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1.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072505

RESUMO

To develop cost-effective and efficient bone substitutes for improved regeneration of bone defects, heparin-modified mineralized collagen scaffolds were functionalized with concentrated, naturally occurring bioactive factor mixtures derived from adipose tissue, platelet-rich plasma and conditioned medium from a hypoxia-treated human bone marrow-derived mesenchymal stem cell line. Besides the analysis of the release kinetics of functionalized scaffolds, the bioactivity of the released bioactive factors was tested with regard to chemotaxis and angiogenic tube formation. Additionally, functionalized scaffolds were seeded with human bone marrow-derived mesenchymal stromal cells (hBM-MSC) and their osteogenic and angiogenic potential was investigated. The release of bioactive factors from the scaffolds was highest within the first 3 days. Bioactivity of the released factors could be confirmed for all bioactive factor mixtures by successful chemoattraction of hBM-MSC in a transwell assay as well as by the formation of prevascular structures in a 2D co-culture system of hBM-MSC and human umbilical vein endothelial cells. The cells seeded directly onto the functionalized scaffolds were able to express osteogenic markers and form tubular networks. In conclusion, heparin-modified mineralized collagen scaffolds could be successfully functionalized with naturally occurring bioactive factor mixtures promoting cell migration and vascularization.


Assuntos
Indutores da Angiogênese/farmacologia , Materiais Biocompatíveis , Produtos Biológicos/farmacologia , Regeneração Óssea/efeitos dos fármacos , Quimiotaxia/efeitos dos fármacos , Colágeno , Tecidos Suporte , Tecido Adiposo/metabolismo , Adulto , Biomarcadores , Substitutos Ósseos , Linhagem Celular , Células Cultivadas , Feminino , Expressão Gênica , Humanos , Masculino , Adulto Jovem
2.
J Med Life ; 14(2): 181-197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104241

RESUMO

The present study investigated the capacity of Suprathel® (a copolymer membrane, so far validated for skin regeneration) to also regenerate oral tissue - mucosa and bone, by comparing this biomaterial, in a split-mouth rabbit model, to Mucoderm®, a xenogeneic collagen matrix certified for keratinized oral mucosa healing. The clinical reason behind this experimental animal model was to determine whether the benefits of this advanced skin regeneration product (Suprathel®) could be conveyed for future evaluation in clinical trials of oral tissue regeneration in humans. The outcomes of this study validated the use of Suprathel®, a terpolymer of polylactide with trimethylene carbonate and ε-caprolactone, for stimulation of oral epithelium and alveolar bone regeneration in rabbits. Both Suprathel® and Mucoderm® exhibited comparable results and the null hypothesis stating a comparable regenerating effect of these two materials could not be rejected.


Assuntos
Osso e Ossos/patologia , Epitélio/patologia , Boca/fisiologia , Poliésteres/química , Regeneração , Cicatrização , Animais , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Osso Esponjoso/patologia , Regeneração Tecidual Guiada , Masculino , Mucosa Bucal/patologia , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Coelhos , Cicatrização/efeitos dos fármacos
3.
Int J Mol Sci ; 22(9)2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062885

RESUMO

The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration.


Assuntos
Substitutos Ósseos/farmacologia , Transplante Ósseo , Osteogênese/efeitos dos fármacos , Crânio/crescimento & desenvolvimento , Animais , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/química , Interface Osso-Implante/crescimento & desenvolvimento , Interface Osso-Implante/patologia , Humanos , Ácido Hialurônico/farmacologia , Hidroxiapatitas/farmacologia , Teste de Materiais , Ratos , Ratos Wistar , Crânio/efeitos dos fármacos , Água/química , Cicatrização/efeitos dos fármacos
4.
Int J Nanomedicine ; 16: 4209-4224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188470

RESUMO

Background and Purpose: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration. Methods: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy. Results: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups. Conclusion: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Portadores de Fármacos/química , Ácido Hialurônico/química , Nanopartículas/química , Polietilenoglicóis/química , Coluna Vertebral/fisiologia , Tiofenos/administração & dosagem , Tiofenos/farmacologia , Animais , Comunicação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacologia , Hidrogéis/química , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Coelhos , Ratos Wistar , Coluna Vertebral/efeitos dos fármacos
5.
Molecules ; 26(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068232

