein expression analyses indicated significant upregulation of osteogenic markers in HTF-treated MSCs. The integration of MSCs into a Alg/GelMa 3D-bioprinted scaffold enhanced their viability and proliferation, validating its biocompatibility. Additionally, HTF promoted calcium deposition and ALP activity in the MSC-laden 3D-bioprinted scaffold. In vivo assessment in a rat calvarial defect model, demonstrated accelerated bone regeneration with HTF-treated scaffolds. The improved bone regeneration, vascularization, and collagen formation in HTF-treated defects were confirmed by histopathology results. ConclusionThis study underscores the significant role of the HTF in promoting osteogenesis, advocating for its incorporation into advanced tissue engineering strategies for bone regeneration.

A Stone‐Cottage‐Inspired Printing Strategy to Build Microsphere Patterned Scaffolds for Accelerated Bone Regeneration

AbstractThe physical microtopography, in an effective and stable manner, can powerfully confer biomaterials with enhanced osteoconduction for the repair of critical‐sized bone defects. However, the realization of the osteoconductive microtopography within a 3D porous scaffold is still unmet. Herein, this work presents a stone‐cottage‐inspired printing strategy to build microsphere patterned scaffolds with a tunable microtopography for accelerated bone regeneration. The customized composite inks of poly (lactic‐co‐glycolic acid) microspheres as “Stone” and alginate hydrogels as “Mortar” endow the fibers of as‐printed scaffolds with a stable and tunable groove‐ridge microstructure. Owing to this microtopography, microsphere patterned scaffolds significantly promote cell recruitment, immune response, angiogenesis, and osteogenesis. Meanwhile, compared to 55 and 85 µm, 25 µm width of groove‐ridge microstructure displays the most osteoconduction for repair of critical bone defects. Mechanistically, while cells prefer to adhere to microstructure with a bigger width and higher modulus in the early phase, this microstructure should also act as a barrier for cell growth and its smaller width is more beneficial for cell communication and differentiation in the later phase. Overall, it provides a robust strategy to fabricate the osteoconductive microtopography within a 3D scaffold, broadening the manipulation of physical morphology in tissue engineering.

NIR-stimulated rGO-HAMC hydrogel enhances fracture healing through regulating B-cell signaling

Bone fractures are frequently encountered in clinical practice and pose significant challenges, due to the high incidence of delayed healing or non-union. Reduced graphene oxide (rGO) stands out for its unique sensitivity to a wide range of light wavelengths, especially in the near-infrared (NIR) spectrum. In this study, we developed an approach to promote fracture healing using an rGO-HAMC hydrogel activated by NIR stimulation. In vitro experiments demonstrated that NIR-stimulated rGO hydrogel significantly enhanced osteogenesis in bone marrow stromal cells (BMSCs). In an in vivo mouse fracture model, the rGO hydrogel was applied to the fracture site, and NIR light was delivered transdermally, showing promising results in accelerating bone regeneration. These results demonstrate that NIR-stimulated rGO hydrogel significantly accelerates fracture healing, as evidenced by increased bone volume and trabecular thickness. Additionally, transcriptomic analysis revealed that pathways related to B-cell activation are implicated in the enhanced healing effects mediated by NIR-stimulated rGO hydrogel. These findings highlight the potential of the NIR-stimulated rGO hydrogel as an innovative strategy for bone regeneration, offering promising new avenues for the treatment and management of bone fractures.

Tauroursodeoxycholic acid combined with selenium accelerates bone regeneration in ovariectomized rats.

More recently, increased studies have revealed that antioxidants can cure osteoporosis by inhibiting oxidative stress. Tauroursodeoxycholic acid (TUDCA) and Selenium (Se) have been confirmed to possess potent anti-oxidative effects and accelerate bone regeneration. In addition, very little is currently known about the effects of a combination with Se and TUDCA on bone defects in osteoporotic states. We, therefore, aimed to assess the protective effect of combination with Se and TUDCA on bone regeneration and investigate the effect and underlying mechanisms. When MC3T3-E1 was cultured in the presence of H2H2, Se, TUDCA and Se/TUDCA therapy could increase the matrix mineralization and promote expression of anti-oxidative stress markers in MC3T3-E1, while reducing intracellular reactive oxygen species (ROS) and mitochondrial ROS levels. Meanwhile, silent information regulator type 1 (SIRT1) was upregulated in response to Se, TUDCA and Se/TUDCA exposures in H2H2 treated-MC3T3-E1. In the OVX rat model, Se, TUDCA and Se/TUDCA showed a clear positive effect against impaired bone repair in osteoporosis. The results above demonstrate that Se/TUDCA exhibits superior efficacy in both cellular and animal experiments, as compared to Se and TUDCA. In conclusion, combination with Se and TUDCA stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis.

