Bone Regeneration Research Articles

Bone Disease in Primary Hyperparathyroidism-Changes Occurring in Bone Metabolism and New Potential Treatment Strategies.

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, predominantly caused by a single parathyroid adenoma that is responsible for the excessive secretion of parathyroid hormone (PTH)-the hallmark of disease. Excess of this hormone causes remarkable changes in bone metabolism, including an increased level of bone remodeling with a predominance of bone resorption. Those changes lead to deterioration of bone structure and density, especially in cortical bone. The main treatment for PHPT is surgical removal of the adenoma, which normalizes PTH levels and terminates the progression of bone disease and leads to its regeneration. However, because not all the patients are suitable candidates for surgery, alternative therapies are needed. Current non-surgical treatments targeting bone disease secondary to PHPT include bisphosphonates and denosumab. Those antiresorptives prevent further bone loss, but they lack the ability to regenerate already degraded bone. There is ongoing research to find targeted drugs capable of halting resorption alongside stimulating bone formation. This review presents the advancements in understanding the molecular mechanisms responsible for bone disease in PHPT and assesses the efficacy of new potential therapeutic approaches (e.g., allosteric inhibitors of the PTH receptor, V-ATPase, or cathepsin inhibitors) aimed at mitigating bone loss and enhancing bone regeneration in affected patients.

Enocyanin promotes osteogenesis and bone regeneration by inhibiting MMP9.

Enocyanin (ENO), an anthocyanin extracted from grapes, has been shown to exert inhibitory effects on acid phosphatase and inflammation; however, its role in osteogenesis and bone formation is currently unknown. The present study aimed to investigate the effects of ENO on osteogenesis in vitro and bone formation in vivo, and to explore the rudimentary mechanisms. KusaO cells were employed to evaluate the osteogenic role of ENO in vitro by Alizarin red S staining, ALP staining, quantitative PCR and western blotting, and an in vivo analysis of the therapeutic effects of ENO on a femoral fracture model was performed using stereo microscope, micro‑CT and histological staining. To further investigate the underlying mechanisms, mRNA sequencing was employed to investigate the changes in gene expression and the downstream pathways after ENO treatment. The results showed that ENO could promote the osteogenic differentiation of KusaO cells in vitro and bone fracture regeneration in vivo. Mechanistically, ENO was highly related to bone formation, including the 'Wnt signalling pathway', 'bone development' and 'bone mineralization'. In addition, matrix metalloproteinase 9 (MMP9) was identified as one of the targets of ENO in its promotional role in osteogenesis. In conclusion, ENO may represent a therapeutic candidate for bone regeneration in bone fractures by regulating osteogenesis and bone formation via MMP9.

Three-Dimensional Scaffolds Designed and Printed Using CAD/CAM Technology: A Systematic Review

The objective of this work is to review the literature on the use of three-dimensional scaffolds obtained by printing for the regeneration of bone defects in the maxillofacial area. The research question asked was: what clinical experiences exist on the use of bone biomaterials manufactured by CAD/CAM in the maxillofacial area? Prospective and retrospective studies and randomized clinical trials in humans with reconstruction area in the maxillofacial and intraoral area were included. The articles had to obtain scaffolds for bone reconstruction that were designed by computer processing and printed in different materials. Clinical cases, case series, in vitro studies and those that were not performed in humans were excluded. Six clinical studies were selected that met the established inclusion criteria. The selected studies showed heterogeneity in their objectives, materials used and types of regenerated bone defects. A high survival rate was found for dental implants placed on 3D-printed scaffolds, with rates ranging from 94.3% to 98%. The materials used included polycaprolactone, coral-derived hydroxyapatite, biphasic calcium phosphate (BCP) and bioceramics. The use of CAD/CAM technology is seen as key for satisfying variations in the shapes and requirements of different fabrics and size variations between different individuals. Furthermore, the possibility of using the patient’s own stem cells could revolutionize the way bone defects are currently treated in oral surgery. The results indicate a high survival rate of dental implants placed on 3D-printed scaffolds, suggesting the potential of this technology for bone regeneration in the maxillofacial mass.