RESUMO

In this study, a potential hard tissue substitute was mimicked using collagen/mangosteen porous scaffolds. Collagen was extracted from Tilapia fish skin and mangosteen from the waste peel of the respective fruit. Sodium trimetaphosphate was used for the phosphorylation of these scaffolds to improve the nucleation sites for the mineralization process. Phosphate groups were incorporated in the collagen structure as confirmed by their attenuated total reflection Fourier transform infrared (ATR-FTIR) bands. The phosphorylation and mangosteen addition increased the thermal stability of the collagen triple helix structure, as demonstrated by differential scanning calorimetry (DSC) and thermogravimetry (TGA) characterizations. Mineralization was successfully achieved, and the presence of calcium phosphate was visualized by scanning electron microscopy (SEM). Nevertheless, the porous structure was maintained, which is an essential characteristic for the desired application. The deposited mineral was amorphous calcium phosphate, as confirmed by energy dispersive X-ray spectroscopy (EDX) results.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/fisiologia , Calcificação Fisiológica , Colágeno/farmacologia , Garcinia mangostana/química , Pele/química , Tecidos Suporte/química , Animais , Osso e Ossos/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Fosfatos de Cálcio/química , Varredura Diferencial de Calorimetria , Peixes , Fosforilação/efeitos dos fármacos , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Termogravimetria
6.
Int J Mol Sci ; 22(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072888

RESUMO

Hybrid biomaterials allow for the improvement of the biological properties of materials and have been successfully used for implantology in medical applications. The covalent and selective functionalization of materials with bioactive peptides provides favorable results in tissue engineering by supporting cell attachment to the biomaterial through biochemical cues and interaction with membrane receptors. Since the functionalization with bioactive peptides may alter the chemical and physical properties of the biomaterials, in this study we characterized the biological responses of differently functionalized chitosan analogs. Chitosan analogs were produced through the reaction of GRGDSPK (RGD) or FRHRNRKGY (HVP) sequences, both carrying an aldehyde-terminal group, to chitosan. The bio-functionalized polysaccharides, pure or "diluted" with chitosan, were chemically characterized in depth and evaluated for their antimicrobial activities and biocompatibility toward human primary osteoblast cells. The results obtained indicate that the bio-functionalization of chitosan increases human-osteoblast adhesion (p < 0.005) and proliferation (p < 0.005) as compared with chitosan. Overall, the 1:1 mixture of HVP functionalized-chitosan:chitosan is the best compromise between preserving the antibacterial properties of the material and supporting osteoblast differentiation and calcium deposition (p < 0.005 vs. RGD). In conclusion, our results reported that a selected concentration of HVP supported the biomimetic potential of functionalized chitosan better than RGD and preserved the antibacterial properties of chitosan.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Transplante Ósseo/métodos , Quitosana/química , Osteogênese/efeitos dos fármacos , Engenharia Tecidual , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/genética , Osso e Ossos/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quitosana/análogos & derivados , Quitosana/síntese química , Quitosana/farmacologia , Durapatita/química , Durapatita/farmacologia , Humanos , Oligopeptídeos/síntese química , Oligopeptídeos/química , Osteoblastos/efeitos dos fármacos , Tecidos Suporte/química
7.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063742

RESUMO

Three-dimensional (3D) printing is perceived as an innovative tool for change in tissue engineering and regenerative medicine based on research outcomes on the development of artificial organs and tissues. With advances in such technology, research is underway into 3D-printed artificial scaffolds for tissue recovery and regeneration. In this study, we fabricated artificial scaffolds by coating bone demineralized and decellularized extracellular matrix (bdECM) onto existing 3D-printed polycaprolactone/tricalcium phosphate (PCL/TCP) to enhance osteoconductivity and osteoinductivity. After injecting adipose-derived stem cells (ADSCs) in an aggregate form found to be effective in previous studies, we examined the effects of the scaffold on ossification during mandibular reconstruction in beagle dogs. Ten beagles were divided into two groups: group A (PCL/TCP/bdECM + ADSC injection; n = 5) and group B (PCL/TCP/bdECM; n = 5). The results were analyzed four and eight weeks after intervention. Computed tomography (CT) findings showed that group A had more diffuse osteoblast tissue than group B. Evidence of infection or immune rejection was not detected following histological examination. Goldner trichrome (G/T) staining revealed rich ossification in scaffold pores. ColI, Osteocalcin, and Runx2 gene expressions were determined using real-time polymerase chain reaction. Group A showed greater expression of these genes. Through Western blotting, group A showed a greater expression of genes that encode ColI, Osteocalcin, and Runx2 proteins. In conclusion, intervention group A, in which the beagles received the additional ADSC injection together with the 3D-printed PCL/TCP coated with bdECM, showed improved mandibular ossification in and around the pores of the scaffold.


