Complications Following Intraosseous Injections of Calcium Phosphate Bone Cement in Subchondroplasty.

An alternative approach to the major problem of osteoarthritis that has begun to pique the interest of researchers focuses on the pathology of the subchondral bone, its constant cross-talk with the articular cartilage, and its interaction with the joint. The presence of bone marrow lesions, detectable on MRI scans, has proven to be a cause of pain as well as a predictor of the progression of degenerative changes. Subchondroplasty is a relatively new surgical procedure for the treatment of these lesions, in which injectable calcium phosphate bone cement is infused into the affected area percutaneously, under fluoroscopic guidance. In its use as a synthetic scaffold, calcium phosphate bone cement exhibits considerable osteoconductivity, bioabsorbability, and low toxicity, thus showing great potential for restoring subchondral biomechanical properties through structural remodeling. Although published results appear quite promising, there are certain complications that the surgeon should be aware of. We reviewed the published data regarding complications of the procedure, highlighting possible causes according to these data, and suggesting safety measures. Avascular necrosis of the talus is the most reported concern. Postsurgical pain, infection, and continuous wound drainage due to bone substitute material extravasation to the joint or soft tissue are also mentioned, necessitating further standardization of the procedure. There are no reports of permanent postoperative disability or fatal outcomes.

Osteosarcoma cell death induced by innovative scaffolds doped with chemotherapeutics.

Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. In the last years, novel treatment approaches have been proposed, which employ a drug-delivery system to prevent offside effects and improves treatment efficacy. Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour-killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium-doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC-MTX and SrCPC-DOX, respectively. The drug-loaded cements were tested in an in vitro model of human OS cell line SAOS-2, engineered OS cell line (SAOS-2-eGFP) and U2-OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase-3/7 activities, respectively. To determine if OS cells grown on doped-scaffolds change their migratory ability and invasiveness, a wound-healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived-mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme-linked immunosorbent assay test, and (iii) the osteogenic process was studied by real-time polymerase chain reaction array. The delivery system induced cell-killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug-loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy.

In Vitro and In Vivo Efficacy of New Composite for Direct Pulp Capping.

OBJECTIVES: To investigate physicochemical properties, dentin bonding, cytotoxicity, and in vivo pulp response of experimental self-adhesive composites tailored to direct pulp capping. MATERIALS AND METHODS: Experimental composites were prepared with beta-tricalcium phosphate and hydroxyapatite nanoparticles adsorbed with simvastatin and glutathione added at 0% (control resin), 1 wt% (Res 1%), and 10 wt% (Res 10%). A commercial light-curable calcium hydroxide (Ca(OH)2) (Ultra-Blend Plus) was used as control material. The physicochemical properties investigated were flexural strength and modulus, calcium release, and degree of conversion. Dentin bonding was assessed by the push-out test. Proliferation and cell counting assays were performed to evaluate in vitro cytotoxicity using fluorescence microscopy. In vivo pulp capping was performed on molars of Wistar rats, which were euthanized after 14 days and evaluated by histological analysis. RESULTS: No statistical difference was observed in flexural strength and cell viability (p > 0.05). Res 10% presented higher modulus than control resin and Ca(OH)2. Also, Res 10% attained statistically higher degree of conversion when compared to other experimental composites. Ca(OH)2 showed higher calcium release after 28 and 45 days of storage, with no statistical difference at 45 days to Res 10%. All experimental composites achieved significantly higher bond strength when compared to Ca(OH)2. While no significant difference was observed in the cell proliferation rates, resins at lower concentrations showed higher cell viability. In vivo evaluation of pulp response demonstrated no pulp damage with experimental composites. CONCLUSIONS: The experimental composite investigated in this study achieved adequate physicochemical properties with minor in vivo pulpal inflammation and proved to be a valuable alternative for direct pulp capping.

Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration.

