Osteogenic Growth Factors Research Articles

Evaluation of biocompatibility and osteoconductivity of a hybrid cell-tissue graft for bone regenerative medicine

Aim – to evaluate in vitro the biocompatibility and osteoconductivity of a hybrid graft based on a bioorganic matrix, human bone marrow mesenchymal stromal cells (BM-MSC) and osteogenic growth factors. Material and methods. Bioorganic matrices were studied for biocompatibility with human BM-MSC culture used in traumatology and orthopedics. For promoted osteogenic differentiation of BM-MSCs, allogeneic plasma enriched with soluble platelet factors was used. The osteogenic potential of BM-MSCs by the synthesis of mRNAs of early (transcription factor 2 (Run X2), alkaline phosphatase (ALP)) and late genes (osteopontin (OSP)) osteogenesis was analyzed. The properties of cell adhesion and proliferation of MSCs in the conditions of a three-dimensional hybrid graft by the MTT test and fluorescence microscopy were assessed. Results. The biocompatibility of the studied bioorganic matrices with human BM-MSCs was established. The collagen matrix promoted rapid cell adhesion and proliferation between the scaffold fibrils. It has also been established that allogeneic platelet-rich plasma affects the osteogenic differentiation of human BM-MSCs in vitro, increasing the expression of marker genes RunX2, ALP, OSP. When modeling a hybrid graft in vitro, the formation of a tight contact between the alloimplant and collagen biopolymer using MSCs was shown. Conclusion. The biological properties of the developed hybrid cell-tissue graft characterize its biocompatibility and osteoconductivity of its constituent components, which makes it promising for use in regenerative medicine, especially in reconstructive surgery of bone defects.

A strategy for introducing biopotency-enhanced chirality coating on bio-magnesium

Biomedical magnesium alloys (Mg) are often considered potential metallic materials for bone repair scaffolds due to their excellent biomechanical properties, biocompatibility, and biodegradability. However, their rapid degradation behavior is insufficient to support the rapid growth and repair of living tissues. The new surface modification methods to slow down the degradation rate of Mg scaffolds and promote the rapid growth of living tissues is urgent. Here, we developed a chiral-enhanced composite functional coating on the surface of biomedical magnesium. Specifically, a chiral supramolecular hydrogel with graphene oxide (GO) was used to simulate the chiral environment of biological systems, enhancing the adsorption of osteogenic growth factors. Additionally, the silane layers cleverly crosslink traditional silane chains with supramolecular chiral fibers through a hydrogen bond network, which allows the bonding strength (critical loads) of the composite coating to be maintained between 245–275 mN and retains structural integrity when soaked in SBF for 7 days. It was found that both MC3T3-E1 cells growth and BMP-2 adhesion were significantly enhanced by GO-added left-handed chiral coatings, which exhibit superior bone growth-promoting effects. In summary, incorporating chiral features into functional coatings represents a transformative approach in the design and application of bone defect repair materials.

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.

ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration

To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH2 nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn2+ and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects.

Using Laponite to Deliver BMP‐2 for Bone Tissue Engineering – In Vitro, Chorioallantoic Membrane Assay and Murine Subcutaneous Model Validation

AbstractFracture non‐union occurs due to various factors, leading to the development of potentially substantial bone defects. While autograft and allograft are the current gold standards for non‐union fractures, challenges related to availability and immune rejection highlight the need for improved treatments. A strategy in bone tissue engineering is to harness growth factors to induce an effect on cells to change their phenotype, behavior and initiate signaling pathways which lead to increased matrix deposition and tissue formation. Bone morphogenetic protein‐2 (BMP‐2) is a potent osteogenic growth factor however, given its rapid clearance time in vivo, there is a specific therapeutic window for efficacy while avoiding potential deleterious side‐effects. It is demonstrated that a Laponite nanoclay coating on a 3D printable and bioresorbable poly(caprolactone) trimethacrylate‐based resin enables binding of BMP‐2, decreases the rate of release, enabling reduced concentrations to be used while enhancing osteoinduction in both in vitro and in vivo models.

