Formation Of New Bone Research Articles

DLP fabricating of precision GelMA/HAp porous composite scaffold for bone tissue engineering application

The hydrogel composited hydroxyapatite (HAp) scaffold shown biomimetic extracellular matrix and osteogenic activity, which is a promising bone regeneration biomaterial. 3D printing has been widely used in fabrication of customized and complex bone regeneration scaffold. However, it is still a challenge to prepare high-precision HAp reinforced composites by digital light processing (DLP) printing that can effectively promote bone regeneration. In this study, shear-thinning gelatin methacrylamide (GelMA)/hydroxyapatite (HAp) composite inks were prepared to fabricate high-precision scaffolds by DLP printing for bone repair. Firstly, GelMA hydrogels with adjustable mechanical, rheological and printing properties were synthesized to screen hydrogel concentration and degree of substitution. Then carefully selected biocompatible dispersants to reduce the agglomeration of hydroxyapatite. The actual printing resolution of the GelMA/HAp porous composite scaffolds with excellent mechanical strength through DLP 3D printing was up to about 100 μm. In vitro, the 3D printed composite scaffold significantly promoted the adhesion and proliferation of osteoblasts, as well as promoted osteogenic differentiation. In vivo, the GelMA/HAp porous composite scaffolds showed excellent ability in accelerating the formation of new bone in rabbit skull defects. The GelMA/HAp porous composite scaffolds fabricated by the composite inks with good printability, mechanical properties and osteogenic activity have fascinating potential in bone repair application.

Factors impacting new bone formation in transcrestal sinus floor elevation followed by implant placement: a cross-sectional study

ObjectivesThis study aimed to evaluate factors related to new bone formation (NBF) following simultaneous implant placement with transcrestal sinus floor elevation (TSFE).Materials and methodsBetween 2008 and 2020, 357 implants (276 patients) were placed with TSFE. Clinical and radiographic examinations were performed at the preoperative, postoperative, restoration, and follow-up stages. Marginal bone loss, during healing, and the survival rate were retrospectively analyzed.ResultsImplant protrusion lengths (IPL: 3–5 mm) significantly influenced NBF during the healing period (P-value = 0.026, Odds Ratio = 1.15, 95% confidence interval = 1.02- 1.30). Bone grafting was correlated with NBF (P-value = 0.001). The distance between the implant and lateral wall of the sinus (mesial: P-value = 0.041, distal: P-value = 0.019, buccal: P-value = 0.032, lingual: P-value = 0.043) and angle between the implant and sinus floor significantly influenced NBF in four directions (mesial: P-value = 0.041, distal: P-value = 0.02, buccal: P-value = 0.047, lingual: P-value = 0.005). Implant shape (cylindrical or conical), perforations, smoking, and diabetes did not significantly affect NBF during the healing period (P > 0.05).ConclusionIncreasing the distance and angle between the implant and lateral wall of the sinus floor corresponded with reduced NBF. IPL may be an important factor that should be considered.Clinical relevanceOur study analyzed new bone formation following transcrestal sinus floor elevation among patients who underwent this procedure with simultaneous implant placement, several factors (including angle and distance between sinus and lateral wall and implant protrusion length) were included in our study.

3D printed MXene (Ti2AlN)/polycaprolactone composite scaffolds for in situ maxillofacial bone defect repair

Obtaining a safe and reliable scaffold that can be rapidly fabricated and used for clinical bone defect repair has always been a challenge. In this study, polycaprolactone (PCL) composite scaffolds with various MXene (Ti2AlN) contents were prepared using 3D printing technology. The effects of different contents of Ti2AlN on the mechanical properties, hydrophilicity, cytocompatibility, and osteogenic differentiation ability were systematically studied and analysed. In vitro experiments showed that scaffolds containing 5% Ti2AlN (PCL@5#Ti2AlN) obtained the best cell adhesion and proliferation ability and significantly upregulated the alkaline phosphatase (ALP) level. In vivo experiments of tibial defect repair in rats showed that the PCL scaffold containing 5% Ti2AlN (PCL@5#Ti2AlN) could significantly promote the formation of new bone, and the experimental results of rabbit maxillofacial bone defect repair further proved that the PCL@5#Ti2AlN scaffold could effectively promote the repair of bone defects. Transcriptome analysis indicated that Ti2AlN may promote osteogenic differentiation by the Wnt/β-catenin signaling pathway and calcium-binding proteins. These findings suggest that Ti2AlN/PCL composite scaffolds with improved in situ bone repair ability represent an intelligent strategy for bone defect repair.

