RESUMO
Objective: To investigate the presence of a distinct stem cell populations different from mesenchymal stem cells in the mandibular periosteum of both human and non-human primates (macaca mulatta), to explore its properties during intramembranous osteogenesis and to establish standard protocols for the isolation, culturing and expanding of mandibular periosteal stem cells (PSC) distinguished from other PSCs in other anatomical regions. Methods: Periosteum was harvested from the bone surface during flap bone removal in patients aged 18-24 years undergoing third molar extraction and from the buccal side of the mandibular premolar region of 6-year-old macaca mulatta respectively, and then subjected to single-cell sequencing using the Illumina platform Novaseq 6000 sequencer. Cross-species single-cell transcriptome sequencing results were compared using homologous gene matching. PSC were isolated from primary tissues using two digestion methods with body temperature and low temperature, and their surface markers (CD200, CD31, CD45 and CD90) were identified by cell flow cytometry. The ability of cell proliferation and three-lineage differentiation of PSC expanded to the third generation in vitro in different species were evaluated. Finally, the similarities and differences in osteogenic properties of PSC and bone marrow mesenchymal stem cells (BMSC) were compared. Results: The single-cell sequencing results indicated that 18 clusters of cell populations were identified after homologous gene matching for dimensionality reduction, and manual cellular annotation was conducted for each cluster based on cell marker databases. The comparison of different digestion protocols proved that the low-temperature overnight digestion protocol can stably isolate PSC from the human and m. mulatta mandibular periosteum and the cells exhibited a fibroblast-like morphology. This research confirmed that PSC of human and m. mulatta had similar proliferation capabilities through the cell counting kit-8 assay. Flow cytometry analysis was then used to identify the cells isolated from the periosteum expressed CD200(+), CD31(-), CD45(-), CD90(-). Then, human and m. mulatta PSC were induced into osteogenesis, adipogenesis, and chondrogenesis to demonstrate their corresponding multi-lineage differentiation capabilities. Finally, comparison with BMSC further clarified the oesteogenesis characteristics of PSC. The above experiments proved that the cells isolated from the periosteum were peiosteal cells with characteristics of stem cells evidenced by their cell morphology, proliferation ability, surface markers, and differentiation ability, and that this group of PSC possessed characteristics different from traditional mesenchymal stem cells. Conclusions: In this study, normal mandibular PSC from humans and m. mulatta were stably isolated and identified for the first time, providing a cellular foundation for investigating the mechanism of mandibular intramembranous osteogenesis, exploring ideal non-human primate models and establishing innovative strategies for clinically mandibular injury repair.
Assuntos
Diferenciação Celular , Macaca mulatta , Mandíbula , Periósteo , Análise de Célula Única , Animais , Humanos , Periósteo/citologia , Mandíbula/citologia , Osteogênese , Células-Tronco/citologia , Células-Tronco Mesenquimais/citologia , Citometria de Fluxo , Adulto Jovem , Adolescente , Separação Celular/métodosRESUMO
BACKGROUND: A variety of congenital or acquired conditions can cause craniomaxillofacial bone defects, resulting in a heavy financial burden and psychological stress. Guided bone self-generation with periosteum-preserved has great potential for reconstructing large bone defects. METHODS: A swine model of guided bone regeneration with occlusive periosteum was established, the rib segment was removed, and the periosteum was sutured to form a closed regeneration chamber. Hematoxylin and eosin staining, Masson's staining, and Safranine O-Fast Green staining were done. Nine-time points were chosen for collecting the periosteum and regenerated bone tissue for gene sequencing. The expression level of each secreted frizzled-related protein (SFRP) member and the correlations among them were analyzed. RESULTS: The process of bone regeneration is almost complete 1 month after surgery, and up to 1 week after surgery is an important interval for initiating the process. The expression of each SFRP family member fluctuated greatly. The highest expression level of all members ranged from 3 days to 3 months after surgery. The expression level of SFRP2 was the highest, and the difference between 2 groups was the largest. Secreted frizzled-related protein 2 and SFRP4 showed a notable positive correlation between the control and model groups. Secreted frizzled-related protein 1, SFRP2, and SFRP4 had a significant spike in fold change at 1 month postoperatively. Secreted frizzled-related protein 1 and SFRP2 had the strongest correlation. CONCLUSIONS: This study revealed the dynamic expression of the SFRP family in guided bone regeneration with occlusive periosteum in a swine model, providing a possibility to advance the clinical application of bone defect repair.
