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1.
Biomater Adv ; 159: 213813, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38428122

RESUMO

The ability of human tissues to self-repair is limited, which motivates the scientific community to explore new and better therapeutic approaches to tissue regeneration. The present manuscript provides a comparative study between a marine-based composite biomaterial, and another composed of well-established counterparts for bone tissue regeneration. Blue shark skin collagen was combined with bioapatite obtained from blue shark's teeth (mColl:BAp), while bovine collagen was combined with synthetic hydroxyapatite (bColl:Ap) to produce 3D composite scaffolds by freeze-drying. Collagens showed similar profiles, while apatite particles differed in their composition, being the marine bioapatite a fluoride-enriched ceramic. The marine-sourced biomaterials presented higher porosities, improved mechanical properties, and slower degradation rates when compared to synthetic apatite-reinforced bovine collagen. The in vivo performance regarding bone tissue regeneration was evaluated in defects created in femoral condyles in New Zealand rabbits twelve weeks post-surgery. Micro-CT results showed that mColl:BAp implanted condyles had a slower degradation and an higher tissue formation (17.9 ± 6.9 %) when compared with bColl:Ap implanted ones (12.9 ± 7.6 %). The histomorphometry analysis provided supporting evidence, confirming the observed trend by quantifying 13.1 ± 7.9 % of new tissue formation for mColl:BAp composites and 10.4 ± 3.2 % for bColl:Ap composites, suggesting the potential use of marine biomaterials for bone regeneration.


Assuntos
Materiais Biocompatíveis , Alicerces Teciduais , Humanos , Animais , Coelhos , Bovinos , Materiais Biocompatíveis/uso terapêutico , Apatitas , Regeneração Óssea , Colágeno/farmacologia
2.
Clin Oral Investig ; 28(4): 213, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38480533

RESUMO

OBJECTIVE: The limitations of spontaneous bone healing underscore the necessity for exploring alternative strategies to enhance bone regeneration in maxillary radicular cyst cases. This retrospective study aimed to assess the impact of a bone substitute material (i.e., Bio-Oss) on bone volume regeneration following maxillary radicular cyst enucleation using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Seventy-three patients with maxillary radicular cysts were divided into two groups: one undergoing guided bone regeneration (GBR) with Bio-Oss and absorbable collagen membrane (n = 35), and the other receiving cyst excision alone (n = 38). Volumetric measurements using Amira software on CBCT scans evaluated bone regeneration, with cystic lesion shrinkage rates calculated. Intergroup comparisons utilized independent sample t-tests (P < 0.05), and linear regression analysis assessed the influence of preoperative cyst volume and group on bone healing. RESULTS: Both groups showed similar success rates in bone formation at the 12-month follow-up, with no significant differences between them (mean (SD), control: 75.16 (19.17) vs. GBR: 82 (20.22), P > 0.05). Linear regression analysis revealed a negative correlation between preoperative cyst volume and bone regeneration in both groups (P < 0.05). CONCLUSION: Bio-Oss may not significantly enhance bone augmentation in maxillary radicular cysts. In addition, preoperative cyst volume negatively affected the shrinkage rate of cystic lesions. CLINICAL RELEVANCE: Clinicians should consider patient-specific factors such as anatomy and lesion size when determining the need for bone substitute materials. Future research could focus on optimizing treatment protocols and alternative regenerative strategies to improve patient outcomes in maxillary cyst cases.


Assuntos
Substitutos Ósseos , Minerais , Cisto Radicular , Humanos , Transplante Ósseo/métodos , Estudos Retrospectivos , Cisto Radicular/cirurgia , Substitutos Ósseos/uso terapêutico , Regeneração Óssea
3.
Cytotherapy ; 26(4): 372-382, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38363250