Medication-related osteonecrosis of the jaw (MRONJ) is related to impaired bone healing conditions in the maxillomandibular bone region as a complication of bisphosphonate intake. Although there are several hypotheses for the onset of MRONJ symptoms, one of the possible causes is the inhibition of bone turnover and blood supply leading to bone necrosis. The optimal treatment strategy for MRONJ has not been established either. BMP-2, a member of the TGF-ß superfamily, is well known for regulating bone remodeling and homeostasis prenatally and postnatally. Therefore, the objectives of this study were to evaluate whether cyclophosphamide/zoledronate (CY/ZA) induces necrosis of the bone surrounding the tooth extraction socket, and to examine the therapeutic potential of BMP-2 in combination with the hard osteoinductive biomaterial, ß-tricalcium phosphate (ß-TCP), in the prevention and treatment of alveolar bone loss around the tooth extraction socket in MRONJ-like mice models. First, CY/ZA was intraperitoneally administered for three weeks, and alveolar bone necrosis was evaluated before and after tooth extraction. Next, the effect of BMP-2/ß-TCP was investigated in both MRONJ-like prevention and treatment models. In the prevention model, CY/ZA was continuously administered for four weeks after BMP-2/ß-TCP transplantation. In the treatment model, CY/ZA administration was suspended after transplantation of BMP-2/ß-TCP. The results showed that CY/ZA induced a significant decrease in the number of empty lacunae, a sign of bone necrosis, in the alveolar bone around the tooth extraction socket after tooth extraction. Histological analysis showed a significant decrease in the necrotic alveolar bone around tooth extraction sockets in the BMP-2/ß-TCP transplantation group compared to the non-transplanted control group in both MRONJ-like prevention and treatment models. However, bone mineral density, determined by micro-CT analysis, was significantly higher in the BMP-2/ß-TCP transplanted group than in the control group in the prevention model only. These results clarified that alveolar bone necrosis around tooth extraction sockets can be induced after surgical intervention under CY/ZA administration. In addition, transplantation of BMP-2/ß-TCP reduced the necrotic alveolar bone around the tooth extraction socket. Therefore, a combination of BMP-2/ß-TCP could be an alternative approach for both prevention and treatment of MRONJ-like symptoms.

Temporal response of an injectable calcium phosphate material in a critical size defect.

BACKGROUND: Calcium phosphate-based bone graft substitutes are used to facilitate healing in bony defects caused by trauma or created during surgery. Here, we present an injectable calcium phosphate-based bone void filler that has been purposefully formulated with hyaluronic acid to offer a longer working time for ease of injection into bony defects that are difficult to access during minimally invasive surgery. METHODS: The bone substitute material deliverability and physical properties were characterized, and in vivo response was evaluated in a critical size distal femur defect in skeletally mature rabbits to 26 weeks. The interface with the host bone, implant degradation, and resorption were assessed with time. RESULTS: The calcium phosphate bone substitute material could be injected as a paste within the working time window of 7-18 min, and then self-cured at body temperature within 10 min. The material reached a maximum ultimate compressive strength of 8.20 ± 0.95 MPa, similar to trabecular bone. The material was found to be biocompatible and osteoconductive in vivo out to 26 weeks, with new bone formation and normal bone architecture observed at 6 weeks, as demonstrated by histological evaluation, microcomputed tomography, and radiographic evaluation. CONCLUSIONS: These findings show that the material properties and performance are well suited for minimally invasive percutaneous delivery applications.

In vivostudy of iron oxide-calcium phosphate composite nanoparticles for delivery to atherosclerosis.

Atherosclerosis is a macrophage-related inflammatory disease that remains a leading cause of death worldwide. Magnetic iron oxide (IO) nanocrystals are clinically used as magnetic resonance imaging contrast agents and their application as a detection agent for macrophages in arterial lesions has been studied extensively. We recently fabricated heparin-modified calcium phosphate (CaP) nanoparticles loaded with a large number of IO nanocrystals via coprecipitation from a supersaturated CaP solution supplemented with heparin and ferucarbotran (IO nanocrystals coated with carboxydextran). In this study, we further increased the content of IO nanocrystals in the heparin-modified IO-CaP composite nanoparticles by increasing the ferucarbotran concentration in the supersaturated CaP solution. The increase in nanoparticle IO content caused a decrease in particle diameter without impairing its dispersibility; the nanoparticles remained dispersed in water for up to 2 h due to electrostatic repulsion between particles due to the surface modification with heparin. The nanoparticles were more effectively taken up by murine RAW264.7 macrophages compared to free ferucarbotran without showing significant cytotoxicity. A preliminaryin vivostudy showed that the nanoparticles injected intravenously into mice delivered more IO nanocrystals to macrophage-rich carotid arterial lesions than free ferucarbotran. Our nanoparticles have potential as a delivery agent of IO nanocrystals to macrophages in arterial lesions.