Assuntos
Regeneração Óssea , Periósteo , Animais , Suínos , Regeneração Óssea/genética , Perfilação da Expressão Gênica , Regeneração Tecidual Guiada/métodos , Modelos Animais , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
The need to promote calvaria bone healing as a consequence of injury or craniotomy is a major clinical issue. Previous reports tested recombinant human Jagged1 (rhJagged1) treatment for critical-size calvaria defects in the absence of periosteum, and this resulted in significant new bone formation. As the periosteum contributes to healing by serving as a source of progenitor cells, the present study aimed to examine whether significantly more bone is formed when the periosteum is intact for using rhJagged1 to treat critical-size parietal bone defects in mice. Fifteen healthy adult mice, 34 to 65 weeks of age, 26.9 to 48.2 g, were divided into different groups that compared the critical-size defects treated with either phosphate-buffered saline or rhJagged1 protein in either the presence or absence of periosteum. The results indicated that more bone was formed in the presence of periosteum when rhJagged1 is delivered [35% bone volume per tissue volume (BV/TV); P = 0.02] relative to nonperiosteum. Recombinant human Jagged1 protein delivered in the absence of periosteum had the next most new bone formed (25% BV/TV). Defects with phosphate-buffered saline delivered in the absence or presence of periosteum had the least new bone formed (15% and 18% BV/TV, respectively; P = 0.48). The results also show that rhJagged1 does not form ectopic or hypertrophic bone. The usage of rhJagged1 to treat critical-size defects in calvaria is promising clinically, but to maximize clinical efficacy it will require that the periosteum be intact on the noninjured portions of calvaria.
Assuntos
Regeneração Óssea , Proteína Jagged-1 , Periósteo , Proteínas Recombinantes , Animais , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Camundongos , Regeneração Óssea/efeitos dos fármacos , Humanos , Crânio/cirurgia , Cicatrização/efeitos dos fármacos , Osso Parietal/cirurgia , Masculino , Osteogênese/efeitos dos fármacos , Microtomografia por Raio-XRESUMO
Cell surface marker expression is one of the criteria for defining human mesenchymal stem or stromal cells (MSC) in vitro. However, it is unclear if expression of markers including CD73 and CD90 reflects the in vivo origin of cultured cells. We evaluated expression of 15 putative MSC markers in primary cultured cells from periosteum and cartilage to determine whether expression of these markers reflects either the differentiation state of cultured cells or the self-renewal of in vivo populations. Cultured cells had universal and consistent expression of various putative stem cell markers including > 95% expression CD73, CD90 and PDPN in both periosteal and cartilage cultures. Altering the culture surface with extracellular matrix coatings had minimal effect on cell surface marker expression. Osteogenic differentiation led to loss of CD106 and CD146 expression, however CD73 and CD90 were retained in > 90% of cells. We sorted freshly isolated periosteal populations capable of CFU-F formation on the basis of CD90 expression in combination with CD34, CD73 and CD26. All primary cultures universally expressed CD73 and CD90 and lacked CD34, irrespective of the expression of these markers ex vivo indicating phenotypic convergence in vitro. We conclude that markers including CD73 and CD90 are acquired in vitro in most 'mesenchymal' cells capable of expansion. Overall, we demonstrate that in vitro expression of many cell surface markers in plastic-adherent cultures is unrelated to their expression prior to culture.