Hydrolyzed egg yolk powder promotes bone growth and development in rats: A multidimensional mechanistic study

Given the growing worldwide focus on bone health, exploring safe and effective interventions to maintain skeletal integrity is imperative. This study involved intragastrically administering hydrolyzed egg yolk powder (HEYP) to 3-week-old Sprague‒Dawley (SD) rats over a period of six weeks. The effects of HEYP on bone growth and the underlying mechanisms were comprehensively investigated by evaluating known bone growth parameters, bone microstructural features, serum biochemical parameters, the metabolome, and the gut microbiome. HEYP administration significantly increased longitudinal bone growth while concurrently increasing the serum levels of osteogenic growth factors. Subsequent metabolomic analyses revealed significant alterations in the serum levels of metabolites associated with bone metabolism, highlighting the profound impact of HEYP on amino acid metabolism. Additionally, gut microbiome analyses revealed HEYP-induced changes in the gut microbiota (GM), identifying key bacterial genera, including Blautia, Parasutterella, Marvinbryantia and Prevotella, that were potentially beneficial for bone formation and linked to bone growth. Correlation analyses further highlighted associations between significantly altered serum metabolites, distinct bacterial genera, and bone growth-related parameters. These findings emphasized that HEYP might promote bone growth through various pathways, offering insights into the potential development and application of functional foods that promote bone health and potentially aid in osteoporosis prevention.

A new mRNA structure prediction based approach to identifying improved signal peptides for bone morphogenetic protein 2

BackgroundSignal peptide (SP) engineering has proven able to improve production of many proteins yet is a laborious process that still relies on trial and error. mRNA structure around the translational start site is important in translation initiation and has rarely been considered in this context, with recent improvements in in silico mRNA structure potentially rendering it a useful predictive tool for SP selection. Here we attempt to create a method to systematically screen candidate signal peptide sequences in silico based on both their nucleotide and amino acid sequences. Several recently released computational tools were used to predict signal peptide activity (SignalP), localization target (DeepLoc) and predicted mRNA structure (MXFold2). The method was tested with Bone Morphogenetic Protein 2 (BMP2), an osteogenic growth factor used clinically for bone regeneration. It was hoped more effective BMP2 SPs could improve BMP2-based gene therapies and reduce the cost of recombinant BMP2 production.ResultsAmino acid sequence analysis indicated 2,611 SPs from the TGF-β superfamily were predicted to function when attached to BMP2. mRNA structure prediction indicated structures at the translational start site were likely highly variable. The five sequences with the most accessible translational start sites, a codon optimized BMP2 SP variant and the well-established hIL2 SP sequence were taken forward to in vitro testing. The top five candidates showed non-significant improvements in BMP2 secretion in HEK293T cells. All showed reductions in secretion versus the native sequence in C2C12 cells, with several showing large and significant decreases. None of the tested sequences were able to increase alkaline phosphatase activity above background in C2C12s. The codon optimized control sequence and hIL2 SP showed reasonable activity in HEK293T but very poor activity in C2C12.ConclusionsThese results support the use of peptide sequence based in silico tools for basic predictions around signal peptide activity in a synthetic biology context. However, mRNA structure prediction requires improvement before it can produce reliable predictions for this application. The poor activity of the codon optimized BMP2 SP variant in C2C12 emphasizes the importance of codon choice, mRNA structure, and cellular context for SP activity.