Assuntos
Tecido Adiposo/citologia , Fosfatos de Cálcio/química , Matriz Extracelular/fisiologia , Mandíbula/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Poliésteres/química , Células-Tronco/citologia , Tecidos Suporte/química , Adipócitos/citologia , Animais , Regeneração Óssea/efeitos dos fármacos , Cães , Osteoblastos/efeitos dos fármacos , Impressão Tridimensional , Engenharia Tecidual/métodos
8.
Int J Nanomedicine ; 16: 3473-3485, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34040373

RESUMO

Background: Synthetic biomaterials have played an increasingly prominent role in the substitution of naturally derived biomaterials in current surgery practice. In vitro and in vivo characterization studies of new synthetic biomaterials are essential to analyze their physicochemical properties and the underlying mechanisms associated with the modulation of the inflammatory process and bone healing. Purpose: This study compares the in vivo tissue behavior of a synthetic biomaterial nano-hydroxyapatite/beta-tricalcium phosphate (nano-HA/ß-TCP mixture) and deproteinized bovine bone mineral (DBBM) in a rat calvarial defect model. The innovation of this work is in the comparative analysis of the effect of new synthetic and commercially xenogenic biomaterials on the inflammatory response, bone matrix gain, and stimulation of osteoclastogenesis and osteoblastogenesis. Methods: Both biomaterials were inserted in rat defects. The animals were divided into three groups, in which calvarial defects were filled with xenogenic biomaterials (group 1) and synthetic biomaterials (group 2), or left unfilled (group 3, controls). Sixty days after calvarial bone defects filled with biomaterials, periodic acid Schiff (PAS) and Masson's trichrome staining, immunohistochemistry tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-9 (MMP-9), and electron microscopy analyses were conducted. Results: Histomorphometric analysis revealed powerful effects such as a higher amount of proteinaceous matrix and higher levels of TNF-α and MMP-9 in bone defects treated with alloplastic nano-HA/ß-TCP mixture than xenogenicxenogic biomaterial, as well as collagen-proteinaceous material in association with hydroxyapatite crystalloids. Conclusion: These data indicate that the synthetic nano-HA/ß-TCP mixture enhanced bone formation/remodeling in rat calvarial bone defects. The nano-HA/ß-TCP did not present risks of cross-infection/disease transmission. The synthetic nano-hydroxyapatite/beta-tricalcium phosphate mixture presented adequate properties for guided bone regeneration and guided tissue regeneration for dental surgical procedures.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Hidroxiapatitas/química , Hidroxiapatitas/farmacologia , Nanoestruturas/química , Crânio/efeitos dos fármacos , Crânio/fisiologia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Colágeno/metabolismo , Masculino , Osteogênese/efeitos dos fármacos , Ratos , Crânio/metabolismo , Crânio/patologia
9.
Cell Prolif ; 54(6): e13035, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33939201

RESUMO

OBJECTIVES: Adiponectin signalling has been considered to be a promising target to treat diabetes-related osteoporosis. However, contradictory results regarding bone formation were observed due to the various isoforms of adiponectin. Therefore, it would be necessary to investigate the effect of adiponectin receptor signals in regulating bone-fat balance. MATERIALS AND METHODS: We primarily applied a newly found specific activator for adiponectin receptor, AdipoRon, to treat bone metabolism-related cells to investigate the role of Adiponectin receptor signals on bone-fat balance. We then established femur defect mouse model and treated them with AdipoRon to see whether adiponectin receptor activation could promote bone regeneration. RESULTS: We found that AdipoRon could slightly inhibit the proliferation of pre-osteoblast and pre-osteoclast, but AdipoRon showed no effect on the viability of mesenchymal stromal cells. AdipoRon could remarkably promote cell migration of mesenchymal stromal cells. Additionally, AdipoRon promoted osteogenesis in both pre-osteoblasts and mesenchymal cells. Besides, AdipoRon significantly inhibited osteoclastogenesis via its direct impact on pre-osteoclast and its indirect inhibition of RANKL in osteoblast. Moreover, mesenchymal stromal stems cells showed obviously decreased adipogenesis when treated with AdipoRon. Consistently, AdipoRon-treated mice showed faster bone regeneration and repressed adipogenesis. CONCLUSIONS: Our study demonstrated a pro-osteogenic, anti-adipogenic and anti-osteoclastogenic effect of adiponectin receptor activation in young mice, which suggested adiponectin receptor signalling was involved in bone regeneration and bone-fat balance regulation.