Assuntos
5'-Nucleotidase , Biomarcadores , Diferenciação Celular , Células-Tronco Mesenquimais , Osteogênese , Fenótipo , Antígenos Thy-1 , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Humanos , Biomarcadores/metabolismo , Células Cultivadas , Antígenos Thy-1/metabolismo , 5'-Nucleotidase/metabolismo , Periósteo/citologia , Periósteo/metabolismo , Cartilagem/metabolismo , Cartilagem/citologia , Proteínas Ligadas por GPIRESUMO
Congenital pseudarthrosis of the forearm poses a considerable challenge because of its rarity. The objective of this report is to introduce a novel surgical technique for its treatment. Here, we document a case of congenital pseudarthrosis of the radius in a 3-year-old boy diagnosed with type-1 neurofibromatosis. The surgical treatment involved the excision of approximately 9 cm of native radial periosteum and a bifocal radius osteotomy, which was supplemented with a vascularized tibial periosteal transplant to facilitate bone healing. Anastomosis between the anterior tibial vessels and radial vessels was performed. No immediate or late postoperative complications were observed. After 3 weeks, a robust callus formation was observed, and during a follow-up examination 3 years and 4 months later, a wide range of active forearm rotation was noted. This report suggests that vascularized periosteal flaps show promise as a viable treatment option for congenital pseudarthrosis of the forearm. They offer an alternative to vascularized fibular grafts or single-bone forearm constructs.
Assuntos
Periósteo , Pseudoartrose , Tíbia , Humanos , Pseudoartrose/congênito , Pseudoartrose/cirurgia , Masculino , Pré-Escolar , Periósteo/transplante , Tíbia/cirurgia , Neurofibromatose 1/complicações , Neurofibromatose 1/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/transplante , Osteotomia/métodos , Rádio (Anatomia)/transplante , Rádio (Anatomia)/cirurgia , Rádio (Anatomia)/anormalidades , Transplante Ósseo/métodosRESUMO
BACKGROUND: Periosteal expansion (PEO) results in the formation of new bone in the space created between existing bone by expanding the periosteum. PEO has already been performed on rabbit parietal bone and effective new bone formation has been demonstrated. In this study, the utility of a polyethylene terephthalate (PET) membrane as an activator was evaluated in the more complex morphology of the mandible. METHODS: A PET membrane coated with hydroxyapatite (HA)/gelatine was placed in the rabbit mandibular bone at lower margin of mandibular molar region underneath periosteum, and screw-fixed. In the experimental group, the membrane was bent and screw-fixed along the lateral surface of the bone, with removal of the outer screw after 7 days followed by activation of the membrane. The experimental group was divided into two subgroups: with and without a waiting period for activation. Three animals were euthanized at 3 weeks and another three at 5 weeks postoperatively. Bone formation was assessed using micro-CT as well as histomorphometric and histological methods. RESULTS: No PET membrane-related complications were observed. The area of newly formed bone and the percentage of new bone in the space created by the stretched periosteum did not significantly differ between the control and experimental groups. However, in the experimental group a greater volume was present after 5 weeks than after 3 weeks. Histologically, bone formation occurred close to the site of cortical bone perforation, with many sinusoidal vessels extending through the perforations in the new bone into the overlying fibrous tissue. Inflammatory cells were not seen in the bone.
Assuntos
Regeneração Óssea , Mandíbula , Membranas Artificiais , Polietilenotereftalatos , Animais , Coelhos , Polietilenotereftalatos/química , Mandíbula/cirurgia , Mandíbula/diagnóstico por imagem , Microtomografia por Raio-X , Gelatina , Durapatita , Osteogênese/fisiologia , Regeneração Tecidual Guiada/métodos , Periósteo , Masculino , Parafusos ÓsseosRESUMO
We evaluated the effect of periosteal-releasing incisions on flap displacement in anterior maxillary sites following implant placement and simultaneously guided bone regeneration. Thirty patients, each requiring a single dental implant and guided bone regeneration in the maxillary esthetic zone, were recruited. After full-thickness flap elevation, the displacement of the flap was measured under a standardized tension of 1 Ncm. Then, a 2-step periosteal releasing incision was placed in the internal aspect of the flap, and the displacement was remeasured using the same standardized tension. Keratinized tissue width and mucosal thickness at the surgical site were recorded. Patient-reported outcomes were assessed at the 7- and 14-day recall visits. Flap displacement (primary outcome) was calculated before and after periosteal-releasing incisions. Multivariable linear regression models were used to evaluate the influence of mucosal thickness on flap displacement and adjusted for Keratinized tissue width. Primary wound closure was achieved in all patients. The mean difference in flap coronal displacement before and after the periosteal-releasing incisions was 8.2 mm (p < .0001). Adjusted regression models showed no association between mucosal thickness and keratinized tissue width with the amount of flap displacement (p = .770). Patient-reported outcome measures for pain, swelling, and bleeding amounted to 1.28 ± 1.93, 1.36 ± 1.87, and 0.0 ± 0.0 at 7 days and 0.11 ± 0.57, 0.56 ± 1.03, and 0.0 ± 0.0 at 14 days, respectively. Periosteal-releasing incisions using the 2-step procedure described here are a predictable technique to obtain coronal flap displacements >8 mm without increased surgical complications.
