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1.
J Am Acad Orthop Surg ; 32(10): e476-e481, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38700858

RESUMO

With an aging population, and an anticipated increase in overall fracture incidence, a sound understanding of bone healing and how technology can optimize this process is crucial. Concentrated bone marrow aspirate (cBMA) is a technology that capitalizes on skeletal stem and progenitor cells (SSPCs) to enhance the regenerative capacity of bone. This overview highlights the science behind cBMA, discusses the role of SSPCs in bone homeostasis and fracture repair, and briefly details the clinical evidence supporting the use of cBMA in fracture healing. Despite promising early clinical results, a lack of standardization in harvest and processing techniques, coupled with patient variability, presents challenges in optimizing the use of cBMA. However, cBMA remains an emerging technology that may certainly play a crucial role in the future of fracture healing augmentation.


Assuntos
Consolidação da Fratura , Humanos , Consolidação da Fratura/fisiologia , Transplante de Medula Óssea/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Regeneração Óssea/fisiologia , Fraturas Ósseas/terapia , Células da Medula Óssea/citologia
2.
Swiss Dent J ; 134(1): 144-157, 2024 Apr 05.
Artigo em Alemão | MEDLINE | ID: mdl-38741457

RESUMO

The clinical impact of platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF®) respectively has been studied extensively in the field of regenerative dentistry during the last two decades. Literature supports evidence for additional benefits in regenerative periodontal therapy, alveolar ridge preservation, management of extraction sockets, implantology including guided bone regeneration as well as defect management in oral surgery. Regarding gingival wound healing and soft tissue regeneration, there is sufficient evidence for their positive effects which have been confirmed in several systematic reviews. The effects seem less clear in conjunction with osseous regenerative treatments, where the inter-study heterogenity in terms of different PRF-protocols, indications and application forms might hinder a systematic comparison. Nevertheless there is evidence that PRF might have beneficial effects on hard-tissue or its regeneration respectively.For being able to facilitate conclusions in systematic reviews, precise reporting of the used PRF-protocols is mandatory for future (clinical) research in the field of autologous platelet concentrates.


Assuntos
Fibrina Rica em Plaquetas , Plasma Rico em Plaquetas , Humanos , Regeneração Tecidual Guiada Periodontal/métodos , Plaquetas/fisiologia , Regeneração Óssea/fisiologia , Regeneração Óssea/efeitos dos fármacos , Cicatrização/fisiologia , Cicatrização/efeitos dos fármacos , Medicina Regenerativa/métodos
3.
J Orthop Surg Res ; 19(1): 299, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755635

RESUMO

BACKGROUND: This study aims to evaluate the optimal ratio of synthetic bone graft (SBG) material and platelet rich fibrin (PRF) mixed in a metal 3D-printed implant to enhance bone regeneration. METHODS: Specialized titanium hollow implants (5 mm in diameter and 6 mm in height for rabbit; 6 mm in diameter and 5 mm in height for pig) were designed and manufactured using 3D printing technology. The implants were divided into three groups and filled with different bone graft combinations, namely (1) SBG alone; (2) PRF to SBG in 1:1 ratio; (3) PRF to SBG in 2:1 ratio. These three groups were replicated tightly into each bone defect in distal femurs of rabbits (nine implants, n = 3) and femoral shafts of pigs (fifteen implants, n = 5). Animal tissue sections were obtained after euthanasia at the 8th postoperative week. The rabbit specimens were stained with analine blue, while the pig specimens were stained with Masson-Goldner's trichrome stain to perform histologically examination. All titanium hollow implants were well anchored, except in fracture specimens (three in the rabbit and one fracture in the pig). RESULT: Rabbit specimens under analine blue staining showed that collagen tissue increased by about 20% and 40% in the 1:1 ratio group and the 2:1 ratio group, respectively. Masson-Goldner's trichrome stain results showed that new bone growth increased by 32% in the 1:1 ratio PRF to SBG, while - 8% in the 2:1 ratio group. CONCLUSION: This study demonstrated that placing a 1:1 ratio combination of PRF and SBG in a stabilized titanium 3D printed implant resulted in an optimal increase in bone growth.


