Bone Regeneration Process Research Articles

Dental pulp stem cells for reconstructing bone defects: A systematic review and meta-analysis.

Bone reconstruction with appropriate quality and quantity for dental implant replacement in the alveolar ridge is a challenge in dentistry. As dental pulp stem cells (DPSCs) could be a new perspective in bone regeneration in the future, this study investigated the bone regeneration process by DPSCs. Electronic searches for articles in the PubMed, EMBASE, and Scopus databases were completed until 21 April 2022. The most important inclusion criteria for selecting in vivo studies reporting quantitative data based on new bone volume and new bone area. The quality assessment was performed based on Cochrane's checklist. After the title, abstract, and full-text screening of 762 studies, 23 studies were included. A meta-analysis of 70 studies that reported bone regeneration based on new bone area showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P<0.00001, standardized mean difference [SMD]=2.40, 95% CI: 1.55‒3.26; I2=83%). Also, the meta-analysis of 14 studies that reported new bone regeneration based on bone volume showed a statistically significant favorable influence on bone tissue regeneration compared to the control groups (P=0.0003, SMD=1.85, 95% CI: 0.85‒2.85; I2=84%). This systematic review indicated that DPSCs in tissue regeneration therapy significantly affected bone tissue complex regeneration. However, more and less diverse preclinical studies will enable more powerful meta-analyses in the future.

Advances in bone regeneration with growth factors for spinal fusion: A literature review

Bone tissue is regenerated via the spatiotemporal involvement of various cytokines. Among them, the bone morphogenetic protein (BMP), which plays a vital role in the bone regeneration process, has been applied clinically for the treatment of refractory orthopedic conditions.Although BMP therapy using a collagen carrier has shown efficiency in bone regeneration over the last two decades, a major challenge—considerable side effects associated with the acute release of high doses of BMPs—has also been revealed. To improve BMP efficiency, the development of new carriers and biologics that can be used in conjunction with BMPs is currently underway.In this review, we describe the current status and future prospects of bone regeneration therapy, with a focus on BMPs. Furthermore, we outline the characteristics and molecular signaling pathways involving BMPs, clinical applications of BMPs in orthopedics, clinical results of BMP use in human spinal surgeries, drugs combined with BMPs to provide synergistic effects, and novel BMP carriers.

Chitosan as Bone Scaffold and Graft Materials for Bone Regeneration: A Systematic Review

Chitosan is a natural biodegradable polymer made from crustacean exoskeletons (shrimp and crab). Recently, natural material is preferably used in order to prevent any side effects from synthetic material. Previous research showed that chitosan has anti-bacterial properties, which can act as a bone graft scaffold material to increase in bone regeneration process. This article discusses the antibacterial effect of chitosan in the bone regeneration process. Bone graft consists of many primary graft materials which focus on alloplastic graft composite type. Bone graft is related to bone regeneration which associated with the process of secondary/indirect bone healing. The main trait of bone graft material is that it is not toxic to the chitosan’s host cell. Chitosan’s anti-bacterial effects can be associated with one of the three phases of bone defect healing, which is inflammation phase that acts to prevent bacterial invasion as an infectious disease in bone injury. Because of this, it can accelerate the polarization of macrophage M1 (secrete pro-inflammatory cytokine) to macrophage M2 (secrete anti-inflammatory cytokine) that relates to osteoblastogenesis. Osteoblastogenesis relates to the increase of osteoblast synthesis, deposition and mineralization of extracellular matrix leading to the maturation of osteoblast become osteocyte called ossification process.