Assuntos
Maxila , Periósteo , Humanos , Periósteo/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Maxila/cirurgia , Regeneração Óssea , Implantação Dentária Endóssea/métodos , Regeneração Tecidual Guiada Periodontal/métodos , Retalhos Cirúrgicos/cirurgia , Adulto , Medidas de Resultados Relatados pelo Paciente , Idoso , Implantes Dentários para Um Único DenteRESUMO
Gradual elevation of the periosteum from the original bone surface, based on the principle of distraction osteogenesis, induces endogenous hard and soft tissue formation. This study aimed to assess the impact of alternating protocols of activation with relaxation (periosteal pumping) on bone modeling and remodeling. One hundred and sixty-two adult male Wistar rats were used in this study. Four test groups with different pumping protocols were created based on the relaxation applied. Two control groups underwent an activation period without relaxation or only a single activation. One group was sham-operated. Periosteal pumping without period of activation induced gene expression in bone and bone remodeling, and following activation period enhanced bone modeling. Four test groups and control group with activation period equaled the values of bone modeling at the end-consolidation period, showing significant downregulation of Sost in the bone and periosteum compared to that in the sham group (p < 0.001 and p < 0.001, respectively). When all test groups were pooled together, plate elevation from the bony surface increased bone remodeling on day 45 of the observation period (p = 0.003). Furthermore, bone modeling was significantly affected by plate elevation on days 17 and 45 (p = 0.047 and p = 0.005, respectively) and by pumping protocol on day 31 (p = 0.042). Periosteal pumping was beneficial for increasing bone repair when the periosteum remained in contact with the underlaying bony surface during the manipulation period. Following periosteal elevation, periosteal pumping accelerated bone formation from the bony surface by the modeling process.
Assuntos
Remodelação Óssea , Periósteo , Ratos Wistar , Animais , Periósteo/metabolismo , Masculino , Remodelação Óssea/fisiologia , Ratos , Osteogênese/fisiologia , Osteogênese por Distração/métodosRESUMO
The most challenging and time-consuming step in the free gingival graft (FGG) for keratinized mucosa augmentation is the compression suture anchoring the FGG to the periosteum. This article proposed a novel "microscrew with tie-down sutures" technique to anchor the FGG to the recipient site without the traditional trans-periosteum suture. This patient's keratinized mucosa width (KMW) around the healing abutments of teeth #29 and #30 was less than 1 mm. After an apically positioned flap (AFP) was prepared, 2 microscrews were placed at the buccal plate of the alveolar ridge bone, which is the coronal margin of the AFP. Then, the sutures winded between the microscrews and the healing abutments to anchor the FGG. In conclusion, the "microscrew with tie-down sutures" technique offers a feasible and straightforward alternative for the trans-periosteum compression suture, mainly when the periosteum is fragile, thin, or injured.