Impacts of permeability and effective diffusivity of porous scaffolds on bone ingrowth: In silico and in vivo analyses

The permeability and the effective diffusivity of a porous scaffold are critical in the bone-ingrowth process. However, design guidelines for porous structures are still lacking due to inadequate understanding of the complex physiological processes involved. In this study, a model integrating the fundamental biological processes of bone regeneration was constructed to investigate the roles of permeability and effective diffusivity in regulating bone deposition in scaffolds. The in silico analysis results were confirmed in vivo by examining bone depositions in three diamond lattice scaffolds manufactured using selective laser melting. The findings show that the scaffolds with better permeability and effective diffusivity had deeper bone ingrowth and greater bone volume. Compared to permeability, effective diffusivity exhibited greater sensitivity to the orientation of porous structures, and bone ingrowth was deeper in the directions with higher effective diffusivity in spite of identical pore size. A 4.8-fold increase in permeability and a 1.6-fold increase in effective diffusivity by changing the porous structure led to a 1.5-fold increase in newly formed bone. The effective diffusivity of the porous scaffold affects the distribution of osteogenic growth factor, which in turn impacts cell migration and bone deposition through chemotaxis effects. Therefore, effective diffusivity may be a more suitable indicator for porous scaffolds because our study shows changes in this parameter determine changes in bone distribution and bone volume.

CA1 Modulates the Osteogenic Differentiation of Dental Follicle Stem Cells by Activating the BMP Signaling Pathway In Vitro.

Carbonic anhydrase 1 (CA1) has been found to be involved in osteogenesis and osteoclast in various human diseases, but the molecular mechanisms are not completely understood. In this study, we aim to use siRNA and lentivirus to reduce or increase the expression of CA1 in Dental follicle stem cells (DFSCs), in order to further elucidate the role and mechanism of CA1 in osteogenesis, and provide better osteogenic growth factors and stem cell selection for the application of bone tissue engineering in alveolar bone fracture transplantation. The study used RNA interference and lentiviral vectors to manipulate the expression of the CA1 gene in DFSCs during in vitro osteogenic induction. The expression of osteogenic marker genes was evaluated and changes in CA1, alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and Bone morphogenetic proteins (BMP2) were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). The osteogenic effect was assessed through Alizarin Red staining. The mRNA and protein expression levels of CA1, ALP, RUNX2, and BMP2 decreased distinctly in the si-CA1 group than other groups (p < 0.05). In the Lentivirus-CA1 (LV-CA1) group, the mRNA and protein expressions of CA1, ALP, RUNX2, and BMP2 were amplified to varying degrees than other groups (p < 0.05). Apart from CA1, BMP2 (43.01%) and ALP (36.69%) showed significant upregulation (p < 0.05). Alizarin red staining indicated that the LV-CA1 group produced more calcified nodules than other groups, with a higher optical density (p < 0.05), and the osteogenic effect was superior. CA1 can impact osteogenic differentiation via BMP related signaling pathways, positioning itself upstream in osteogenic signaling pathways, and closely linked to osteoblast calcification and ossification processes.

Promising osteoplastic materials and surgical technologies in reconstructive treatment of patients with bone nonunion and defects

Introduction Some progress has been made in the development of innovative implantation materials for osteoplastic surgery. However, the problem of bone defect management still remains relevant due to the continued high prevalence of injuries resulting from road accidents, catatrauma, man-made disasters and military operations.The purpose of the work was to analyze the relevant literature and to identify options for solving the problems of bone nonunion and defect management using materials developed on the principles of orthobiology and surgical technologies based on autologous repair.Materials and methods The search for sources was carried out with the ConnectedPapers analytical tool and the capabilities of the eLibrary electronic library using keywords and without restrictions on publication date.Results and discussion Recent publications contain information about the effectiveness of the combination of Masquelet technology and Ilizarov bone transport in patients with acquired and congenital defects, including in the conditions of active purulent infection. According to the literature, a promising autologous bone plastic material is the contents of the bone marrow cavity, containing osteogenic growth factors and bone morphogenetic proteins. Biomaterial is collected using the Reamer-Irrigator-Aspirator system (RIA) from the intramedullary canal of the femur or tibia. Currently, the effectiveness of bone morphogenetic proteins rhBMP-2 and rhBMP-7 in the restorative treatment of patients with bone defects and nonunion of various etiologies has actually been proven. The use of bone morphogenetic proteins has been introduced into foreign treatment protocols. Recent positive results of a combination of surgical technologies have proposed the combined use of the Ilizarov and Masquelet technologies, supplemented by PRP therapy. The basis for the expected effect from the combination of surgical technologies and orthobiological materials are the results of preclinical studies of the osteogenic potential of PRP therapy.Conclusion There are grounds for studying the clinical effect of the combined use of surgical technologies based on autologous reparative processes and materials developed on the principles of orthobiology. It is necessary and advisable to clinically implement the use of bone morphogenetic proteins rhBMP-2 and rhBMP-7 in the reconstructive treatment of patients with bone defects and nonunion of various etiologies. Multicenter clinical studies of a high level of evidence are needed to determine the effectiveness of PRP therapy in the reconstructive treatment of patients with bone nonunion and defects.