Assuntos
Osso e Ossos/efeitos dos fármacos , Osso e Ossos/lesões , Gorduras/metabolismo , Osteogênese/efeitos dos fármacos , Piperidinas/farmacologia , Receptores de Adiponectina/agonistas , Células 3T3 , Animais , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Células Cultivadas , Modelos Animais de Doenças , Masculino , Camundongos , Piperidinas/uso terapêutico , Ratos Sprague-Dawley , Receptores de Adiponectina/metabolismo
10.
Nat Commun ; 12(1): 2885, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001887

RESUMO

Despite the widespread observations on the osteogenic effects of magnesium ion (Mg2+), the diverse roles of Mg2+ during bone healing have not been systematically dissected. Here, we reveal a previously unknown, biphasic mode of action of Mg2+ in bone repair. During the early inflammation phase, Mg2+ contributes to an upregulated expression of transient receptor potential cation channel member 7 (TRPM7), and a TRPM7-dependent influx of Mg2+ in the monocyte-macrophage lineage, resulting in the cleavage and nuclear accumulation of TRPM7-cleaved kinase fragments (M7CKs). This then triggers the phosphorylation of Histone H3 at serine 10, in a TRPM7-dependent manner at the promoters of inflammatory cytokines, leading to the formation of a pro-osteogenic immune microenvironment. In the later remodeling phase, however, the continued exposure of Mg2+ not only lead to the over-activation of NF-κB signaling in macrophages and increased number of osteoclastic-like cells but also decelerates bone maturation through the suppression of hydroxyapatite precipitation. Thus, the negative effects of Mg2+ on osteogenesis can override the initial pro-osteogenic benefits of Mg2+. Taken together, this study establishes a paradigm shift in the understanding of the diverse and multifaceted roles of Mg2+ in bone healing.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Macrófagos/metabolismo , Magnésio/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Fêmur/metabolismo , Fêmur/patologia , Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Macrófagos/citologia , Macrófagos/imunologia , Magnésio/administração & dosagem , Magnésio/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Proteínas Serina-Treonina Quinases/genética , Ratos Sprague-Dawley , Células THP-1 , Canais de Cátion TRPM/genética
11.
Int J Mol Sci ; 22(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33920046

RESUMO

SmartBone® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-ß.


Assuntos
Matriz Óssea/química , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/farmacologia , Transplante de Células-Tronco Mesenquimais , Animais , Substitutos Ósseos/química , Bovinos , Diferenciação Celular/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Vesículas Extracelulares/química , Vesículas Extracelulares/genética , Humanos , Células-Tronco Mesenquimais/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Procedimentos Cirúrgicos Reconstrutivos/métodos
12.
Int J Mol Sci ; 22(7)2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33800710