Assuntos
Gengiva , Técnicas de Sutura , Humanos , Aumento do Rebordo Alveolar/métodos , Gengiva/cirurgia , Periósteo/cirurgiaRESUMO
INTRODUCTION: The periosteum is a readily available tissue at the hamstring harvest site that could be utilized to enhance graft healing and prevent tunnel widening without additional cost or morbidity. This study aimed to compare graft healing using magnetic resonance imaging (MRI) and functional clinical outcome scores in a matched cohort of patients who underwent anterior cruciate ligament (ACL) reconstruction with hamstring autografts with or without periosteal augmentation. MATERIAL AND METHODS: Forty-eight patients who underwent ACL reconstruction (ACLR) were prospectively enrolled: 25 with standard ACLR (ST-ACLR) and 23 with periosteal augmented grafts (PA-ACLR). The same surgical techniques, fixation methods, and postoperative protocol were used in both groups. Signal-to-noise quotient (SNQ), graft healing at the bone-graft interface, graft signal according to the Howell scale, and femoral tunnel widening were evaluated using MRI after 1 year of follow-up. International knee documentation score (IKDC), Lysholm, Tegner activity scale, and visual analog scale for pain were used for functional evaluation at a minimum of 2 years postoperative. RESULTS: The mean SNQ of the proximal part of the graft was 9.6 ± 9.2 and 2.9 ± 3.3 for the ST-ACLR and PA-ACLR groups, respectively (P = 0.005). The mean femoral tunnel widening was 30.3% ± 18.3 and 2.3% ± 9.9 for the ST-ACLR, PA-ACLR groups, respectively (P < 0.001). Complete graft tunnel healing was observed in 65% and 28% of cases in the PA-ACLR and ST-ACLR groups, respectively. Both groups showed marked improvements in functional scores, with no statistically significant differences. CONCLUSION: Periosteal wrapping of hamstring tendon autografts is associated with better graft healing and maturation and lower incidence of femoral tunnel widening based on MRI analysis 1 year after ACL reconstruction. However, patient-reported outcomes and measured laxity were similar between the two groups at 2 years follow up. TRIAL REGISTRATION: Trail registration number: PACTR202308594339018, date of registration: 1/5/2023, retrospectively registered at the Pan African Clinical Trial Registry (pactr.samrc.ac.za) database.
Assuntos
Reconstrução do Ligamento Cruzado Anterior , Autoenxertos , Tendões dos Músculos Isquiotibiais , Imageamento por Ressonância Magnética , Periósteo , Humanos , Reconstrução do Ligamento Cruzado Anterior/métodos , Tendões dos Músculos Isquiotibiais/transplante , Adulto , Masculino , Feminino , Periósteo/transplante , Estudos Prospectivos , Adulto Jovem , Cicatrização , Transplante Autólogo/métodos , Lesões do Ligamento Cruzado Anterior/cirurgia , AdolescenteRESUMO
BACKGROUND: Reconstructive microsurgery techniques using vascularized bone grafts have revolutionized the treatment of complex cases associated with recalcitrant non-unions or osteomyelitis. The medial femoral corticoperiosteal flap (MFCP flap) has emerged as a valuable option in bone reconstruction. Its clinical applications have been extended over the years considering this flap from non-unions with minimal bone lost, up to large intercalary defects of the upper and lower extremities. This article aims to present the clinical applications and outcomes of the MFCP flap in various reconstructive scenarios. METHODS: Seventy-nine patients with persistent non-union and bone defects of the upper and lower limb were evaluated from June 2008 to October 2020. All of them were reconstructed with a corticoperiosteal flap from the medial femoral condyle in our hospital. Previous procedures, bone gap and type of flap used were recorded. Postoperative functional status was assessed with time of bone healing, complications and clinical final outcome. RESULTS: Radiological evidence of bone union was observed at 4.09 months (range 2-9). Healing rate was 97% with periosteal corticocancellous flaps (PCC flaps) and 93% with corticoperiosteal flaps (CP flaps). Average follow-up was 14.5 months (range 5-28). There were no significant donor site complications. CONCLUSIONS: The MFCP flap offers a versatile and reliable option for bone reconstruction. Its ability to provide vascularized bone tissue with low morbidity enhances the healing process and improves outcomes. The MFCP flap has been increasing its applications and it serves as a valuable option in the treatment of recalcitrant non-unions or bony defects irrespective of site and size up to 5 cm in the upper and lower extremities.