Engineered 3D-Printed Polyvinyl Alcohol Scaffolds Incorporating β-Tricalcium Phosphate and Icariin Induce Bone Regeneration in Rat Skull Defect Model.

The skull defects are challenging to self-heal, and autologous bone graft repair has numerous drawbacks. The scaffolds for the rapid and effective repair of skull defects have become an important research topic. In this study, polyvinyl alcohol (PVA)/β-tricalcium phosphate(β-TCP) composite scaffolds containing icariin (ICA) were prepared through direct-ink three-dimensional (3D) printing technology. β-TCP in the composite scaffold had osteoconductive capability, and the ICA molecule had osteoinductive capacity. The β-TCP and ICA components in the composite scaffold can enhance the capability to repair skull defects. We show that ICA exhibited a slow-release behaviour within 80 days. This behaviour helped the scaffold to continuously stimulate the formation of new bone. The results of in vitro cell compatibility experiments showed that the addition of ICA molecules contributed to the adhesion and proliferation of MC-3T3-E1 cells. The level of alkaline phosphatase secretion demonstrated that the slow release of ICA can promote the osteogenic differentiation of MC-3T3-E1 cells. The introduction of ICA molecules accelerated the in situ bone regeneration in in vivo. It is concluded that the 3D-printed PVA scaffold with β-TCP and ICA has a wide range of potential applications in the field of skull defect treatment.

Injectable Hyaluronic Acid/Human Umbilical Cord Mesenchymal Stem Cells/Bone Morphogenetic Protein-2 Promotes the Repair of Radial Bone Defects in Rabbits

Background: Bone defects are common in orthopedics and can be caused by congenital diseases, trauma, infection, tumors and other reasons. The treatment of large-scale bone defects is a clinical problem faced by orthopedists. The development of tissue engineering technology is expected to solve this problem. Objective: To explore the effect of injectable hyaluronic acid/hUCMSC/BMP-2 on the healing of rabbit radial bone defects. Methods: X-ray examination and tissue specimens were examined to macroscopically observe bone defect healing; tetracycline fluorescence and vonKossa staining were performed to observe the formation of new bone, and H&E staining was performed to examine cartilage and trabecular bone formation. Results: The injectable hyaluronic acid/hUCMSC/BMP-2 could significantly promote the early repair of bone defects and accelerate the process of bone formation. Conclusion: The direct injection of hyaluronic acid/hUCMSC/BMP-2 into afresh bone defect site has a significant beneficial effect on early repair of the bone defect.

Alendronate prolongs the reversal-resorption phase in human cortical bone remodeling.

Despite their ability to reduce fracture-risk and increase Bone Mineral Density (BMD) in osteoporotic women, bisphosphonates are reported to reduce formation of new bone. Reduced bone formation has been suggested to lead to accumulation of microfractures and contribute to rare side effects in cortical bone such as atypical femur fractures. However, most studies are limited to trabecular bone. In this study, the cortical bone remodeling in human iliac bone specimens of 65 non-treated and 24 alendronate-treated osteoporotic women was investigated using a new histomorphometric classification of intracortical pores. The study showed that only 12.4±11% of the cortical pore area reflected quiescent pores/osteons in alendronate-treated patients versus 8.5±5% in placebo, highlighting that new cortical remodeling events remain to be activated. The percent and size of eroded pores (events in resorption-reversal phase) remained unchanged, but their contribution to total pore area was 1.4-fold higher in alendronate versus placebo treated patients (66±22% vs 48±22%, p<0.001). On the other hand, the mixed eroded-formative pores (events with mixed resorption-reversal-formation phases) was 2-fold lower in alendronate versus placebo treated patients (19±14% vs 39±23% of total pore area, p<0.001), and formative pores (event in formation phase) was 2.2-fold lower in alendronate versus placebo treated patients (2.1± 2.4% vs 4.6±3.6%, p<0.01), and their contribution to total pore area was 2.4-fold lower (1.3±2.1% vs 3.1±4.4%, p<0.05). Importantly, these differences between alendronate and placebo treated patients were significant in patients after 3years of treatment, not after 2years of treatment. Collectively, the results support that cortical remodeling events activated during alendronate treatment has a prolonged reversal-resorption phase with a delayed transition to formation, becoming increasingly evident after 3-years of treatment. A potential contributor to atypical femur fractures associated with long-term bisphosphonate treatment.

