Smart Implantable Hydrogel for Large Segmental Bone Regeneration
Menghan LiHaiping WuKe GaoYubo WangJiaqi HuZiling GuoRuiwei HuMengxuan ZhangXiaoxiao PangMinghui GuoYuanjie LiuLina ZhaoHe WenShijia DingWenyang LiWei Cheng
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Abstract Large segmental bone defects often lead to nonunion and dysfunction, posing a significant challenge for clinicians. Inspired by the intrinsic bone defect repair logic of “vascularization and then osteogenesis”, this study originally reports a smart implantable hydrogel (PDS‐DC) with high mechanical properties, controllable scaffold degradation, and timing drug release that can proactively match different bone healing cycles to efficiently promote bone regeneration. The main scaffold of PDS‐DC consists of polyacrylamide, polydopamine, and silk fibroin, which endows it with superior interfacial adhesion, structural toughness, and mechanical stiffness. In particular, the adjustment of scaffold cross‐linking agent mixing ratio can effectively regulate the in vivo degradation rate of PDS‐DC and intelligently satisfy the requirements of different bone defect healing cycles. Ultimately, PDS hydrogel loaded with free desferrioxamine (DFO) and CaCO 3 mineralized ZIF‐90 loaded bone morphogenetic protein‐2 (BMP‐2) to stimulate efficient angiogenesis and osteogenesis. Notably, DFO is released rapidly by free diffusion, whereas BMP‐2 is released slowly by pH‐dependent layer‐by‐layer disintegration, resulting in a significant difference in release time, thus matching the intrinsic logic of bone defect repair. In vivo and in vitro results confirm that PDS‐DC can effectively realize high‐quality bone generation and intelligently regulate to adapt to different demands of bone defects.Keywords:
Fibroin
Objective To investigate the therapeutic effect of different concentrations of autologous bone marrow transplantation on bone nonunion so as to provide reliable basis for treating bone nonunion in clinic.Methods 36 healthy New Zealand rabbits were selected to make bone nonunion models.All the experimental animals were randomly divided into 3 groups:group A with 1:1 marrow;group B with 1:2 marrow;group C with 1:4 marrow.The healing state of bone fracture and callus quality were evaluated by regular X-ray examination,bone densitometry and histological observation.Results At 2,4,8 weeks after the operation,the healing state of bone fracture and callus quality were improved in group A,B,C in turn.Conclusion Autologous bone marrow transplantation can enhance healing speed and quality of bone fracture.Healing speed and quality of bone fracture are positively correlated with transplanted bone marrow concentration.
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Objective To review the application of silk fibroin scaffold in bone tissue engineering. Methods The related literature about the application of silk fibroin scaffold in bone tissue engineering was reviewed, analyzed, and summarized. Results Silk fibroin can be manufactured into many types, such as hydrogel, film, nano-fiber, and threedimensional scaffold, which have superior biocompatibility, slow biodegradability, nontoxic degradation products, and excellent mechanical strength. Meanwhile these silk fibroin biomaterials can be chemically modified and can be used to carry stem cells, growth factors, and compound inorganic matter. Conclusion Silk fibroin scaffolds can be widely used in bone tissue engineering. But it still needs further study to prepare the scaffold in accordance with the requirement of tissue engineering.
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Bone tissue
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Low-intensity pulsed ultrasound (LIPUS) is used clinically to enhance fracture healing. Level-I clinical studies demonstrate that a specific signal (1.5 MHz ultrasound pulsed at 1 kHz, 20% duty cycle, 30 mW/cm2 SATA) can accelerate the healing of acute fractures. This result remains a unique benefit of LIPUS, and to date, no other drug or device has been approved by the FDA for accelerated fracture repair. The same signal has been shown in many studies to heal a high proportion of non-union fractures. LIPUS appears to be effective for all three types of non-unions—atrophic, oligotrophic and hypertrophic—even in the absence of revision surgery. The findings are broadly applicable to orthopedics, with similar results regardless of fracture type, fracture location and fracture-management technique. Given the varied causes of non-union, the ability of LIPUS to overcome a high proportion of obstacles to healing indicates that the signal is likely to have pleiotropic effects on multiple cell types within the healing process. Smoking, age, and diabetes are known risk factors for delayed union and nonunion. Clinical data, including randomized controlled trials and a registry of 1546 nonunion patients, suggest that LIPUS mitigates these risks and restores the course of normal bone healing.
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Sustained release carrier for the bone morphogenetic protein-2 (BMP-2) is currently a hot subject of research on the bone tissue engineering. In this work, two kinds of heparinized silk fibroin scaffolds were prepared. The binding ability to BMP-2, in vitro sustained release property and the alkaline phosphatase (ALP) activity of the scaffolds were investigated. Results showed that the heparinized silk fibroin scaffolds could bind BMP-2 well and sustained release the BMP-2. The scaffolds with BMP-2 could improve the MG-63 cell growth and cell differentiation with high ALP activity. So the heparinized silk fibroin scaffolds could be an ideal sustained release carrier for BMP-2.
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To review the application of silk fibroin scaffold in bone tissue engineering.The related literature about the application of silk fibroin scaffold in bone tissue engineering was reviewed, analyzed, and summarized.Silk fibroin can be manufactured into many types, such as hydrogel, film, nano-fiber, and three-dimensional scaffold, which have superior biocompatibility, slow biodegradability, nontoxic degradation products, and excellent mechanical strength. Meanwhile these silk fibroin biomaterials can be chemically modified and can be used to carry stem cells, growth factors, and compound inorganic matter.Silk fibroin scaffolds can be widely used in bone tissue engineering. But it still needs further study to prepare the scaffold in accordance with the requirement of tissue engineering.
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Bone tissue
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Objective:To observe the effect of extracorporeal shock wave(ESW)for the treatment of bone nonunion and promotion of fracture healing.Methods:Twenty-two patients with fractures of delayed union and nonunion were treated with ESW.The X-ray of the fracture was taken every 4-6 weeks to observe condition of fracture healing.The second procedure of ESW was delivered to fractures while the X-ray did not show obvious callus formation at 12 weeks after the first treatment.The energy of ESW was 0.4 mJ/mm2 and the total pulse of each time was 1 600-2 400 times.Results:The time of callus formation in the patients was 4-12 weeks after treatment.Twenty cases had obvious callus formation,in which 17 cases achieved fracture healing in 3 to 6 months.Two patients of distal tibial fracture showed no effect after treatment.Conclusion:ESW has marked effect for treating bone nonunion and promoting fracture healing,which is promising in the future.
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In this study, two types of scaffolds were fabricated by 3D printing. Morphology, physical properties, biochemical were evaluated. Cell morphology and distribution were observed. It was found that the silk fibroin/collagen (SF/C) scaffold-based material had significantly higher values than the silk fibroin/chitosan (SF/CS) scaffold-based material. Hematoxylin and eosin staining of the scaffolds revealed that the number of cells in the SF/C scaffold was higher. Cells grew well inside the SF/C scaffold as measured by scanning electron microscope. Reverse Transcriotion-Polymerase Chain Reaction (RT-PCR) and Western blot showed that type II collagen and Sox9 can be found in SF/C scaffold. Therefore, the SF/C scaffold exhibited better overall performance compared with the SF/CS scaffold.
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