Development and characterisation of strontium-doped sol-gel coatings to optimise the initial bone regeneration processes

Strontium plays an important role in bone regeneration; it promotes the differentiation and maturation of osteoblasts and inhibits the activity of osteoclasts. Our principal objective in this study was to formulate new organic-inorganic hybrid sol-gel coatings applied to titanium discs. These coatings were functionalised with different amounts of SrCl 2 and examined using in vitro tests and proteomics. The chemical and morphological characteristics of obtained coatings were scrutinised. The in vitro evaluation using the MC3T3-E1 osteoblasts and RAW264.7 macrophages showed the osteogenic and anti-inflammatory effects of strontium doping. The proteomic assay identified 111 different proteins adhering to the coatings. Six of these proteins reduced their adhesion affinity as a result of Sr-doping, whereas 40 showed increased affinity. Moreover, the proteomic analysis revealed osteogenic and anti-inflammatory properties of these biomaterials. The analysis also showed increased adhesion of proteins related to the coagulation system. We can conclude that proteomic methods are invaluable in developing new biomaterials and represent an important tool for predicting the biocompatibility of dental implants. • A new sol-gel coating doped with SrCl 2 was developed and characterized. • New Sr-enriched coatings with osteogenic, coagulatory and anti-inflammatory properties. • Protein adsorption patterns on Sr-coatings correlates with their in vitro results.

The Role of PEMFs on Bone Healing: An In Vitro Study.

Bone responses to pulsed electromagnetic fields (PEMFs) have been extensively studied by using devices that expose bone cells to PEMFs to stimulate extracellular matrix (ECM) synthesis for bone and cartilage repair. The aim of this work was to highlight in which bone healing phase PEMFs exert their action. Specifically, we evaluated the effects of PEMFs both on human adipose mesenchymal stem cells (hASCs) and on primary human osteoblasts (hOBs) by testing gene and protein expression of early bone markers (on hASCs) and the synthesis of late bone-specific proteins (on hOBs) as markers of bone remodeling. Our results indicate that PEMFs seem to exert their action on bone formation, acting on osteogenic precursors (hASCs) and inducing the commitment towards the differentiation pathways, unlike mature and terminally differentiated cells (hOBs), which are known to resist homeostasis perturbation more and seem to be much less responsive than mesenchymal stem cells. Understanding the role of PEMFs on bone regenerative processes provides important details for their clinical application.

Aucubin Impeded Preosteoclast Fusion and Enhanced CD31hi EMCNhi Vessel Angiogenesis in Ovariectomized Mice.

Osteogenesis is tightly correlated with angiogenesis during the process of bone development, regeneration, and remodeling. In addition to providing nutrients and oxygen for bone tissue, blood vessels around bone tissue also secrete some factors to regulate bone formation. Type H vessels which were regulated by platelet-derived growth factor-BB (PDGF-BB) were confirmed to couple angiogenesis and osteogenesis. Recently, preosteoclasts have been identified as the most important source of PDGF-BB. Therefore, inhibiting osteoclast maturation, improving PDGF-BB secretion, stimulating type H angiogenesis, and subsequently accelerating bone regeneration may be potent treatments for bone loss disease. In the present study, aucubin, an iridoid glycoside extracted from Aucuba japonica and Eucommia ulmoides, was found to inhibit bone loss in ovariectomized mice. We further confirmed that aucubin could inhibit the fusion of tartrate-resistant acid phosphatase (TRAP)+ preosteoclasts into mature osteoclasts and indirectly increasing angiogenesis of type H vessel. The underlying mechanism is the aucubin-induced inhibition of MAPK/NF-κB signaling, which increases the preosteoclast number and subsequently promotes angiogenesis via PDGF-BB. These results prompted that aucubin could be an antiosteoporosis drug candidate, which needs further research.

Eco‐Sustainable Approaches in Bone Tissue Engineering: Evaluating the Angiogenic Potential of Different Poly(3‐Hydroxybutyrate‐Co‐3‐Hydroxyhexanoate)–Nanocellulose Composites with the Chorioallantoic Membrane Assay

Additive manufacturing (AM) has opened new frontiers in precision medicine, giving the possibility of fabricating patient‐customized scaffolds to replace damaged tissues. In particular, bone tissue engineering (BTE) has benefited the most from the introduction of AM. In contrast, the impelling environmental issues are moving all the industrial sectors toward a sustainable development, avoiding the use of nonrenewable resources. Since thermoplastic polymers, such as poly(lactic acid) (PLA) and polycaprolactone (PCL), are massively used in the biomedical field, the primary objective of this study is to encourage the use of biodegradable and compostable materials also in BTE. Focusing on poly(3‐hydroxybutyrate‐co‐3‐hydroxyhexanoate) (PHBH), an eco‐friendly material with good biocompatibility and biodegradability, reinforced with cellulose nanocrystals (CNCs), 3D‐printed scaffolds through fused filament fabrication (FFF) are realized. Since vascularization is mandatory for bone regeneration processes and for a successful scaffold integration, the angiogenic potential of different PHBH–CNC formulations in vitro is tested, evaluating the colonization of the scaffolds by endothelial cells, and in ovo with the chorioallantoic membrane (CAM) assay. The final goal is to define the best geometry of the scaffold and PHBH–CNC composition that can trigger vascularization in BTE applications, with the ultimate aim of giving greater guarantees of osseointegration.

