A Biomimetic Fibrous Composite Scaffold with Nanotopography-Regulated Mineralization for Bone Defect Repair.

The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.

Tetrahedral Framework Nucleic Acids Inhibit Muscular Mitochondria-Mediated Apoptosis and Ameliorate Muscle Atrophy in Sarcopenia.

Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.

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Bacterial cellulose (BC) is a type of extracellular polymeric nanomaterial secreted by microorganisms over the course of their growth. It has gained significant attention in the field of bone tissue engineering due to its unique structure of three-dimensional fibrous network, excellent biocompatibility, biodegradability, and exceptional mechanical properties. Nevertheless, BC still has some weaknesses, including low osteogenic activity, a lack of antimicrobial properties, small pore size, issues with the degradation rate, and a mismatch in bone tissue regeneration, limiting its standalone use in the field of bone tissue engineering. Therefore, the modification of BC and the preparation of BC composite materials have become a recent research focus. Herein, we summarized the relationships between the production, modification, and bone repair applications of BC. We introduced the methods for the preparation and the modification of BC. Additionally, we elaborated on the new advances in the application of BC composite materials in the field of bone tissue engineering. We also highlighted the existing challenges and future prospects of BC composite materials.

Rhythm disturbance in osteoarthritis.

Osteoarthritis (OA) is one of the main causes of disabilities among older people. To date, multiple disease-related molecular networks in OA have been identified, including abnormal mechanical loadings and local inflammation. These pathways have not, however, properly elucidated the mechanism of OA progression. Recently, sufficient evidence has suggested that rhythmic disturbances in the central nervous system (CNS) and local joint tissues affect the homeostasis of joint and can escalate pathological changes of OA. This is accompanied with an exacerbation of joint symptoms that interfere with the rhythm of CNS in reverse. Eventually, these processes aggravate OA progression. At present, the crosstalk between joint tissues and biological rhythm remains poorly understood. As such, the mechanisms of rhythm changes in joint tissues are worth study; in particular, research on the effect of rhythmic genes on metabolism and inflammation would facilitate the understanding of the natural rhythms of joint tissues and the OA pathology resulting from rhythm disturbance. Video Abstract.

Posterior decompression and fusion versus laminoplasty for cervical ossification of posterior longitudinal ligament: a systematic review and meta-analysis.

Both posterior decompression and fusion (PDF) and laminoplasty (LAMP) have been used to treat cervical myelopathy due to multilevel ossification of posterior longitudinal ligament (OPLL). However, considerable controversy exists over the choice of the two surgical strategies. Thus, the aim of this study is to compare clinical outcomes of PDF and LAMP for treatment of cervical myelopathy due to multilevel OPLL. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials database to identify relevant clinical studies compared with clinical outcomes of PDF and LAMP for cervical OPLL. The primary outcomes including Japanese Orthopaedic Association (JOA) score and recovery rate of JOA were evaluated, and the secondary outcomes involving visual analogue scale (VAS), cervical curvature, OPLL progression rate, complication rate, reoperation rate and surgical trauma were also evaluated using Stata software. A total of nine studies were included in the current study, involving 324 patients. The current study suggests that compared with LAMP, PDF achieves a lower OPLL progression rate, better postoperative cervical curvature and similar neurological improvement in the treatment of multilevel cervical OPLL. However, PDF has a higher complication rate, more surgical trauma and higher postoperative VAS than LAMP.

Are craniocervical angulations or syrinx risk factors for the initiation and progression of scoliosis in Chiari malformation type I?