Comparison of Freshly Isolated Adipose Tissue-derived Stromal Vascular Fraction and Bone Marrow Cells in a Posterolateral Lumbar Spinal Fusion Model.

STUDY DESIGN: Rat posterolateral lumbar fusion model. OBJECTIVE: The aim of this study was to compare the efficacy of freshly isolated adipose tissue-derived stromal vascular fraction (A-SVF) and bone marrow cells (BMCs) cells in achieving spinal fusion in a rat model. SUMMARY OF BACKGROUND DATA: Adipose tissue-derived stromal cells (ASCs) offer advantages as a clinical cell source compared to bone marrow-derived stromal cells (BMSCs), including larger available tissue volumes and reduced donor site morbidity. While pre-clinical studies have shown that ex vivo expanded ASCs can be successfully used in spinal fusion, the use of A-SVF cells better allows for clinical translation. METHODS: A-SVF cells were isolated from the inguinal fat pads, whereas BMCs were isolated from the long bones of syngeneic 6- to 8-week-old Lewis rats and combined with Vitoss (Stryker) bone graft substitute for subsequent transplantation. Posterolateral spinal fusion surgery at L4-L5 was performed on 36 female Lewis rats divided into three experimental groups: Vitoss bone graft substitute only (VO group); Vitoss + 2.5 × 106 A-SVF cells/side; and, Vitoss + 2.5 × 106 BMCs/side. Fusion was assessed 8 weeks post-surgery via manual palpation, micro-computed tomography (µCT) imaging, and histology. RESULTS: µCT imaging analyses revealed that fusion volumes and µCT fusion scores in the A-SVF group were significantly higher than in the VO group; however, they were not significantly different between the A-SVF group and the BMC group. The average manual palpation score was highest in the A-SVF group compared with the BMC and VO groups. Fusion masses arising from cell-seeded implants yielded better bone quality than nonseeded bone graft substitute. CONCLUSION: In a rat model, A-SVF cells yielded a comparable fusion mass volume and radiographic rate of fusion to BMCs when combined with a clinical-grade bone graft substitute. These results suggest the feasibility of using freshly isolated A-SVF cells in spinal fusion procedures.Level of Evidence: N/A.

Knee Intraosseous Injections: A Systematic Review of Clinical Evidence of Different Treatment Alternatives.

OBJECTIVE: To systematically review the available clinical evidence regarding the safety and efficacy of knee intraosseous injections for the treatment of bone marrow lesions in patients affected by knee osteoarthritis. DESIGN: A literature search was carried out on PubMed, Embase, and Google Scholar databases in January 2020. The following inclusion criteria were adopted: (1) studies of any level of evidence, dealing with subchondral injection of bone substitute materials and/or biologic agents; (2) studies with minimum 5 patients treated; and (3) studies with at least 6 months' follow-up evaluation. All relevant data concerning clinical outcomes, adverse events, and rate of conversion to arthroplasty were extracted. RESULTS: A total of 12 studies were identified: 7 dealt with calcium phosphate administration, 3 with platelet-rich plasma, and 2 with bone marrow concentrate injection. Only 2 studies were randomized controlled trials, whereas 6 studies were prospective and the remaining 4 were retrospective. Studies included a total of 459 patients treated with intraosseous injections. Overall, only a few patients experienced adverse events and clinical improvement was documented in the majority of trial. The lack of any comparative evaluation versus subchondral drilling alone is the main limitation of the available evidence. CONCLUSIONS: Knee intraosseous injections are a minimally invasive and safe procedure to address subchondral bone damage in osteoarthritic patients. They are able to provide beneficial effects at short-term evaluation. More high-quality evidence is needed to confirm their potential and to identify the best product to adopt in clinical practice.