Effect of the accordion technique on bone regeneration during distraction osteogenesis: A computational study

Background and objectiveDistraction osteogenesis (DO), a bone lengthening technique, is widely employed to treat congenital and acquired limb length discrepancies and large segmental bone defects. However, a major issue of DO is the prolonged consolidation phase (10–36 months) during which patients must wear a cumbersome external fixator. Attempts have been made to accelerate the healing process of DO by an alternating distraction and compression mode (so-called “accordion” technique or AT). However, it remains unclear how varied AT parameters affect DO outcomes and what the most effective AT mode is. MethodsBased on an experimentally-verified mechanobiological model, we performed a parametric analysis via in silico simulation of the bone regeneration process of DO under different AT modes, including combinations of varied application times (AT began at week 1–8 of the consolidation phase), durations (AT was used continuously for 1 week, 2 weeks or 4 weeks) and rates (distraction or compression at 0.25, 0.5, 0.75, and 1 mm/12 h). The control group had no AT applied during the consolidation phase. ResultsCompared with the control group (no AT), AT applied at an early consolidation stage (e.g. week 1 of the consolidation phase) significantly enhanced bone formation and reduced the overall healing time. However, the effect of AT on bone healing was dependent on its duration and rate. Specifically, a moderate rate of AT (e.g. 0.5 mm/12 h) lasting for two weeks promoted blood perfusion recovery and bone regeneration, ultimately shortening the healing time. Conversely, over-high rates (e.g. 1 mm/12 h) and longer durations (e.g. 4 weeks) of AT adversely affected bone regeneration and blood perfusion recovery, thereby delaying bone bridging. ConclusionsThese results suggest that the therapeutic effects of AT on DO are highly dependent of the AT parameters of choice. Under appropriate durations and rates, the AT applied at an early consolidation phase is beneficial for blood recovery and bone regeneration. These results may provide a basis for selecting effective AT modes to accelerate consolidation and reduce the overall treatment period of DO.

Major approaches to melatonin and nutrients regulation in the bone regeneration process with exosomes and microRNAs: a systematic review

Introduction: Bone diseases comprise a large group of common diseases, including fractures, osteoporosis, and osteoarthritis that affect a large number of individuals. Without intervention, the prevalence of osteopenia is projected to increase to 64.3 million Americans and that of osteoporosis to 11.9 million by the year 2030. Melatonin exerts numerous physiological effects, including the induction of anti-inflammatory and antioxidants, resetting circadian rhythms, and promoting wound healing and tissue regeneration, participating in the maintenance and regenerative processes of bones and cartilage. Objective: A systematic review was carried out to present the state of the art of melatonin regulation, mesenchymal stem cells, exosomes, microRNAs, and nutrients in the bone regeneration process. Methods: The systematic review rules (PRISMA) were followed. The search was carried out from July to September 2022 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using scientific articles from 2019 to 2022. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 126 articles were found. A total of 59 articles were fully evaluated and 46 were included in this systematic review. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 9 studies at high risk of bias and 24 studies that did not meet the GRADE. Most studies showed homogeneity in their results, with I2 =97.8%&gt;50%. The symmetrical funnel plot does not suggest a risk of bias between small sample-size studies. Based on the results, melatonin has important functions in regulating the regenerative activities of mesenchymal stem cells that modulate, together with nutrients, the activities of exosomes and microRNAs in the bone regeneration process.