The pathophysiology behind the instigation and progression of scoliosis in Chiari malformation type I (CMI) patients has not been elucidated yet. This study aims to explore the initiating and progressive factors for scoliosis secondary to CMI. Pediatric patients with CMI were retrospectively reviewed for radiological characteristics of tonsillar herniation, craniocervical anomaly, syrinx morphology, and scoliosis. Subgroup analyses of the presence of syrinx, scoliosis, and curve progression were also performed. A total of 437 CMI patients were included in the study; 62% of the subjects had syrinx, and 25% had scoliosis. In the subgroup analysis of 272 CMI patients with syrinx, 78 of them (29%) had scoliosis, and multiple logistic regression analysis showed that tonsillar herniation ≥ 10 mm (OR 2.13; P = 0.033) and a clivus canal angle ≤ 130° (OR 1.98; P = 0.025) were independent risk factors for scoliosis. In the subgroup analysis of 165 CMI patients without syrinx, 31 of them (19%) had scoliosis, and multiple logistic regression analysis showed that a clivus canal angle ≤ 130° (OR 3.02; P = 0.029) was an independent risk factor for scoliosis. In the subgroup analysis of curve progression for 97 CMI patients with scoliosis, multiple logistic regression analysis showed that anomalies of the craniocervical junction and syrinx were not risk factors for curve progression. Many complex factors including craniocervical angulation, tonsillar herniation, and syrinx might participate in the instigation of scoliosis for CMI patients, and the relationship between craniocervical angulation and scoliosis deserves further study.

Systematic screening identifies a 2-gene signature as a high-potential prognostic marker of undifferentiated pleomorphic sarcoma/myxofibrosarcoma.

The Cancer Genome Atlas (TCGA) Research Network confirmed that undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) share a high level of genomic similarities and fall into a single spectrum of tumour. However, no molecular prognostic biomarkers have been identified in UPS/MFS. In this study, by extracting data from TCGA-Sarcoma (SARC), we explored relapse-related genes, their prognostic value and possible mechanisms of the dysregulations. After systematic screening, ITGA10 and PPP2R2B were included to construct a 2-gene signature. The 2-gene signature had an AUC value of 0.83 and had an independent prognostic value in relapse-free survival (RFS) (HR: 2.966, 95%CI: 1.995-4.410 P < .001), and disease-specific survival (DSS) (HR: 2.283, 95%CI: 1.358-3.835, P = .002), as a continuous variable. Gene-level copy number alterations (CNAs) were irrelevant to their dysregulation. Two CpG sites (cg15585341 and cg04126335) around the promoter of ITGA10 showed strong negative correlations with ITGA10 expression (Pearson's r < -0.6). Transcript preference was observed in PPP2R2B expression. The methylation of some CpG sites in two gene body regions showed at least moderate positive correlations (Pearson's r > .4) with PPP2R2B expression. Besides, the 2-gene signature showed a moderate negative correlation with CD4 + T cell infiltration. High-level CD4 + T cell infiltration and neutrophil infiltration were associated with significantly better RFS. Based on these findings, we infer that the 2-gene signature might be a potential prognostic marker in patients with UPS/MFS. Considering the potential benefits of immunotherapy for UPS/MFS patients, it is imperative to explore the predictive value of this signature in immunotherapeutic responses in the future.

The efficacy and safety of ipriflavone in postmenopausal women with osteopenia or osteoporosis: A systematic review and meta-analysis.

OBJECTIVES: Ipriflavone (IP) is one of the over-the-counter drugs and found in foods, which is available for prevention of osteoporosis (OP) since 1989 in over 22 countries. Although some clinical trials have suggested that IP is appropriate for treatment of OP, there continues to be controversy regarding the efficacy and safety due to some contradictory reports. With the wide usage of IP for osteoporotic women, there is a critical need for evaluation of the evidence for IP in clinical practice. METHODS AND MATERIALS: We searched randomized control trials (RCTs) in PubMed, CENTRAL and CNKI which used the regimen of IP in postmenopausal women with osteopenia or OP. The efficacy referred to the absolute change and relative change in bone mineral density (BMD) and bone turnover markers. The safety profiles were associated with adverse events and the number of subject withdrawals due to adverse reactions. RESULTS: Eleven RCTs (n = 1605) met the eligibility criteria were included. The increase of the BMD in lumbar spine of the IP group is greater than that of the placebo group (random effect model: SMD = 0.36; 95%CI= (0.09, 0.62)). For safety profile, most frequent reactions are gastrointestinal symptoms, but withdrawals due to adverse reactions are similar in both the IP group and placebo control at the same time intervals. CONCLUSIONS: IP significantly increases BMD and has inhibitory effect on bone resorption markers in postmenopausal women with osteopenia or OP. Gastrointestinal symptoms may occur, but adverse drug withdrawal events were not statistically increased when compared with placebo group.