Histological and histomorphometric evaluation of alveolar ridge preservation using an allograft and nonresorbable membrane with and without primary closure: A pilot randomized controlled clinical trial.

The aim of this article is to assess the formation of new vital bone (VB) using histomorphometric analysis in alveolar ridge preservation (ARP), with and without primary closure. Eight patients needed bilateral tooth extraction and planned for ARP. All patients had a nonresorbable membrane with freeze-dried bone allograft after the extractions. Biopsies were obtained 6 months after ARP and were evaluated using histomorphometric analysis. The study included 6 males and 2 females, with an average age of 54.2 years (standard deviation, 9.7). The teeth requiring extraction included a bilateral canine (1 case), premolars (5 cases), and molars (2 cases). Histomorphometric values of new VB, residual bone (RB) substitute particles, and marrow tissue formation were 71.1 %, 16.2%, and 9.69% for closed flap and 50.9%, 15.3%, and 8.19 for open flap. P values were 0.066, 0.878, and 0.326, respectively. The present findings indicate that leaving the flap without primary closure did not have any effect on new VB, RB particles, and immature bone marrow compared with closed flap. However, the results favored the closed-flap technique.

Investigating the Effects of Dehydrated Human Amnion-Chorion Membrane on Periodontal Healing.

Each growth factor (GF) has different effects and targets, and plays a critical role in periodontal healing. Dehydrated human amnion-chorion membrane (dHACM) contains various GFs and has been used to enhance wound healing. The purpose of this study was to evaluate the effects of dHACM on periodontal healing, using in vitro and in vivo experimental approaches. Standardized periodontal defects were created in rats. The defects were randomly divided into three groups: Unfilled, filled with hydroxypropyl cellulose (HPC), and dHACM+HPC. At 2 and 4 weeks postoperatively, periodontal healing was analyzed by microcomputed tomography (micro-CT), and histological and immunohistochemical analyses. In vitro, periodontal ligament-derived cells (PDLCs) isolated from rat incisors were incubated with dHACM extract. Cell proliferation and migration were evaluated by WST-1 and wound healing assay. In vivo, micro-CT examination at 2 weeks revealed enhanced formation of new bone in the dHACM+HPC group. At 4 weeks, the proportions of vascular endothelial growth factor (VEGF)-positive cells and α-smooth muscle actin (α-SMA)-positive blood vessels in the dHACM+HPC group were significantly greater than those in the Unfilled group. In vitro, dHACM extracts at 100 µg/mL significantly increased cell proliferation and migration compared with control. These findings suggest that GFs contained in dHACM promote proliferation and migration of PDLCs and angiogenesis, which lead to enhanced periodontal healing.