Assuntos
Regeneração Óssea , Fibrina Rica em Plaquetas , Impressão Tridimensional , Titânio , Animais , Coelhos , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Suínos , Fêmur/cirurgia , Substitutos Ósseos , Transplante Ósseo/métodos , Próteses e Implantes
4.
Int J Implant Dent ; 10(1): 25, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38760582

RESUMO

PURPOSE: This retrospective cohort study evaluates the influence of connective tissue grafts (CTG) on bone regeneration at implant sites with total loss of the buccal bone wall treated with flapless immediate implant placement (IIP) and reconstruction with autogenous bone chips (AB) within a follow-up of up to 13 years. METHODS: Sixty implants were inserted in 55 patients in sites with total loss of the buccal bone wall between 2008 and 2021. The implants were inserted and the buccal gaps were grafted by AB. A subgroup of 34 sites was grafted additionally with CTG using tunnel technique. Primary outcome was the vertical bone regeneration in height and thickness. Secondary outcome parameters were interproximal marginal bone level, recession, soft tissue esthetics (PES), width of keratinized mucosa (KMW) and probing depths (PPD). RESULTS: Mean follow-up period was 60.8 months. In 55 sites a complete vertical bone regeneration was documented. The mean buccal bone level increased by 10.6 mm significantly. The thickness of the buccal bone wall ranged between 1.7 and 1.9 mm, and was significantly thicker in sites without CTG. Interproximal marginal bone level was at implant shoulder level. The mean recession improved significantly by 1.2 mm. In sites with CTG, recessions and PES improved significantly more. CONCLUSIONS: Additional CTG in extraction sites with total buccal bone loss followed by IIP with simultaneous AB grafting led to improved PES and recession, but also to a thinner buccal bone wall compared to sites grafted just with AB.


Assuntos
Tecido Conjuntivo , Carga Imediata em Implante Dentário , Humanos , Estudos Retrospectivos , Tecido Conjuntivo/transplante , Feminino , Masculino , Pessoa de Meia-Idade , Carga Imediata em Implante Dentário/métodos , Adulto , Transplante Ósseo/métodos , Idoso , Regeneração Óssea/fisiologia , Aumento do Rebordo Alveolar/métodos , Perda do Osso Alveolar/cirurgia
5.
Foot Ankle Clin ; 29(2): 281-290, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679439

RESUMO

Bone Marrow Stimulation of osteochondral lesions of the talus has been shown to be a successful way to treat cartilage injuries. Newer data suggest that Bone Marrow Stimulation is best reserved for osteochondral lesions of the talus Sizes Less Than 107.4 mm2 in area. Additionally, newer smaller and deeper techniques to perform bone marrow stimulation have resulted in less subchondral bone damage, less cancellous compaction, and superior bone marrow access with multiple trabecular access channels. Biologic adjuvants such as platelet-rich plasma (PRP), hyaluronic acid (HA), and bone marrow aspirate concentrate (BMAC) may lead to better functional outcomes when used concomitant to bone marrow stimulation.


Assuntos
Tálus , Humanos , Tálus/lesões , Tálus/cirurgia , Cartilagem Articular/lesões , Cartilagem Articular/cirurgia , Cartilagem Articular/fisiologia , Plasma Rico em Plaquetas , Medula Óssea , Regeneração Óssea/fisiologia
6.
Int J Oral Sci ; 16(1): 33, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654018

RESUMO

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.


Assuntos
Regeneração Óssea , Alicerces Teciduais , Transcriptoma , Animais , Regeneração Óssea/fisiologia , Poliésteres , Crânio/cirurgia , Células-Tronco Mesenquimais , Mesoderma/citologia , Diferenciação Celular , Engenharia Tecidual/métodos , Suturas Cranianas , Materiais Biocompatíveis
7.
Calcif Tissue Int ; 114(6): 625-637, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643416