RESUMO

Granulocyte colony-stimulating factor (G-CSF) was shown to promote bone regeneration and mobilization of vascular and osteogenic progenitor cells. In this study, we investigated the effects of a systemic low dose of G-CSF on both bone consolidation and mobilization of hematopoietic stem/progenitor cells (HSPCs), endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) in a rat model of distraction osteogenesis (DO). Neovascularization and mineralization were longitudinally monitored using positron emission tomography and planar scintigraphy. Histological analysis was performed and the number of circulating HSPCs, EPCs and MSCs was studied by flow cytometry. Contrary to control group, in the early phase of consolidation, a bony bridge with lower osteoclast activity and a trend of an increase in osteoblast activity were observed in the distracted callus in the G-CSF group, whereas, at the late phase of consolidation, a significantly lower neovascularization was observed. While no difference was observed in the number of circulating EPCs between control and G-CSF groups, the number of MSCs was significantly lower at the end of the latency phase and that of HSPCs was significantly higher 4 days after the bone lengthening. Our results indicate that G-CSF accelerates bone regeneration and modulates mobilization of progenitor cells during DO.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Osteogênese por Distração , Células-Tronco/citologia , Animais , Modelos Animais de Doenças , Durapatita/química , Citometria de Fluxo , Mobilização de Células-Tronco Hematopoéticas , Cinética , Masculino , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Tomografia por Emissão de Pósitrons , Ratos , Ratos Sprague-Dawley , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Células-Tronco/metabolismo
13.
Molecules ; 26(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799902

RESUMO

Electrospun carbon nanofibers (CNFs), which were modified with hydroxyapatite, were fabricated to be used as a substrate for bone cell proliferation. The CNFs were derived from electrospun polyacrylonitrile (PAN) nanofibers after two steps of heat treatment: stabilization and carbonization. Carbon nanofibrous (CNF)/hydroxyapatite (HA) nanocomposites were prepared by two different methods; one of them being modification during electrospinning (CNF-8HA) and the second method being hydrothermal modification after carbonization (CNF-8HA; hydrothermally) to be used as a platform for bone tissue engineering. The biological investigations were performed using in-vitro cell counting, WST cell viability and cell morphology after three and seven days. L929 mouse fibroblasts were found to be more viable on the hydrothermally-modified CNF scaffolds than on the unmodified CNF scaffolds. The biological characterizations of the synthesized CNF/HA nanofibrous composites indicated higher capability of bone regeneration.


Assuntos
Durapatita/química , Nanotubos de Carbono/química , Engenharia Tecidual/métodos , Animais , Desenvolvimento Ósseo/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Carbono/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/metabolismo , Camundongos , Nanocompostos/química , Nanofibras/química , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Tecidos Suporte/química
14.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808303

RESUMO

(1) Background: The aim of this study was examining the ex vivo and in vivo properties of a composite made from polycaprolactone (PCL) and biphasic calcium phosphate (BCP) (synprint, ScientiFY GmbH) fabricated via fused deposition modelling (FDM); (2) Methods: Scaffolds were tested ex vivo for their mechanical properties using porous and solid designs. Subcutaneous implantation model analyzed the biocompatibility of PCL + BCP and PCL scaffolds. Calvaria implantation model analyzed the osteoconductive properties of PCL and PCL + BCP scaffolds compared to BCP as control group. Established histological, histopathological and histomorphometrical methods were performed to evaluate new bone formation.; (3) Results Mechanical testing demonstrated no significant differences between PCL and PCL + BCP for both designs. Similar biocompatibility was observed subcutaneously for PCL and PCL + BCP scaffolds. In the calvaria model, new bone formation was observed for all groups with largest new bone formation in the BCP group, followed by the PCL + BCP group, and the PCL group. This finding was influenced by the initial volume of biomaterial implanted and remaining volume after 90 days. All materials showed osteoconductive properties and PCL + BCP tailored the tissue responses towards higher cellular biodegradability. Moreover, this material combination led to a reduced swelling in PCL + BCP; (4) Conclusions: Altogether, the results show that the newly developed composite is biocompatible and leads to successful osteoconductive bone regeneration. The new biomaterial combines the structural stability provided by PCL with bioactive characteristics of BCP-based BSM. 3D-printed BSM provides an integration behavior in accordance with the concept of guided bone regeneration (GBR) by directing new bone growth for proper function and restoration.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/química , Hidroxiapatitas/farmacologia , Animais , Materiais Biocompatíveis/química , Desenvolvimento Ósseo , Regeneração Óssea/fisiologia , Masculino , Osteogênese , Poliésteres/química , Porosidade , Impressão Tridimensional , Ratos , Ratos Wistar , Tecidos Suporte/química
15.
Molecules ; 26(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804968