Assuntos
Fraturas não Consolidadas , Retalhos Cirúrgicos , Humanos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Retalhos Cirúrgicos/irrigação sanguínea , Fraturas não Consolidadas/cirurgia , Periósteo/transplante , Adulto Jovem , Idoso , Adolescente , Transplante Ósseo/métodos , Procedimentos de Cirurgia Plástica/métodos , Fêmur/cirurgia , Estudos Retrospectivos , Osteomielite/cirurgiaRESUMO
We present a transcriptomic analysis that provides a better understanding of regulatory mechanisms within the healthy and injured periosteum. The focus of this work is on characterizing early events controlling bone healing during formation of periosteal callus on day 3 after fracture. Building on our previous findings showing that induced Notch1 signaling in osteoprogenitors leads to better healing, we compared samples in which the Notch 1 intracellular domain is overexpressed by periosteal stem/progenitor cells, with control intact and fractured periosteum. Molecular mechanisms and changes in skeletal stem/progenitor cells (SSPCs) and other cell populations within the callus, including hematopoietic lineages, were determined. Notably, Notch ligands were differentially expressed in endothelial and mesenchymal populations, with Dll4 restricted to endothelial cells, whereas Jag1 was expressed by mesenchymal populations. Targeted deletion of Dll4 in endothelial cells using Cdh5CreER resulted in negative effects on early fracture healing, while deletion in SSPCs using α-smooth muscle actin-CreER did not impact bone healing. Translating these observations into a clinically relevant model of bone healing revealed the beneficial effects of delivering Notch ligands alongside the osteogenic inducer, BMP2. These findings provide insights into the regulatory mechanisms within the healthy and injured periosteum, paving the way for novel translational approaches to bone healing.
Assuntos
Células Endoteliais , Consolidação da Fratura , Proteína Jagged-1 , Periósteo , Transdução de Sinais , Animais , Camundongos , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Células Endoteliais/metabolismo , Periósteo/metabolismo , Periósteo/citologia , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Células-Tronco Mesenquimais/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 2/genética , Osteogênese/genética , Receptor Notch1/metabolismo , Receptor Notch1/genética , Masculino , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
Bone injury is often associated with tears in the periosteum and changes in the internal stress microenvironment of the periosteum. In this study, we investigated the biological effects of periosteal prestress release on periosteum-derived cells (PDCs) and the potential mechanisms of endogenous stem cell recruitment. Decellularized periosteum with natural extracellular matrix (ECM) components was obtained by a combination of physical, chemical, and enzymatic decellularization. The decellularized periosteum removed immunogenicity while retaining the natural network structure and composition of the ECM. The Young's modulus has no significant difference between the periosteum before and after decellularization. The extracted PDCs were further composited with the decellularized periosteum and subjected to 20% stress release. It was found that the proliferative capacity of PDCs seeded on decellularized periosteum was significantly enhanced 6 h after stress release of the periosteum. The cell culture supernatant obtained after periosteal prestress release was able to significantly promote the migration ability of PDCs within 24 h. Enzyme-linked immunosorbnent assay (ELISA) experiments showed that the expression of stroma-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in the supernatant increased significantly after 3 h and 12 h of stress release, respectively. Furthermore, periosteal stress release promoted the high expression of osteogenic markers osteocalcin (OCN), osteopontin (OPN), and collagen type I of PDCs. The change in stress environment caused by the release of periosteal prestress was sensed by integrin ß1, a mechanoreceptor on the membrane of PDCs, which further stimulated the expression of YAP in the nucleus. These investigations provided a novel method to evaluate the importance of mechanical stimulation in periosteum, which is also of great significance for the design and fabrication of artificial periosteum with mechanical regulation function.
Assuntos
Diferenciação Celular , Movimento Celular , Proliferação de Células , Osteogênese , Periósteo , Estresse Mecânico , Periósteo/citologia , Periósteo/metabolismo , Osteogênese/fisiologia , Animais , Matriz Extracelular/metabolismo , Células Cultivadas , Humanos , Engenharia TecidualRESUMO
Existing artificial periostea face many challenges, including difficult-to-replicate anisotropy in mechanics and structure, poor tissue adhesion, and neglected synergistic angiogenesis and osteogenesis. Here, inspired by natural wood (NW), a wood-derived elastic artificial periosteum is developed to mimic the structure and functions of natural periosteum, which combines an elastic wood (EW) skeleton, a polydopamine (PDA) binder layer, and layer-by-layer (LBL) biofunctional layers. Specifically, EW derived from NW is utilized as the anisotropic skeleton of artificial periosteum to guide cell directional behaviors, moreover, it also shows a similar elastic modulus and flexibility to natural periosteum. To further enhance its synergistic angiogenesis and osteogenesis, surface LBL biofunctional layers are designed to serve as spatiotemporal release platforms to achieve sequential and long-term release of pamidronate disodium (PDS) and deferoxamine (DFO), which are pre-encapsulated in chitosan (CS) and hyaluronic acid (HA) solutions, respectively. Furthermore, the combined effect of PDA coating and LBL biofunctional layers enables the periosteum to tightly adhere to damaged bone tissue. More importantly, this novel artificial periosteum can boost angiogenesis and bone formation in vitro and in vivo. This study opens up a new path for biomimetic design of artificial periosteum, and provides a feasible clinical strategy for bone repair.