RESUMO

BACKGROUND AIMS: Human mesenchymal stromal cells (hMSCs) and their secreted products show great promise for treatment of musculoskeletal injury and inflammatory or immune diseases. However, the path to clinical utilization is hampered by donor-tissue variation and the inability to manufacture clinically relevant yields of cells or their products in a cost-effective manner. Previously we described a method to produce chemically and mechanically customizable gelatin methacryloyl (GelMA) microcarriers for culture of hMSCs. Herein, we demonstrate scalable GelMA microcarrier-mediated expansion of induced pluripotent stem cell (iPSC)-derived hMSCs (ihMSCs) in 500 mL and 3L vertical wheel bioreactors, offering several advantages over conventional microcarrier and monolayer-based expansion strategies. METHODS: Human mesenchymal stromal cells derived from induced pluripotent cells were cultured on custom-made spherical gelatin methacryloyl microcarriers in single-use vertical wheel bioreactors (PBS Biotech). Cell-laden microcarriers were visualized using confocal microscopy and elastic light scattering methodologies. Cells were assayed for viability and differentiation potential in vitro by standard methods. Osteogenic cell matrix derived from cells was tested in vitro for osteogenic healing using a rodent calvarial defect assay. Immune modulation was assayed with an in vivo peritonitis model using Zymozan A. RESULTS: The optical properties of GelMA microcarriers permit noninvasive visualization of cells with elastic light scattering modalities, and harvest of product is streamlined by microcarrier digestion. At volumes above 500 mL, the process is significantly more cost-effective than monolayer culture. Osteogenic cell matrix derived from ihMSCs expanded on GelMA microcarriers exhibited enhanced in vivo bone regenerative capacity when compared to bone morphogenic protein 2, and the ihMSCs exhibited superior immunosuppressive properties in vivo when compared to monolayer-generated ihMSCs. CONCLUSIONS: These results indicate that the cell expansion strategy described here represents a superior approach for efficient generation, monitoring and harvest of therapeutic MSCs and their products.


Assuntos
Técnicas de Cultura de Células , Células-Tronco Mesenquimais , Humanos , Técnicas de Cultura de Células/métodos , Reatores Biológicos , Osteogênese , Regeneração Óssea , Proliferação de Células , Diferenciação Celular , Células Cultivadas
4.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255941

RESUMO

Many studies have been exploring the use of bone graft materials (BGMs) and mesenchymal stem cells in bone defect reconstruction. However, the regeneration potential of Algipore (highly purified hydroxyapatite) and Biphasic (hydroxyapatite/beta-tricalcium phosphate) BGMs combined with bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we evaluated their osseointegration capacities in reconstructing peri-implant bone defects. The cellular characteristics of BMSCs and the material properties of Algipore and Biphasic were assessed in vitro. Four experimental groups-Algipore, Biphasic, Algipore+BMSCs, and Biphasic+BMSCs-were designed in a rabbit tibia peri-implant defect model. Implant stability parameters were measured. After 4 and 8 weeks of healing, all samples were evaluated using micro-CT, histological, and histomorphometric analysis. In the energy-dispersive X-ray spectroscopy experiment, the Ca/P ratio was higher for Algipore (1.67) than for Biphasic (1.44). The ISQ values continuously increased, and the PTV values gradually decreased for all groups during the healing period. Both Algipore and Biphasic BGM promoted new bone regeneration. Higher implant stability and bone volume density were observed when Algipore and Biphasic BGMs were combined with BMSCs. Biphasic BGM exhibited a faster degradation rate than Algipore BGM. Notably, after eight weeks of healing, Algipore with BSMCs showed more bone-implant contact than Biphasic alone (p < 0.05). Both Algipore and Biphasic are efficient in reconstructing peri-implant bone defects. In addition, Algipore BGM incorporation with BSMCs displayed the best performance in enhancing implant stability and osseointegration potential.


Assuntos
Células-Tronco Mesenquimais , Procedimentos de Cirurgia Plástica , Animais , Coelhos , Osseointegração , Regeneração Óssea , Durapatita
5.
Comput Biol Med ; 165: 107381, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37611419

RESUMO

Mechanical environment plays a crucial role in regulating bone regeneration in bone defects. Assessing the mechanobiological behavior of patient-specific orthopedic scaffolds in-silico could help guide optimal scaffold designs, as well as intra- and post-operative strategies to enhance bone regeneration and improve implant longevity. Additively manufactured porous scaffolds, and specifically triply periodic minimal surfaces (TPMS), have shown promising structural properties to act as bone substitutes, yet their ability to induce mechanobiologially-driven bone regeneration has not been elucidated. The aim of this study is to i) explore the bone regeneration potential of TPMS scaffolds made of different stiffness biocompatible materials, to ii) analyze the influence of pre-seeding the scaffolds and increasing the post-operative resting period, and to iii) assess the influence of patient-specific parameters, such as age and mechanosensitivity, on outcomes. To perform this study, an in silico model of a goat tibia is used. The bone ingrowth within the scaffold pores was simulated with a mechano-driven model of bone regeneration. Results showed that the scaffold's architectural properties affect cellular diffusion and strain distribution, resulting in variations in the regenerated bone volume and distribution. The softer material improved the bone ingrowth. An initial resting period improved the bone ingrowth but not enough to reach the scaffold's core. However, this was achieved with the implantation of a pre-seeded scaffold. Physiological parameters like age and health of the patient also influence the bone regeneration outcome, though to a lesser extent than the scaffold design. This analysis demonstrates the importance of the scaffold's geometry and its material, and highlights the potential of using mechanobiological patient-specific models in the design process for bone substitutes.