Multifunctional sericin-based biomineralized nanoplatforms with immunomodulatory and angio/osteo-genic activity for accelerated bone regeneration in periodontitis

Periodontitis is a chronic inflammation caused by dental plaque. It is characterized by the accumulation of excessive reactive oxygen species (ROS) and inflammatory mediators in the periodontal area. This affects the function of host cells, activates osteoclasts, and destroys periodontal tissue. Treatments such as local debridement or antibiotic therapy for ameliorating the overactive inflammatory microenvironment and repairing periodontal tissues are challenging. This paper reports multifunctional nanoplatforms (Se-CuSrHA@EGCG) based on sericin with ROS-scavenging, immunomodulatory, angiogenic, and osteogenic capabilities. The natural protein sericin, derived from silk cocoons, is used in water/oil emulsification and cross-linking processes to create sericin nanoparticles (Se NPs). Numerous binding sites are present on the surface of Se NPs. Ion-doped hydroxyapatite nanoparticles (Se-CuSrHA NPs) can be constructed using the force between positive and negative charges. After mineralization, an antioxidant coating is formed on the surface using polyethyleneimine (PEI)/epigallocatechin gallate (EGCG). Research conducted both in vitro and in vivo demonstrates that Se-CuSrHA@EGCG NPs can efficiently scavenge ROS, regulate macrophage polarization, increase the secretion of anti-inflammatory cytokines, and balance the immune microenvironment. In addition, Se-CuSrHA@EGCG stimulates angiogenesis, inhibits osteoclasts, and accelerates periodontal tissue repair. Therefore, this is a preferable strategy to accelerate bone regeneration in patients with periodontitis.

Biomimetic Scaffolds Regulating the Iron Homeostasis for Remolding Infected Osteogenic Microenvironment.

The treatment of infected bone defects (IBDs) needs simultaneous elimination of infection and acceleration of bone regeneration. One mechanism that hinders the regeneration of IBDs is the iron competition between pathogens and host cells, leading to an iron deficient microenvironment that impairs the innate immune responses. In this work, an in situ modification strategy is proposed for printing iron-active multifunctional scaffolds with iron homeostasis regulation ability for treating IBDs. As a proof-of-concept, ultralong hydroxyapatite (HA) nanowires are modified through in situ growth of a layer of iron gallate (FeGA) followed by incorporation in the poly(lactic-co-glycolic acid) (PLGA) matrix to print biomimetic PLGA based composite scaffolds containing FeGA modified HA nanowires (FeGA-HA@PLGA). The photothermal effect of FeGA endows the scaffolds with excellent antibacterial activity. The released iron ions from the FeGA-HA@PLGA help restore the iron homeostasis microenvironment, thereby promoting anti-inflammatory, angiogenesis and osteogenic differentiation. The transcriptomic analysis shows that FeGA-HA@PLGA scaffolds exert anti-inflammatory and pro-osteogenic differentiation by activating NF-κB, MAPK and PI3K-AKT signaling pathways. Animal experiments confirm the excellent bone repair performance of FeGA-HA@PLGA scaffolds for IBDs, suggesting the promising prospect of iron homeostasis regulation therapy in future clinical applications.

Methods to Enhance Mechanical Strength of 3D Printed Chitosan Scaffolds for Jawbone Regeneration

Current jaw reconstruction methods using autografts and allografts have limitations such as donor site morbidity, limited bone volume, and immunological rejection. As opposed to surgical methods synthetic biomaterials are used however they often fall short in providing the optimal combination of biocompatibility, mechanical strength, and customizable design required for effective jawbone reconstruction. 3D-printed chitosan scaffolds offer a promising alternative due to their biocompatibility, ease of customization, and potential for improved mechanical strength. This review explores strategies to optimize 3D-printed chitosan scaffolds for jaw reconstruction. We examine ways to increase their mechanical strength without compromising biocompatibility, with a particular emphasis on chemical modifications such as hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) cross-linking and chitosan polyelectrolyte complex formation. We also discuss the critical roles that 3D printing processes (FDM and SLA) and intrinsic chitosan qualities (degree of deacetylation) play in making an ink printable. Optimizing 3D printing methods for chitosan-ceramic composites and exploring biocompatible additives to enhance printability are identified as key areas for further research. By addressing these challenges, 3D-printed chitosan scaffolds have the potential to become next-generation biomaterials for jaw reconstruction, revolutionizing the field through precise anatomical adaptation, enhanced osteoconductivity, controlled biodegradation, and the capacity for incorporating bioactive molecules, ultimately leading to accelerated bone regeneration and improved functional and aesthetic outcomes.

