-
Advanced Healthcare Materials Jun 2024Healing bone erosions in rheumatoid arthritis (RA) remains greatly challenging via biomaterial strategies. Given the unsuccessful innate bone erosion healing due to an...
Healing bone erosions in rheumatoid arthritis (RA) remains greatly challenging via biomaterial strategies. Given the unsuccessful innate bone erosion healing due to an inflammatory disorder, over-activated osteoclasts, and impaired osteoblasts differentiation, RA pathogenesis-guided engineering of an innovative hydrogel platform is needed for remodeling osteoimmune and osteogenic microenvironment of bone erosion healing. Herein, in situ adaptable and injectable interpenetrating polymer network (IPN) hydrogel is developed through an ingenious combination of a bio-orthogonal reaction between hyaluronic acid and collagen, along with effective electrostatic interactions leveraging bisphosphonate (BP)-functionalized hyaluronic acid (HA) macromers (HABP) and nanorod shaped zinc (Zn)-doped biphasic calcium phosphate (ZnBCP). IPN hydrogel exhibits exceptional adaptability to the local shape complexity at bone erosions, and by integrating ZnBCP and HABP, a multi-stage releasing platform is engineered, facilitating controlled cargo delivery for remodeling more anti-inflammatory M2 cells and reducing over-activated osteoclastic activities, thereby reconstructing the bone regeneration microenvironment. Sustainedly co-delivering multiple ions (calcium and phosphate) could display excellent osteogenic properties and be conducive to the bone formation process, by effects of osteogenesis-associated cell differentiation. Overall, our introduced bioactive IPN hydrogel therapy remodels the osteoimmune environment by synergistic pro-inflammation-resolving, osteogensis and anti-osteoclastic activities, displaying excellent bone reconstruction in the collagen-induced arthritis rabbit model. This article is protected by copyright. All rights reserved.
PubMed: 38925602
DOI: 10.1002/adhm.202304668 -
The Journal of Biological Chemistry Jun 2024The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and...
The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect hPSC-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide ChIP enrichment and mechanistic studies show that p38 MAPK-mediated CEBPD upregulation is required for CORIN-modulated osteogenesis. Contrastingly, the type I transmembrane heparan sulfate proteoglycan SDC1 enriched in MSCs exerts a negative regulatory effect on osteogenesis through a similar mechanism. ChIP-seq, bulk and single-cell transcriptomes, and functional validations indicated that CEBPD plays a critical role in controlling osteogenesis. In summary, our findings uncover previously unrecognized CORIN-mediated CEBPD transcriptomic networks in driving human osteoblast lineage commitment.
PubMed: 38925326
DOI: 10.1016/j.jbc.2024.107494 -
Colloids and Surfaces. B, Biointerfaces Jun 2024In the field of orthopedics, surgeons have long been facing the challenge of loosening of external fixation screws due to inherent material characteristics. Despite...
In the field of orthopedics, surgeons have long been facing the challenge of loosening of external fixation screws due to inherent material characteristics. Despite Polyetheretherketone (PEEK) being employed as an orthopedic implant material for many years, its bio-inert nature often hinders bone healing due to the limited bioactivity, which restricts its clinical applications. Herein, a new type of orthopedic implant (Sr-SPK) was developed by introducing strontium (Sr)-doped mesoporous bioactive glass (Sr-MBG) onto the surface of PEEK implants through a simple and feasible method. In vitro experiments revealed that Sr-SPK effectively promotes osteogenic differentiation while concurrently suppressing the formation of osteoclasts. The same results were validated in vivo with Sr-SPK significantly improving bone integration. Upon investigation, it was found that Sr-SPK promotes adhesion among bone marrow mesenchymal stem cells (BMSCs) thereby promoting osteogenesis by activating the regulation of actin cytoskeletal and focal adhesion pathways, as identified via transcriptome analysis. In essence, these findings suggest that the newly constructed Sr-doped biofunctionalized PEEK implant developed in this research can promote osteoblast differentiation and suppress osteoclast activity by enhancing cell adhesion processes. These results underline the immense potential of such an implant for wide-ranging clinical applications in orthopedics.
PubMed: 38924850
DOI: 10.1016/j.colsurfb.2024.114042 -
ACS Nano Jun 2024Osteoporosis disrupts the fine-tuned balance between bone formation and resorption, leading to reductions in bone quantity and quality and ultimately increasing fracture...