Enhanced bone regeneration in rat calvarial defects through BMP2 release from engineered poly(ethylene glycol) hydrogels

The clinical standard therapy for large bone defects, typically addressed through autograft or allograft donor tissue, faces significant limitations. Tissue engineering offers a promising alternative strategy for the regeneration of substantial bone lesions. In this study, we harnessed poly(ethylene glycol) (PEG)-based hydrogels, optimizing critical parameters including stiffness, incorporation of arginine-glycine-aspartic acid (RGD) cell adhesion motifs, degradability, and the release of BMP2 to promote bone formation. In vitro we demonstrated that human bone marrow derived stromal cell (hBMSC) proliferation and spreading strongly correlates with hydrogel stiffness and adhesion to RGD peptide motifs. Moreover, the incorporation of the osteogenic growth factor BMP2 into the hydrogels enabled sustained release, effectively inducing bone regeneration in encapsulated progenitor cells. When used in vivo to treat calvarial defects in rats, we showed that hydrogels of low and intermediate stiffness optimally facilitated cell migration, proliferation, and differentiation promoting the efficient repair of bone defects. Our comprehensive in vitro and in vivo findings collectively suggest that the developed hydrogels hold significant promise for clinical translation for bone repair and regeneration by delivering sustained and controlled stimuli from active signaling molecules.

Platelet rich fibrin as a bioactive matrix with proosteogenic and proangiogenic properties on human healthy primary cells in vitro

Blood concentrates like platelet rich fibrin (PRF) have been established as a potential autologous source of cells and growth factors with regenerative properties in the field of dentistry and regenerative medicine. To further analyze the effect of PRF on bone tissue regeneration, this study investigated the influence of liquid PRF matrices on human healthy primary osteoblasts (pOB) and co-cultures composed of pOB and human dermal vascular endothelial cells (HDMEC) as in vitro model for bone tissue regeneration. Special attention was paid to the PRF mediated influence on osteoblastic differentiation and angiogenesis. Based on the low-speed centrifugation concept, cells were treated indirectly with PRF prepared with a low (44 g) and high relative centrifugal force (710 g) before the PRF mediated effect on osteoblast proliferation and differentiation was assessed via gene and protein expression analyses and immunofluorescence. The results revealed a PRF-mediated positive effect on osteogenic proliferation and differentiation accompanied by increased concentration of osteogenic growth factors and upregulated expression of osteogenic differentiation factors. Furthermore, it could be shown that PRF treatment resulted in an increased formation of angiogenic structures in a bone tissue mimic co-culture of endothelial cells and osteoblasts induced by the PRF mediated increased release of proangiogenic growth factors. The effects on osteogenic proliferation, differentiation and vascularization were more evident when low RCF PRF was applied to the cells. In conclusion, PRF possess proosteogenic, potentially osteoconductive as well as proangiogenic properties, making it a beneficial tool for bone tissue regeneration.