RESUMO

Loss of p21 leads to increased bone formation post-injury; however, the mechanism(s) by which this occurs remains undetermined. E2f1 is downstream of p21 and as a transcription factor can act directly on gene expression; yet it is unknown if E2f1 plays a role in the osteogenic effects observed when p21 is differentially regulated. In this study we aimed to investigate the interplay between p21 and E2f1 and determine if the pro-regenerative osteogenic effects observed with the loss of p21 are E2f1 dependent. To accomplish this, we employed knockout p21 and E2f1 mice and additionally generated a p21/E2f1 double knockout. These mice underwent burr-hole injuries to their proximal tibiae and healing was assessed over 7 days via microCT imaging. We found that p21 and E2f1 play distinct roles in bone regeneration where the loss of p21 increased trabecular bone formation and loss of E2f1 increased cortical bone formation, yet loss of E2f1 led to poorer bone repair overall. Furthermore, when E2f1 was absent, either individually or simultaneously with p21, there was a dramatic decrease of the number of osteoblasts, osteoclasts, and chondrocytes at the site of injury compared to p21-/- and C57BL/6 mice. Together, these results suggest that E2f1 regulates the cell populations required for bone repair and has a distinct role in bone formation/repair compared to p21-/-E2f1-/-. These results highlight the possibility of cell cycle and/or p21/E2f1 being potential druggable targets that could be leveraged in clinical therapies to improve bone healing in pathologies such as osteoporosis.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21 , Fator de Transcrição E2F1 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteogênese , Animais , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Osteogênese/fisiologia , Camundongos , Regeneração Óssea/fisiologia , Osteoblastos/metabolismo
8.
Int J Biol Macromol ; 264(Pt 1): 130608, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447840

RESUMO

Bone defects pose significant challenges in orthopedic surgery, often leading to suboptimal outcomes and complications. Addressing these challenges, we employed a three-electrode electrochemical system to fabricate surface-controlled polyaniline nano-tulips (PANINTs) decorated polycaprolactone (PCL) reinforced chitosan functionalized iron oxide nanoparticles (CS-f-Fe2O3) scaffolds. These structures were designed to emulate the natural extracellular matrix (ECM) and promote enhanced osseointegration by establishing a continuous interface between host bone and graft, thereby improving both biological processes and mechanical stability. In vitro experiments demonstrated that PANINTs-PCL/CS-f-Fe2O3 substrates significantly promoted the proliferation, differentiation, and spontaneous outgrowth and extension of MC3T3-E1 cell activity. The nanomaterials exhibited increased cell viability and osteogenic differentiation, as evidenced by elevated expression of bone-related markers such as ALP, ARS, COL-I, RUNX2, and SPP-I, as determined by qRT-PCR. Our findings underscore the regenerative potential of in situ cell culture systems for bone defects, emphasizing the targeted stimulation of essential cell subpopulations to facilitate rapid bone tissue regeneration.


Assuntos
Compostos de Anilina , Quitosana , Quitosana/química , Osteogênese , Alicerces Teciduais/química , Regeneração Óssea/fisiologia , Técnicas Eletroquímicas , Engenharia Tecidual/métodos , Diferenciação Celular , Proliferação de Células , Poliésteres/química
9.
Adv Healthc Mater ; 13(12): e2303600, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38303119

RESUMO

Bone regenerative scaffolds with a bionic natural bone hierarchical porous structure provide a suitable microenvironment for cell migration and proliferation. Here, a bionic scaffold (DP-PLGA/HAp) with directional microchannels is prepared by combining 3D printing and directional freezing technology. The 3D printed framework provides structural support for new bone tissue growth, while the directional pore embedded in the scaffolds provides an express lane for cell migration and nutrition transport, facilitating cell growth and differentiation. The hierarchical porous scaffolds achieve rapid infiltration and adhesion of bone marrow mesenchymal stem cells (BMSCs) and improve the expression of osteogenesis-related genes. The rabbit cranial defect experiment presents significant new bone formation, demonstrating that DP-PLGA/HAp offers an effective means to guide cranial bone regeneration. The combination of 3D printing and directional freezing technology might be a promising strategy for developing bone regenerative biomaterials.