Assuntos
Substitutos Ósseos , Alicerces Teciduais , Humanos , Alicerces Teciduais/química , Porosidade , Substitutos Ósseos/química , Regeneração Óssea , Osso e Ossos
6.
ACS Biomater Sci Eng ; 9(8): 4673-4685, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37399249

RESUMO

In this work, a titanium-doped hydroxyapatite (HAp) scaffold was produced from two different sources (natural eggshell and laboratory-grade reagents) to compare the efficacy of natural and synthetic resources of HAp materials on new bone regeneration. This comparative study also reports the effect of Ti doping on the physical, mechanical, and in vitro as well as in vivo biological properties of the HAp scaffold. Pellets were prepared in the conventional powder metallurgy route, compacted, and sintered at 900 °C, showing sufficient porosity for bony ingrowth. The physical-mechanical characterizations were performed by density, porosity evaluation, XRD, FTIR, SEM analysis, and hardness measurement. In vitro interactions were evaluated by bactericidal assay, hemolysis, MTT assay, and interaction with simulated body fluid. All categories of pellets showed absolute nonhemolytic and nontoxic character. Furthermore, significant apatite formation was observed on the Ti-doped HAp samples in the simulated body fluid immersion study. The developed porous pellets were implanted to assess the bone defect healing in the femoral condyle of healthy rabbits. A 2 month study after implantation showed no marked inflammatory reaction for any samples. Radiological analysis, histological analysis, SEM analysis, and oxytetracycline labeling studies depicted better invasion of mature osseous tissue in the pores of doped eggshell-derived HAp scaffolds as compared to the undoped HAp, and laboratory-made samples. Quantification using oxytetracycline labeling depicted 59.31 ± 1.89% new bone formation for Ti-doped eggshell HAp as compared to Ti-doped pure HAp (54.41 ± 1.93) and other undoped samples. Histological studies showed the presence of abundant osteoblastic and osteoclastic cells in Ti-doped eggshell HAp in contrast to other samples. Radiological and SEM data also showed similar results. The results indicated that Ti-doped biosourced HAp samples have good biocompatibility, new bone-forming ability, and could be used as a bone grafting material in orthopedic surgery.


Assuntos
Durapatita , Oxitetraciclina , Animais , Coelhos , Durapatita/farmacologia , Titânio/farmacologia , Casca de Ovo , Regeneração Óssea , Modelos Animais
7.
Int J Mol Sci ; 24(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37108772

RESUMO

This research aimed to substantiate the potential practicality of utilizing a matrix-like platform, a novel 3D-printed biomaterial scaffold, to enhance and guide host cells' growth for bone tissue regeneration. The 3D biomaterial scaffold was successfully printed using a 3D Bioplotter® (EnvisionTEC, GmBH) and characterized. Osteoblast-like MG63 cells were utilized to culture the novel printed scaffold over a period of 1, 3, and 7 days. Cell adhesion and surface morphology were examined using scanning electron microscopy (SEM) and optical microscopy, while cell viability was determined using MTS assay and cell proliferation was evaluated using a Leica microsystem (Leica MZ10 F). The 3D-printed biomaterial scaffold exhibited essential biomineral trace elements that are significant for biological bone (e.g., Ca-P) and were confirmed through energy-dispersive X-ray (EDX) analysis. The microscopy analyses revealed that the osteoblast-like MG63 cells were attached to the printed scaffold surface. The viability of cultured cells on the control and printed scaffold increased over time (p < 0.05); however, on respective days (1, 3, and 7 days), the viability of cultured cells between the two groups was not significantly different (p > 0.05). The protein (human BMP-7, also known as growth factor) was successfully attached to the surface of the 3D-printed biomaterial scaffold as an initiator of osteogenesis in the site of the induced bone defect. An in vivo study was conducted to substantiate if the novel printed scaffold properties were engineered adequately to mimic the bone regeneration cascade using an induced rabbit critical-sized nasal bone defect. The novel printed scaffold provided a potential pro-regenerative platform, rich in mechanical, topographical, and biological cues to guide and activate host cells toward functional regeneration. The histological studies revealed that there was progress in new bone formation, especially at week 8 of the study, in all induced bone defects. In conclusion, the protein (human BMP-7)-embedded scaffolds showed higher regenerative bone formation potential (week 8 complete) compared to the scaffolds without protein (e.g., growth factor; BMP-7) and the control (empty defect). At 8 weeks postimplantation, protein (BMP-7) significantly promoted osteogenesis as compared to other groups. The scaffold underwent gradual degradation and replacement by new bones at 8 weeks in most defects.