RESUMO

Gelatin, a natural polymer, provides excellent tissue compatibility for use in tissue rehabilitation. Bioactive glasses (BAG) offer superior capacity in stimulating a bioactive response but show high variability in uptake and solubility. To tackle these drawbacks, a combination of gelatin with BAG is proposed to form composites, which then offer a synergistic response. The cross-linked gelatin structure's mechanical properties are enhanced by the incorporation of the inorganic BAG, and the rate of BAG ionic supplementation responsible for bioactivity and regenerative potential is better controlled by a protective gelatin layer. Several studies have demonstrated the cellular benefits of these composites in different forms of functional modification such as doping with zinc or incorporation of zinc such as ions directly into the BAG matrix. This review presents a comprehensive perspective on the individual characteristics of BAG and gelatin, including the synthesis and mechanism of action. Further, adaptation of the composite into various applications for bone tissue engineering is discussed and future challenges are highlighted.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Gelatina , Vidro/química , Engenharia Tecidual , Tecidos Suporte/química , Zinco , Animais , Gelatina/química , Gelatina/farmacologia , Humanos , Zinco/química , Zinco/farmacologia
16.
Molecules ; 26(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804244

RESUMO

Periodontal diseases are multifactorial disorders, mainly due to severe infections and inflammation which affect the tissues (i.e., gum and dental bone) that support and surround the teeth. These pathologies are characterized by bleeding gums, pain, bad breath and, in more severe forms, can lead to the detachment of gum from teeth, causing their loss. To date it is estimated that severe periodontal diseases affect around 10% of the population worldwide thus making necessary the development of effective treatments able to both reduce the infections and inflammation in injured sites and improve the regeneration of damaged tissues. In this scenario, the use of 3D scaffolds can play a pivotal role by providing an effective platform for drugs, nanosystems, growth factors, stem cells, etc., improving the effectiveness of therapies and reducing their systemic side effects. The aim of this review is to describe the recent progress in periodontal regeneration, highlighting the influence of materials' properties used to realize three-dimensional (3D)-scaffolds, their bio-physical characteristics and their ability to provide a biocompatible platform able to embed nanosystems.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Doenças Periodontais/terapia , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Humanos , Engenharia Tecidual/métodos
17.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801825

RESUMO

The loss of bone following tooth extraction poses a significant clinical problem for maxillofacial esthetics, function, and future implant placement. In the present study, the efficacy of an erythropoietin-impregnated collagen scaffold as an alveolar ridge augmentation material versus a conventional collagen scaffold and a BioOss inorganic bovine bone xenograft was examined. The collagen/Erythropoietin (EPO) scaffold exhibited significantly more rapid and complete osseous regeneration of the alveolar defect when compared to bone xenograft and the collagen membrane alone. The new EPO induced extracellular matrix was rich in Collagen I, Collagen III, Fibronectin (Fn) and E-cadherin, and featured significantly increased levels of the osteogenic transcription factors Runt-related transcription factor 2 (Runx2) and Osterix (Osx). Histomorphometric evaluation revealed a significant two-fold increase in the number of capillaries between the EPO and the BioOss group. Moreover, there was a highly significant 3.5-fold higher level of vascular endothelial growth factor (VEGF) in the collagen/EPO-treated group compared to controls. The significant effect of EPO on VEGF, FN, and RUNX2 upregulation was confirmed in vitro, and VEGF pathway analysis using VEGF inhibitors confirmed that EPO modulated extracellular matrix protein expression through VEGF even in the absence of blood vessels. Together, these data demonstrate the effectiveness of an EPO-impregnated collagen scaffold for bone regeneration as it induces rapid matrix production and osseoinduction adjacent to new capillaries via VEGF.


Assuntos
Processo Alveolar/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Capilares/efeitos dos fármacos , Eritropoetina/farmacologia , Matriz Extracelular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Processo Alveolar/fisiologia , Aumento do Rebordo Alveolar/métodos , Animais , Transplante Ósseo/métodos , Capilares/fisiologia , Bovinos , Células Cultivadas , Matriz Extracelular/metabolismo , Humanos , Minerais/farmacologia , Ratos Sprague-Dawley , Transplante Heterólogo , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
J Mater Chem B ; 9(10): 2469-2482, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33646220

