scholarly journals Titanium alloy composited with dual-cytokine releasing polysaccharide hydrogel to enhance osseointegration via osteogenic and macrophage polarization signaling pathways

2022 ◽  
Author(s):  
Yaping Wang ◽  
Zujian Feng ◽  
Xiang Liu ◽  
Chunfang Yang ◽  
Rui Gao ◽  
...  
Keyword(s):  
Titanium Alloy ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Large Scale ◽  
Composite Scaffold ◽  
Macrophage Polarization ◽  
Occurrence Rate ◽  
Great Promise ◽  
Signal Pathways ◽  
Polysaccharide Hydrogel

Abstract Titanium alloy has been widely used in orthopedic surgeries as bone defect filling. However, the regeneration of high-quality new bones is limited due to the pro-inflammatory microenvironment around implants, resulting in a high occurrence rate of implant loosening or failure in osteological therapy. In this study, extracellular matrix (ECM)-mimetic polysaccharide hydrogel co-delivering BMP-2 and IL-4 was composited with 3D printed titanium alloy to promote the osseointegration and regulate macrophage response to create a pro-healing microenvironment in bone defect. Notably, it is discovered from the bioinformatics data that IL-4 and BMP-2 could affect each other through multiple signal pathways to achieve a synergistic effect towards osteogenesis. The composite scaffold significantly promoted the osteoblast differentiation and proliferation of human bone marrow mesenchyme stem cells (hBMSCs). The repair of large-scale femur defect in rat indicated that the dual-cytokine-delivered composite scaffold could manipulate a lower inflammatory level in situ by polarizing macrophages to M2 phenotype, resulting in superior efficacy of mature new bone regeneration over the treatment of native titanium alloy or that with an individual cytokine. Collectively, this work highlights the importance of M2-type macrophages-enriched immune-environment in bone healing. The biomimetic hydrogel-metal implant composite is a versatile and advanced scaffold for accelerating in vivo bone regeneration, holding great promise in treating orthopedic diseases.

scholarly journals An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tian Ding ◽  
Wenyan Kang ◽  
Jianhua Li ◽  
Lu Yu ◽  
Shaohua Ge
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Bone Repair ◽  
Macrophage Polarization ◽  
Tissue Engineering Scaffold ◽  
Bone Morphogenetic Protein 2 ◽  
In Situ Tissue Engineering

Abstract Background The regeneration of periodontal bone defect remains a vital clinical challenge. To date, numerous biomaterials have been applied in this field. However, the immune response and vascularity in defect areas may be key factors that are overlooked when assessing the bone regeneration outcomes of biomaterials. Among various regenerative therapies, the up-to-date strategy of in situ tissue engineering stands out, which combined scaffold with specific growth factors that could mimic endogenous regenerative processes. Results Herein, we fabricated a core/shell fibrous scaffold releasing basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in a sequential manner and investigated its immunomodulatory and angiogenic properties during periodontal bone defect restoration. The in situ tissue engineering scaffold (iTE-scaffold) effectively promoted the angiogenesis of periodontal ligament stem cells (PDLSCs) and induced macrophage polarization into pro-healing M2 phenotype to modulate inflammation. The immunomodulatory effect of macrophages could further promote osteogenic differentiation of PDLSCs in vitro. After being implanted into the periodontal bone defect model, the iTE-scaffold presented an anti-inflammatory response, provided adequate blood supply, and eventually facilitated satisfactory periodontal bone regeneration. Conclusions Our results suggested that the iTE-scaffold exerted admirable effects on periodontal bone repair by modulating osteoimmune environment and angiogenic activity. This multifunctional scaffold holds considerable promise for periodontal regenerative medicine and offers guidance on designing functional biomaterials. Graphic Abstract

scholarly journals Comparison of Osteogenesis between Adipose-Derived Mesenchymal Stem Cells and Their Sheets on Poly-ε-Caprolactone/β-Tricalcium Phosphate Composite Scaffolds in Canine Bone Defects

