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Small · 2019 ·Vol. 15 ·期 31 ·1901617 · IF 10.856

Synergistic Effects of Novel Superparamagnetic/Upconversion HA Material and Ti/Magnet Implant on Biological Performance and Long-Term In Vivo Tracking

Xiyu Li,Qin Zou,Yi Man,Wei Li

To solve the clinical challenges presented by the long-term tracking of implanted hydroxyapatite (HA) bone repair material and to investigate the synergistic effects of superparamagnetic HA and a static magnetic field (SMF) on the promotion of osteogenesis, herein a new type of superparamagnetic/upconversion-generating HA material (HYH-Fe) is developed via a two-step doping method, as well as a specially-designed titanium implant with a built-in magnet to provide a local static magnetic field in vivo. The results show that the prepared HYH-Fe material maintains the crystal structure of HA and exhibits good cytocompatibility. The combined use of the superparamagnetic HYH-Fe material and SMF can effectively and synergistically promote osteogenesis/osteointegration surrounding the Ti implants. In addition, the HYH-Fe material exhibits distinct advantages in terms of both long-term fluorescence tracking and microcomputed tomography (micro-CT) tracking. The new material and tracking strategy in this study provide scientific feasibility and will have important clinical value for long-term tracking and evaluation of implanted materials and the bone repair effect.

CAS / MDL: 14483-18-2 13494-98-9
研究领域: 材料科学 · 生物材料 · 生物医学工程 · 骨科
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Bioactive Materials · 2021 · IF 14.593

Injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues

Xiaohui Wu,Xin Wang,Xiaobin Chen,Xiaowei Yang,Qian Ma,Guohua Xu,Lin Yu,Jiandong Ding

It is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content > 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation in vivo . Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials.

研究领域: 材料科学 · 生物医学工程 · 成像技术 · 聚合物化学
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Bioactive Materials · 2022 · IF 16.874

An anti-bacterial porous shape memory self-adaptive stiffened polymer for alveolar bone regeneration after tooth extraction

Weijun Zhang,Meilin Yu,Yongqiang Cao,Zihan Zhuang,Kunxi Zhang,Dong Chen,Wenguang Liu,Jingbo Yin

The regeneration of alveolar bone after tooth extraction is critical for the placement of dental implants. Developing a rigid porous scaffold with defect shape adaptability is of great importance but challenging for alveolar bone regeneration. Herein, we design and synthesize a biocompatible poly( l -glutamic acid)- g -poly( ε -caprolactone) (PLGA- g -PCL) porous shape memory (SM) polymer. The PLGA- g -PCL is then copolymerized with acryloyl chloride grafted poly( ω -pentadecalactone) (PPDLDA) having a higher phase transition temperature than shape recovery temperature to maintain stiffness after shape recovery to resist chewing force. The hybrid polydopamine/silver/hydroxyapatite (PDA/Ag/HA) is coated to the surface of (PLGA- g -PCL)-PPDL scaffold to afford the anti-bacterial activity. The porous SM scaffold can be deformed into a compact size and administered into the socket cavity in a minimally invasive mode, and recover its original shape with a high stiffness at body temperature, fitting well in the socket defect. The SM scaffold exhibits robust antibacterial activity against Staphylococcus aureus ( S. aureus ). The porous microstructure and cytocompatibility of PLGA allow for the ingrowth and proliferation of stem cells, thus facilitating osteogenic differentiation. The micro-CT and histological analyses demonstrate that the scaffold boosts efficient new bone regeneration in the socket of rabbit mandibular first premolar. This porous shape memory self-adaptive stiffened polymer opens up a new avenue for alveolar bone regeneration.

研究领域: 牙科材料 · 生物材料 · 组织工程 · 再生医学
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Applied Materials Today · 2021 · IF 10.041

Construction of a reactive oxygen species-responsive biomimetic multilayered titanium implant for in situ delivery of α-melanocyte-stimulating hormone to improve bone remolding in osteoporotic rats

Maohua Chen,Yan Hu,Yanhua Hou,Yuting Sun,Maowen Chen,Menghuan Li,Lu Tan,Zhong Luo,Kaiyong Cai