Assuntos
Materiais Biocompatíveis , Engenharia Tecidual , Animais , Humanos , Coelhos , Materiais Biocompatíveis/farmacologia , Alicerces Teciduais , Proteína Morfogenética Óssea 7 , Osteogênese , Regeneração Óssea , Impressão Tridimensional
8.
Colloids Surf B Biointerfaces ; 223: 113152, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36739675

RESUMO

Fabricating bioartificial bone graft ceramics retaining structural, mechanical, and bone induction properties akin to those of native stem-cell niches is a major challenge in the field of bone tissue engineering and regenerative medicine. Moreover, the developed materials are susceptible to microbial invasion leading to biomaterial-centered infections which might limit their clinical translation. Here, we successfully developed biomimetic porous scaffolds of polyurethane-reinforcedL-cysteine-anchored polyaniline capped strontium oxide nanoparticles to improve the scaffold's biocompatibility, osteo-regeneration, mechanical, and antibacterial properties. The engineered nanocomposite substrate PU/L-Cyst-SrO2 @PANI (0.4 wt%) significantly promotes bone repair and regeneration by modulating osteolysis and osteogenesis. ALP activity, collagen-I, ARS staining, as well as biomineralization of MC3T3-E1 cells, were used to assess the biocompatibility and cytocompatibility of the developed scaffolds in vitro, confirming that the scaffold provided a favorable microenvironment with a prominent effect on cell growth, proliferation, and differentiation. Furthermore, osteogenic protein markers were studied using qRT-PCR with expression levels of runt-related transcription factor 2 (RUNX2), secreted phosphoprotein 1 (Spp-I), and collagen type I (Col-I). The overall results suggest that PU/L-Cyst-SrO2 @PANI (0.4 wt%) scaffolds showed superior interfacial biocompatibility, antibacterial properties, load-bearing ability, and osteoinductivity as compared to pristine PU. Thus, prepared bioactive nanocomposite scaffolds perform as a promising biomaterial substrate for bone tissue regeneration.


Assuntos
Nanofibras , Osteogênese , Cisteína/farmacologia , Alicerces Teciduais/química , Poliuretanos/farmacologia , Nanofibras/química , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Regeneração Óssea , Diferenciação Celular , Colágeno Tipo I/farmacologia , Antibacterianos/farmacologia
9.
BMC Oral Health ; 23(1): 118, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36810076

RESUMO

OBJECTIVES: To analyze morphological, volumetric, and linear hard tissue changes following horizontal ridge augmentation using a three-dimensional radiographic method. METHODS: As part of a larger ongoing prospective study, 10 lower lateral surgical sites were selected for evaluation. Horizontal ridge deficiencies were treated with guided bone regeneration (GBR) using a split-thickness flap design and a resorbable collagen barrier membrane. Following the segmentation of baseline and 6-month follow-up cone-beam computed tomography scans, volumetric, linear, and morphological hard tissue changes and the efficacy of the augmentation were assessed (expressed by the volume-to-surface ratio). RESULTS: Volumetric hard tissue gain averaged 605.32 ± 380.68 mm3. An average of 238.48 ± 127.82 mm3 hard tissue loss was also detected at the lingual aspect of the surgical area. Horizontal hard tissue gain averaged 3.00 ± 1.45 mm. Midcrestal vertical hard tissue loss averaged 1.18 ± 0.81 mm. The volume-to-surface ratio averaged 1.19 ± 0.52 mm3/mm2. The three-dimensional analysis showed slight lingual or crestal hard tissue resorption in all cases. In certain instances, the greatest extent of hard tissue gain was observed 2-3 mm apical to the initial level of the marginal crest. CONCLUSIONS: With the applied method, previously unreported aspects of hard tissue changes following horizontal GBR could be examined. Midcrestal bone resorption was demonstrated, most likely caused by increased osteoclast activity following the elevation of the periosteum. The volume-to-surface ratio expressed the efficacy of the procedure independent of the size of the surgical area.