Assuntos
Regeneração Óssea , Células-Tronco Mesenquimais , Osteogênese , Impressão Tridimensional , Alicerces Teciduais , Regeneração Óssea/fisiologia , Animais , Coelhos , Alicerces Teciduais/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Porosidade , Diferenciação Celular , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Engenharia Tecidual/métodos , Proliferação de Células , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Durapatita/química
10.
Adv Sci (Weinh) ; 11(17): e2309491, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38380490

RESUMO

The regeneration of bone defects in diabetic patients still faces challenges, as the intrinsic healing process is impaired by hyperglycemia. Inspired by the discovery that the endoplasmic reticulum (ER) is in a state of excessive stress and dysfunction under hyperglycemia, leading to osteogenic disorder, a novel engineered exosome is proposed to modulate ER homeostasis for restoring the function of mesenchymal stem cells (MSCs). The results indicate that the constructed engineered exosomes efficiently regulate ER homeostasis and dramatically facilitate the function of MSCs in the hyperglycemic niche. Additionally, the underlying therapeutic mechanism of exosomes is elucidated. The results reveal that exosomes can directly provide recipient cells with SHP2 for the activation of mitophagy and elimination of mtROS, which is the immediate cause of ER dysfunction. To maximize the therapeutic effect of engineered exosomes, a high-performance hydrogel with self-healing, bioadhesive, and exosome-conjugating properties is applied to encapsulate the engineered exosomes for in vivo application. In vivo, evaluation in diabetic bone defect repair models demonstrates that the engineered exosomes delivering hydrogel system intensively enhance osteogenesis. These findings provide crucial insight into the design and biological mechanism of ER homeostasis-based tissue-engineering strategies for diabetic bone regeneration.


Assuntos
Regeneração Óssea , Retículo Endoplasmático , Exossomos , Homeostase , Hidrogéis , Células-Tronco Mesenquimais , Exossomos/metabolismo , Regeneração Óssea/fisiologia , Regeneração Óssea/genética , Animais , Homeostase/fisiologia , Hidrogéis/química , Camundongos , Retículo Endoplasmático/metabolismo , Células-Tronco Mesenquimais/metabolismo , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Osteogênese/fisiologia , Modelos Animais de Doenças , Engenharia Tecidual/métodos , Masculino , Humanos
11.
Adv Sci (Weinh) ; 11(16): e2304861, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38355304

RESUMO

An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single-component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA-PBA-SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear-thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post-injection "self-curing," which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs-containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA-based hydrogel enabled efficient gelation with shear-thinning and self-curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration.


Assuntos
Regeneração Óssea , Ácidos Borônicos , Diferenciação Celular , Hidrogéis , Células-Tronco Mesenquimais , Animais , Regeneração Óssea/fisiologia , Ratos , Hidrogéis/química , Células-Tronco Mesenquimais/citologia , Humanos , Ácido Hialurônico/química , Ratos Sprague-Dawley , Encapsulamento de Células/métodos , Proliferação de Células , Osteogênese/fisiologia , Modelos Animais de Doenças , Espermidina/farmacologia , Espermidina/química
12.
ACS Nano ; 18(10): 7504-7520, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38412232

RESUMO

The essential role of the neural network in enhancing bone regeneration has often been overlooked in biomaterial design, leading to delayed or compromised bone healing. Engineered mesenchymal stem cells (MSCs)-derived exosomes are becoming increasingly recognized as potent cell-free agents for manipulating cellular behavior and improving therapeutic effectiveness. Herein, MSCs are stimulated with nerve growth factor (NGF) to regulate exosomal cargoes to improve neuro-promotive potential and facilitate innervated bone regeneration. In vitro cell experiments showed that the NGF-stimulated MSCs-derived exosomes (N-Exos) obviously improved the cellular function and neurotrophic effects of the neural cells, and consequently, the osteogenic potential of the osteo-reparative cells. Bioinformatic analysis by miRNA sequencing and pathway enrichment revealed that the beneficial effects of N-Exos may partly be ascribed to the NGF-elicited multicomponent exosomal miRNAs and the subsequent regulation and activation of the MAPK and PI3K-Akt signaling pathways. On this basis, N-Exos were delivered on the micropores of the 3D-printed hierarchical porous scaffold to accomplish the sustained release profile and extended bioavailability. In a rat model with a distal femoral defect, the N-Exos-functionalized hierarchical porous scaffold significantly induced neurovascular structure formation and innervated bone regeneration. This study provided a feasible strategy to modulate the functional cargoes of MSCs-derived exosomes to acquire desirable neuro-promotive and osteogenic potential. Furthermore, the developed N-Exos-functionalized hierarchical porous scaffold may represent a promising neurovascular-promotive bone reparative scaffold for clinical translation.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Ratos , Animais , Exossomos/metabolismo , Diferenciação Celular/genética , Porosidade , Fosfatidilinositol 3-Quinases , Fator de Crescimento Neural/análise , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/farmacologia , Regeneração Óssea/fisiologia , Osteogênese , Impressão Tridimensional
13.
Sci Adv ; 10(6): eadk6722, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38324693