Osteoporosis disrupts the fine-tuned balance between bone formation and resorption, leading to reductions in bone quantity and quality and ultimately increasing fracture risk. Prevention and treatment of osteoporotic fractures is essential for reductions in mortality, morbidity, and the economic burden, particularly considering the aging global population. Extreme bone loss that mimics time-accelerated osteoporosis develops in the paralyzed limbs following complete spinal cord injury (SCI). In vitro nanoscale vibration (1 kHz, 30 or 90 nm amplitude) has been shown to drive differentiation of mesenchymal stem cells toward osteoblast-like phenotypes, enhancing osteogenesis and inhibiting osteoclastogenesis simultaneously. Here, we develop and characterize a wearable device designed to deliver and monitor continuous nanoamplitude vibration to the hindlimb long bones of rats with complete SCI. We investigate whether a clinically feasible dose of nanovibration (two 2 h/day, 5 days/week for 6 weeks) is effective at reversing the established SCI-induced osteoporosis. Laser interferometry and finite element analysis confirmed transmission of nanovibration into the bone, and microcomputed tomography and serum bone formation and resorption markers assessed effectiveness. The intervention did not reverse SCI-induced osteoporosis. However, serum analysis indicated an elevated concentration of the bone formation marker procollagen type 1 -terminal propeptide (P1NP) in rats receiving 40 nm amplitude nanovibration, suggesting increased synthesis of type 1 collagen, the major organic component of bone. Therefore, enhanced doses of nanovibrational stimulus may yet prove beneficial in attenuating/reversing osteoporosis, particularly in less severe forms of osteoporosis.
PubMed: 38924391
DOI: 10.1021/acsnano.4c02104 -
Journal of Biochemical and Molecular... Jul 2024Osteomyelitis is an invasive bone infection that can lead to severe pain and even disability, posing a challenge for orthopedic surgery. Naringin can reduce bone-related...
Osteomyelitis is an invasive bone infection that can lead to severe pain and even disability, posing a challenge for orthopedic surgery. Naringin can reduce bone-related inflammatory conditions. This study aimed to elucidate the function and mechanism of naringin in a Staphylococcus aureus-induced mouse model of osteomyelitis. Femurs of S. aureus-infected mice were collected after naringin administration and subjected to microcomputed tomography to analyze cortical bone destruction and bone loss. Bacterial growth in femurs was also assessed. Proinflammatory cytokine levels in mouse femurs were measured using enzyme-linked immunosorbent assays. Pathological changes and bone resorption were analyzed using hematoxylin and eosin staining and tartrate-resistant acid phosphatase staining, respectively. Quantitative reverse transcription polymerase chain reaction and western blot analysis were used to quantify the messenger RNA and protein expression of osteogenic differentiation-associated genes in the femurs. The viability of human bone marrow-derived stem cells (hBMSCs) was determined using cell counting kit-8. Alizarin Red S staining and alkaline phosphatase staining were performed to assess the formation of mineralization nodules and bone formation in vitro. Notch signaling-related protein levels in femur tissues and hBMSCs were assessed using western blot analysis. Experimental results revealed that naringin alleviated S. aureus-induced cortical bone destruction and bone loss in mice by increasing the bone volume/total volume ratio. Naringin suppressed S. aureus-induced bacterial growth and inflammation in femurs. Moreover, it alleviated histopathological changes, inhibited bone resorption, and increased the expression of osteogenic markers in osteomyelitic mice. It increased the viability of hBMSCs and promoted their differentiation and bone mineralization in vitro. Furthermore, naringin activated Notch signaling by upregulating the protein levels of Notch1, Jagged1, and Hes1 in the femurs of model mice and S. aureus-stimulated hBMSCs. In conclusion, naringin reduces bacterial growth, inflammation, and bone resorption while upregulating the expression of osteogenic markers in S. aureus-infected mice and hBMSCs by activating Notch signaling.
Topics: Animals; Flavanones; Mice; Osteomyelitis; Staphylococcus aureus; Staphylococcal Infections; Anti-Bacterial Agents; Anti-Inflammatory Agents; Humans; Male; Osteogenesis; Femur
PubMed: 38923626
DOI: 10.1002/jbt.23753 -
Oral Diseases Jun 2024Porphyromonas gingivalis-LPS regulated bone metabolism by triggering dysfunction of osteoblasts directly, and affecting activity of osteoclasts through intracellular...