Effects of platelet-rich fibrin on osteogenic differentiation of Schneiderian membrane derived mesenchymal stem cells and bone formation in maxillary sinus

BackgroundThe existence of mesenchymal stem cells (MSCs) in Schneiderian membrane has not been determined. The aim of this study is to investigate whether there are MSCs in Schneiderian membrane, and the effect of platelet-rich fibrin (PRF) on osteogenic differentiation of these cells and on new bone formation in maxillary sinus after maxillary sinus floor elevation.MethodsSchneiderian membrane derived mesenchymal stem cells (SM-MSCs) were isolated from rabbit maxillary sinus. Cells were identified by flow cytometry and multipotential differentiation. Real-time cell analysis assay, fluorescence staining, transwell assay, and wound healing assay were used to determine the effects of PRF stimulation on cell proliferation and migration. The osteogenic differentiation ability of cells stimulated by PRF or osteoinductive medium was evaluated by alkaline phosphatase staining, alizarin red staining, PCR and Western blot. Equivalent volume Bio-oss and the mixture of Bio-oss and PRF were used as bone graft materials for maxillary sinus floor elevation. Micro-CT, bone double-staining, HE staining, Masson staining, and toluidine blue staining were used to evaluate the osteogenic effect in 8 and 12 weeks after surgery.ResultsThe cell surface markers were positive for expression of CD90, CD105, and negative for expression of CD34, CD45. SM-MSCs had the ability of osteogenic, adipogenic and chondrogenic differentiation. PRF could stimulate proliferation, migration and osteogenic differentiation of SM-MSCs, which was achieved by up-regulating ERK 1/2 signaling pathway. PRF could accelerate the formation of new bone in maxillary sinus and increase the amount of new bone formation.ConclusionsMSCs existed in Schneiderian membrane, and PRF stimulation could promote cell proliferation, migration and osteogenic differentiation. The application of PRF in maxillary sinus floor elevation could accelerate bone healing and increase the quantity and quality of new bone. PRF, as autologous graft materials, might offer a promising strategy for the clinical bone formation during MSFE procedure.Graphical abstract6kDexyoSUyN5j1q7bTF377Video .

In Vivo Evaluation of 3D-Printed Silica-Based Bioactive Glass Scaffolds for Bone Regeneration.

Bioactive glasses are often designed as porous implantable templates in which newly-formed bone can grow in three dimensions (3D). This research work aims to investigate the bone regenerative capability of silicate bioactive glass scaffolds produced by robocasting in comparison with powder and granule-like materials (oxide system: 47.5SiO2-10Na2O-10K2O-10MgO-20CaO-2.5P2O5, mol.%). Morphological and compositional analyses performed by scanning electron microscopy (SEM), combined with energy dispersive spectroscopy (EDS) after the bioactivity studies in a simulated body fluid (SBF) confirmed the apatite-forming ability of the scaffolds, which is key to allowing bone-bonding in vivo. The scaffolds exhibited a clear osteogenic effect upon implantation in rabbit femur and underwent gradual resorption followed by ossification. Full resorption in favor of new bone growth was achieved within 6 months. Osseous defect healing was accompanied by the formation of mature bone with abundant osteocytes and bone marrow cells. These in vivo results support the scaffold’s suitability for application in bone tissue engineering and show promise for potential translation to clinical assessment.

Đặc điểm mô bệnh học bệnh lý hoại tử vô khuẩn chỏm xương đùi được phẫu thuật thay khớp háng

Aseptic necrosis of the femoral head (ANFH) accounts for about 2.24% of common joint diseases. The pathophysiological mechanism of ANFH is a lack of blood supply to the femoral head, leading to the death of bone cells and marrow, leading to the collapse and deformation of the femoral head. Objectives: To characterize microscopic damage to femoral head crest in non-traumatic ANFH.Subjects and methods: The study design was a cross-sectional, descriptive study of 31 femoral heads on 31 patients with ANFH who underwent hip replacement surgery at Viet Duc University. The samples were analyzed, processed, and fixed using the HE-stained histological method. Results: All samples had bone marrow damage, of which bone marrow infarction accounted for 58.1%; granulomatous lesions accounted for 71%, fat necrosis and hematopoietic cells accounted for 80.6%; dead bone accounted for 93.3% and new bone formation on dead bone area accounted for 61.3%. Conclusion: Infarct bone marrow injury, fat necrosis, and hematopoietic cells are associated with the formation of granulomatous tissue surrounding the necrotic area. The loss of bone cells in the trabecular is associated with the formation of dead bone fragments. With age, the formation of new bone on the basis of dead bone decreases. * Keywords: Aseptic necrosis; Femoral head; Histopathology.