RESUMO

Reconstructing extensive cranial defects represents a persistent clinical challenge. Here, we reported a hybrid three-dimensional (3D) printed scaffold with modification of QK peptide and KP peptide for effectively promoting endogenous cranial bone regeneration. The hybrid 3D printed scaffold consists of vertically aligned cryogel fibers that guide and promote cell penetration into the defect area in the early stages of bone repair. Then, the conjugated QK peptide and KP peptide further regulate the function of the recruited cells to promote vascularization and osteogenic differentiation in the defect area. The regenerated bone volume and surface coverage of the dual peptide-modified hybrid scaffold were significantly higher than the positive control group. In addition, the dual peptide-modified hybrid scaffold demonstrated sustained enhancement of bone regeneration and avoidance of bone resorption compared to the collagen sponge group. We expect that the design of dual peptide-modified hybrid scaffold will provide a promising strategy for bone regeneration.


Assuntos
Osteogênese , Alicerces Teciduais , Criogéis , Regeneração Óssea/fisiologia , Peptídeos , Impressão Tridimensional
14.
Stem Cell Res Ther ; 15(1): 33, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38321490

RESUMO

BACKGROUND: There is growing evidence that extracellular vesicles (EVs) play a crucial role in the paracrine mechanisms of transplanted human mesenchymal stem cells (hMSCs). Little is known, however, about the influence of microenvironmental stimuli on the osteogenic effects of EVs. This study aimed to investigate the properties and functions of EVs derived from undifferentiated hMSC (Naïve-EVs) and hMSC during the early stage of osteogenesis (Osteo-EVs). A further aim was to assess the osteoinductive potential of Osteo-EVs for bone regeneration in rat calvarial defects. METHODS: EVs from both groups were isolated using size-exclusion chromatography and characterized by size distribution, morphology, flow cytometry analysis and proteome profiling. The effects of EVs (10 µg/ml) on the proliferation, migration, and osteogenic differentiation of cultured hMSC were evaluated. Osteo-EVs (50 µg) or serum-free medium (SFM, control) were combined with collagen membrane scaffold (MEM) to repair critical-sized calvarial bone defects in male Lewis rats and the efficacy was assessed using µCT, histology and histomorphometry. RESULTS: Although Osteo- and Naïve-EVs have similar characteristics, proteomic analysis revealed an enrichment of bone-related proteins in Osteo-EVs. Both groups enhance cultured hMSC proliferation and migration, but Osteo-EVs demonstrate greater efficacy in promoting in vitro osteogenic differentiation, as evidenced by increased expression of osteogenesis-related genes, and higher calcium deposition. In rat calvarial defects, MEM with Osteo-EVs led to greater and more consistent bone regeneration than MEM loaded with SFM. CONCLUSIONS: This study discloses differences in the protein profile and functional effects of EVs obtained from naïve hMSC and hMSC during the early stage of osteogenesis, using different methods. The significant protein profile and cellular function of EVs derived from hMSC during the early stage of osteogenesis were further verified by a calvarial bone defect model, emphasizing the importance of using differentiated MSC to produce EVs for bone therapeutics.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Ratos , Masculino , Animais , Osteogênese/genética , Proteômica , Células-Tronco Mesenquimais/metabolismo , Ratos Endogâmicos Lew , Regeneração Óssea/fisiologia , Diferenciação Celular , Vesículas Extracelulares/metabolismo
15.
QJM ; 117(2): 95-108, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-37252831