The Deposition of Hydroxyapatite Particles Within an Organic Matrix on the Surface of Poly(lactic acid).

Hydroxyapatite (HAP) is a well-established material in biomedical applications, especially for bone tissue regeneration, dental implants, and drug delivery systems. Recent research emphasizes enhancing the biocompatibility and osteoconductivity of orthopedic implants using HAP. This study explores the potential of combining HAP with a lipid matrix to improve the surface properties and biocompatibility of poly(lactic acid) (PLA)-based, 3D-printed, resorbable bone implants. We utilized the Langmuir-Blodgett method to deposit HAP within a dihexadecyl phosphate (DHP) matrix onto PLA substrates. This study demonstrates that DHP and HAP form stable monolayers at the air/water interface with HAP particles distributed within a homogeneous lipid matrix. The presence of HAP and the resulting changes in surface free energy (SFE) are hypothesized to enhance the biocompatibility of PLA implants. Our findings indicate that films composed of DHP + HAP 5:1 are particularly effective in altering PLA surface characteristics, potentially improving osteointegration, and reducing microbial adherence. Overall, this work highlights that surface modification of PLA with HAP and lipid matrices is the first step towards new, promising, and cost-effective strategies for developing advanced biomaterials for bone regeneration.

Highly Porous 3D Nanofibrous Scaffold of Polylactic Acid/Polyethylene Glycol/Calcium Phosphate for Bone Regeneration by a Two-Step Solution Blow Spinning (SBS) Facile Route.

This work presents the successful production of highly porous 3D nanofibrous hybrid scaffolds of polylactic acid (PLA)/polyethylene glycol (PEG) blends with the incorporation of calcium phosphate (CaP) bioceramics by a facile two-step process using the solution blow spinning (SBS) technique. CaP nanofibers were obtained at two calcium/phosphorus (Ca/P) ratios, 1.67 and 1.1, by SBS and calcination at 1000 °C. They were incorporated in PLA/PEG blends by SBS at 10 and 20 wt% to form 3D hybrid cotton-wool-like scaffolds. Morphological analysis showed that the fibrous scaffolds obtained had a randomly interconnected and highly porous structure. Also, the mean fiber diameter ranged from 408 ± 141 nm to 893 ± 496 nm. Apatite deposited considerably within 14 days in a simulated body fluid (SBF) test for hybrid scaffolds containing a mix of hydroxyapatite (HAp) and tri-calcium phosphate-β (β-TCP) phases. The scaffolds with 20 wt% CaP and a Ca/P ration of 1.1 showed better in vitro bioactivity to induce calcium mineralization for bone regeneration. Cellular tests evidenced that the developed scaffolds can support the osteogenic differentiation and proliferation of pre-osteoblastic MC3T3-E1 cells into mature osteoblasts. The results showed that the developed 3D scaffolds have potential applications for bone tissue engineering.

A photo-triggered bioactive nanohydrogel loaded with niobium carbide for stem cell osteogenic differentiation

Photo-Cross-Linkable hydrogel has attracted immense interest in the regeneration of bone repair and regeneration strategies due to its superior biocompatibility and tunable mechanical properties. Recently, Nb was reported to strongly promote the bone regeneration process via an accelerated osteoblast-modulated alkaline phosphatase activity mechanism. In particular, Nb2C MXenes have drawn widespread attention due to their excellent biocompatibility and ability to induce bone formation. However, the easy agglomeration of Nb2C nanosheets and subsequent low cell endocytosis efficacy greatly suppressed the osteogenesis effect. In this study, a subtractive nanopore-engineered Nb2C MXene was prepared through a microwave combustion method, gelatin methacrylate was used as the carrier hydrogel, and the photo-triggered Porous-Nb2C@GelMA hydrogel was fabricated by a photo-triggered process. The pore-forming strategy not only successfully improved the distribution of Nb2C and formed more homogenous Porous-Nb2C@GelMA hydrogels but also guided bone marrow mesenchymal stem cells (BMSCs) toward osteoblast differentiation. Porous Nb2C provided convenient cellular grasping and endocytosis for BMSCs, which further created a favorable environment for differentiation and osteogenesis. This, in turn, leads to an increase in the expression of osteogenic markers, such as ALP and ARS, as well as osteogenic factors, such as BMP-2, COL-1, OCN, and OPN. Consequently, enhancing the regenerative microenvironment by incorporating porous Nb2C composite hydrogels shows promise for application in bone regeneration.