A Combined Treatment of BMP2 and Soluble VEGFR1 for the Enhancement of Tendon-Bone Healing by Regulating Injury-Activated Skeletal Stem Cell Lineage

Background: Bone morphogenetic protein 2 (BMP2) is an appealing osteogenic and chondrogenic growth factor for promoting tendon-bone healing. Recently, it has been reported that soluble vascular endothelial growth factor (VEGF) receptor 1 (sVEGFR1) (a VEGF receptor antagonist) could enhance BMP2-induced bone repair and cartilage regeneration; thus, their combined application may represent a promising treatment to improve tendon-bone healing. Moreover, BMP2 could stimulate skeletal stem cell (SSC) expansion and formation, which is responsible for wounded tendon-bone interface repair. However, whether the codelivery of BMP2 and sVEGFR1 increases tendon enthesis injury–activated SSCs better than does BMP2 alone needs further research. Purpose: To study the effect of BMP2 combined with sVEGFR1 on tendon-bone healing and injury-activated SSC lineage. Study Design: Controlled laboratory study. Methods: A total of 128 C57BL/6 mice that underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to 4 groups: (1) untreated control group; (2) hydrogel group, which received a local injection of the blank hydrogel at the injured site; (3) BMP2 group, which received an injection of hydrogel with BMP2; and (4) BMP2 with sVEGFR1 group, which received an injection of hydrogel with BMP2 and sVEGFR1. Histology, micro–computed tomography, and biomechanical tests were conducted to evaluate tendon-bone healing at 4 and 8 weeks after surgery. In addition, flow cytometry was performed to detect the proportion of SSCs and their downstream differentiated subtypes, including bone, cartilage, and stromal progenitors; osteoprogenitors; and pro-chondrogenic progenitors within supraspinatus tendon enthesis at 1 week postoperatively. Results: The repaired interface in BMP2 with sVEGFR1 group showed a significantly improved collagen fiber continuity, increased fibrocartilage, greater newly formed bone, and elevated mechanical properties compared with the other 3 groups. There were more SSCs; bone, cartilage, and stromal progenitors; osteoprogenitors; and pro-chondrogenic progenitors in the BMP2 with sVEGFR1 group than that in the other groups. Conclusion: Our study suggests that the combined delivery of BMP2 and sVEGFR1 could promote tendon-bone healing and stimulate the expansion of SSCs and their downstream progeny within the injured tendon-bone interface. Clinical Relevance: Combining BMP2 with sVEGFR1 may be a good clinical treatment for wounded tendon enthesis healing.

Engineered Surfaces That Promote Capture of Latent Proteins to Facilitate Integrin-Mediated Mechanical Activation of Growth Factors.

Conventional osteogenic platforms utilize active growth factors to repair bone defects that are extensive in size, but they can adversely affect patient health. Here, an unconventional osteogenic platform is reported that functions by promoting capture of inactive osteogenic growth factor molecules to the site of cell growth for subsequent integrin-mediated activation, using a recombinant fragment of latent transforming growth factor beta-binding protein-1 (rLTBP1). It is shown that rLTBP1 binds to the growth-factor- and integrin-binding domains of fibronectin on poly(ethyl acrylate) surfaces, which immobilizes rLTBP1 and promotes the binding of latency associated peptide (LAP), within which inactive transforming growth factor beta 1 (TGF-β1) is bound. rLTBP1 facilitates the interaction of LAP with integrin β1 and the subsequent mechanically driven release of TGF-β1 to stimulate canonical TGF-β1 signaling, activating osteogenic marker expression in vitro and complete regeneration of a critical-sized bone defect in vivo.

Engineered three-dimensional bioactive scaffold for enhanced bone regeneration through modulating transplanted adipose derived mesenchymal stem cell and stimulating angiogenesis.