Assuntos
Osteogênese , Periósteo , Madeira , Periósteo/efeitos dos fármacos , Madeira/química , Animais , Osteogênese/efeitos dos fármacos , Liberação Controlada de Fármacos , Regeneração Óssea/efeitos dos fármacos , Humanos , Anisotropia , Indóis/química , Indóis/farmacologia , Camundongos , Polímeros/química , Quitosana/química , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Neovascularização Fisiológica/efeitos dos fármacosAssuntos
Veias Jugulares , Trombose Venosa , Humanos , Forâmen Jugular , Veias Jugulares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Periósteo/diagnóstico por imagem , Periósteo/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologiaRESUMO
A deleterious effect of elevated levels of vitamin A on bone health has been reported in clinical studies. Mechanistic studies in rodents have shown that numbers of periosteal osteoclasts are increased, while endocortical osteoclasts are simultaneously decreased by vitamin A treatment. The present study investigated the in vitro and in vivo effect of all-trans retinoic acid (ATRA), the active metabolite of vitamin A, on periosteal osteoclast progenitors. Mouse calvarial bone cells were cultured in media containing ATRA, with or without the osteoclastogenic cytokine receptor activator of nuclear factor kappa B-ligand (RANKL), on plastic dishes or bone discs. Whereas ATRA did not stimulate osteoclast formation alone, the compound robustly potentiated the formation of RANKL-induced bone resorbing osteoclasts. This effect was due to stimulation by ATRA (half-maximal stimulation â¼3 nM) on the numbers of macrophages/osteoclast progenitors in the bone cell cultures, as assessed by mRNA and protein expression of several macrophage and osteoclast progenitor cell markers, such as macrophage colony-stimulating factor receptor, receptor activator of nuclear factor kappa B, F4/80, and CD11b, as well as by flow cytometry (FACS) analysis of CD11b+/F480+/Gr1- cells. The stimulation of macrophage numbers in the periosteal cell cultures was not mediated by increased macrophage colony-stimulating factor or interleukin-34. In contrast, ATRA did not enhance macrophages in bone marrow cell cultures. Importantly, ATRA treatment upregulated the mRNA expression of several macrophage-related genes in the periosteum of tibia in adult mice. These observations demonstrate a novel mechanism by which vitamin A enhances osteoclast formation specifically on periosteal surfaces.
Assuntos
Macrófagos , Osteoclastos , Periósteo , Ligante RANK , Vitamina A , Animais , Camundongos , Osteoclastos/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Periósteo/metabolismo , Periósteo/citologia , Ligante RANK/metabolismo , Vitamina A/farmacologia , Vitamina A/metabolismo , Células-Tronco/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/citologia , Células Cultivadas , Tretinoína/farmacologia , Osteogênese/efeitos dos fármacos , Camundongos Endogâmicos C57BL , MasculinoRESUMO
This study investigates the efficacy of a collagen membrane as a substitute for autologous periosteum in atelocollagen-assisted autologous chondrocyte implantation (ACI) using J-TEC autologous cultured cartilage (JACC®). Sixty-nine patients with knee joint chondral defects underwent ACI using JACC®-34 with periosteum-covered ACI (P-ACIs) and 35 with collagen-covered ACI (C-ACIs). Clinical outcomes were compared through patient-reported measures, International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) scores at second-look arthroscopy one year postoperatively, and adverse event incidence. Postoperative subjective scores significantly improved up to two years, with no significant differences between P-ACI and C-ACI groups. However, C-ACI exhibited a lower adverse event rate (p = 0.034) and significantly higher ICRS CRA scores (p = 0.0001). Notably, C-ACI outperformed P-ACI in both femoral condyle and trochlea assessments (p = 0.0157 and 0.0005, respectively). While clinical outcomes were comparable, the use of a collagen membrane demonstrated superiority in ICRS CRA during second-look arthroscopy and adverse event occurrence.