Assuntos
Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Regeneração Óssea , Humanos , Aumento do Rebordo Alveolar/métodos , Transplante Ósseo/métodos , Implantação Dentária Endóssea/métodos , Estudos Prospectivos , Retalhos Cirúrgicos
10.
J Mech Behav Biomed Mater ; 138: 105587, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36446181

RESUMO

The present work reports the effect of decellularized platelet-rich fibrin (dPRF) loaded strontium (Sr) doped porous magnesium phosphate (MgP) bioceramics on biocompatibility, biodegradability, and bone regeneration. Sustained release of growth factors from dPRF is a major objective here, which conformed to the availability of dPRF on the scaffold surface even after 7 days of in vitro degradation. dPRF-incorporated MgP scaffolds were implanted in the rabbit femoral bone defect and bone rejuvenation was confirmed by radiological examination, histological examination, fluorochrome labeling study, and micro-CT. µ-CT examination of the regained bone samples exhibited that invasion of mature bone in the pores of the MgP2Sr-dPRF sample was higher than the MgP2Sr which indicated better bone maturation capability of this composition. Quantifiable assessment using oxytetracycline labeling showed 73.55 ± 1.12% new osseous tissue regeneration for MgP2Sr-dPRF samples in contrast to 65.47 ± 1.16% for pure MgP2Sr samples, after 3 months of implantation. Histological analysis depicted the presence of abundant osteoblastic and osteoclastic cells in dPRF-loaded Sr-doped MgP samples as compared to other samples. Radiological studies also mimicked similar results in the MgP2Sr-dPRF group with intact periosteal lining and significant bridging callus formation. The present results indicated that dPRF-loaded Sr-doped magnesium phosphate bioceramics have good biocompatibility, bone-forming ability, and suitable biodegradability in bone regeneration.


Assuntos
Fibrina Rica em Plaquetas , Alicerces Teciduais , Animais , Coelhos , Porosidade , Regeneração Óssea , Magnésio/farmacologia , Estrôncio/farmacologia , Osteogênese
11.
Vet Comp Orthop Traumatol ; 36(1): 29-38, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35760364

RESUMO

OBJECTIVE: The aim of this study was to assess bone density, bone architecture and clinical function of canine nonunion distal appendicular long bone fractures with a defect treated with fixation, compression-resistant matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2). STUDY DESIGN: Prospective cohort study with dogs at least 1-year post treatment. Computed tomography was performed and quantitative measurements from previous fracture sites were compared with measurements from contralateral limbs. Subjective evaluation included gait assessment and palpation. RESULTS: Six patients met the inclusion criteria. The rhBMP-2 treated bone exhibited higher density at the periphery and lower density in the centre, similar to the contralateral limb. All patients were weight bearing on the treated limb and all fractures were healed. CONCLUSION: The rhBMP-2-treated bone underwent restoration of normal architecture and density. Acceptable limb function was present in all patients. The results of this study can serve as a basis for long-term response in treating nonunion fractures in veterinary patients.


Assuntos
Doenças do Cão , Fraturas Ósseas , Fraturas não Consolidadas , Humanos , Cães , Animais , Estudos Prospectivos , Consolidação da Fratura , Fator de Crescimento Transformador beta/uso terapêutico , Proteína Morfogenética Óssea 2/uso terapêutico , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/tratamento farmacológico , Fraturas Ósseas/cirurgia , Fraturas Ósseas/veterinária , Fraturas não Consolidadas/diagnóstico por imagem , Fraturas não Consolidadas/tratamento farmacológico , Fraturas não Consolidadas/cirurgia , Fraturas não Consolidadas/veterinária , Proteínas Recombinantes/uso terapêutico , Regeneração Óssea , Doenças do Cão/tratamento farmacológico
12.
Front Endocrinol (Lausanne) ; 13: 935391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120459

RESUMO

Angiogenesis is important for successful fracture repair. Aging negatively affects the number and activity of endothelial cells (ECs) and subsequently leads to impaired bone healing. We previously showed that implantation of lung-derived endothelial cells (LECs) improved fracture healing in rats. In this study, we characterized and compared neonatal lung and bone marrow-derived endothelial cells (neonatal LECs and neonatal BMECs) and further asses3sed if implantation of neonatal BMECs could enhance bone healing in both young and aged mice. We assessed neonatal EC tube formation, proliferation, and wound migration ability in vitro in ECs isolated from the bone marrow and lungs of neonatal mice. The in vitro studies demonstrated that both neonatal LECs and neonatal BMECs exhibited EC traits. To test the function of neonatal ECs in vivo, we created a femoral fracture in young and aged mice and implanted a collagen sponge to deliver neonatal BMECs at the fracture site. In the mouse fracture model, endochondral ossification was delayed in aged control mice compared to young controls. Neonatal BMECs significantly improved endochondral bone formation only in aged mice. These data suggest BMECs have potential to enhance aged bone healing. Compared to LECs, BMECs are more feasible for translational cell therapy and clinical applications in bone repair. Future studies are needed to examine the fate and function of BMECs implanted into the fracture sites.