Halide-containing bioactive glasses enhance osteogenesis in vitro and in vivo

The application of bone substitutes to reconstruct bone defects is a strategy for repairing alveolar bone loss caused by periodontal disease. Bioactive glasses (BGs) are attractive synthetic bone substitutes owing to their abilities to degrade, form bone-like mineral and stimulate bone regeneration. Our previous studies showed that the incorporation of fluoride into alkali-free bioactive silicate glass promoted osteogenesis to some extent in vitro, while the incorporation of chloride facilitated glass degradation and accelerated the formation of hydroxyapatite. However, whether there is a synergistic effect of incorporating fluoride and chloride on further enhancement of osteogenesis and angiogenesis in vitro and in vivo was not known. Therefore, we synthesized three halide-containing BGs with fluoride only, or chloride only, or mixed fluoride and chloride, investigated their physicochemical properties and osteogenic and angiogenic effects both in vitro and in vivo. The results showed that the addition of both fluoride and chloride in a bioactive silicate glass could combine the structural roles of both, leading to a faster apatite formation than the glass with the presence of fluoride only and a more stable fluorapatite formation than the glass with the presence of chloride only, which formed hydroxyapatite upon immersion. The studied BGs were cytocompatible, as suggested by the cytotoxicity evaluation of hPDLSCs cultivated in the extracted BGs-conditioned culture media. More importantly, these BGs stimulated osteogenic differentiation of hPDLSCs without adding growth factors as indicated by the fact that BGs-conditioned media up-regulated the expression of BMP-2, OPN and VEGF of hPDLSCs and promoted the formation of bone nodules and collagen in vitro. By comparison, the incorporation of fluoride facilitated the expression of osteogenic-related biomarkers and bone nodule formation preferentially, while the incorporation of chloride induced the expression of angiogenic-related biomarkers and collagen formation. The in vivo investigation results demonstrated that the developed halide-containing BGs accelerated the process of bone regeneration, while the glass with mixed fluoride and chloride showed the most significant promotion effect among the three BGs. Therefore, our findings revealed a synergistic effect of incorporating fluoride and chloride into a BG on osteogenesis and angiogenesis in vitro and in vivo and highlighted the potential of fluoride and chloride containing bioactive glasses being bone substitutes for clinical use.

Major approaches to bone regeneration process with gut microbiota, exosomes, and microRNAs: a systematic review

Introduction: The incidence and mortality of bone diseases are still steadily increasing, creating a significant financial burden for societies across the world. To prevent the occurrence of bone diseases, slow their progression, or reverse the injuries they cause, new alternatives or complementary treatments need to be developed. The gut microbiota plays a role in bone metabolism and the pathogenesis of osteoporosis. Objective: It was to analyze through a systematic review the main considerations and clinical findings of the bone formation process through the modulation of the gut microbiota, as well as the functions of microRNAs and exosomes. Methods: The systematic review rules (PRISMA) were followed. The search was carried out from August to September 2022 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using scientific articles from 2001 to 2022. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 126 articles were found. A total of 34 articles were fully evaluated and 26 were included in this systematic review. Most studies showed homogeneity in their results, with I2 =98.8%&gt;50%. The symmetrical funnel plot does not suggest a risk of bias between small sample-size studies. The gut microbiota plays an important role in the modulation of bone healing and bone health through the traffic of inflammatory TNF+ T and Th17 cells to the bone marrow, influencing the inflammatory state of the patient, determining the “brain-gut-bone” axis. It has been shown that the diversity of the gut microbiota is decreased in patients with osteoporosis, leading to a state of dysbiosis. There is a relationship between the microbiome, osteoblasts, osteoclasts, and nuclear factor ligand receptor-kappa-B (RANKL) activator. Studies have proposed several mechanisms of gut microbiome interaction with osteoclastogenesis and bone health, including microRNA, insulin-like growth factor 1, and immune system mediation. Therefore, bone regeneration requires that the basic biological principles of osteogenesis, osteoinduction, osteoconduction, and biocompatibility are followed.