Spirulina protein concentrate hydrogel reinforced by hydroxyapatite nanoparticles and hydroxychloroquin: A novel platform for bone regeneration

Among the fabrication methods, hydrogels have received significant attention due to their excellent ability to mimic the extracellular matrix structure. Spirulina is a type of unicellular blue-green algae. It is an excellent source of protein and a wide variety of other nutrients. Hydroxychloroquin (HCQ) reduces bone resorption and osteoclasts growth. This study hypothesized that the hydrogel, which is composed of Spirulina protein cross-linked by transglutaminase and reinforced by hydroxyapatite (HAP) nanoparticles loaded with HCQ, could potentially aid in bone regeneration. The protein from Spirulina was extracted using the probe sonication method. Afterwards, hydrogels were prepared by incorporating the Spirulina protein with gelatin and cross-linked with varying percentages of transglutaminase. HCQ-loaded HAP nanoparticles were used to enhance not only the mechanical properties of the hydrogels but also to stimulate bone mineralization. Hydrogels were studied for their mechanical and rheological properties in vitro, as well as their ability to swell, break down, injectability, and release HCQ. Cell adhesion, proliferation, and bone mineralization on MG-63 osteoblast cells were also studied using Alizarine red and alkaline phosphatase markers. The loading efficiency of HCQ in HAP nanoparticles was about 97 %. The HCQ release rate from hydrogel containing HAP was 85 % in 9 hours. The tensile strength and injectability force of the optimized hydrogel were in the range of 530.75 KPa and 21 N, respectively. The results showed that hydrogels made with 10 % protein, 150 units of transglutaminase, 6 % gelatin, and HAP loaded with HCQ had the best cell behavior and improved markers of bone regeneration. The promising results obtained suggest that the prepared hydrogel may act as a suitable construct for accelerating bone regeneration.

Development of liposomal amniotic mesenchymal stem cell metabolite products (AMSC-MP) loaded-scaffold for in vitro osteogenesis induction

The use of scaffolds with good biocompatibility and mechanical properties largely determines the success of bone defect therapy intended to improve quality-adjusted life years. Furthermore, amniotic mesenchymal stem cell metabolite product (AMSC-MP) is required to accelerate bone regeneration with sustained release required to maximize the effectiveness of therapy. This study aims to evaluate the effect of different phospholipids on the osteogenesis capacity of AMSC-MP liposome loaded into scaffold. The thin layer hydration method was employed to create the AMSC-MP liposomes which had different lipid components: L-α-phosphatidylcholine (PC) an unsaturated or hydrogenated soybean phosphatidylcholine (HSPC), a saturated phospholipid, with different types of charged phospholipids i.e., 1,2-dioleoyltrimethylammoniumpropane (DOTAP) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), which were cationic and non-ionic lipids respectively.AMSC-MP liposomes were embedded in the scaffold during a 24-hour incubation period. The results indicated that the particle sizes of liposomes prepared with saturated phospholipids, HS-DOTAP (132.35 ± 2.75 nm) and HS-DOTAP (152.85 ± 5.86 nm) were larger than those with saturated phospholipids, namely PC-DOTAP (139.355 ± 2.75 nm) and PC-DOTAP (91.85 ± 0.07 nm). The use of DOTAP in AMSC-liposomes resulted in positively charged vesicles i.e., +5 mV for HSPC-DOTAP and +10 mV for PC-DOTAP. Moreover, the results of an MTT viability test conducted on 7f2 cells and MSC indicated that all the formulas demonstrate good in vitro biocompatibility. Formulations containing DOPE produced high cellular uptake values and had superior sustain release properties compared to the others. This result correlates positively with cell attachment to the liposome scaffold which was higher than the others. Moreover, DOPE-containing formulations increased RUNX2 expression, indicating enhanced in vitro osteogenesis capacity. Therefore, Liposome AMSC-MP loaded scaffold demonstrates high potential for use in bone regeneration therapy.