Therapeutic Potential of Stearoyl-CoA Desaturase1 (SCD1) in Modulating the Effects of Fatty Acids on Osteoporosis.

Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment.

Mesoporous Biosilica Beads for Controlled Selenium Nanoparticle Delivery from Collagen‐Chitosan Scaffolds: Promoting Bone Formation and Suppressing Prostate Cancer Growth

The controlled delivery of selenium nanoparticles (Se‐NPs) is promising for bone cancer treatment due to their dual benefits in bone regeneration and tumor inhibition, yet achieving an optimal dosing regimen remains challenging. Natural mesoporous biosilica (BS) beads have shown promise for drug delivery due to their microporous structure. This study explores incorporating BS beads into collagen‐chitosan (Coll‐CS) scaffolds, known for bone repair, to control Se‐NP delivery. Two approaches are compared: loading Se‐NPs into BS beads before integrating them into Coll‐CS scaffolds versus directly loading Se‐NPs into Coll‐CS scaffolds. The scaffold properties, Se release kinetics, cytocompatibility, and effects on mesenchymal stem cells (MSCs) and prostate cancer cells (LNCaP) are evaluated. BS bead‐loaded scaffolds provide controlled Se‐NP release and enhanced mechanical properties compared to directly loaded scaffolds. Higher Se‐NP concentrations in BS‐loaded scaffolds effectively promote MSC osteogenic differentiation and mineralisation while inhibiting LNCaP cell viability. In contrast, low Se‐NP concentrations not only induce early osteogenic differentiation but also promote cancer cell proliferation, underscoring the need for optimal Se‐NP concentration and release. These findings suggest that BS bead‐loaded Coll‐CS scaffolds are a promising strategy for controlled Se‐NP delivery, addressing the dual challenges of bone formation and cancer recurrence prevention in bone cancer treatment.

Reduced Graphene Oxide-Substituted Nanohydroxyapatite: Rejuvenating Bone-Nerve Crosstalk with Electrical Cues in a Fragility Fracture Rat Model under Hyperglycemia.

Diabetes has currently acquired the status of epidemic worldwide, and among its various pathological consequences like retinopathy and nephropathy, bone fragility fractures from diabetic osteopathy occurs in later stages and is equally destructive. Chronic hyperglycemia culminates into deteriorating microvasculature and quality of bone, making it prone to fractures. Among these, hip fractures are most common, especially in older diabetic patients apart from underlying neuropathy. Our study is an attempt to ameliorate hip fragility fracture and nerve trauma with electrical stimulation as an interface in a chronic diabetic rat model. We have fabricated reduced graphene oxide-substituted hydroxyapatite as an electroactive bone substitute and incorporated it into chitosan gelatin cryogels. The in situ reduction of graphene oxide during sintering of hydroxyapatite imparts higher potential to the fabricated composite in dealing with problem at question. The cryogels depicted optimum in vitro biocompatibility and enhanced mineralization after ectopic subcutaneous implantation in rats. The therapeutic potency of composite cryogels was evaluated in a hip fracture model with compression to the sciatic nerve in diabetic rats, mimicking the severe clinical trauma. The presence of cryogels in the femoral neck canal coupled with electrical stimulation and biochemical factors significantly improved bone regeneration in diabetic rats as depicted with microcomputed tomography analysis and histology images. The application of electrical stimulation also ameliorated the nerve trauma observed with 70% improvement in electrophysiological parameters such as the compound muscle action potential with combinatorial therapy. We therefore report the successful implication of a multitarget therapy in a chronic diabetic rat model unraveling the bone-nerve crosstalk with electroactive smart cryogels.