BIOMECHANICAL AND PHYSIOLOGICAL PRINCIPLES APPLIED IN CHEST WALL RECONSTRUCTION ASSOCIATED WITH RIB FRACTURES

TYPE: Abstract TOPIC: Cardiothoracic Surgery PURPOSE: The aim of this study was to describe osseointegration of osteosynthesis material and risk of surgical intervention when biomechanical and physiological principles are applied in chest wall reconstruction (CWR). METHODS: All adult patients with pulmonary contusion, multiple rib fractures, flail chest, hemothorax or pneumothorax associated with rib fractures who underwent CWR between March 2012 and December 2016 in emergency department retrospectively included.Titanium clips pressure-fitted at 2 cm proximal and distal were used at each fracture site. Curvature of the clip was made to simulate the natural curvature of the costal arch. In all cases the vascular and nervous package was released. Postoperative follow-ups were obtained from medical records and the integration of the osteosynthesis material was assessed. RESULTS: The 60 patients were 37 men and 23 woman, average age of 44 years. Hospital stays between 7 and 16 days. At 30 days postoperative complications had been recorded such as respiratory insufficiency (n=2) and acute myocardial infarction (n=1).Osteointegration of the osteosynthesis material was found in 59 patients (98.3%) and 1 patient (1.6%) present refracture and mobilization of a titanium implant, for which it was surgery reintervened and the defect corrected CONCLUSIONS: In our study, we found a very high percentage of osseointegration when using the biomechanical principles in the techniques for CWR. CLINICAL IMPLICATIONS: The healing process near fracture sites relies in a correct immobilization,adequate vascularization and formation of bone callus and new bone therefore, by using titanium clips combined with different biomechanical principles they help this purpose by improving the conditions at the fracture site. DISCLOSURE: Nothing to declare. KEYWORD: CHEST WALL RECONSTRUCTION

Comparative analysis of lateral maxillary sinus augmentation with a xenogeneic bone substitute material in combination with piezosurgical preparation and bony wall repositioning or rotary instrumentation and membrane coverage: a prospective randomized clinical and histological study

ObjectivesThe present randomized controlled clinical study aimed to investigate if, in lateral maxillary sinus augmentation, the repositioned bony wall or the application of a collagen membrane results in more preferable new hard tissue formation.Materials and methodsForty patients were divided into two study groups. Both groups received a xenogeneic bone substitute material (BSM) during lateral sinus augmentation. In the bony wall group (BW), following piezosurgery, the retrieved bony wall was repositioned. In the collagen membrane group (CM), following rotary instrument preparation, collagen membrane coverage was applied. After 6 months, biopsies were taken to histologically analyze the percentage of BSM, connective tissue (CT), and newly formed bone (NFB) following both approaches.ResultsForty implants were placed and 29 harvested biopsies could be evaluated. Duration of surgery, membrane perforations, and VAS were detected. Histomorphometrical analysis revealed comparable amounts of all analyzed parameters in both groups in descending order: CT (BW: 39.2 ± 9%, CM: 37,9 ± 8.5%) > BSM (BW: 32.9 ± 6.3%, CM: 31.8 ± 8.8%) > NB (BW: 27.8 ± 11.2%, CM: 30.3 ± 4.5%).ConclusionsThe results of the present study show that the closure of the access window by means of the retrieved bony wall or a native collagen membrane led to comparable bone augmentation results.Clinical trialclinicaltrials.gov NCT04811768.Clinical relevanceLateral maxillary sinus augmentation with the application of a xenogeneic BSM in combination with a native collagen membrane for bony window coverage represents a reliable method for surgical reconstruction of the posterior maxilla. Piezosurgery with bony window repositioning delivers comparable outcomes without membrane coverage.

β-type TiNbSn Alloy Plates With Low Young Modulus Accelerates Osteosynthesis in Rabbit Tibiae.

β-type TiNbSn Alloy Plates With Low Young Modulus Accelerates Osteosynthesis in Rabbit Tibiae.