Assuntos
Condrócitos , Colágeno , Periósteo , Transplante Autólogo , Humanos , Condrócitos/transplante , Feminino , Masculino , Adulto , Transplante Autólogo/métodos , Resultado do Tratamento , Cartilagem Articular/cirurgia , Articulação do Joelho/cirurgia , Pessoa de Meia-Idade , Artroscopia/métodos , Adulto JovemRESUMO
STUDY DESIGN: Case report. Osteoradionecrosis (ORN) of the jaw is a potentially devastating consequence of head and neck irradiation. The progression of ORN can lead to loss of bone, teeth, soft tissue necrosis, pathologic fracture, and oro-cutaneous fistula. Reconstructive surgery has mostly been reserved for late-stage disease where segmental resections are frequently necessary. Evidence is emerging to support earlier treatment in the form of debridement in combination with soft tissue free flaps for intermediate-stage ORN. The authors present a case of a 76-year-old male with persistent Notani 2 ORN of the mandible, treated with surgical removal of all remaining mandibular teeth, transoral debridement of all necrotic mandibular bone, and bone coverage with a left medial femoral condyle (MFC) periosteal free flap based on the descending genicular artery. Treatment was uneventful both intraoperatively and postoperatively. Since surgery (15 mo) the patient has remained free from clinical and radiologic signs of ORN. The MFP periosteal free flap provided an excellent result with minimal surgical complexity and morbidity in this case. Such treatment at an intermediate stage likely results in a reduction in segmental resections, less donor site morbidity, less operative time, less overall treatment time, and possibly fewer postoperative complications compared with the status quo.
Assuntos
Desbridamento , Retalhos de Tecido Biológico , Osteorradionecrose , Humanos , Masculino , Osteorradionecrose/cirurgia , Idoso , Fêmur/cirurgia , Doenças Mandibulares/cirurgia , Periósteo/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Extração DentáriaRESUMO
Diabetes-related skin ulcers are of significant clinical concern. Although conventional dressings have been developed, their outcomes have not been adequate, indicating the need to investigate functional dressings for the treatment of diabetic ulcers. Copper selenide nanoparticles (Cu2Se NPs) demonstrate outstanding photoresponsiveness, which is critical to the healing process. However, their limited solubility in water restricts their application. To synthesize the ODT-PMMA@Cu2Se NP-doped decellularized periosteumsodium alginate functional dressing-ODT-PMMA@Cu2Se/ECM-S (OP@Cu2Se/ECM-S), Cu2Se NPs were modified by n-octadecanethiol (ODT) end-functionalized poly (methacrylic acid) (PMAA) ligands homogeneously dispersed in a decellularized periosteum/sodium alginate matrix. This process improved the water solubility and stability. Moreover, under near-infrared irradiation (NIR), ODT-PMMA@Cu2Se demonstrated robust photo-responsiveness along with photothermal and photodynamic effects, leading to rapid heating and stimulation of reactive oxygen species (ROS) generation. These two processes work in concert to exhibit excellent antibacterial ability; at 20 µg/mL concentration of Cu2Se NPs, the bacterial activities of S. aureus and E. coli were 5.40 % and 0.96 %, respectively. Without the NIR laser irradiation, OP@Cu2Se/ECM-S rapidly increased the vascular endothelial growth factor (VEGF) expression, triggered the phosphatidylinositide 3-kinases (PI3K) and protein kinase B (AKT) signaling pathway, affected the expression of bFGF and CD31, and promoted neovascularization, proliferation, and cell migration. In a diabetic mouse wound model, OP@Cu2Se/ECM-S exhibited good biocompatibility and promoted epidermal regeneration, collagen deposition, and neovascularization. In a mouse model of subcutaneous abscesses, OP@Cu2Se/ECM-S also showed excellent antibacterial activity, in vivo experiments confirmed a decrease in bacterial activity to 1.97 %. Thus, OP@Cu2Se/ECM-S is a potentially useful approach for healing diabetic wounds.
Assuntos
Alginatos , Bandagens , Cobre , Diabetes Mellitus Experimental , Periósteo , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Camundongos , Alginatos/química , Alginatos/farmacologia , Cobre/química , Cobre/farmacologia , Periósteo/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Masculino , Staphylococcus aureus/efeitos dos fármacosRESUMO
Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.