RESUMO

Efficient regeneration of bone defects caused by disease or significant trauma is a major challenge in current medicine, which is particularly difficult yet significant under the emerging psychological stress in the modern society. Notably, the brain-bone axis has been proposed as a prominent new concept in recent years, among which autonomic nerves act as an essential and emerging skeletal pathophysiological factor related to psychological stress. Studies have established that sympathetic cues lead to impairment of bone homeostasis mainly through acting on mesenchymal stem cells (MSCs) and their derivatives with also affecting the hematopoietic stem cell (HSC)-lineage osteoclasts, and the autonomic neural regulation of stem cell lineages in bone is increasingly recognized to contribute to the bone degenerative disease, osteoporosis. This review summarizes the distribution characteristics of autonomic nerves in bone, introduces the regulatory effects and mechanisms of autonomic nerves on MSC and HSC lineages, and expounds the crucial role of autonomic neural regulation on bone physiology and pathology, which acts as a bridge between the brain and the bone. With the translational perspective, we further highlight the autonomic neural basis of psychological stress-induced bone loss and a series of pharmaceutical therapeutic strategies and implications toward bone regeneration. The summary of research progress in this field will add knowledge to the current landscape of inter-organ crosstalk and provide a medicinal basis for the achievement of clinical bone regeneration in the future.


Assuntos
Doenças Ósseas , Osso e Ossos , Humanos , Regeneração Óssea/fisiologia , Encéfalo , Estresse Psicológico
16.
Small ; 20(8): e2307062, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37824284

RESUMO

Vascularization and innervation play irreplaceable roles in bone regeneration and bone defect repair. However, the reconstruction of blood vessels and neural networks is often neglected in material design. This study aims to design a genetically functionalized matrix (GFM) and enable it to regulate angiogenesis and neurogenesis to accelerate the process of bone defect repair. The dual small interfering RNA (siRNA)-polyvinylimide (PEI) (siRP) complexes that locally knocked down soluble vascular endothelial growth factor receptor 1 (sFlt-1) and p75 neurotrophic factor receptor (p75NTR ) are prepared. The hybrid cell membrane (MM) loaded siRP is synthesized as siRNA@MMs to coat on polylactone (PCL) electrospun fibers for mimicking the natural bone matrix. The results indicates that siRNA@MMs could regulate the expression of vascular-related and neuro-related cytokines secreted by mesenchymal stem cells (MSCs). GFMs promote the expression of osteogenic differentiation through paracrine function in vitro. GFMs attenuates inflammation and promotes osseointegration by regulating the coupling of vascularization and innervation in vivo. This study uses the natural hybrid cell membrane to carry genetic material and assist in the vascularization and innervation function of two siRNA. The results present the significance of neuro-vascularized organoid bone and may provide a promising choice for the design of bone tissue engineering scaffold.


Assuntos
Osteogênese , Fator A de Crescimento do Endotélio Vascular , Osteogênese/genética , RNA Interferente Pequeno/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Angiogênese , Regeneração Óssea/fisiologia , Alicerces Teciduais , Diferenciação Celular , Neurogênese , Membrana Celular/metabolismo
17.
Stomatologiia (Mosk) ; 102(6. Vyp. 2): 8-14, 2023.
Artigo em Russo | MEDLINE | ID: mdl-38096388

RESUMO

Gene therapy is one of the most promising approaches in regenerative medicine for the restoration of extensive bone defects in dentistry and maxillofacial surgery. Matrices obtained using three-dimensional printing from bioresorbable polymers, impregnated with adenoviral constructs with genes for osteoinductive factors, can ensure safe and effective formation of bone tissue. OBJECTIVE: To study the properties of three-dimensional matrices based on polylactic-co-glycolic acid and adenoviral constructs with the GFP gene in vitro. MATERIALS AND METHODS: The matrices were obtained by antisolvent three-dimensional printing. Transduction efficiency was assessed by fluorescence microscopy and flow cytometry. The cytocompatibility of the matrices was assessed by the MTT test and by staining cells with fluorescent dyes. RESULTS: Matrices based on polylactic-co-glycolic acid have high cytocompatibility on adipose tissue-derived mesenchymal stem cells. Impregnation of adenoviral vectors with the green fluorescent protein gene in 3D matrices ensures the release of viral particles within a week, maintaining their high transducing ability. CONCLUSION: The developed method for obtaining gene-activated matrices can serve as the basis for the creation of effective osteoplastic materials for bone regeneration.