Polydopamine-functionalized calcium-deficient hydroxyapatite 3D-printed scaffold with sustained doxorubicin release for synergistic chemo-photothermal therapy of osteosarcoma and accelerated bone regeneration

Interior bone-tissue regeneration and rapid tumor recurrence post-resection are critical challenges in osteosarcoma and other bone cancers. Conventional bone tissue engineering scaffolds lack inhibitory effects on bone tumor recurrence. Herein, multifunctional scaffolds (named DOX/PDA@CDHA) were designed through the spontaneous polymerization of Dopamine (PDA) on the surface of Calcium Deficient Hydroxyapatite (CDHA) scaffolds, followed by in situ loading of the chemotherapeutic drug Doxorubicin (DOX). The PDA coating endowed the scaffolds with significant photothermal properties, while the gradual release of DOX provided an effective chemotherapeutic effect. The on-demand release of DOX at tumor sites, triggered by dual stimulation (near-infrared (NIR) light and the acidic pH typical of tumor microenvironments), specifically targets cancer cells, thereby mitigating systemic side effects. These unique characteristics facilitated effective osteosarcoma eradication both in vitro and in vivo. Moreover, the scaffold's composition, which mimics the mineral phase of natural bone and is enhanced by PDA's biocompatibility, promotes critical osteogenic and angiogenic processes. This facilitates not only tumor eradication but also the regeneration of healthy bone tissue. Collectively, this study presents a potent candidate for the regeneration of bone defects induced by osteosarcoma.

Evaluation of the Regenerative Capacity of Demineralized Bone Matrix vs Fat Graft in Alveolar Cleft Model in Albino Rats.

This study was performed to evaluate the regenerative capacity of demineralized bone matrix vs fat graft, both guided by pericardium membrane in alveolar cleft model in albino rats. A total of 72 rats were required in this study. A surgical bone defect with a 7 mm length × 4 mm width × 3 mm depth was created as a model of an alveolar cleft, then the rats were divided randomly into four equal groups each group contained 18 rats: control group (defect only), the membrane group (the defect was covered by the pericardium membrane), the demineralized bone matrix (DBM) group (the defect was filled with DBM guided by pericardium membrane) and fat group (the defect was filled with a fat graft guided by the pericardium membrane). Around 6 rats from each group were euthanized after 2, 4, and 8 weeks. Skulls were scanned with cone beam computed tomography (CBCT) and harvested for histological evaluation with routine H&E immunohistochemical stains (Anti-osteocalcin and Anti-Wnt5a). The data was recorded and statistically analyzed by a two-way ANOVA. The study showed a notable formation of new bone, and expression of OCN and Wnt5a were notably increased by time in the fat group. However, the density of bone grafts and OCN and Wnt5a expression decreased with time in the DBM group. Control and membrane groups showed negative OCN and Wnt5a immune-reactivity in the cleft site. Fat graft results were superior to DBM results with regard to mucosal closure and accelerated bone regeneration, and may represent an effective treatment for alveolar cleft reconstruction. Finding an inexpensive, accessible, biocompatible and easily manipulated treatment for craniofacial reconstruction and fat graft fulfilled the desired aims. Further investigations with prolonged evaluation periods are needed. How to cite this article: Abdel Raouf E, Elsherbini AM, Abdel Salam Yousef Y, et al. Evaluation of the Regenerative Capacity of Demineralized Bone Matrix vs Fat Graft in Alveolar Cleft Model in Albino Rats. J Contemp Dent Pract 2024;25(6):554-562.

Oxygen plasma-modified polycaprolactone nanofiber membrane activates the biological function in cell adhesion, proliferation, and migration through the phosphorylation of FAK and ERK1/2, enhancing bone regeneration

Bone defects present significant clinical challenges in orthopedics, orthodontics, and maxillofacial surgeries. Accelerated bone regeneration can be facilitated by incorporating mesenchymal stem cells, but limitations in cell survival and growth remain concerns for complete bone repair. Biomaterial-based membranes have been developed to form biocompatible, degradable, and mechanically stable barriers in guided bone regeneration processes. Polycaprolactone (PCL) is a biodegradable polymer widely used as a bone regenerative material because of its favorable mechanical properties. However, its inherent hydrophobicity limits cell adhesion and proliferation, which are necessary for effective bone regeneration. To address this, we fabricated cell-regulatory PCL nanofiber membranes using plasma treatment to enhance induced pluripotent stem cell-derived mesenchymal stem cells and osteoblast growth. The plasma treatment parameters (gas type, flow rate, power, and exposure time) were optimized to enhance PCL’s surface hydrophilicity and protein adsorption properties while maintaining its mechanical integrity. The optimized oxygen plasma-modified PCL membrane demonstrated notable improvements in cell viability, adhesion, and proliferation. In addition, there was improved migration, regulated by cell surface markers and signaling proteins, of the induced pluripotent stem cell-derived mesenchymal stem cells and osteoblasts. In vivo studies in a rat calvarial defect model showed that the plasma-modified PCL membrane dramatically improved new bone formation, facilitating bone regeneration. These findings highlight the potential of plasma treatment of PCL nanofibers to produce effective cell-regulatory membranes for bone defect reconstruction.