Assuntos
Células Endoteliais , Fraturas Ósseas , Animais , Medula Óssea , Regeneração Óssea , Colágeno , Modelos Animais de Doenças , Pulmão , Camundongos , Ratos
13.
Drug Dev Ind Pharm ; 48(3): 98-108, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35659167

RESUMO

BACKGROUND: Gellan gum is obtained from the bacterium Sphingomonas elodea and is a polysaccharide with carboxylic acid functional groups. The goal of this project was to investigate the osteoinductive effect of local administration of calcitonin through an injectable scaffold of gellan gum containing salmon calcitonin loaded in silsesquioxane nanoparticles, hydroxyapatite, and platelets rich plasma. METHODS: The femur of rats was defected by creating a 2 × 5 mm2 hole using an electric drill. The defect was filled with an injectable hydrogel scaffold composed of gellan gum enriched with salmon calcitonin loaded in silsesquioxane nanoparticles, hydroxyapatite, platelets rich plasma, and then the radiologic images were taken. Bone densitometry and the histologic studies were carried out by Hematoxylin & Eosin test. Biochemical analysis was done to measure the serum alkaline phosphatase (ALP), calcium, and calcitonin concentration. RESULTS: Healing of the bone defects and bone densitometry in the treated group by calcitonin-loaded scaffold was significantly higher (p < 0.05) and bone formation occupied 75% of the defect was greater than in other groups. Serum ALP and calcium levels in the scaffold-loaded calcitonin group were more than in the other groups (p < 0.05). The osteogenic marker genes also increased significantly (p < 0.05) with free calcitonin and the scaffold. CONCLUSIONS: Gellan gum-based scaffold loaded with calcitonin may be considered a promising local treatment to progress bone formation in repairing skeletal injuries.


Assuntos
Nanocompostos , Plasma Rico em Plaquetas , Animais , Regeneração Óssea , Calcitonina/farmacologia , Cálcio/farmacologia , Durapatita , Ratos , Engenharia Tecidual/métodos , Alicerces Teciduais
14.
J Biomed Mater Res B Appl Biomater ; 110(9): 2133-2145, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35388573

RESUMO

Bone tissue engineering (BTE) has made significant progress in developing and assessing different types of bio-substitutes. However, scaffolds production through standardized methods, as required for good manufacturing process (GMP), and post-transplant in vivo monitoring still limit their translation into the clinic. 3D printed 5% GelMA scaffolds have been prepared through an optimized and reproducible process in this work. Mesenchymal stem cells (MSC) were encapsulated in the 3D printable GelMA ink, and their biological properties were assessed in vitro to evaluate their potential for cell delivery application. Moreover, in vivo implantation of the pristine 3D printed GelMA has been performed in a rat condyle defect model. Whereas optimal tissue integration was observed via histology, no signs of fibrotic encapsulation or inhibited bone formation were attained. A multimodal imaging workflow based on computed tomography (CT) and magnetic resonance imaging (MRI) allowed the simultaneous monitoring of both new bone formation and scaffold degradation. These outcomes point out the direction to undertake in developing 3D printed-based hydrogels for BTE that can allow a faster transition into clinical use.


Assuntos
Bioimpressão , Gelatina , Animais , Regeneração Óssea , Gelatina/farmacologia , Hidrogéis/farmacologia , Metacrilatos/farmacologia , Impressão Tridimensional , Ratos , Engenharia Tecidual/métodos , Alicerces Teciduais
15.
Sci Rep ; 12(1): 1424, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35082347

RESUMO

Despite the current advances in micro-CT analysis, the influence of some image acquisition parameters on the morphometric assessment outcome have not been fully elucidated. The aim of this study was to determine whether data binning and frame averaging affect the morphometric outcome of bone repair assessment using micro-CT. Four Wistar rats' tibiae with a surgically created bone defect were imaged with micro-CT six times each, frame averaging set to 1 and 2, and data binning set to 1, 2 and 4, for each of the averaging values. Two-way ANOVA followed by Bonferroni tests assessed the significance of frame averaging and data binning on a set of morphometric parameters assessed in the image volumes (p < 0.01). The effect of frame averaging was not significant for any of the assessed parameters. Increased data binning led to larger trabecular thickness. In contrast, smaller bone volume fraction and bone volume were found as data binning increased. Trabeculae number and trabecular separation were not influenced by any of the parameters. In conclusion, the morphometric outcome of bone repair assessment in micro-CT demonstrated dependency upon data binning, but not frame averaging. Therefore, image acquisition of small anatomical structures (e.g., rat trabeculae) should be performed without data binning.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/normas , Tíbia/diagnóstico por imagem , Microtomografia por Raio-X/normas , Animais , Regeneração Óssea/fisiologia , Masculino , Ratos , Ratos Wistar , Tíbia/lesões
16.
J Periodontol ; 93(3): 343-353, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34245016