Titanium alloy materials are commonly used in orthopedic clinical treatments. However, conventional titanium implants usually lead to insufficient bone regeneration and integration because of mismatched biomechanics and poor bioactivities. To tackle these challenges, a porous titanium alloy scaffold with suitable mechanical properties was prepared using three-dimensional (3D) printing, and then an adipose-derived mesenchymal stem cell (ADSC) loaded platelet-rich plasma (PRP) gel was placed into the pores of the porous scaffold to construct a bioactive scaffold with dual functions of enhancing angiogenesis and osteogenesis. This bioactive scaffold showed good biocompatibility and supported cell viability proliferation and morphology of encapsulated ADSCs. Osteogenic and angiogenic growth factors in the PRP gel promoted the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro and enhanced osteogenic-related gene and protein expression in ADSCs, thus promoting osteogenic differentiation. After implantation into the femoral defects of rabbits, the bioactive scaffold promoted vascular network formation and the expression of osteogenesis-related proteins, thus effectively accelerating bone regeneration. Therefore, the osteogenic and angiogenic bioactive scaffold comprising a 3D printed porous titanium alloy scaffold, PRP, and ADSCs provides a promising design for orthopedic biomaterials with clinical transformation prospects and an effective strategy for bone defect treatment.

Evaluation of the genotoxicity, cytotoxicity, and bioactivity of calcium silicate-based cements

BackgroundAs calcium silicate-based cements (CSCs) have found success in various vital pulp therapy applications, several new CSC products have emerged. This study aimed to assess the genotoxicity, cytotoxicity, and bioactivity of four CSCs by comparing the newly introduced materials Bio MTA+ and MTA Cem with previously studied materials, Biodentine and NeoMTA.MethodsGenotoxicity was evaluated using the micronucleus (MN) assay in human peripheral blood lymphocyte cells, measuring MN frequency and nuclear division index (NDI). Cytotoxicity was assessed in human dental pulp stem cells through the Water-Soluble Tetrazolium Salt-1 (WST-1) colorimetric assay. Bioactivity was determined by ELISA, measuring the levels of angiogenic and odontogenic markers (BMP-2, FGF-2, VEGF, and ALP). Statistical analyses included ANOVA, Dunnet and Sidak tests, and Wald chi-square test. (p < .05).ResultsThe MN frequency in the groups was significantly lower than that in the positive control group (tetraconazole) (p < .05). NDI values decreased with increasing concentration (p < .05). Bio MTA+ and NeoMTA showed decreased cell viability at all concentrations in 7-day cultures (p < .01). All materials increased BMP-2, FGF-2, and VEGF levels, with Biodentine and NeoMTA showing the highest levels of BMP-2 and FGF-2 on day 7. Biodentine displayed the highest VEGF levels on day 7. Biodentine and NeoMTA groups exhibited significantly higher ALP activity than the Bio MTA+ and MTA Cem groups by day 7.ConclusionBio MTA+ and MTA Cem demonstrated no genotoxic or cytotoxic effects. Moreover, this study revealed bioactive potentials of Bio MTA+ and MTA Cem by enhancing the expression of angiogenic and osteogenic growth factors.

Chondrocytes supplemented to bone graft-containing scaffolds expedite cranial defect repair

Critical maxillofacial bone fractures do not heal spontaneously, thus, often there is a need to facilitate repair via surgical intervention. Gold standard approaches, include the use of autologous bone graft, or devices supplemented with osteogenic growth factors and bone substitutes. This research aimed to employ a critical size calvaria defect model, to determine if the addition of chondrocytes to collagen-containing bone graft substitute, may expedite bone repair. As such, using a critical size rat calvaria defect, we implanted a collagen scaffold containing bone graft substitute (i.e., Bone graft scaffold, BG) or BG supplemented with costal chondrocytes (cBG). The rats were subjected to live CT imaging at 1, 6, 9, and 12 weeks following the surgical procedure and sacrificed for microCT imaging of the defect site. Moreover, serum markers and histological evaluation were assessed to determine osseous tissue regeneration and turnover. Live CT and microCT indicated cBG implants displayed expedited bone repair vs, BG alone, already at 6 weeks post defect induction. cBG also displayed a shorter distance between the defect edges and greater mineral apposition distance compared to BG. Summerizing, the data support the addition of chondrocytes to bone substitute, accelerates the formation of new bone within a critical size defect.

Lactoferrin-Anchored Tannylated Mesoporous Silica Nanomaterials-Induced Bone Fusion in a Rat Model of Lumbar Spinal Fusion.