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Yongsun Kim ◽  
Seung Hoon Lee ◽  
Byung-jae Kang ◽  
Wan Hee Kim ◽  
Hui-suk Yun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Tricalcium Phosphate ◽  
Composite Scaffold ◽  
Bone Defects ◽  
Osteogenic Potential ◽  
Mrna Levels

Multipotent mesenchymal stem cells (MSCs) and MSC sheets have effective potentials of bone regeneration. Composite polymer/ceramic scaffolds such as poly-ε-caprolactone (PCL)/β-tricalcium phosphate (β-TCP) are widely used to repair large bone defects. The present study investigated thein vitroosteogenic potential of canine adipose-derived MSCs (Ad-MSCs) and Ad-MSC sheets. Composite PCL/β-TCP scaffolds seeded with Ad-MSCs or wrapped with osteogenic Ad-MSC sheets (OCS) were also fabricated and their osteogenic potential was assessed following transplantation into critical-sized bone defects in dogs. The alkaline phosphatase (ALP) activity of osteogenic Ad-MSCs (O-MSCs) and OCS was significantly higher than that of undifferentiated Ad-MSCs (U-MSCs). TheALP, runt-related transcription factor 2, osteopontin,andbone morphogenetic protein 7 mRNA levels were upregulated in O-MSCs and OCS as compared to U-MSCs. In a segmental bone defect, the amount of newly formed bone was greater in PCL/β-TCP/OCS and PCL/β-TCP/O-MSCs/OCS than in the other groups. The OCS exhibit strong osteogenic capacity, and OCS combined with a PCL/β-TCP composite scaffold stimulated new bone formation in a critical-sized bone defect. These results suggest that the PCL/β-TCP/OCS composite has potential clinical applications in bone regeneration and can be used as an alternative treatment modality in bone tissue engineering.

scholarly journals Osteoinductive 3D Printed Scaffold Healed 5 cm Segmental Bone Defects in the Ovine Metatarsus

2020 ◽  
Author(s):  
Yunzhi Peter Yang ◽  
Kevin Labus ◽  
Benjamin Gadomski ◽  
Arnaud Bruyas ◽  
Jeremiah Easley ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Large Scale ◽  
Composite Scaffold ◽  
Bone Grafts ◽  
Bone Defects ◽  
Collagen Sponge ◽  
Bone Morphogenetic Protein 2 ◽  
3D Printed ◽  
Autologous Bone ◽  
Autologous Bone Grafts

Abstract Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in the sheep metatarsus. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

scholarly journals Osteoinductive 3D printed scaffold healed 5 cm segmental bone defects in the ovine metatarsus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunzhi Peter Yang ◽  
Kevin M. Labus ◽  
Benjamin C. Gadomski ◽  
Arnaud Bruyas ◽  
Jeremiah Easley ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Large Scale ◽  
Composite Scaffold ◽  
Bone Grafts ◽  
Bone Defects ◽  
Collagen Sponge ◽  
Bone Morphogenetic Protein 2 ◽  
3D Printed ◽  
Autologous Bone ◽  
Autologous Bone Grafts

AbstractAutologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

scholarly journals Construction of hollow polydopamine nanoparticle based drug sustainable release system and its application in bone regeneration

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lu Wang ◽  
Shuwei Liu ◽  
Chunxia Ren ◽  
Siyuan Xiang ◽  
Daowei Li ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Load Capacity ◽  
Good Prospect ◽  
Alizarin Red ◽  
Drug Load ◽  
Load Rate ◽  
Low Toxicity

