Elevación de seno conBetafosfato Tricálcico yposterior colocación deimplantes. A propósito deun caso / Sinus lift with tricalcium beta-phosphate and subsequent implant placement. Case report

La extracción o pérdida dental supone la remodelación del alveolo y una pérdida progresiva del hueso alveolar residual. Esta disminución en altura, debido a la presencia delseno maxilar en el sector posterosuperior, puede comprometer la disponibilidad ósea adecuada para la colocación de implantes. Como solución a esto, surge la técnica de elevación de seno. En esta técnica, se emplean diversos materiales de injerto, entre los que se encuentran el betafosfatotricálcico (b-TCP). Este material presenta propiedades osteoconductivas y osteoinductivas. Además, se reabsorbe más fácil que otros sustitutos óseos y es fácilmente reemplazado por nuevo hueso. Se ha comparado su comportamiento clínico con otros materiales de injerto, sin encontrar diferencias significativas. Además, a 10 años, los implantes colocados en elevaciones de seno realizadas con b-TCP han mostrado altas tasas de supervivencia. Caso clínico. Se presenta el caso clínico de una paciente, mujer de 52 años de edad, sin antecedentes médicos de interés. Acude a consulta por dolor en el 26. Tras la exploración diagnóstica radiológica e intrabucal se aconsejó a la paciente la extracción del 26. Ocho meses después, y realizando un estudio con CBCT se informó a la paciente sobre la posibilidad de rehabilitación con implantes, previa cirugía de elevación sinusal. Se realizó la elevación sinusal con b-TCP como material de injerto. Pasados tres meses, se procedió a la colocación de tres implantes, adquiriendo estos una buena estabilidad primaria Discusión y conclusiones. Se utilizan diversos materiales de injerto en la técnica de elevación sinusal, injertos de hueso autólogo, xenoinjertos e injerto aloplásticos. Se ha comparado el comportamiento clínico del b-TCP con otros materiales de injerto sin mostrar diferencias significativas. Por otro lado, se ha estudiado un periodo de espera menor a 6 (AU)

Tooth extraction or loss involves alveolar remodelling and progressive loss of residual alveolar bone. This reduction in height, due to the presence of the maxillary sinus in the posterosuperior sector, can compromise adequate bone availability for implant placement. The sinus lift technique has emerged as a solution to this problem. In this technique, various grafting materials are used, including beta-phosphatidic acid (b-TCP). This material has osteoconductive and osteoinductive properties. In addition, it is more easily resorbed than other bone substitutes and is easily replaced by new bone. Its clinical behaviour has been compared with other graft materials, without finding significant differences. In addition, at 10 years, implants placed in sinus lifts performed with b-TCP have shown high survival rates. Clinical case: The clinical case of a 52-year-old female patient with no medical history of interest is presented. She went for consultation due to pain in tooth 26. Following the radiological and intraoral diagnostic examination, the patient was advised to have tooth 26 extracted. Eight months later, and after a CBCT study, the patient was informed about the possibility of rehabilitation with implants, following sinus lift surgery. The sinus lift was performed with b-TCP as graft material. After three months, three implants were placed, acquiring a good primary stability. Discussion and conclusions: different graft materials are used in the sinus lift technique, autologous bone grafts, xenografts and alloplastic grafts. The clinical performance of b-TCP has been compared with no significant differences found. Furthermore, a waiting period of less than 6 months has been studied for the placement of implants. These implants showed high primary stability and survival rates of 99-100%. Therefore, b-TCP is a safe material for sinus lifts and allows the placement of implants in a healing time of less than 6 months (AU)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The Efficacy of Recombinant Platelet-Derived Growth Factor on Beta-Tricalcium Phosphate to Regenerate Femoral Critical Sized Segmental Defects: Longitudinal In Vivo Micro-CT Study in a Rat Model.

Background and Objectives: Beta-tricalcium phosphate (beta-TCP) has been used for bone regeneration. The objective of this study was to assess longitudinally, the regeneration of critical sized segmental defects (CSSD) in rat femur using beta-TCP with or without recombinant platelet-derived growth factor (PDGF) through in vivo micro-computed tomography (micro-CT). Materials and Methods: Following ethical approval unilateral femoral CSSD measuring 5 mm was surgically created, under general anesthesia, in 30 male Wistar-Albino rats (aged 12-18 months; weighing 450-500 g). CSSD was stabilized using titanium mini-plate (4 holes, 1.0 mm thick with 8 mm bar). Depending upon biomaterial used for regeneration, the animals were randomly divided into: Control group (N = 10): CSSD covered with resorbable collagen membrane (RCM) only; Beta-TCP group (N = 10): CSSD filled with beta-TCP and covered by RCM; Beta-TCP + PDGF group (N = 10): CSSD filled with beta-TCP soaked in recombinant PDGF and covered by RCM. Longitudinal in vivo micro-CT analysis of the CSSD was done postoperatively at baseline, 2nd, 4th, 6th, and 8th weeks to assess volume and mineral density of newly formed bone (NFB) and beta-TCP. Results: Significant increase in NFB volume (NFBV) and mineral density (NFBMD) were observed from baseline to 8-weeks in all groups. Based on longitudinal in vivo micro-CT at 8-weeks, beta-TCP + PDGF group had significantly higher (p < 0.01) NFBV (38.98 ± 7.36 mm3) and NFBMD (3.72 ± 0.32 g/mm3) than the beta-TCP (NFBV-31.15 ± 6.68 mm3; NFBMD-2.28 ± 0.86g/mm3) and control (NFBV: 5.60 ± 1.06 mm3; NFBMD: 0.27 ± 0.02 g/mm3) groups. Significantly, higher reduction in beta-TCP volume (TCPV) and mineral density (TCPMD) were 1 observed in the beta-TCP + PDGF group when compared to the beta-TCP group. Conclusion: Addition of recombinant PDGF to beta-TCP enhanced bone regeneration within rat femoral CSSD and increased resorption rates of beta-TCP particles.

Chemotherapy-induced oral mucositis management: A retrospective analysis of MuGard, Caphosol, and standard supportive care measures.

BACKGROUND: Oral mucositis, a common complication of several different anticancer therapies, causes significant morbidity in cancer patients. It is characterized by the destruction of the mucosa throughout the gastrointestinal tract including the oral cavity. Limited data exist regarding the treatment of established oral mucositis with oral mucoadhesive hydrogel (MuGard) or supersaturated calcium phosphate oral rise (Caphosol) compared to standard topical therapies. OBJECTIVES: To evaluate the effects of MuGard and Caphosol compared to standard topical therapy in the treatment of established oral mucositis. METHODS: A retrospective chart review was performed including adults receiving MuGard, Caphosol, and/or standard topical therapy for the treatment of established oral mucositis while admitted to a community teaching hospital. A post hoc propensity score was used to match patients receiving newer agents (Mugard/Caphosol) to those receiving standard topical therapy (ST). RESULTS: One hundred and forty-seven patients were included for analysis (125 ST, 15 MuGard, 7 Caphosol). From this population, 14 patients in each group were matched. The primary endpoint of median change in average daily pain score at days 3 and 7, compared to baseline, demonstrated no difference between matched groups at day 3 (ST 0, MuGard/Caphosol 0.18, p = 0.830) or day 7 (ST 0, MuGard/Caphosol 0.8, p = 0.494). No differences were noted between groups in opioid usage, oral mucositis symptom duration or progression, or incidence of documented infection. CONCLUSION: MuGard and Caphosol did not demonstrate any benefits compared to standard topical therapy at reducing pain scores or increasing mucosal recovery in the treatment of oral mucositis.