Drug-free extracellular vesicles: A spatiotemporally controlled release engineering strategy for osteogenesis and anti-inflammatory niches in rotator cuff regeneration

Natural small-molecule drugs have promising potential to promote tissue regeneration in various fields. Therefore, maximizing drug efficiency while minimizing potential side effects is imperative. Peiminine, a natural product extracted from natural Fritillaria, is one of small-molecule drugs in the field of bone regeneration due to its good bone-promoting and anti-inflammatory abilities. However, its application is limited by a lack of biological activity, poor biocompatibility at high concentrations, and difficulty in achieving long-term slow-release and therapeutic effects. Extracellular vesicles (EVs) produced by preconditioned cells are considered to have special biological functions, and their potential to further retain, buffer, and transmit drug effects and expand the therapeutic effect has been widely studied. Thus, our study provides a drug-free bioengineering strategy by preconditioning bone marrow mesenchymal stem cells (BMSC) with Peiminine, then EVs, secreted as Peim-EVs, were extracted and combined with a decellularized extracellular matrix (dECM). The final EVs-dECM system with a spatiotemporally controlled release system was formed. In vitro studies demonstrated that Peim-EVs solved the problem of Peiminine biocompatibility and exhibited osteogenic and anti-inflammatory effects, which may be related to PI3K/AKT, MAPK/NF-κB, and Hippo signaling pathways. An in vivo model of rotator cuff injury in rats also showed that EVs-dECM had a good effect on rotator cuff repair. Combined with engineering strategy, this study provides verification and scenario expansion for drug application, especially for drug-free strategies that retain the biological effects of drugs, and has broad significance.

Preclinical Evaluation of a Poly (Lactic Acid/Caprolactone) Bilayer Membrane and a Carbonate Apatite for Periodontal Regeneration: A Canine One-Wall Intrabony Defect Model.

This preclinical study aimed to evaluate the periodontal tissue regenerative capacities of poly (lactic acid/caprolactone) (PLCL) bilayer membrane in one-wall intrabony defects in dogs. No study has assessed the efficacy of PLCL bilayer membrane for periodontal regeneration therapy despite the fact that PLCL bilayer membrane has proved efficient for bone regeneration. In five beagle dogs, the bilateral mandibular second and fourth premolars were extracted 8 weeks before the experimental surgery. Standardized bone defects (5 mm in height and 6 mm in width) were surgically created on the mesial and distal roots of the bilateral third premolars in the mandible. The test groups were set up as follows: (i) carbonate apatite (CO3Ap) + PLCL, (ii) CO3Ap, (iii) xenograft (DBBM) + collagen membrane (CM), and (iv) DBBM. The control group was left empty. Radiological, histologic and histomorphometric characteristics were compared 8 weeks after surgery. No infectious complications were detected at any of the tested sites. The test groups exhibited a greater height and volume of the newly formed bone than the control group. They also showed a greater height of the newly formed cementum than the control group. However, the results were not statistically significant. The newly formed periodontal ligaments were inserted into newly formed bone and cementum in the test groups. The combined use of PLCL bilayer membrane and CO3Ap demonstrated comparable performance for periodontal tissue regeneration in one-wall intrabony defects compared to conventional therapies.

Bone Healing via Carvacrol and Curcumin Nanoparticle on 3D Printed Scaffolds.