RESUMO

BACKGROUND: The aim of this study was to examine osseous changes following lateral bone augmentation using a novel scaffold (OV) alone and compare it to combination therapy using freeze-dried bone allograft (FDBA) and resorbable collagen membrane (FDBA/CM). METHODS: Thirty patients completed this 9-months prospective two-center cohort clinical trial. Before surgery and 9-months re-entry, linear measurements were performed, and impressions taken. Cone-beam computed tomography (CBCT) were done at baseline and 9 months. DICOM slice data were converted into volumetric images using 3D Slicer. Following 3D volumetric image construction, pre- and post-op Standard Triangle Language files were superimposed and volumetric data were extracted for a 10-mm region of interest. Linear measurements were compared similarly. RESULTS: Baseline clinical parameters were similar in both groups (4.22 and 4.53 mm for OV and FDBA/CM at -2 mm, respectively). Following treatment, vertical distance from the stent had changed minimally (-0.36 and -0.12 mm, respectively). Similarly, lateral bone gain ranged from 0 to 0.4 mm, for both groups. To the contrary, the CBCT measurements showed a significantly greater increase in horizontal width in the control at -2 mm (0.95 ± 0.2 mm) compared with -0.62 mm for the OV (P = 0.000). Similar changes were observed at -5 mm (0.63 and -0.41 mm, respectively, P = 0.01). Sites volume had increased from 266 ± 149 mm3 to 360 ± 138 mm3 (P = 0.001) for FDBA/CM with negligible changes for OV (from 334 to 335 mm3 , P = 0.952). these between-group changes being statistically significant (P = 0.023). CONCLUSION: FDBA/CM yielded better albeit moderate increase in the volume of the edentulous ridge, while OV scaffolds failed to produce similar results.


Assuntos
Aumento do Rebordo Alveolar , Aloenxertos/cirurgia , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , Regeneração Óssea , Transplante Ósseo/métodos , Colágeno/uso terapêutico , Humanos , Estudos Prospectivos , Extração Dentária , Alvéolo Dental/cirurgia
17.
Int J Mol Sci ; 22(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34884557

RESUMO

Octacalcium phosphate (OCP, Ca8H2(PO4)6·5H2O) is known to be a possible precursor of biological hydroxyapatite formation of organic bone tissue. OCP has higher biocompatibility and osseointegration rate compared to other calcium phosphates. In this work, the synthesis of low-temperature calcium phosphate compounds and substituted forms of those at physiological temperatures is shown. Strontium is used to improve bioactive properties of the material. Strontium was inserted into the OCP structure by ionic substitution in solutions. The processes of phase formation of low-temperature OCP with theoretical substitution of strontium for calcium up to 50 at.% in conditions close to physiological, i.e., temperature 35-37 °C and normal pressure, were described. The effect of strontium substitution range on changes in the crystal lattice of materials, the microstructural features, surface morphology and biological properties in vitro has been established. The results of the study indicate the effectiveness of using strontium in OCP for improving biocompatibility of OCP based composite materials intended for bone repair.


Assuntos
Materiais Biocompatíveis/farmacologia , Regeneração Óssea , Osso e Ossos/citologia , Fosfatos de Cálcio/síntese química , Fosfatos de Cálcio/farmacologia , Mesoderma/citologia , Animais , Materiais Biocompatíveis/síntese química , Osso e Ossos/efeitos dos fármacos , Durapatita/química , Técnicas In Vitro , Mesoderma/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C3H , Espécies Reativas de Oxigênio/metabolismo , Estrôncio/química , Engenharia Tecidual
18.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638753

RESUMO

A novel fluorapatite/glucan composite ("FAP/glucan") was developed for the treatment of bone defects. Due to the presence of polysaccharide polymer (ß-1,3-glucan), the composite is highly flexible and thus very convenient for surgery. Its physicochemical and microstructural properties were evaluated using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), mercury intrusion, mechanical testing and compared with the reference material, which was a hydroxyapatite/glucan composite ("HAP/glucan") with hydroxyapatite granules (HAP) instead of FAP. It was found that FAP/glucan has a higher density and lower porosity than the reference material. The correlation between the Young's modulus and the compressive strength between the materials is different in a dry and wet state. Bioactivity assessment showed a lower ability to form apatite and lower uptake of apatite-forming ions from the simulated body fluid by FAP/glucan material in comparison to the reference material. Moreover, FAP/glucan was determined to be of optimal fluoride release capacity for osteoblasts growth requirements. The results of cell culture experiments showed that fluoride-containing biomaterial was non-toxic, enhanced the synthesis of osteocalcin and stimulated the adhesion of osteogenic cells.