RESUMO

Inspired by the nanostructure of bone, biomimetic nanocomposites comprising natural polymers and inorganic nanoparticles have gained much attention for bone regenerative applications. However, the mechanical and biological performances of nanocomposites are largely limited by the inhomogeneous distribution, uncontrolled size and irregular morphology of inorganic nanoparticles at present. In this work, an innovative in situ precipitation method has been developed to construct a biomimetic nanocomposite which consists of spherical hydroxyapatite (HA) nanoparticles and gelatin (Gel). The homogeneous dispersion of HA nanoparticles in nHA-Gel endowed it with a low swelling ratio, enhanced mechanical properties and slow degradation. Moreover, strontium (Sr) was incorporated into HA nanoparticles to further enhance the bioactivity of nanocomposites. In vitro experiments suggested that nHA-Gel and Sr-nHA-Gel facilitated cell spreading and promoted osteogenic differentiation of bone-marrow-derived mesenchymal stem cells (BMSCs) as compared to pure Gel and mHA-Gel conventional composites developed by mechanical mixing. In vivo rat critical-sized calvarial defect repair further confirmed that nHA-Gel and Sr-nHA-Gel possessed relatively effective bone regenerative abilities among the four groups. Collectively, the biomimetic nanocomposites of nHA-Gel and Sr-nHA-Gel have good efficacy in inducing bone regeneration and would be a promising alternative to bone grafts for clinical applications.


Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Regeneração Óssea/efeitos dos fármacos , Durapatita/química , Nanocompostos/química , Nanopartículas/química , Animais , Diferenciação Celular/efeitos dos fármacos , Gelatina/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ratos , Estrôncio/química
19.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652598

RESUMO

The search for the perfect bone graft material is an important topic in material science and medicine. Despite human bone being the ideal material, due to its composition, morphology, and familiarity with cells, autografts are widely considered demanding and cause additional stress to the patient because of bone harvesting. However, human bone from tissue banks can be used to prepare materials in eligible form for transplantation. Without proteins and fats, the bone becomes a non-immunogenic matrix for human cells to repopulate in the place of implantation. To repair bone losses, the granulate form of the material is easy to apply and forms an interconnected porous structure. A granulate composed of ß-tricalcium phosphate, pulverized human bone, and chitosan-a potent biopolymer applied in tissue engineering, regenerative medicine, and biotechnology-has been developed. A commercial encapsulator was used to obtain granulate, using chitosan gelation upon pH increase. The granulate has been proven in vitro to be non-cytotoxic, suitable for MG63 cell growth on its surface, and increasing alkaline phosphatase activity, an important biological marker of bone tissue growth. Moreover, the granulate is suitable for thermal sterilization without losing its form-increasing its convenience for application in surgery for guided bone regeneration in case of minor or non-load bearing voids in bone tissue.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Fosfatos de Cálcio , Quitosana , Teste de Materiais , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Linhagem Celular , Quitosana/química , Quitosana/farmacologia , Humanos
20.
Carbohydr Polym ; 260: 117769, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33712127

RESUMO

Periodontal defect poses a significant challenge in orthopedics. Guided Bone Regeneration (GBR) membrane is considered as one of the most successful methods applied to reconstruct alveolar bone and then to achieve periodontal defect repair/regeneration. In this paper, a novel polyamide-6/chitosan@nano-hydroxyapatite/polyamide-6 (PA6/CS@n-HA/PA6) bilayered tissue guided membranes by combining a solvent casting and an electrospinning technique was designed. The developed PA6/CS@n-HA/PA6 composites were characterized by a series of tests. The results show that n-HA/PA6 and electrospun PA6/CS layers are tightly bound by molecular interaction and chemical bonding, which enhances the bonding strength between two distinct layers. The porosity and adsorption average pore diameter of the PA6/CS@n-HA/PA6 membranes are 36.90 % and 22.61 nm, respectively. The tensile strength and elastic modulus of PA6/CS@n-HA/PA6 composites are 1.41 ± 0.18 MPa and 7.15 ± 1.09 MPa, respectively. In vitro cell culture studies demonstrate that PA6/CS@n-HA/PA6 bilayered scaffolds have biological safety, good bioactivity, biocompatibility and osteoconductivity.


Assuntos
Regeneração Óssea , Caprolactama/análogos & derivados , Quitosana/química , Durapatita/química , Membranas Artificiais , Nanoestruturas/química , Polímeros/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Caprolactama/química , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Nanofibras/química , Nanoestruturas/toxicidade , Porosidade , Propriedades de Superfície , Resistência à Tração
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