Carvacrol is a potent antimicrobial and anti-inflammatory agent, while curcumin possesses antioxidant, anti-inflammatory, and anticancer properties. These phytochemicals have poor solubility, bioavailability, and stability in their free form. Nanoencapsulation can reduce these limitations with enhanced translational capability. Integrating nanocarriers with 3D-printedcalcium phosphate (CaP)scaffolds presents a novel strategy for bone regeneration. Carvacrol and curcumin-loaded nanoparticles (CC-NP) synthesized with melt emulsification produced negatively charged, monodispersed particles with a hydrodynamic diameter of ≈127nm. Their release from the scaffold shows a biphasic release under physiological and acidic conditions. At pH 5.0, the CC-NP exhibits a 53% release of curcumin and nearly 100% release of carvacrol, compared to 19% and 36% from their respective drug solutions. At pH 7.4, ≈40% of curcumin and 76% of carvacrol releases, highlighting their pH-sensitive release mechanism. In vitro studies demonstrate a 1.4-fold increase in osteoblast cell viability with CC-NP treatment. CC-NP exhibit cytotoxic effects against osteosarcoma cells, reducing cell viability by ≈2.9-fold. The antibacterial efficacy of CC-NP evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) exhibiting 98% antibacterial efficacy. This approach enhances therapeutic outcomes and minimizes the potential side effects associated with conventional treatments, paving the way for innovative applications in regenerative medicine.

Acute hyperlipidemia has transient effects on large-scale bone regeneration in male mice

Excessive dietary fat intake increases plasma lipid levels and has been associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fracture, especially in older postmenopausal women. The objective of this study was to investigate whether there are sex-related differences in lipid metabolism that could have an impact on large-scale bone regeneration. Because ribs provide a unique exception as the only bones capable of completely regenerating large-scale defects, we used a rib resection mouse model in which human features are recapitulated. After 10 days of exposure to a low-fat diet or high-fat diet (HFD), we performed large-scale rib resection surgeries on male and female mice (6–7 weeks old) with deletion of the low-density lipoprotein (LDL) receptor (Ldlr−/−) and age- and sex-matched wild-type (WT) mice were used as controls. Plasma analysis showed that short-term exposure to HFD significantly increases total cholesterol, LDL cholesterol, and triglycerides levels in Ldlr−/− mice but not in WT, with no differences between males and females. However, under HFD, callus bone volume was significantly reduced exclusively in male Ldlr−/− mice when compared to WT, although these differences were no longer apparent by 21 days after resection. Regardless of diet or genotype, BMD of regenerated ribs did not differ significantly between groups, although male mice typically had lower average BMD values. Together, these results suggest that short-term hyperlipidemia has transient effects on large-scale bone regeneration exclusively in male mice.

Investigating the Biological Efficacy of Albumin-Enriched Platelet-Rich Fibrin (Alb-PRF): A Study on Cytokine Dynamics and Osteoblast Behavior.

The development of effective biomaterials for tissue regeneration has led to the exploration of blood derivatives such as leucocyte- and platelet-rich fibrin (L-PRF). A novel variant, Albumin-Enriched Platelet-Rich Fibrin (Alb-PRF), has been introduced to improve structural stability and bioactivity, making it a promising candidate for bone regeneration. This study aimed to evaluate Alb-PRF's capacity for cytokine and growth factor release, along with its effects on the proliferation, differentiation, and mineralization of human osteoblasts in vitro. Alb-PRF membranes were analyzed using histological, scanning electron microscopy, and fluorescence microscopy techniques. Cytokine and growth factor release was quantified over seven days, and osteoinductive potential was evaluated with MG-63 osteoblast-like cells. Structural analysis showed Alb-PRF as a biphasic, highly cellularized material that releases lower levels of inflammatory cytokines and higher concentrations of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) compared to L-PRF. Alb-PRF exhibited higher early alkaline phosphatase activity and in vitro mineralization (p < 0.05) and significantly increased the OPG/RANKL mRNA ratio (p < 0.05). These results indicate that Alb-PRF has promising potential as a scaffold for bone repair, warranting further in vivo and clinical assessments to confirm its suitability for clinical applications.

Aging alters the effect of adiponectin receptor signaling on bone marrow-derived mesenchymal stem cells.