Biomaterial-induced macrophage polarization for bone regeneration

As the main target cells of immune regulation, macrophages play an important role in the bone regeneration process. Macrophages can be polarized into the M1 and M2 types under the stimulation of different factors. They have proinflammatory and anti-inflammatory effects, respectively, and play key roles in different stages of bone regeneration. The ratio of M1 to M2 macrophages can be regulated by immunomodulatory biomaterials to promote bone repair and regeneration. In this paper, we review the recent literature on the chemical, physical and biological properties of biomaterials and the regulation of macrophage polarization under the influence of other factors. We also cover new methods for preparing immunomodulatory biomaterials for bone regeneration. This paper will provide new design ideas for the development of biomaterials with immunological properties and will support the clinical translation of bone-related medical biomaterials.

Mg2+-doped carbon dots synthesized based on Lycium ruthenicum in cell imaging and promoting osteogenic differentiation in vitro

The construction of biomaterials suitable for bone regeneration has been a serious challenge in the medical field. Considering that the process of bone regeneration is difficult to monitor, the application of fluorescent carbon dots (CDs) materials for bone regeneration has received much attention. Here, we developed a Mg2+-doped biogenic carbon dot material and characterized it to determine the optimal ratio of carbon and magnesium sources in the synthesis of the material. Subsequently, its biocompatibility with MC3T3-E1 Subclone 4 (MC3T3) was investigated, and its high biocompatibility was supported by the preparation of biocarbon dots using natural lycium ruthenicum as the carbon source. In addition, our experimental results showed that the appropriate concentration of Mg-CDs was suitable for long-term cell growth and the cells had better growth, proliferation, and osteogenic differentiation ability. This Mg2+-doped biomass carbon dot shows great potential in bone tissue regeneration.

Modulation of Osteogenesis and Angiogenesis Activities Based on Ionic Release from Zn-Mg Alloys.

The enhancement of osteogenesis and angiogenesis remains a great challenge for the successful regeneration of engineered tissue. Biodegradable Mg and Zn alloys have received increasing interest as potential biodegradable metallic materials, partially due to the biological functions of Mg2+ and Zn2+ with regard to osteogenesis and angiogenesis, respectively. In the present study, novel biodegradable Zn–xMg (x = 0.2, 0.5, 1.0 wt.%) alloys were designed and fabricated, and the effects of adding different amounts of Mg to the Zn matrix were investigated. The osteogenesis and angiogenesis beneficial effects of Zn2+ and Mg2+ release during the biodegradation were characterized, demonstrating coordination with the bone regeneration process in a dose-dependent manner. The results show that increased Mg content leads to a higher amount of released Mg2+ while decreasing the Zn2+ concentration in the extract. The osteogenesis of pre-osteoblasts was promoted in Zn–0.5Mg and Zn–1Mg due to the higher concentration of Mg2+. Moreover, pure Zn extract presented the highest activity in angiogenesis, owing to the highest concentration of Zn2+ release (6.415 μg/mL); the proliferation of osteoblast cells was, however, inhibited under such a high Zn2+ concentration. Although the concentration of Zn ion was decreased in Zn–0.5Mg and Zn–1Mg compared with pure Zn, the angiogenesis was not influenced when the concentration of Mg in the extract was sufficiently increased. Hence, Mg2+ and Zn2+ in Zn–Mg alloys show a dual modulation effect. The Zn–0.5Mg alloy was indicated to be a promising implant candidate due to demonstrating the appropriate activity in regulating osteogenesis and angiogenesis. The present work evaluates the effect of the Mg content in Zn-based alloys on biological activities, and the results provide guidance regarding the Zn–Mg composition in designs for orthopedic application.