Variable neuroprotective role of Filipendula ulmaria extract in rat hippocampus.

We evaluated the influence of an antioxidant-rich extract of Filipendula ulmaria L. on anxiety levels induced by nano-sized particles of different calcium phosphates. Rats in experimental groups were administered with either nano-sized hydroxyapatite, tricalcium phosphate, or amorphous calcium phosphate in the presence of Filipendula ulmaria extract. Appropriate behavioral tests were performed to assess anxiety levels, while oxidative status and apoptosis parameters were determined in the hippocampus samples. The applied calcium phosphates increased oxidative stress markers in hippocampal tissue, accompanied by an enhanced pro-apoptotic mechanism. Moreover, the hippocampal immunoreactivity for brain-derived neurotrophic factor and GABAergic-A receptors was significantly lower following calcium phosphate nanoparticles intake. The observed functional and morphological alterations in the rat hippocampus occurred simultaneously with the anxiogenic response estimated in behavioral testing. The neuroprotective effect of Filipendula ulmaria was markedly manifested by the attenuation of oxidative damage induced by amorphous calcium phosphate and enhanced anti-apoptotic action in the rat hippocampus. The increased hippocampal immunoreactivity for brain-derived neurotrophic factor, GABAergic-A receptors and significant anxiolytic-like effects of Filipendula ulmaria may suggest a beneficial role of antioxidant supplementation in preventing anxiogenic response to nano-sized calcium phosphates.

Cement-augmented screw fixation for calcaneal fracture treatment: a biomechanical study comparing two injectable bone substitutes.

BACKGROUND: The role of cement-augmented screw fixation for calcaneal fracture treatment remains unclear. Therefore, this study was performed to biomechanically analyze screw osteosynthesis by reinforcement with either a calcium phosphate (CP)-based or polymethylmethacrylate (PMMA)-based injectable bone cement. METHODS: A calcaneal fracture (Sanders type IIA) including a central cancellous bone defect was generated in 27 synthetic bones, and the specimens were assigned to 3 groups. The first group was fixed with four screws (3.5 mm and 6.5 mm), the second group with screws and CP-based cement (Graftys® QuickSet; Graftys, Aix-en-Provence, France), and the third group with screws and PMMA-based cement (Traumacem™ V+; DePuy Synthes, Warsaw, IN, USA). Biomechanical testing was conducted to analyze peak-to-peak displacement, total displacement, and stiffness in following a standardized protocol. RESULTS: The peak-to-peak displacement under a 200-N load was not significantly different among the groups; however, peak-to-peak displacement under a 600- and 1000-N load as well as total displacement exhibited better stability in PMMA-augmented screw osteosynthesis compared to screw fixation without augmentation. The stiffness of the construct was increased by both CP- and PMMA-based cements. CONCLUSION: Addition of an injectable bone cement to screw osteosynthesis is able to increase fixation strength in a biomechanical calcaneal fracture model with synthetic bones. In such cases, PMMA-based cements are more effective than CP-based cements because of their inherently higher compressive strength. However, whether this high strength is required in the clinical setting for early weight-bearing remains controversial, and the non-degradable properties of PMMA might cause difficulties during subsequent interventions in younger patients.

A radiological study of bone remodeling with two different types of porous ß-tricalcium phosphate in humans.