Adiponectin receptor signaling represents a promising therapeutic target for age-related conditions such as osteoporosis and diabetes. However, the literature presents conflicting evidence regarding the role of adiponectin signaling in bone homeostasis and fracture repair across different health states, ages, and disease conditions. These inconsistencies may arise from the complex endocrine and paracrine feedback mechanisms regulating adiponectin, as well as the variability in adiponectin isoforms and receptor expressions. In this study, we observed differential expression of adiponectin receptors in the bone marrow (BM) of aged mice, characterized by elevated levels of adiponectin receptor 2 and reduced levels of receptor 1, as corroborated by both single-cell sequencing and invivo staining. Additionally, circulating levels of adiponectin and its local expression were significantly higher in aged mice compared to younger counterparts. Treatment with adiponectin receptor agonist, AdipoRon, enhanced bone regeneration and repair in young mice by promoting osteogenesis and reducing osteoclastogenesis. Conversely, in aged mice, AdipoRon treatment led to cellular senescence, delayed bone repair, and inhibited osteogenic activity. Notably, the adiponectin receptor 1-Wnt and adiponectin receptor 2-MAPK and mTOR signaling pathways were differentially activated in AdipoRon-treated BM mesenchymal stem cells from young and aged mice. Additionally, the NF-κB, and AKT pathways were consistently downregulated in BM macrophages of both age groups following AdipoRon administration. In conclusion, aging significantly modulates the impact of adiponectin receptor signaling on BM mesenchymal stem cells. This modulation is potentially attributable to changes in receptor transcription and distribution, as well as differential activation of downstream signaling pathways.

Safety and efficacy of Mg-Dy membrane with poly-L-lactic acid coating for guided bone regeneration

The aim of this study was to evaluate safety and efficacy of a poly-L-lactic acid (PLLA)-coated magnesium (Mg)-Dysprosium (Dy) membrane in guided bone regeneration (GBR) using a rabbit calvarium model. The microstructure of the Mg-Dy membrane surface and thickness of the PLLA coating were examined. In vitro degradation and cytotoxicity test was conducted. The in vivo study used 24 white male rabbits with two 8 mm-diameter defects created on the calvaria; 12 defects were randomly assigned per group: (1) Negative control, (2) positive control, (3) uncoated Mg, and (4) PLLA-coated Mg group. Specimens were harvested at 4, 8, and 12 weeks postoperatively for radiological, histological, and histomorphometric analyses. The PLLA-coated Mg-Dy membrane showed a low degree of degradation, indicating that the coating exerted a protective effect. In the cytotoxicity test, no deformed or degenerated cells were observed. In the in vivo study, radiographic and histomorphometric analyses indicated favorable new bone formation and maintenance of the graft material for PLLA-coated Mg group. PLLA-coated Mg group, compared to the uncoated counterpart, restored the bony contour more completely, without inducing significant inflammatory response. Our results support the safety and efficacy of PLLA-coated Mg-Dy membranes for GBR both in vitro and in vivo.

Comparison of Activated PRF and Standard PRF in Terms of Evaluation of Quality Bone Regeneration in Extraction Sockets of Impacted Third Molar: A Split-Mouth Double-Blind Control Trial

Comparison of Activated PRF and Standard PRF in Terms of Evaluation of Quality Bone Regeneration in Extraction Sockets of Impacted Third Molar: A Split-Mouth Double-Blind Control Trial

Bone Regeneration with Dental Pulp Stem Cells in an Experimental Model

Background/Objectives: The therapeutic approach to bone mass loss and bone’s limited self-regeneration is a major focus of research, emphasizing new biomaterials and cell therapy. Tissue bioengineering emerges as a potential alternative to conventional treatments. In this study, an experimental model of a critical bone lesion in rats was used to investigate bone regeneration by treating the defect with biomaterials Evolution® and Gen-Os® (OsteoBiol®, Turín, Italy), with or without mesenchymal stromal cells from dental pulp (DP-MSCs). Methods: Forty-six adult male Wistar rats were subjected to a 5-mm critical bone defect in the right mandible, which does not regenerate without intervention. The rats were randomly assigned to a Simulated Group, Control Group, or two Study Groups (using Evolution®, Gen-Os®, and DP-MSCs). The specimens were euthanized at three or six months, and radiological, histological, and ELISA tests were conducted to assess bone regeneration. Results: The radiological results showed that the DP-MSC group achieved uniform radiopacity and continuity in the bone edge, with near-complete structural defect restitution. Histologically, full bone regeneration was observed, with well-organized, vascularized lamellar bone and no lesion edges. These findings were supported by increases in endoglin, transforming growth factor-beta 1 (TGF-β1), protocollagen, parathormone, and calcitonin, indicating a conducive environment for bone regeneration. Conclusions: The use of DP-MSCs combined with biomaterials with appropriate three-dimensional matrices is a promising therapeutic option for further exploration.