AbstractNanomaterial-based drug sustainable release systems have been tentatively applied to bone regeneration. They, however, still face disadvantages of high toxicity, low biocompatibility, and low drug-load capacity. In view of the low toxicity and high biocompatibility of polymer nanomaterials and the excellent load capacity of hollow nanomaterials with high specific surface area, we evaluated the hollow polydopamine nanoparticles (HPDA NPs), in order to find an optimal system to effectively deliver the osteogenic drugs to improve treatment of bone defect. Data demonstrated that the HPDA NPs synthesized herein could efficiently load four types of osteogenic drugs and the drugs can effectively release from the HPDA NPs for a relatively longer time in vitro and in vivo with low toxicity and high biocompatibility. Results of qRT-PCR, ALP, and alizarin red S staining showed that drugs released from the HPDA NPs could promote osteogenic differentiation and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Image data from micro-CT and H&E staining showed that all four osteogenic drugs released from the HPDA NPs effectively promoted bone regeneration in the defect of tooth extraction fossa in vivo, especially tacrolimus. These results suggest that the HPDA NPs, the biodegradable hollow polymer nanoparticles with high drug load rate and sustainable release ability, have good prospect to treat the bone defect in future clinical practice.

scholarly journals Bone defect reconstruction via endochondral ossification: A developmental engineering strategy

2021 ◽  
Vol 12 ◽  
pp. 204173142110042
Author(s):  
Rao Fu ◽  
Chuanqi Liu ◽  
Yuxin Yan ◽  
Qingfeng Li ◽  
Ru-Lin Huang
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Bone Repair ◽  
Endochondral Ossification ◽  
Current Knowledge ◽  
Endochondral Bone ◽  
Defect Reconstruction ◽  
Hypoxic Conditions ◽  
Bone Defect Reconstruction

Traditional bone tissue engineering (BTE) strategies induce direct bone-like matrix formation by mimicking the embryological process of intramembranous ossification. However, the clinical translation of these clinical strategies for bone repair is hampered by limited vascularization and poor bone regeneration after implantation in vivo. An alternative strategy for overcoming these drawbacks is engineering cartilaginous constructs by recapitulating the embryonic processes of endochondral ossification (ECO); these constructs have shown a unique ability to survive under hypoxic conditions as well as induce neovascularization and ossification. Such developmentally engineered constructs can act as transient biomimetic templates to facilitate bone regeneration in critical-sized defects. This review introduces the concept and mechanism of developmental BTE, explores the routes of endochondral bone graft engineering, highlights the current state of the art in large bone defect reconstruction via ECO-based strategies, and offers perspectives on the challenges and future directions of translating current knowledge from the bench to the bedside.

scholarly journals Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Wei Ge ◽  
Xiao-Liang Liu ◽  
De-gang Yu ◽  
Zhen-An Zhu ◽  
Qin-Fei Ke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Bone Metastases ◽  
Bone Regeneration ◽  
Caspase 3 ◽  
Macrophage Polarization ◽  
Tunel Staining ◽  
Alizarin Red ◽  
Arginase 1 ◽  
Local Bone

Abstract Background Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. Methods Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. Results Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. Conclusion The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

scholarly journals Leucocyte- and Platelet-Rich Fibrin Block: Its Use for the Treatment of a Large Cyst with Implant-Based Rehabilitation

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 180 ◽  
Author(s):  
Rodolfo Mauceri ◽  
Denise Murgia ◽  
Orazio Cicero ◽  
Luigi Paternò ◽  
Luca Fiorillo ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Defect ◽  
Bone Healing ◽  
Bone Substitute ◽  
Alveolar Bone ◽  
Critical Size ◽  
Large Bone ◽  
Alveolar Bone Defect ◽  
Positive Results ◽  
Autologous Platelet

The management of critical-size bone defects is still demanding. Recently, autologous platelet concentrates in combination with bone substitute have been applied and reported in a few studies. Our aim is to report the healing of a critical-size alveolar bone defect treated with a new bone regeneration technique by means of L-PRF and L-PRF blocks. A 45-year-old woman presented a large cystic lesion; the extraction of three teeth, a cyst removal procedure, and bone regeneration procedures with L-PRF and L-PRF blocks were planned. The L-PRF block was prepared by mixing a bone substitute with a piece of L-PRF membrane and liquid fibrinogen. Additionally, after bone healing an implant-based rehabilitation was optimally performed. On the basis of the positive results, in terms of bone healing and tissue regeneration in a large bone defect, the application of L-PRF and L-PRF blocks, in agreement with the scarce literature, is suggested as a feasible procedure in selected cases.

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