In this study we compared the bone remodeling of unidirectional (UDPTCP) and spherical porous ß-tricalcium phosphate (SPTCP) radiologically in humans. We performed a retrospective analysis of the data of 14 patients (sex, nine men and five women; age, 37-70 years) who underwent medial opening-wedge high tibial osteotomy (MOWHTO) and were followed up for 12 months after surgery. Two wedge-shaped ß-TCPs (one UDPTCP and one SPTCP) were cut and placed parallel to each other in the gap. In Group A (eight knees), UDPTCP was implanted anteriorly and SPTCP posteriorly, while in Group B (six knees), SPTCP was implanted anteriorly and UDPTCP posteriorly. Computed tomography (CT) was performed at 1 week, 6 months, and 12 months after surgery, with the CT attenuation values calculated for UDPTCP and SPTCP. In Groups A and B, the CT attenuation values for UDPTCP were significantly lower at 6 and 12 months after surgery compared to those at 1 week (P < 0.05); nevertheless, no statistical difference in the comparison with SPTCP was observed. After a short-term follow-up of 12 months following MOWHTO, UDPTCP provided earlier bone remodeling than SPTCP. This outcome was achieved regardless of the position, anterior or posterior, in the MOWHTO gap.

Anterior cervical discectomy and fusion with recombinant human bone morphogenetic protein-2-adsorbed ß-tricalcium phosphate granules: a preliminary report.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is an alternative to conservative therapy in the treatment of cervical spondylopathy. This study evaluated the clinical outcome of ACDF with BMP-2-adsorbed ß-tricalcium phosphate granules. METHODS: Thirty-two patients with cervical spondylopathy received treatment of ACDF with BMP-2-adsorbed ß-tricalcium phosphate granules. The clinical outcomes were evaluated with the Japanese Orthopedic Association (JOA) scores and Neck Disability Index (NDI). Meanwhile, the cervical curvature and intervertebral heights were obtained through lateral cervical X-ray films pre- and postoperatively at each interval, and the precision of cervical fusion was assessed by three-dimensional computed tomography scan. RESULTS: The follow-up averaged 15.2 months (range 13-18). Average JOA scores significantly increased from a preoperative point (7.4 ± 1.2) to each interval after surgery (P < 0.05). NDI decreased from preoperative point (43.1 ± 9.0) to each interval after surgery (P < 0.05). The angles of cervical curvature and intervertebral heights were improved postoperatively and kept throughout the follow-up period. CT scan demonstrated a fusion rate of 82.9% at 6 months postoperatively and was improved to 100% at 12 months postoperatively. In all cases, no complications appeared and reported due to any lapse in surgical procedure skills throughout the follow-up period. CONCLUSIONS: Our preliminary findings suggest that BMP-2-adsorbed ß-tricalcium phosphate granules will be an effective alternative to autogenous bone grafting for cervical fusion in treating cervical spondylopathy. Our surgical procedure usingß-tricalcium phosphate granules could improve neurological function, recover intervertebral height and cervical curvature, and could be potentially exploitable in the clinical setting.

Talar Avascular Necrosis After Calcium Phosphate Injection Treatment of Talar Bone Marrow Lesions: A Report of 2 Cases.

CASE: We report on 2 patients who developed avascular necrosis (AVN) of the talus and poor patient outcomes after undergoing calcium phosphate injection into talar dome bone marrow lesions. CONCLUSION: Subchondroplasty, defined as calcium phosphate injection for the treatment of articular bone marrow edema, is a recently described procedure for use in the ankle joint. In our opinion, the limited available research is of poor quality and describes equivocal improvement in patient symptoms after this procedure. Given the debilitating outcomes and extensive AVN we observed in 2 patients, we strongly advise caution in the use of this procedure in the talus.

Bone Marrow Edema, Clinical Significance, and Treatment Options: A Review.

Bone marrow edema (BME) is a descriptive term used to describe high-signal intensity changes detected on magnetic resonance fluid-sensitive sequences that could be attributed to a number of underlying pathologies. Regardless of the cause, physiologic remodeling of the subchondral bone can be limited because of ongoing joint forces, increased focalization of stress, and reduced healing capacity of the subchondral bone. BME is a known prognostic factor associated with pain, dysfunction, and progressive cartilage damage. This review summarizes the current known causes of BMEs, theories related to histopathological changes, and current treatment options including novel biologic surgical options.

In vivo biodistribution of calcium phosphate nanoparticles after intravascular, intramuscular, intratumoral, and soft tissue administration in mice investigated by small animal PET/CT.