THE ROLE OF PERICYTES IN BONE TISSUE REGENERATION AND THERAPEUTIC APPLICATIONS

The regeneration of massive bone defects poses a significant challenge in traumatology and orthopedics, often requiring bone grafting procedures following tumor resection, surgery, or severe injury. Current treatment methods include autologous and allogeneic bone grafts, as well as bone substitutes. While autologous transplantation is considered the standard, it is limited by donor site morbidity and availability. Allogeneic transplantation presents risks such as graft rejection and disease transmission. Bone substitutes may not fully restore bone defects. Tissue-engineered biomaterials offer promise for effective regeneration, utilizing stem cells, growth factors, and scaffolds. Adipose tissue, rich in mesenchymal stem cells and perivascular stem cells (pericytes), is a promising cell source for tissue engineering. This thesis explores the therapeutic potential of pericytes combined with various biological carriers and stimulating factors to enhance bone tissue regeneration. Pericytes, contractile cells surrounding small blood vessels, are crucial for vessel integrity and blood flow regulation. They express markers like α-SMA and PDGFR-β and participate in angiogenesis, immune function, and tissue repair. Interactions with endothelial cells via signaling pathways involving molecules like VEGF and TGF-β are vital for vessel formation and stability. With their multipotent nature, pericytes show promise for regenerative medicine. Ongoing research is essential to address challenges in pericyte biology, including identification and understanding their roles in tissue regeneration. Studies highlight the potential of adipose tissue-derived pericytes in bone regeneration, particularly CD146+ pericytes, showing efficacy in spinal fusion and nonunion fracture treatment when combined with DBM. Preclinical studies confirm their effectiveness, especially when incorporated into various scaffold materials. Clinical studies using adipose-derived stem cells and autologous microfragmented adipose tissue have shown promise, with pericyte-enriched fractions holding potential for improved outcomes. Future research into pericyte application, combined with growth factors and scaffolds, could significantly advance bone tissue regeneration and regenerative medicine. Human pericytes show promise for bone tissue regeneration due to their mesenchymal stem cell properties and role in vascular stabilization. Injectable hydrogels are crucial for bone tissue engineering, with various biomaterials developed for this purpose. Studies using injectable hydrogels with pericytes have demonstrated their efficacy in accelerating bone regeneration in different models. Further advancements in injectable hydrogel technology incorporating stem cells and osteoinductive factors are needed for more efficient bone tissue restoration.

Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.

In this study, a novel bionic periosteum (BP)-bioactive glass fiber membrane (BGFM) is designed. The introduction of magnesium ion (Mg2+) and zinc ion (Zn2+) change the phase separation during the electrospinning (ES) jet stretching process. The fiber's pore structure transitions from connected to closed pores, resulting in a decrease in the rapid release of metal ions while also improving degradation via reducing filling quality. Additionally, the introduction of magnesium (Mg) and zinc (Zn) lead to the formation of negative charged tetrahedral units (MgO4 2- and ZnO4 2-) in the glass network. These units effectively trap positive charged metal ions, further inhibiting ion release. In vitro experiments reveal that the deigned bionic periosteum regulates the polarization of macrophages toward M2 type, thereby establishing a conducive immune environment for osteogenic differentiation. Bioinformatics analysis indicate that BP enhanced bone repair via the JAK-STAT signaling pathway. The slow release of metal ions from the bionic periosteum can directly enhance osteogenic differentiation and vascularization, thereby accelerating bone regeneration. Finally, the bionic periosteum exhibits remarkable capabilities in angiogenesis and osteogenesis, demonstrating its potential for bone repair in a rat calvarial defect model.

Development of in situ forming autologous fibrin scaffold incorporating synthetic teriparatide peptide for bone tissue engineering.