Defects of long bones — a brief history of the development of technology of their compensation

The Ilizarov bone reconstruction method involves bone reconstruction and the formation of new bone. It is based on the biological phenomenon of distraction osteogenesis, which is used to lengthen bone and correct deformities. Ilizarov bone grafting is a lifesaving procedure for a number of conditions, including large bone defects and orthopedic infection complications. The method has given rise to new developments in bone reconstruction surgery based on the regenerative potential of bone tissue. The acceleration of distraction regenerate consolidation is one of the objectives of modern research in the field of new bone formation.

The Effect of an Alloplastic Bone Substitute and Enamel Matrix Derivative on the Preservation of Single Anterior Extraction Sockets: A Histologic Study in Humans

This study was designed to assess the effect of enamel matrix derivative (Emdogain, Straumann) and alloplastic bone substitute (BoneCeramic, Straumann) on new bone formation in postextraction alveolar sockets. Twenty-one patients requiring anterior single-tooth extractions and subsequent implant placement were recruited and randomly assigned to one of three treatment groups. Postextraction sockets were filled with either an alloplastic bone substitute (BoneCeramic [BC]), BC combined with Emdogain (EMD+BC), or left to heal spontaneously (SO). Histologic and histomorphometric analyses of the results were performed at 6 months postextraction. A significant increase in the percentage of new bone tissue area was found in EMD+BC compared to SO and BC groups. These findings demonstrate that compared with BC or SO, EMD+BC allowed for better formation of new bone in postextraction sockets after 6 months of healing.

Coating Ti6Al4V implants with nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix mineralization in vitro and faster osseointegration in vivo

The present study investigates the effect of an oxidized nanocrystalline diamond (O-NCD) coating functionalized with bone morphogenetic protein 7 (BMP-7) on human osteoblast maturation and extracellular matrix mineralization in vitro and on new bone formation in vivo. The chemical structure and the morphology of the NCD coating and the adhesion, thickness and morphology of the superimposed BMP-7 layer have also been assessed. The material analysis proved synthesis of a conformal diamond coating with a fine nanostructured morphology on the Ti6Al4V samples. The homogeneous nanostructured layer of BMP-7 on the NCD coating created by a physisorption method was confirmed by AFM. The osteogenic maturation of hFOB 1.19 cells in vitro was only slightly enhanced by the O-NCD coating alone without any increase in the mineralization of the matrix. Functionalization of the coating with BMP-7 resulted in more pronounced cell osteogenic maturation and increased extracellular matrix mineralization. Similar results were obtained in vivo from micro-CT and histological analyses of rabbit distal femurs with screws implanted for 4 or 12 weeks. While the O-NCD-coated implants alone promoted greater thickness of newly-formed bone in direct contact with the implant surface than the bare material, a further increase was induced by BMP-7. It can be therefore concluded that O-NCD coating functionalized with BMP-7 is a promising surface modification of metallic bone implants in order to improve their osseointegration.

Spectrum of voriconazole-associated periostitis in clinical characteristics, diagnosis and management.

Previous knowledge about the relationship between voriconazole exposure and periostitis was mainly based on limited case reports and few retrospective studies. The purpose of this study was to assess the clinical characteristics, diagnosis and management of voriconazole-associated periostitis. Case reports and case series from 1998 to November 30, 2021 on periostitis induced by voriconazole were collected for retrospective analysis. Forty four patients (18 male and 26 female) from 34 studies were includedin total. The median age was 58years (29-74). The majority of patients had undergone organ transplantation (50.0%) or suffered from hematologic malignancy (31.81%). The median onset time of symptoms was 6months after the start of voriconazole. The most common initial symptom was diffuse skeletal pain (68.28%) which can be severe and even disabling (66.7%). Ribs (37.21%), femurs (32.56%), scapulae (25.58%), humerus (23.26%), and clavicle (23.26%) were the common involved locations. Most cases were accompanied by different degrees of elevated serum alkaline phosphatase and fluoride level, while some presented with elevated bone-specific alkaline phosphatase. The main radiological features included periosteal reaction and multifocal high radiotracer uptake on bone scintigraphy. The formation of new bone was characterized with bilateral, irregular, nodular, as well as high density. The resolution of symptoms was observed with discontinuation of voriconazole in all patients, of whom 18 patients (52.94%) were relieved within a week. Itraconazole, posaconazole or isavuconazole were safe alternatives to voriconazole in voriconazole-induced periostitis. Voriconazole-induced periostitis is an infrequent complication characterized by bone inflammation involving one or multiple skeletal areas. Bony pain, elevated serum alkaline phosphatase as well as fluoride level are suspicious signs during voriconazole treatment.