Assuntos
Células-Tronco Mesenquimais , Humanos , Polímeros/metabolismo , Regeneração Óssea/fisiologia , Osso e Ossos , Impressão Tridimensional , Alicerces Teciduais
18.
Artigo em Inglês | MEDLINE | ID: mdl-37612166

RESUMO

OBJECTIVE: Because of the anatomical complexity of the oral and maxillofacial sites, repairing bone defects in these regions is very difficult. This review article aims to consider the application of biocomposites-based strategies for dental bone regeneration. STUDY DESIGN: Research papers related to the topic, published over the last 20 years, were selected using the Web of Science, Pubmed, Scopus, and Google Scholar databases. RESULTS: The strategies of monophasic, biphasic/multiphasic scaffolds, and biopolymer-based nanocomposite scaffolds containing nanomaterials compared with traditional methods used for bone regeneration, such as autografts, allografts, xenografts, and alloplasts are found to be superior because of their ability to overcome the issues (e.g., limited bone sources, pain, immune responses, high cost) related to the applications of the traditional methods. CONCLUSIONS: In addition, additive manufacturing technologies were found to be highly advantageous for improving the efficacy of biocomposite scaffolds for treating dental bone defects.


Assuntos
Regeneração Óssea , Humanos , Regeneração Óssea/fisiologia , Transplante Autólogo
19.
Rev. ADM ; 80(4): 220-227, jul.-ago. 2023. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1527184

RESUMO

Introducción: el hueso está en remodelación constante para mantener la estructura del esqueleto, tener un ciclo de resorción por los osteoclastos y formación de hueso nuevo a cargo de los osteoblastos; el hueso también es susceptible a enfermedades sistémicas, traumas, edad y trastornos genéticos que afectarán el remodelado óseo, produciendo una pérdida masiva de masa ósea regulado por hormonas, citocinas, enzimas, etcétera. El objetivo es realizar una revisión sistemática de artículos que muestren cambio o alteración al utilizar tratamientos con microvibraciones y farmacológicos sobre la catepsina K en el hueso alveolar. Material y métodos: para realizar una comparación entre la efectividad del tratamiento a base de microvibraciones y con inhibidores de la catepsina K, se realizó una revisión sistemática en nueve bases de datos (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO y Springer Link). La población de estudio fueron ratas y ratones. Resultados: en este estudio se incluyeron 20 artículos cuya investigación se realizó en estudios clínicos. En los resultados podemos observar cómo todos los tratamientos de alguna forma mejoran el proceso de remodelado óseo. Es difícil comparar cuál de los tratamientos dentro de cada grupo es mejor que otro, debido a que los resultados expresados son cualitativos. Conclusión: acorde a los resultados expresados se opta por realizar un tratamiento con microvibraciones debido a que el uso de inhibidores de la catepsina K aún no se encuentra completamente desarrollado y no se comprenden sus consecuencias debido a su manera sistémica de actuar (AU)


Introduction: the bone is in constant remodeling to maintain the skeletal structure, having a cycle of resorption by osteoclasts and formation of new bone by osteoblasts, the bone is also susceptible to systemic diseases, trauma, age and genetic disorders that affect bone remodeling, producing a massive loss of bone mass regulated by hormones, cytokines, enzymes, etcetera. The objective is to perform a systematic review of articles that show a change or alteration when using micro-vibration and pharmacological treatments on cathepsin K in the alveolar bone. Material and methods: in order to make a comparison between the effectiveness of micro-vibration and cathepsin K inhibitor treatments, a systemic review was carried out in nine databases (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO and Springer Link). The study population was rats and mice. Results: this study included 20 articles whose research was carried out in clinical studies. In the results we can see how all the treatments in some way improve the bone remodeling process, it is difficult to compare which treatment within each group is better than the other, because the results expressed are qualitative. Conclusion: according to the results expressed, it is decided that it is better to perform a treatment with micro vibrations because the use of cathepsin K inhibitors are not yet fully developed and their consequences are not understood due to their systemic way of acting (AU)