Calcium phosphate nanoparticles were covalently surface-functionalized with the ligand DOTA and loaded with the radioisotope 68Ga. The biodistribution of such 68Ga-labelled nanoparticles was followed in vivo in mice by positron emission tomography in combination with computer tomography (PET-CT). The biodistribution of 68Ga-labelled nanoparticles was compared for different application routes: intravenous, intramuscular, intratumoral, and into soft tissue. The particle distribution was measured in vivo by PET-CT after 5 min, 15 min, 30 min, 1 h, 2 h, and 4 h, and ex vivo after 5 h. After intravenous injection (tail vein), the nanoparticles rapidly entered the lungs with later redistribution into liver and spleen. The nanoparticles remained mostly at the injection site following intramuscular, intratumoral, or soft tissue application, with less than 10 percent being mobilized into the blood stream. STATEMENT OF SIGNIFICANCE: The in vivo biodistribution of DOTA-terminated calcium phosphate nanoparticles was followed by PET/CT. To our knowledge, this is the first study of this kind. Four different application routes of clinical relevance were pursued: Intravascular, intramuscular, intratumoral, and into soft tissue. Given the high importance of calcium phosphate as biomaterial and for nanoparticular drug delivery and immunization, this is most important to assess the biofate of calcium phosphate nanoparticles for therapeutic application and also judge biodistribution of nanoscopic calcium phosphate ceramics, including debris from endoprostheses and related implants.

Effects of available phosphorus source and concentration on performance and expression of sodium phosphate type IIb cotransporter, vitamin D-1α-hydroxylase, and vitamin D-24-hydroxylase mRNA in broiler chicks.

This experiment was conducted to examine the effect of 2 phosphorus (P) sources on broiler performance to day 14. The P bioavailability was estimated using bird performance and tibia ash measurements, whereas P digestibility, intestinal P transporter, kidney vitamin D-1α-hydroxylase, and vitamin D-24-hydroxylase mRNA abundances were also determined. Slope regression analysis was used to determine the bioavailability of dicalcium phosphate (Dical P) and nanocalcium phosphate (Nano P) with dietary available P (AvP) set to 0.20% P (control) using AvP from the major ingredients and Dical P. The experimental treatments were achieved by supplementation with either Dical P or Nano P to generate 0.24, 0.28, 0.32, and 0.36% AvP. A total of 648-day-old unsexed broiler chicks were divided into 72 birds per treatment (8 replicate cages of 9 birds). Slope regression analysis showed positive linear relationships between BW, feed intake (FI), tibia ash weight (TAW), and tibia ash percentage (TAP) with dietary Dical P and Nano P levels. Comparisons between regression slopes for Dical P and Nano P fed birds were not significantly different for BW, feed intake, tibia ash weight, and tibia ash percentage, indicating similar P bioavailability from Dical P and Nano P. There were interactions between P source and AvP for feed efficiency (FE) and apparent ileal P digestibility (AIPD). Dicalcium phosphate had greater FE than Nano P at 0.28% AvP and greater AIPD than Nano P at 0.24% AvP. The addition of AvP from Dical P and Nano P resulted in reduced sodium phosphate cotransporter mRNA abundance in the duodenum in a dose-dependent response. In the kidney, vitamin D-1α-hydroxylase mRNA abundance was greater at 0.36% Nano P compared with control, but there was no difference with Dical P. There was no difference in vitamin D-24-hydroxylase mRNA abundance between control and supplementation with Nano P or Dical P. In conclusion, Nano P and Dical P had the same bioavailability but had different effects on gene expression.

Bioinspired inorganic nanoparticles and vascular factor microenvironment directed neo-bone formation.