Dynamics of homocysteine level in patients with osteoporotic fracture

The research was carried out in order to investigate the blood serum level of homocysteine (HCY) which is involved in bone metabolism and has prognostic significance in the monitoring of the regenerative processes in osteoporosis and osteoporotic fractures. The study was carried out on patients 45-83 years old divided into 3 groups: group I – 14 patients with osteoporosis confirmed by densitometry or X-ray examination­, group II – 15 patients with non-osteoporosis fractures, group III – 25 patients with osteoporotic fractures. The control group consisted of practically healthy 14 people. In patients with various fractures osteosynthesis with Ilizarov apparatus or with metal plates was performed. After the operation, the patients were treated in an inpatient setting for a week, then sent for outpatient treatment and prescribed calcium and vitamin D supplements to accelerate the bone regeneration process. A blood sample was taken at 3 stages to monitor the dynamics of HCY level by Elisa test: on the 1st day before treatment, on the 10th day of treatment and 1 month after it. The results showed that on the 1st day before the treatment HCY concentration was statistically increased 2.7 times in group I, 5.6 times in group II, and 6.5 times in group III compared to the control group. In the month of recovery, a significant decrease in HCY level was observed in all treated groups but it still remained higher than in the control indicating the need to recommend additional therapeutic prescriptions. Keywords: level of homocysteine, osteoporosis, osteoporotic fractures

Co‐delivery of tauroursodeoxycholic acid and dexamethasone using electrospun ultrafine fibers to induce early coupled angiogenesis and osteogenic differentiation

AbstractIn the complicated process of bone regeneration, osteogenic differentiation and angiogenesis are crucial. In this study, a novel dual small molecule composite electrospun scaffold was prepared using polycaprolactone embedded with angiogenic factor tauro‐ursodeoxycholic acid and osteogenic factor dexamethasone to promote early angiogenesis and osteogenesis. Additionally, the related properties, angiogenic activity, and osteogenic activity analyses were conducted for the scaffold. The results demonstrated that the composite scaffold possessed proper mechanical properties and hydrophilicity. During the initial drug release, the release rate of the hydrophilic drug tauro‐ursodeoxycholic acid was higher compared to the hydrophobic drug dexamethasonethe. The drugs were slowly sustained released for more than 528 h. The composite scaffold boosted cell proliferation and accelerated osteogenic differentiation up to 21 days. The alkaline phosphatase activity and mineral deposition were comparatively higher on dual drug‐releasing fibers compared to control scaffolds. Wound healing migration assay and tube formation assay for further in vitro revealed that the composite scaffold exhibited higher efficiency in promoting cell migration and the angiogenesis ductive. Hence, the composite scaffold had a high potential for promoting bone regeneration by enhancing angiogenesis.

Provisional Matrix Formation at Implant Surfaces-The Bridging Role of Calcium Ions.

The success of dental implants lies in their strong and lasting integration into the patient’s receiving bone. The first biological interactions at the implant surface determine the subsequent evolution of the integration process. In this study we set our objective to analyze the mechanistic interaction of the early regenerative matrix at implant surfaces modified with calcium ions (Ca) as compared to standard implant surfaces (NoCa). We put the surfaces in a Quartz Crystal Microbalance with Dissipation (QCM-D) to monitor the frequency shift (f) and the viscoelastic properties of the adsorbed biofilms and used Scanning Electron Microscopy (SEM) to visualize the resulting interfaces. Upon the addition of human blood plasma, Ca surfaces formed an adsorbed three-dimensional film attached to the surface (∆f = −40 Hz), while with NoCa, the biofilm formed but was not attached to the surface (∆f = 0 Hz). After 20 min in blood, two representative commercial implants with Ca and NoCa surfaces showed also distinct interfaces: Ca implants formed a visible clot attached to the implant which was composed mainly of platelets (Surface Coverage: 40 ± 20%) and some red blood cells (SC: 9 ± 3%) entrapped within a fibrin network (SC: 93 ± 5%). The NoCa implants were largely populated by red blood cells (SC: 67 ± 12%) with scarce fibrin remnants (SC: 3 ± 2%), and the implants showed no clot on their surfaces macroscopically. The pre-clinical and clinical results discussed in this work encourage the modification of titanium implant surfaces with calcium ions to improve the bone regenerative process. Taken together, these results add more information about the roles of Ca ions in bridging the formation of the provisional matrix at implant surfaces and their effects on implant osseointegration.

Effect of Vitamin D on Bone Regeneration: A Review.