Lactoferrin (LF) is a potent antiviral, anti-inflammatory, and antibacterial agent found in cow and human colostrum which acts as an osteogenic growth factor. This study aimed to investigate whether LF-anchored tannylated mesoporous silica nanomaterials (TA-MSN-LF) function as a bone fusion material in a rat model. In this study, we created TA-MSN-LF and measured the effects of low (1 μg) and high (100 μg) TA-MSN-LF concentrations in a spinal fusion animal model. Rats were assigned to four groups in this study: defect, MSN, TA-MSN-LF-low (1 μg/mL), and TA-MSN-LF-high (100 μg/mL). Eight weeks after surgery, a greater amount of radiological fusion was identified in the TA-MSN-LF groups than in the other groups. Hematoxylin and eosin staining showed that new bone fusion was induced in the TA-MSN-LF groups. Additionally, osteocalcin, a marker of bone formation, was detected by immunohistochemistry, and its intensity was induced in the TA-MSN-LF groups. The formation of new vessels was induced in the TA-MSN-LF-high group. We also confirmed an increase in the serum osteocalcin level and the mRNA expression of osteocalcin and osteopontin in the TA-MSN-LF groups. TA-MSN-LF showed effective bone fusion and angiogenesis in rats. We suggest that TA-MSN-LF is a potent material for spinal bone fusion.

AuNP-Loaded Electrospinning Membrane Cooperated with CDs for Periodontal Tissue Engineering.

Guided bone regeneration (GBR) is commonly used to regenerate periodontal tissue. However, the bone inductivity and antibacterial properties of the GBR membranes currently in use are severely limited. This issue can be resolved by loading growth factors and antibiotics. Bioactive substitutes, such as Aunanoparticles (AuNPs) and carbon quantum dots (CDs), were proposed to prevent the denaturation of osteogenic growth factors and the induction of antibacterial drug resistance. Ornidazole was initially used as the raw material to prepare the CDs, followed by the incorporation of an optimal ratio of nanoparticles to produce the electrospun membrane doped with AuNPs and novel traceable antibacterial CDs. The morphology of the membrane was characterized. The adhesion, proliferation, and osteogenic differentiation of cells on the membrane were evaluated in vitro. The antimicrobial characteristics of the membrane were also investigated. The electrospun membrane was implanted into a rat skull defect model in vivo to investigate its osteogenic potential. The blending of nanomaterials did not affect the micro morphology of the fiber, resulting in enhanced mechanical properties. Membranes dopedwith AuNPs and CDs exhibited excellent biocompatibility, increased ALP activity, improved calcified nodules, and increased expression of osteogenic-associated proteins, in addition to pronounced antibacterial effects. The membrane also demonstrated excellent osteogenic characteristics in rat models. The synergistic effect of loaded AuNPs electrospun fiber membrane with CDs can promote periodontal bone regeneration and exert antibacterial activity.

Dual-functional coating that inhibits bone resorption and promotes bone formation applied to the surface modification of titanium screws

The purpose of this study was to solve the problem of Ti screw loosening in patients with osteoporosis. Romosozumab (Rom), a bone resorption inhibitor, and bone morphoprotein 2 (BMP-2), an osteogenic growth factor, were encapsulated into TiO2 nanotubes (TNTs) by polydopamine (pDA). The TiO2/Ti materials coated with Rom and BMP-2 were characterized by scanning electron microscopy (SEM), water contact angle (WCA), Fourier transform infrared (FTIR) spectroscopy and CCK-8 assays. Ti screws loaded with Rom and BMP-2 were implanted into the tibia of rats to evaluate their abilities to inhibit bone resorption, promote bone formation and enhance screw mechanical strength by micro-CT and pull-out force tests. The results showed that the loading of Rom in TNT could significantly inhibit bone resorption, while the loading of Rom and BMP-2 could significantly enhance bone formation and screw mechanical ability. The strategy of loading Rom and BMP-2 onto the surface of Ti screws can effectively reduce the risk of screw loosening in patients with osteoporosis.