Assuntos
Apatitas , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Osteoblastos/metabolismo , beta-Glucanas , Apatitas/química , Apatitas/farmacologia , Linhagem Celular , Humanos , Porosidade , beta-Glucanas/química , beta-Glucanas/farmacologia
19.
J Mater Sci Mater Med ; 32(9): 113, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34453610

RESUMO

Tissue regeneration and neovascularisation in cases of major bone loss is a challenge in maxillofacial surgery. The hypothesis of the present study is that the addition of resorbable bioactive ceramic Silica Calcium Phosphate Cement (SCPC) to Declluraized Muscle Scaffold (DSM) can expedite bone formation and maturation. Two surgical defect models were created in 18 nude transgenic mice. Group 1(n = 6), with a 2-mm decortication calvarial defect, was treated with a DSM/SCPC sheet over the corticated bone as an onlay then seeded with human Mesenchymal Stromal Cells hMSC in situ. In Group 2 (n = 6), a critical size (4 mm) calvarial defect was made and grafted with DSM/SCPC/in situ human bone marrow stromal cells (hMSCs). The control groups included Group 3 (n = 3) animals, with a 2-mm decortication defect treated with an onlay DSM sheet, and Group 4 (n = 3) animals, treated with critical size defect grafted with plain DSM. After 8 weeks, bone regeneration in various groups was evaluated using histology, immunohistochemistry and histomorphometry. New bone formation and maturation was superior in groups treated with DSM/SCPC/hMSC. The DMS/SCPC scaffold has the ability to augment and induce bone regeneration and neovascularisation in cases of major bone resorption and critical size defects.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Cerâmica/uso terapêutico , Matriz Extracelular Descelularizada/uso terapêutico , Músculos/química , Implantação de Prótese , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Substitutos Ósseos/química , Substitutos Ósseos/uso terapêutico , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Células Cultivadas , Cerâmica/química , Matriz Extracelular Descelularizada/química , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Nus , Camundongos Transgênicos , Osteogênese/efeitos dos fármacos , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos , Crânio/efeitos dos fármacos , Crânio/patologia , Crânio/fisiopatologia , Engenharia Tecidual/métodos
20.
Clin Implant Dent Relat Res ; 23(4): 600-611, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34139056

RESUMO

BACKGROUND: Innovative customized computer-aided design/computer-assisted manufacture (CAD-CAM) titanium meshes have been proposed for guided alveolar bone regeneration. Histological confirmation on the quality of the regenerated bone is needed. Purpose of the study is to assess the integration capabilities of these innovative meshes and to evaluate the histological features of the regenerated alveolar bone. MATERIALS AND METHODS: Twenty partially edentulous patients, with severe posterior mandibular atrophy, underwent a guided bone regeneration technique by means of customized CAD-CAM titanium mesh in association with a mixture of autologous bone in chips and deproteinized bovine bone (1:1). At 9 months of healing, titanium meshes and bone samples were collected and histomorphometrically analyzed. RESULTS: In all patients, implants were placed according to the original plan. At histologic analysis, mesh appeared well osseointegrated, except that in sites where membrane exposure occurred. In all sites, newly formed tissue resulted highly mineralized, well-organized, and formed by 35.88% of new lamellar bone, 16.42% of woven bone, 10.88% of osteoid matrix, 14.10% of grafted remnants, and 22.72% of medullary spaces. Blood vessels were the 4% of the tissue. CONCLUSIONS: Data from this study support the use of customized CAD/CAM titanium mesh for regeneration of vital, well-structured, and vascularized alveolar bone.


Assuntos
Aumento do Rebordo Alveolar , Implantes Dentários , Animais , Regeneração Óssea , Transplante Ósseo , Bovinos , Estudos de Coortes , Desenho Assistido por Computador , Computadores , Humanos , Mandíbula/cirurgia , Telas Cirúrgicas , Titânio
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