Assuntos
Humanos , Animais , Camundongos , Regeneração Óssea/fisiologia , Catepsina K/fisiologia , Osteoclastos/fisiologia , Técnicas de Movimentação Dentária , Bases de Dados Bibliográficas , Remodelação Óssea/fisiologia
20.
RFO UPF ; 27(1)08 ago. 2023. tab, ilus
Artigo em Português | LILACS, BBO | ID: biblio-1511050

RESUMO

Objetivo: revisar a literatura sobre os diferentes tipos de derivados de plaquetas autólogas e o desempenho clínico do uso do sticky bone para aumento ósseo horizontal de rebordo. Materiais e métodos: Para realização dessa revisão foram realizadas buscas nas bases de dados PubMed, Google Scholar e Web of Science, utilizando os seguintes descritores: "platelet-rich fibrin" AND "sticky bone" OR "alveolar bone grafting" AND "sticky bone" OR "guided bone regeneration" AND "sticky bone" AND "alveolar ridge augmentation" OR "Alveolar ridge augmentation" AND "sticky bone". Foram incluídos artigos publicados em inglês, que abordavam conceitos relacionados aos agregados plaquetários e a regeneração óssea guiada para aumento ósseo horizontal de rebordo utilizando fibrina rica em plaquetas associada à enxertos ósseos (sticky bone). Resultados: Após avaliação dos estudos encontrados foram selecionados 11 artigos sobre o uso do sticky bone para aumento horizontal de rebordo. Para compor este trabalho foram selecionados também 14 estudos de revisão e artigos associados ao tema. Por ser de fácil aplicação e obtenção, muitos autores têm estudado as aplicações cirúrgicas do sticky bone e os resultados demonstram que o aumento horizontal do rebordo utilizando essa técnica pode ser realizado de forma previsível. Conclusão: apesar de haver estudos promissores sobre o uso do sticky bone, falta evidência na literatura sobre seu sucesso clínico. Assim, para compreender o potencial regenerativo desta técnica são necessários um maior número de estudos randomizados, com diferentes materiais de enxerto e protocolos padronizados de obtenção do sticky bone.(AU)


Objective: to review the literature on the different types of autologous platelet derivatives and the clinical performance of using sticky bone for horizontal bone ridge augmentation. Materials and methods: In order to conduct this review, it was conducted searches in the PubMed, Google Scholar, and Web of Science databases using the following descriptors: "platelet-rich fibrin" AND "sticky bone" OR "alveolar bone grafting" AND "sticky bone" OR "guided bone regeneration" AND "sticky bone" AND "alveolar ridge augmentation" OR "Alveolar ridge augmentation" AND "sticky bone". It included articles published in English that addressed concepts related to platelet aggregates and guided bone regeneration for horizontal bone augmentation using platelet-rich fibrin associated with bone grafts (sticky bone). Results: After evaluating the studies found, were selected 11 articles on the use of sticky bone for horizontal ridge augmentation. To compose this work, 14 review studies and articles associated with the topic were also selected. Due to its ease of application and availability, many authors have explored the surgical applications of sticky bone, and the results indicate that horizontal ridge augmentation using this technique can be predictably performed. Conclusion: while there are promising studies on the use of sticky bone, the literature lacks evidence regarding its clinical success. Therefore, to fully understand the regenerative potential of this technique, further randomized studies are needed, involving different graft materials and standardized protocols for obtaining sticky bone.(AU)


Assuntos
Humanos , Regeneração Tecidual Guiada/métodos , Aumento do Rebordo Alveolar/métodos , Enxerto de Osso Alveolar/métodos , Fibrina Rica em Plaquetas , Regeneração Óssea/fisiologia
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