Neural regulation of bone remodeling: Identifying novel neural molecules and pathways between brain and bone.

The metabolism and homeostasis of the skeletal system have historically been considered to be associated with the endocrine system. However, this view has been expanded with the recognition of several neural pathways playing important roles in the regulation of bone metabolism via central relays. In particular, bone metabolism and homeostasis have been reported to be precisely modulated by the central neural signaling. Initiated by the finding of leptin, the axis of neural regulation on bone expands rapidly. The semaphorin-plexin system plays an important role in the cross-talk between osteoclasts and osteoblasts; a complex system has also been identified and includes neuropeptide Y and cannabinoids. These findings facilitate our understanding of the central neuropeptides and neural factors in the modulation of bone metabolism and homeostasis, and these neuronal pathways also represent an area of research scenario that identifies the novel regulation between brain and bone. These regulatory mechanisms correlate with other homeostatic networks and demonstrate a more intricate and synergetic bone biology than previously envisioned. As such, this review summarizes the current knowledge of the neural regulation of bone metabolism and homeostasis, as well as its role in skeletal diseases and discusses the emerging challenges presented in this field.

Extracellular vesicles in bone and tooth: A state-of-art paradigm in skeletal regeneration.

Bone and tooth, fundamental parts of the craniofacial skeleton, are anatomically and developmentally interconnected structures. Notably, pathological processes in these tissues underwent together and progressed in multilevels. Extracellular vesicles (EVs) are cell-released small organelles and transfer proteins and genetic information into cells and tissues. Although EVs have been identified in bone and tooth, particularly EVs have been identified in the bone formation and resorption, the concrete roles of EVs in bone and tooth development and diseases remain elusive. As such, we review the recent progress of EVs in bone and tooth to highlight the novel findings of EVs in cellular communication, tissue homeostasis, and interventions. This will enhance our comprehension on the skeletal biology and shed new light on the modulation of skeletal disorders and the potential of genetic treatment.

Integrated analysis of mRNA-seq and miRNA-seq for host susceptibilities to influenza A (H7N9) infection in inbred mouse lines.

Host genetic factors play an important role in diverse host outcomes after influenza A (H7N9) infection. Studying differential responses of inbred mouse lines with distinct genetic backgrounds to influenza virus infection could substantially increase our understanding of the contributory roles of host genetic factors to disease severity. Here, we utilized an integrated approach of mRNA-seq and miRNA-seq to investigate the transcriptome expression and regulation of host genes in C57BL/6J and DBA/2J mouse strains during influenza virus infection. The differential pathogenicity of influenza virus in C57BL/6J and DBA/2J has been fully demonstrated through immunohistochemical staining, histopathological analyses, and viral replication assessment. A transcriptional molecular signature correlates to differential host response to infection has been uncovered. With the introduction of temporal expression pattern analysis, we demonstrated that host factors responsible for influenza virus replication and host-virus interaction were significantly enriched in genes exhibiting distinct temporal dynamics between different inbred mouse lines. A combination of time-series expression analysis and temporal expression pattern analysis has provided a list of promising candidate genes for future studies. An integrated miRNA regulatory network from both mRNA-seq and miRNA-seq revealed several regulatory modules responsible for regulating host susceptibilities and disease severity. Overall, a comprehensive framework for analyzing host susceptibilities to influenza infection was established by integrating mRNA-seq and miRNA-seq data of inbred mouse lines. This work suggests novel putative molecular targets for therapeutic interventions in seasonal and pandemic influenza.