OBJECTIVES
Porphyromonas gingivalis-LPS regulated bone metabolism by triggering dysfunction of osteoblasts directly, and affecting activity of osteoclasts through intracellular communication. Exosome, as the mediator of intercellular communication, was important vesicle to regulate osteogenesis and osteoclastogenesis. This research was designed for investigating the mechanism of BMSCs-EXO in modulating osteoclastic activity under the P. gingivalis-LPS.
MATERIALS AND METHODS
The cytotoxicity and osteogenic effects of P. gingivalis-LPS on BMSCs was evaluated, and then osteoclastic activity of RAW264.7 co-cultured with exosomes was detected. Besides, Affymetrix miRNA array and luciferase reporter assay were used to identify the target exosomal miRNA signal pathway.
RESULTS
BMSCs' osteogenic differentiation and proliferation were decreased under 1 and 10 μg/mL P. gingivalis-LPS. Osteoclastic-related genes and proteins levels were promoted by P. gingivalis-LPS-stimulated BMSCs-EXO. Based on the miRNA microarray analysis, exosomal miR-151-3p was lessened in BMExo-LPS group, which facilitated osteoclastic differentiation through miR-151-3p/PAFAH1B1.
CONCLUSIONS
Porphyromonas gingivalis-LPS could regulated bone metabolism by inhibiting proliferation and osteogenesis of BMSCs directly. Also, P. gingivalis-LPS-stimulated BMSCs-EXO promoted osteoclastogenesis via activating miR-151-3p/PAFAH1B1 signal pathway.
PubMed: 38923332
DOI: 10.1111/odi.15031 -
Advanced Science (Weinheim,... Jun 2024Inadequate osseointegration at the interface is a key factor in orthopedic implant failure. Mechanistically, traditional orthopedic implant interfaces fail to precisely...
Inadequate osseointegration at the interface is a key factor in orthopedic implant failure. Mechanistically, traditional orthopedic implant interfaces fail to precisely match natural bone regeneration processes in vivo. In this study, a novel biomimetic coating on titanium substrates (DPA-Co/GFO) through a mussel adhesion-mediated ion coordination and molecular clicking strategy is engineered. In vivo and in vitro results confirm that the coating exhibits excellent biocompatibility and effectively promotes angiogenesis and osteogenesis. Crucially, the biomimetic coating targets the integrin α2β1 receptor to promote M2 macrophage polarization and achieves a synergistic effect between immunomodulation and vascularized bone regeneration, thereby maximizing osseointegration at the interface. Mechanical push-out tests reveal that the pull-out strength in the DPA-Co/GFO group is markedly greater than that in the control group (79.04 ± 3.20 N vs 31.47 ± 1.87 N, P < 0.01) and even surpasses that in the sham group (79.04 ± 3.20 N vs 63.09 ± 8.52 N, P < 0.01). In summary, the novel biomimetic coating developed in this study precisely matches the natural process of bone regeneration in vivo, enhancing interface-related osseointegration and showing considerable potential for clinical translation and applications.
PubMed: 38922775
DOI: 10.1002/advs.202401833 -
Child's Nervous System : ChNS :... Jun 2024Treatment of subjects with refractory idiopathic intracranial hypertension (IIH) or shunted hydrocephalus with chronic shunt complications is challenging. What is the...
PURPOSE
Treatment of subjects with refractory idiopathic intracranial hypertension (IIH) or shunted hydrocephalus with chronic shunt complications is challenging. What is the role for cranial vault expansion, particularly utilizing posterior vault distraction osteogenesis (PVDO), in these cases? This study assesses medium-term efficacy of cranial vault expansion in this unique patient population.
METHODS
A retrospective review was conducted of patients who underwent cranial vault expansion from 2008 to 2023 at the Children's Hospital of Philadelphia. Subjects who did not have a diagnosis of primary craniosynostosis were included in the study. Demographic information, medical history, and perioperative details were collected from medical records. Primary outcomes were the rate of CSF diversion procedures and resolution of presenting signs and symptoms. Secondary outcomes were perioperative and 90-day complications and reoperation requirement.