Background and Objectives: Vitamin D (Vit. D) is known for its role in the skeletal system. Vit. D deficiency is also widely researched for its effects on the healing of fractures, bone defects, and osseointegration of implants. In the literature, there are studies that investigated the effects of dietary supplementation with Vit. D to reduce Vit. D deficiency, but increasing the serum level of this vitamin takes time. Therefore, an attempt has been made to combat the effect of Vit. D deficiency through topical applications. The aim of this article was to conduct a review of the existing bibliographic data that investigate the effect of Vit. D on bone regeneration. Materials and Methods: In order to carry out this review, an electronic search was made in several databases and the articles found were selected and analyzed. Results: The in vitro studies’ results demonstrated that Vit. D has a high therapeutic potential by enhancing the differentiation of stem cells in osteoblasts. Human and animal studies were conducting using various methods, but most of them revealed that Vit. D has a positive influence on the process of bone regeneration. Conclusions: The overall results of the research showed that, indeed, Vit. D is beneficial for bone regeneration; however, most of the studies imply that a thorough research is still needed for finding the most effective mode of administration and the dose needed in order to achieve the desired effect.

3D-printed Sr2ZnSi2O7 scaffold facilitates vascularized bone regeneration through macrophage immunomodulation.

Biomaterial-based bone grafts are emerged as an effective strategy for the treatment of large bone defects, especially for the scaffolds with enhanced osteogenic and angiogenic bioactivities. However, most studies focused on the direct interactions between scaffolds and bone-related cells such as osteoblasts and endothelial cells, and ignored the effects of material-triggered immunomodulation and the subsequent immune-regulated bone regeneration process. In this study, we developed a silicate bioceramic (Sr2ZnSi2O7, SZS) scaffold with well-defined pore structures using a three-dimensional (3D) printing technique. The prepared scaffolds were biodegradable, and the released bioactive ions were beneficial for immunomodulation, which stimulated macrophages to release more pro-healing cytokines and less pro-inflammatory cytokines. The obtained scaffold/macrophage conditioned medium further promoted the proliferation and osteogenic differentiation of a murine preosteoblast cell line (MC3T3-E1), as well as the angiogenic activity of human umbilical vein endothelial cells (HUVECs). Moreover, the in vivo experiments of critical-sized calvarial defects in rats revealed that the 3D printed SZS scaffolds could facilitate more vascularized bone regeneration than the 3D printed β-tricalcium phosphate (β-TCP, a typical clinically used bioceramic) scaffolds, suggesting that the 3D-printed SZS scaffolds hold the potential as implantable biomaterials with favorable osteoimmunomodulation for bone repair.

Effect of Human Adipose-Derived Mesenchymal Stem Cell (HADMSC) With Chitosan Scaffold on Bone Defect White Rats (Rattus Norvegicus) on Serum Alkaline Phosphatase (ALP) Levels

Bone defect is one of the challenges for dentists in the process of healing bone tissue. Bone defect can occur in alveolar bone with the etiology of microorganisms and cyst expansion. In addition, cases of bone defects in alveolar bone are also often found in cases with treatment of apex resection and hemisection. Autologous bone graft is a clinical gold standard in the treatment of bone defect. However, the use of bone graft has a limited number of growth factors produced. Tissue engineering is the latest method in terms of bone regeneration. Tissue engineering has three main components; stem cell, growth factor, and scaffold. Stem cells will increase osteoblastogenesis and chitosan scaffold will immobilize alkaline phosphatase (ALP) so that serum ALP levels decrease and bone regeneration and mineralization processes become faster. The aim of this study is analyzing the effect of human adipose-derived mesenchymal stem cell (HADMSC) with chitosan scaffold (CS) in bone defect on serum alkaline phosphatase (ALP) levels. This research was a in vivo laboratory experimental study. Bone defects are planted with chitosan scaffold (CS) and a combination of human adipose-derived mesenchymal stem cells (HADMSC) with chitosan scaffold. Measurement of ALP levels was carried out by the International Federation of Clinical Chemistry (IFCC) method using an analyzer on the 1st, 3rd, 7th and 14th days. Research data were analyzed using multivariate analysis of variance (MANOVA) and Bonferroni tests. The results of the data analysis showed that there were significant differences in ALP levels with CS planting and the combination of HADMSC and CS. the effect of human adipose- derived mesenchymal stem cell (HADMSC) with chitosan scaffold (CS) on bone defect reduces serum alkaline phosphatase (ALP) levels on the 3th and 14th days.