Does the incorporation of strontium into calcium phosphate improve bone repair? A meta-analysis

BackgroundThe application of calcium phosphate (CaP)-based bone substitutes plays an important role in periodontal regeneration, implant dentistry and alveolar bone reconstruction. The incorporation of strontium (Sr) into CaP-based bone substitutes appears to improve their biological properties, but the reported in vivo bone repair performance is inconsistent among studies. Herein, we conducted a systematic review and meta-analysis to investigate the in vivo performance of Sr-doped materials.MethodsWe searched PubMed, EMBASE (via OVIDSP), and reference lists to identify relevant animal studies. The search, study selection, and data extraction were performed independently by two investigators. Meta-analyses and sub-group analyses were conducted using Revman version 5.4.1. The heterogeneity between studies were assessed by I2. Publication bias was investigated through a funnel plot.ResultsThirty-five studies were finally enrolled, of which 16 articles that reported on new bone formation (NBF) were included in the meta-analysis, covering 31 comparisons and 445 defects. The overall effect for NBF was 2.25 (95% CI 1.61–2.90, p < 0.00001, I2 = 80%). Eight comparisons from 6 studies reported the outcomes of bone volume/tissue volume (BV/TV), with an overall effect of 1.42 (95% CI 0.65–2.18, p = 0.0003, I2 = 75%). Fourteen comparisons reported on the material remaining (RM), with the overall effect being -2.26 (95% CI − 4.02 to − 0.50, p = 0.0009, I2 = 86%).ConclusionsOur study revealed that Sr-doped calcium phosphate bone substitutes improved in vivo performance of bone repair. However, more studies are also recommended to further verify this conclusion.

Tough, Flexible, and Bioactive Amphoteric Copolymer-Based Hydrogel for Bone Regeneration without Encapsulation of Seed Cells/Simulating Cues.

Bone tissue scaffolds with good bulk or surface osteoconductivity are always pursued by biomaterial scientists. In this paper, we design a tough and flexible amphoteric copolymer-based (AC) hydrogel with bioactive groups for bone regeneration. In detail, our hydrogels are copolymerized with N-acyl glycinamide (NAGA), anionic acrylate alendronate (AcAln), and cationic (2-(acryloyloxy)ethyl) trimethyl ammonium chloride (DMAEA-Q) by free radical polymerization. There are three kinds of synergetic physical cross-links among our polyamphion hydrogels: (1) double hydrogen bonds between amide groups in NAGA to provide toughness, (2) hydrogen bonds between dual bisphosphite groups in AcAln, and (3) weak ionic pairs between the anionic bisphosphite groups and the cationic quaternary ammonium groups in DMAEA-Q to offer flexibility. The AC hydrogel shows osteoid-like viscoelasticity, which makes the AC hydrogel osteogenesis inductive. During the repairing process, the bioactive bisphosphite groups accelerate the calcium fixation to expedite the mineralization of the new-formed bone. At the same time, the surface charge property of AC hydrogels also prevents fibrous cyst formation, thus guaranteeing osseointegration. Our in vitro data strongly demonstrate that the AC hydrogel is an excellent matrix to induce osteogenesis of rat bone marrow mesenchymal stem cells. More importantly, the following in vivo experiments further prove that the AC hydrogel can reach satisfactory bone regeneration without encapsulation of seed cells or application of external simulating cues. These exciting results demonstrate that our AC hydrogel is a promising scaffold for bone regeneration. Our work can also inspire the constituent and structure design of biomaterial scaffolds for tissue regeneration.