This study investigates the potential of an in-situ forming scaffold using a fibrin-based scaffold derived from autologous plasma combined with Synthetic Teriparatide (TP) for bone regeneration application. TP is known for its bone formation stimulation but has limited clinical use due to side effects. This autologous delivery system aims to provide precise, controlled, localized, and long-term release of TP for accelerating bone regeneration. Fibrinogen from autologous plasma was extracted using ethanol, and thrombin was precipitated with ammonium sulfate to create the fibrin scaffold. Characterization of fibrinogen was done through FTIR, SDS-Page, porosity, SEM, degradation, and rheology tests. Viability was assessed by MTT in five groups with different concentrations of TP in fibrin scaffold (50, 100, and 150 µl/ml), fibrin alone, and a control group against HEK and Wharton's jelly cells. The release profile of different concentrations of TP in the fibrin scaffold was also examined. The formation time of the fibrin scaffold was 4 ± 0.2 s. The highest Infrared absorption for fibrinogen was confirmed. Rheology assessment revealed a higher elastic modulus than the viscous modulus. The created fibrin scaffold displayed a consistent three-dimensional microstructure with an interconnected porous network. Cytotoxicity assays demonstrated good biocompatibility and enhanced cell growth with different concentrations of TP in the fibrin scaffold. The TP release increased with higher concentrations, peaking at an average of 61% over 54 h. Autologous plasma-derived fibrin scaffolds incorporating TP exhibit satisfactory release within the scaffold and hold promise as a versatile bone filler for clinical use, facilitating osteoregeneration.

Photothermal Catalytic Reduction and Bone Tissue Engineering Towards a Three-in-One Therapy Strategy for Osteosarcoma.

Osteosarcoma is one of the most dreadful bone neoplasms in young people, necessitating the development of innovative therapies that can effectively eliminate tumors while minimizing damage to limb function. An ideal therapeutic strategy should possess three essential capabilities: antitumor effects, tissue-protective properties, and the ability to enhance osteogenesis. In this study, self-assembled Ce-substituted molybdenum blue (CMB) nanowheel crystals are synthesized and loaded onto 3D-printed bioactive glass (CMB@BG) scaffolds to develop a unique three-in-one treatment approach for osteosarcoma. The CMB@BG scaffolds exhibit outstanding photothermally derived tumor ablation within the near-infrared-II window due to the surface plasmon resonance properties of the CMB nanowheel crystals. Furthermore, the photothermally synergistic catalytic effect of CMB promotes the rapid scavenging of reactive oxygen species caused by excessive heat, thereby suppressing inflammation and protecting surrounding tissues. The CMB@BG scaffolds possess pro-proliferation and pro-differentiation capabilities that efficiently accelerate bone regeneration within bone defects. Altogether, the CMB@BG scaffolds that combine highly efficient tumor ablation, tissue protection based on anti-inflammatory mechanisms, and enhanced osteogenic ability are likely to be a point-to-point solution for the comprehensive therapeutic needs of osteosarcoma.

Research advances on silence information regulator 6 as a potential therapeutic target for bone regeneration and repair.

Segmental bone defects and nonunion of fractures caused by trauma, infection, tumor or systemic diseases with limited osteogenesis and prolonged bone healing cycles are challenging issues in orthopedic clinical practice. Therefore, identifying regulatory factors for bone tissue regeneration and metabolism is crucial for accelerating bone repair and reconstructing defective areas. Silence information regulator 6 (SIRT6), functioning as a deacetylase and nucleotide transferase, is extensively involved in the regulation of differentiation, apoptosis, metabolism, and inflammation in bone cells including osteoblasts and osteoclasts, and is considered to be an important factor in regulating bone metabolism. SIRT6 forms a complex with B lymphocyte-induced maturation protein 1 (Blimp1), down-regulates the expression of the nuclear factor κB (NF-κB) pathway, and promotes the expression of the ERα-FasL axis signal to inhibit osteoclast formation and maturation differentiation, thereby hindering bone resorption and increasing bone mass. In addition, SIRT6 activates the Akt-mTOR pathway to regulate the autophagy level and osteogenesis of bone marrow mesenchymal stem cells, inhibits glycolysis and reactive oxygen production in osteoblasts, promotes osteoblast differentiation through the CREB/CCN1/COX2 pathway and the bone morphogenetic protein (BMP) signaling pathway, enhances bone formation, and accelerates bone regeneration and repair of skeletal tissue. This article provides an overview of the research progress on SIRT6 in the pathophysiology of bone regeneration, revealing its potential as a novel therapeutic target for bone tissue repair to alleviate the progression of skeletal pathological diseases.