New titanium mesh design method in customized bone regeneration of the jaws: preliminary study on a sample of 11 patients

The aim of this study is 1) to present a new method of virtually-designed custom made scaffolds to be employed in customized bone regeneration (CBR) for segmental jaw atrophies and 2) to evaluate long-term clinical results in terms of bone regeneration success and implant rehabilitation success. A total of 11 patients with edentulousness and bone atrophy in a localized area of the mandible or the maxilla were recruited for the study. To fulfill the research inquiries, CT images of the pre-regeneration mandibular or maxillary arch of each patient were collected. A dedicated Mevislab 2.4 software was employed to virtually design custom bone regeneration meshes designed to fit the atrophic sector of each patient's mandible or maxilla. Subsequently, a second Meshmixer software was used to refine the margins of each of the designed meshes. All patients underwent oral surgery, during which a mixture of autologous and heterologous bone in a 1:1 proportion was grafted into the atrophic site, a custom-made mesh was placed, and a resorbable membrane was inserted. The mesh was removed after this procedure, and implant rehabilitation was performed. All patients underwent the bone regeneration procedure, with eight undergoing titanium mesh removal. A total of seven patients completed implant rehabilitation. Average horizontal bone augmentation was 3.525 ± 1.36 mm; average vertical bone augmentation was 4.45 ± 2.22 mm. Implant survival was 92.85%. During the healing phase, complications occurred in 9.09% of patients. The use of dedicated software, Mevislab 2.4 and Meshmixer, for titanium mesh design is an accurate, predictable, effective, and quick-to-use method. The learning curve for design is uncomplicated and rapid. Mesh exposure does not necessarily lead to bone graft failure; this complication can be treated by chlorhexidine aids.

Single-layer graphene oxide nanosheets induce proliferation and Osteogenesis of single-cell hBMSCs encapsulated in Alginate Microgels

Microfluidics cell encapsulation offers a way to mimic a 3D microenvironment that supports cell growth and proliferation, while also protecting cells from environmental stress. This technique has found extensive applications in tissue engineering and cell therapies. Several studies have demonstrated the advantages of graphene oxide (GO) as an osteogenic inducer; however, the significance of GO on stem cell fate in the single-cell state is still unclear. Here, a microfluidics-based approach is developed for continuous encapsulation of mesenchymal stem cells (MSCs) at the single-cell level using alginate microgels. So, single-layer graphene oxide (slGO) nanosheet is used to be encapsulated inside the alginate droplets. The results of AFM and SEM show that slGO can increase the roughness and reduce the stiffness of alginate hydrogels. The Young’s modulus of the alginate and alginate-slGO was obtained as 1414 kPa and 985.9 kPa, respectively. Live/dead assay and fluorescence microscopy images illustrate that slGO can maintain the viability and proliferation of microencapsulated hBMSCs. The obtained results show that slGO increases the mineralization of the encapsulated hBMSCs, so that microgels containing hBMSCs gradually became opaque during 21 days of culture. RT-qPCR results indicate that the expression of OCN, Runx2, and ALP in the alginate-slGO microgels is significantly higher than in the alginate microgels. The expression of OCN and Runx2 in the alginate-slGO microgels is 4.27 and 5.87-fold higher than in the alginate microgels, respectively. It can be concluded that low doses of slGO nanosheets have the potential to be utilized in the development of tissue engineering and bone regeneration. This finding offers a new method for creating injectable tissue transplants that are minimally invasive.