RESULTS
Among 13 included subjects, nine (69.2%) patients had a primary diagnosis of shunted hydrocephalus and 4 (30.8%) patients had IIH. Twelve (92.3%) subjects underwent posterior vault distraction osteogenesis (PVDO) and one (7.7%) underwent posterior vault remodeling (PVR). All 4 patients with IIH demonstrated symptomatic improvement following PVDO, including resolution of headaches, vomiting, and/or papilledema. Among 9 patients with shunted hydrocephalus, CSF diversion requirement decreased from 2.7 ± 1.6 procedures per year preoperatively to 1.2 ± 1.8 per year following cranial vault expansion (p = 0.030). The mean postoperative follow-up was 4.1 ± 2.1 years and four (30.8%) patients experienced complications within 90 days of surgery, including infection (n = 2), CSF leak (n = 1), and elevated ICP requiring lumbar puncture (n = 1). Four (30.8%) patients underwent repeat cranial vault expansion for recurrence of ICP-related symptoms. At most recent follow-up, 7 of 9 patients with shunted hydrocephalus demonstrated symptomatic improvement.
CONCLUSION
Cranial vault expansion reduced intracranial hypertension-related symptomology as well as the rate of CSF diversion-related procedures in patients with refractory IIH and shunted hydrocephalus without craniosynostosis, and should be considered in those who have significant shunt morbidity.
PubMed: 38922367
DOI: 10.1007/s00381-024-06517-2 -
Journal of Functional Biomaterials May 2024The use of endosseous dental implants may become unfeasible in the presence of significant maxillary bone atrophy; thus, surgical techniques have been proposed to...
Biocompatibility of Subperiosteal Dental Implants: Changes in the Expression of Osteogenesis-Related Genes in Osteoblasts Exposed to Differently Treated Titanium Surfaces.
The use of endosseous dental implants may become unfeasible in the presence of significant maxillary bone atrophy; thus, surgical techniques have been proposed to promote bone regeneration in such cases. However, such techniques are complex and may expose the patient to complications. Subperiosteal implants, being placed between the periosteum and the residual alveolar bone, are largely independent of bone thickness. Such devices had been abandoned due to the complexity of positioning and adaptation to the recipient bone site, but are nowadays witnessing an era of revival following the introduction of new acquisition procedures, new materials, and innovative manufacturing methods. We have analyzed the changes induced in gene and protein expression in C-12720 human osteoblasts by differently surface-modified TiO materials to verify their ability to promote bone formation. The TiO materials tested were (i) raw machined, (ii) electropolished with acid mixture, (iii) sand-blasted + acid-etched, (iv) AlTiColorTM surface, and (v) anodized. All five surfaces efficiently stimulated the expression of markers of osteoblastic differentiation, adhesion, and osteogenesis, such as RUNX2, osteocalcin, osterix, N-cadherin, β-catenin, and osteoprotegerin, while cell viability/proliferation was unaffected. Collectively, our observations document that presently available TiO materials are well suited for the manufacturing of modern subperiosteal implants.
PubMed: 38921520
DOI: 10.3390/jfb15060146 -
Biomimetics (Basel, Switzerland) May 2024In this study, we report on the development of hydroxyapatite (HAp) and samarium-doped hydroxyapatite (SmHAp) nanoparticles using a cost-effective method and their...
In this study, we report on the development of hydroxyapatite (HAp) and samarium-doped hydroxyapatite (SmHAp) nanoparticles using a cost-effective method and their biological effects on a bone-derived cell line MC3T3-E1. The physicochemical and biological features of HAp and SmHAp nanoparticles are explored. The X-ray diffraction (XRD) studies revealed that no additional peaks were observed after the integration of samarium (Sm) ions into the HAp structure. Valuable information regarding the molecular structure and morphological features of nanoparticles were obtained by using Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The elemental composition obtained by using energy-dispersive X-ray spectroscopy (EDS) confirmed the presence of the HAp constituent elements, Ca, O, and P, as well as the presence and uniform distribution of Sm ions. Both HAp and SmHAp nanoparticles demonstrated biocompatibility at concentrations below 25 μg/mL and 50 μg/mL, respectively, for up to 72 h of exposure. Cell membrane integrity was preserved following treatment with concentrations up to 100 μg/mL HAp and 400 μg/mL SmHAp, confirming the role of Sm ions in enhancing the cytocompatibility of HAp. Furthermore, our findings reveal a positive, albeit limited, effect of SmHAp nanoparticles on the actin dynamics, osteogenesis, and cell migration compared to HAp nanoparticles. Importantly, the biological results highlight the potential role of Sm ions in maintaining cellular balance by mitigating disruptions in Ca homeostasis induced by HAp nanoparticles. Therefore, our study represents a significant contribution to the safety assessment of both HAp and SmHAp nanoparticles for biomedical applications focused on bone regeneration.
PubMed: 38921189
DOI: 10.3390/biomimetics9060309