Epigenetics and bone diseases.

Owing to the development of new technologies, the epigenome, a second dimensional method for genome analysis has emerged. Epigenetic mechanisms, including DNA methylation, histone modifications and noncoding RNAs, regulate gene expression without changing the genetic sequence. These epigenetic mechanisms normally modulate gene expression, trans-generational effects and inherited expression states in various biological processes. Abnormal epigenetic patterns typically cause pathological conditions, including cancers, age-related diseases, and specific cartilage and bone diseases. Facing the rapidly developing epigenetic field, we reviewed epigenetic mechanisms and their involvement with the skeletal system and their role in skeletal development, homeostasis and degeneration. Finally, we discuss the prospects for the future of epigenetics.

In search of nucleus pulposus-specific molecular markers.

Intervertebral disc degeneration usually starts from the inner nucleus pulposus (NP). The majority of previous NP-related studies assessed the outcome by the expression of chondrogenic markers since NP cells are chondrocyte like. However, NP cells are unique from chondrocytes and such assessments may be inappropriate. Very recently, several investigators published their findings about the transcriptional differences between NP cells and other related cell types on a genomic scale. In this review we discuss these recent findings and summarize the molecules that may be utilized as NP-specific markers to distinguish normal NP cells from several cell types and as markers that indicate its degeneration. We will revisit markers that distinguish NP cells from the outer surrounding annulus fibrosus (AF) cells and articular chondrocytes so as to facilitate authentic NP cell engineering from stem cells. Our review indicated that N-cadherin and keratin 19 have the potential to serve as common NP markers, as they distinguish healthy NP cells from AF cells, articular cartilage cells and degenerated NP cells.

Taurine-induced fabrication of nano-architectured conducting polypyrrole on biomedical titanium.

In this article, taurine, one of the small biomolecules associated with bone metabolism, is firstly utilized to induce the fabrication of nano-architectured conducting polypyrrole (NCPPy) on biomedical titanium in diverse pH values of phosphate buffer solution (PBS). Accordingly, the possible mechanism for the fabrication of NCPPy is proposed, which is dependent on the states of polytaurine from the polymerization of taurine, i.e., the inability of forming polytaurine and unordered restricted space results in taurine-incorporated and polytaurine-incorporated tightly packed nanoparticles (pH 6.2 and 8.0), respectively, and however, ordered restricted space constructed by polytaurine chains induces the fabrication of polytaurine-incorporated nanopillars (pH 6.8) and polytaurine-incorporated nanowire networks (pH 7.4).

Tetrahedral framework nucleic acids-based delivery of microRNA-155 alleviates intervertebral disc degeneration through targeting Bcl-2/Bax apoptosis pathway.

Intervertebral disc degeneration (IDD) is one of the most common causes of chronic low back pain, which does great harm to patients' life quality. At present, the existing treatment options are mostly aimed at relieving symptoms, but the long-term efficacy is not ideal. Tetrahedral framework nucleic acids (tFNAs) are regarded as a type of nanomaterial with excellent biosafety and prominent performance in anti-apoptosis and anti-inflammation. MicroRNA155 is a non-coding RNA involved in various biological processes such as cell proliferation and apoptosis. In this study, a complex named TR155 was designed and synthesised with microRNA155 attached to the vertex of tFNAs, and its effects on the nucleus pulposus cells of intervertebral discs were evaluated both in vitro and in vivo. The experimental results showed that TR155 was able to alleviate the degeneration of intervertebral disc tissue and inhibit nucleus pulposus cell apoptosis via Bcl-2/Bax pathway, indicating its potential to be a promising option for the treatment of IDD.

MRI-based endplate bone quality score predicts cage subsidence following oblique lumbar interbody fusion.