Various strategies have been explored to stimulate new bone formation. These strategies include using angiogenic stimulants in combination with inorganic biomaterials. Neovascularization during the neo-bone formation provides nutrients along with bone-forming minerals. Therefore, it is crucial to design a bone stimulating microenvironment composed of both pro-angiogenic and osteogenic factors. In this respect, human vascular endothelial growth factor (hVEGF) has been shown to promote blood vessel formation and bone formation. Furthermore, in recent years, whitlockite (WH), a novel phase of magnesium-containing calcium phosphate derivatives that exist in our bone tissue, has been synthesized and applied in bone tissue engineering. In this study, our aim is to explore the potential use of hVEGF and WH for bone tissue engineering. Our study demonstrated that hVEGF and a WH microenvironment synergistically stimulated osteogenic commitment of mesenchymal stem cells both in vitro and in vivo.

Oxytocin-loaded sustained-release hydrogel graft provides accelerated bone formation: An experimental rat study.

Restoration of the lost bone volume is one of the most deliberate issues in dentistry. Sustained-release microspherical oxytocin hormone in a poloxamer hydrogel scaffold combined with a mixture of ß-tricalcium phosphate and hydroxyapatite (CP) may serve as a suitable bone graft. The aim of this study was to design and test a novel thermosensitive hydrogel graft incorporating oxytocin-loaded poly(d, l-lactide-co-glycolide) (PLGA) sustained-release microspheres and CP. Thermosensitive poloxamer hydrogel containing CP (HCP graft) was prepared as a base and combined with hollow microspheres (HCPM) and oxytocin-loaded microspheres (HCPOM). Eighty Wistar rats were used for testing the grafts and a control group in 8-mm-diameter critical-sized calvarial defects (CSD); (n = 20). Bone healing at the 4th and 8th weeks was evaluated by histological, histomorphometric, and radiological (micro-computed tomography [µCT]) analyses. The results were analyzed by two-way analysis of variance (P < .05). Oxytocin-loaded PLGA microspheres prepared by the solvent displacement method yielded a high encapsulation efficiency of 89.5% and a slow drug release. Incorporation of the microspheres into the hydrogel graft slowed the release rate down and the release completed within 32 days. HCPOM revealed the highest new bone formation (26.45% ± 6.65% and 30.76% ± 4.37% at the 4th and 8th weeks, respectively; P < .0001) while HCPM and HCP groups revealed a bone formation of around 10% (P > .05). µCT findings of HCPOM group showed the highest mean bone mineral density values (42.21 ± 5.14 and 46.94 ± 3.30 g/cm3 for the 4th and 8th weeks, respectively; P < .0027). The proposed oxytocin-loaded sustained-release PLGA microspheres containing thermosensitive hydrogel graft (HCPOM) provide an accelerated bone regeneration in the rat calvaria.

First clinical application of octacalcium phosphate collagen composite on bone regeneration in maxillary sinus floor augmentation: A prospective, single-arm, open-label clinical trial.

The overall objective of this study was to assess the safety and efficacy of OCP/Col as a bone substitute material for bone regeneration during sinus floor augmentation. Maxillary sinus floor augmentation was performed thorough lateral window approach. According to the height of host bone, simultaneous approach (≥5 mm) or staged approach (less than 5 mm) was applied. In this research, clinical findings of dental implant treatment after setting the restorations were set as a primary endpoint in both approaches (infection, inflammation around the implant, movement of the implant, pain, sensory disorder, and bone resorption around the implant body on radiological evaluation.). In staged approach, histological evaluation of bone biopsy specimen was also conducted. As secondary endpoints, hounsfield unit (HU) value, vertical bone height, implant stability quotient (ISQ), and adverse events during the research were evaluated. In all cases, as a primary endpoint, clinical findings after setting the restorations were uneventful with no adverse events. Histological structure demonstrated mature bone derived from OCP/Col. In the ossified area, osteogenesis was observed around OCP granules, and osteoblast-like cells were arrayed around OCP granules. Osteocyte encapsulation was recognized in the new bone. HU increased over time with both approaches. Vertical bone height significantly increased at 3 months postoperatively, and maintained during follow-up. ISQ increased with both approaches. In particular, ISQ was significantly increased with the staged approach. This clinical trial demonstrated the safety and efficacy of OCP/Col for bone regeneration in maxillary sinus floor augmentation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:243-252, 2020.