BACKGROUND CONTEXT: Cage subsidence is a common complication after lumbar interbody fusion surgery, with low bone mineral density (BMD) being a significant risk factor. ໿Endplate bone quality (EBQ) obtained from clinical MRI scans has been deemed reliable in determining regional BMD. However, the association between EBQ score and cage subsidence following oblique lumbar interbody fusion (OLIF) has not been clearly established. PURPOSE: This study aims to assess the relationship between EBQ score and cage subsidence in patients who underwent single-level OLIF. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: The study included adults with degenerative spinal conditions who underwent single-level OLIF at our institution. OUTCOME MEASURES: Cage subsidence, disc height, EBQ score, fusion rate. METHODS: This retrospective study analyzed data from patients who underwent single-level OLIF surgery at our institution between October 2017 and August 2022. Postoperative CT scans were used to measure cage subsidence, while the EBQ score was calculated using preoperative non-contrast T1-weighted MRI. To determine the predictive ability of the EBQ score, receiver operating characteristic (ROC) curve analysis was conducted. Additionally, univariable and multivariable logistic regression analyses were performed. RESULTS: In this study, a total of 88 patients were included and followed up for an average of 15.8 months. It was observed that 32.9% (n=29/88) of the patients experienced cage subsidence. The post-surgery disc height was significantly higher in patients who experienced subsidence compared to those who did not. The mean EBQ scores for patients with non-subsidence and subsidence were 2.31±0.6 and 3.48±1.2, respectively, and this difference was statistically significant. The ROC curve analysis showed that the AUC for the EBQ score was 0.811 (95% CI: 0.717-0.905). The most suitable threshold for the EBQ score was determined to be 2.318 (sensitivity: 93.1%, specificity: 55.9%). Additionally, the multivariate logistic regression analysis revealed a significant association between a higher EBQ score and an increased risk of subsidence (odds ratio [OR]=6.204, 95% CI=2.520-15.272, p<.001). CONCLUSIONS: Our findings indicate that higher preoperative EBQ scores are significantly linked to cage subsidence following single-level OLIF. Preoperative measurement of MRI can serve as a valuable tool in predicting cage subsidence.

Congenital epiblepharon in Chinese school-age children: a cross-sectional study.

PURPOSE: To investigate the prevalence and body mass index (BMI) associations of congenital lower epiblepharon in children in China and the difference in the refractive errors between children with and without epiblepharon. METHODS: Children 6-12 years of age in Beichen District of Tianjin were screened for congenital epiblepharon from September to October 2017. All children underwent slit-lamp examination, strabismus screening, visual acuity examination and refraction. Weight and height were also recorded. The prevalence of lower epiblepharon in school-age children was evaluated, and its association with age, sex, BMI, and refractive error was analyzed. RESULTS: A total of 28,225 children were examined; 564 had epiblepharon. The prevalence of epiblepharon was found to be, for 6-year-olds, 2.50%; for 7-year-olds, 2.13%; for 8-year-olds, 2.10%; for 9-year-olds, 1.97%; for 10-year-olds, 1.85%; for 11-year-olds, 1.67%; and for 12-year-olds, 1.19% (P < 0.05). The prevalence of overweight and obesity in children with epiblepharon was found to be 16.7% and 47.2%, respectively. The prevalence and degree of astigmatism was higher than in nonepiblepharon children. We found a possible association between severity of astigmatism and severity of epiblepharon. CONCLUSIONS: In our study, the prevalence of epiblepharon decreased with advancing age, and the majority of children with epiblepharon were found to be overweight or obese. Epiblepharon was associated with astigmatism.

Health-related Quality of Life (HRQOL) Outcomes of Selective/Nonselective Thoracic Fusion for Lenke 1C Adolescent Idiopathic Scoliosis (AIS) Patients with a Minimum 4-year Follow-up.

OBJECTIVE: Both the selective thoracic fusion (STF) and nonselective thoracic fusion (NSTF) are treatments for Lenke 1C adolescent idiopathic scoliosis (AIS). To date, the impacts of the two surgical strategies on patients' long-term quality of life remain unclear. Therefore, the purpose of this study was to explore the long-term effects of STF/NSTF on the quality of life in Lenke 1C AIS patients through a 4-10-year follow-up. METHODS: From January 2011 to April 2018, according to the inclusion and exclusion criteria, a retrospective single-center study of 75 surgical patients with Lenke 1C curves was performed (n = 75). They all underwent posterior fusion, and patients were divided into the selective thoracic fusion (STF) group (n = 42) and the nonselective thoracic fusion (NSTF) group (n = 33) based on their surgical approach. All participants received the survey of the visual analogue scale (VAS), SRS30, SF12, and Oswestry disability index (ODI) scales. Patients' gender, age, body mass index (BMI), surgical approach (STF/NSTF), surgical segments (UIV and LIV), follow-up time, complications, preoperative, postoperative, and last follow-up Cobb angles, and health-related quality of life (HRQOL) outcomes were collected, and analyzed through the Shapiro-Wilks test, Wilcoxon rank-sum test, t-test, and χ2 test. RESULTS: The mean follow-up of the entire cohort was 73 ± 5.6 months. The lumbar Cobb angle in the STF group improved from 31.8 ± 6.5° to 11.5 ± 5.1° after the operation and 10.3 ± 6.9° at the last follow-up. The postoperative correction rate of the lumbar curve was 63.8%, which increased to 67.7% at the last follow-up. In the NSTF group, the lumbar Cobb angle improved from 34.3 ± 11.3° to 4.3 ± 3.7° after the operation, and was 5.1 ± 3.1° at the last follow-up. The postoperative correction rate of the lumbar curve was 87.4%, and 85.1% at the last follow-up. At the last follow-up, the STF group had higher overall HRQOL scores than the NSTF group, and there were statistically differences between the different groups (STF/NSTF) in SRS-30-Mental health (p = 0.03), SRS-30-Satisfaction with management (p = 0.02), SRS-30-Pain (p = 0.03), ODI (p = 0.01), SF-12 PCS (p = 0.03), VAS back pain (p = 0.005) and VAS leg pain (p = 0.001). No statistically differences were found in SF12 MCS, SRS-30-Self-image/Appearance and SRS-30 Function/activity. CONCLUSION: After 4-10 years of follow-up, we found that the STF group achieved satisfactory correction results, and compared with the NSTF group, their overall HRQOL scores were higher, especially in terms of pain and satisfaction, where the STF group shows a significant advantage.

ECM-inspired calcium/zinc laden cellulose scaffold for enhanced bone regeneration.

Cellulose-based polymer scaffolds are highly diverse for designing and fabricating artificial bone substitutes. However, realizing the multi-biological functions of cellulose-based scaffolds has long been challenging. In this work, inspired by the structure and function of the extracellular matrix (ECM) of bone, we developed a novel yet feasible strategy to prepare ECM-like scaffolds with hybrid calcium/zinc mineralization. The 3D porous structure was formed via selective oxidation and freeze drying of bacterial cellulose. Following the principle of electrostatic interaction, calcium/zinc hybrid hydroxyapatite nucleated, crystallized, and precipitated on the 3D scaffold in simulated physiological conditions, which was well confirmed by morphology and composition analysis. Compared with alternative scaffold cohorts, this hybrid ion-loaded cellulose scaffold exhibited a pronounced elevation in alkaline phosphatase (ALP) activity, osteogenic gene expression, and cranial defect regeneration. Notably, the hybrid ion-loaded cellulose scaffold effectively fostered an M2 macrophage milieu and had a strong immune effect in vivo. In summary, this study developed a hybrid multifunctional cellulose-based scaffold that appropriately simulates the ECM to regulate immunomodulatory and osteogenic differentiation, setting a measure for artificial bone substitutes.