By exploiting the high reactive-oxygen-species(ROS) level in osteoporosis fractured sites, a ROS responsive biomimetic multilayer onto titanium(Ti) implant composed of gelatin(Gel)/dextran amine (DA) and α-melanocyte-stimulating hormone (α-MSH) has been constructed using layer-by-layer spin self-assembled technique, which was further cross-linked with 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2) benzyl carbonate (NBC)-grafted-polyethylene glycol (PEG-NBC) for in situ delivery of α-MSH. The PEG-NBC cross-linked Gel/DA multilayer onto Ti substrate (Ti/LBL NBC -MSH) could be broken down when exposed to ROS-rich pathological environment, thus leading to a sustained release of α-MSH from multilayer in a controlled manner. It could maintain the α-MSH concentration at a constant level to promote in situ MSCs differentiation and inhibit osteoclast activity through regulating GSK-3β/β-catenin signal pathways with Runx2 positive feedback regulation loop. Micro-CT analysis, hematoxylin/eosin (HE) staining and Masson's trichrome (MT) staining further confirmed that new bone has fused into mature lamellar bone and trabecularism along the interface of Ti/LBL NBC -MSH in osteoporotic rats. Therefore, this study offers a new perspective on the development of biofunctional Ti implants as supplementary treatment for osteoporotic fracture repair in a clinical context.

研究领域: 生物材料工程 · 组织工程 · 骨科 · 药剂学 · 材料科学
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AMERICAN JOURNAL OF SPORTS MEDICINE · 2025 · IF 4.5

An Aligned-to-Random PLGA/Col1-PLGA/nHA Bilayer Electrospun Nanofiber Membrane Enhances Tendon-to-Bone Healing in a Murine Model

Baoyun Xu,Yunjiao Wang,Gang He,Xu Tao,Shang Gao,Mei Zhou,Yuzhen Tang,Kang-lai Tang,Lin Guo,Wan Chen

Background:The challenge of achieving effective tendon-to-bone healing remains a significant concern in sports medicine, necessitating further exploration. Biomimetic electrospun nanomaterials present promising avenues for improving this critical healing process.Purpose:To investigate the biological efficacy of a novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer electrospun nanofiber membrane in facilitating tendon-to-bone healing.Study Design:Controlled laboratory study.Methods:The bilayer membrane’s composition, combining PLGA/Col1 for tendon attachment and PLGA/nHA for bone integration, was examined using scanning electron microscopy, Fourier transform infrared spectroscopy, and mechanical testing. Positioned between the Achilles tendon and bone, its design aimed for harmonious integration with both types of tissue. In vitro, biocompatibility, cell adhesion, and proliferation of the biomaterial were evaluated using live/dead staining and the CCK-8 assay. Collagen secretion and mineralization were measured for 2 cell types. In vivo, tendon-to-bone insertion samples harvested from mice were analyzed: micro–computed tomography assessed bone formation; histological staining evaluated chondrogenesis, tendinogenesis, and the 4-layer structure of the insertion; and biomechanical testing measured insertion strength. Real-time polymerase chain reaction identified genes involved in tendon-to-bone healing, and transcriptome analysis elucidated the underlying cellular and molecular mechanisms.Results:The optimal composition was determined as 10% 3:1 for aligned PLGA/Col1 and 9% 5:1 for PLGA/nHA. Coculture showed minimal cell death, firm cell adherence, and steady proliferation, with PLGA/Col1 enhancing collagen secretion. In vivo, the material promoted bone and cartilage formation and improved tendon-to-bone interface strength. Transcriptome analysis indicated links to TNF and NF-κB pathways and to genes IL-1β, ADAM8, and EGR2.Conclusion:The novel aligned-to-random PLGA/Col1-PLGA/nHA bilayer nanofiber membrane outperformed other materials in both in vitro and in vivo evaluations, significantly enhancing tendon-to-bone healing. It notably improved cartilage and bone formation, tendon maturation, and biomechanical strength at the surgical interface. These effects may be associated with the TNF and NF-κB pathways and with the genes IL-1β, ADAM8, and EGR2.Clinical Relevance:This study introduces a biomimetic nanofiber membrane enhancing tendon-to-bone healing, which is crucial for sports medicine. Its efficacy in improving healing outcomes, including bone and cartilage formation and biomechanical strength, could significantly lower failure rates in surgical procedures such as rotator cuff repair and anterior cruciate ligament reconstruction. This advancement offers promising implications for patient recovery and the effectiveness of surgical interventions in tendon-to-bone injuries.

研究领域: 运动医学 · 组织工程 · 生物材料科学 · 骨科 · 生物医学工程
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MATERIALS & DESIGN · 2024 · IF 7.6

Triple-layered multi-functional membrane for synergistic enhancement of guided bone regeneration

Abdullrahman M. Al-Bishari,Tingting Liu,Jiatong Zhuang,Qihong Zhang,Jiaquan Chen,Yan Wang,Chuanyang Liu,Peng Gao,Jinsong Liu,Lei Lu

Advancements in guided bone regeneration (GBR) rely on the development of membranes that can effectively control drug delivery and facilitate bone repair. This study introduces a triple-layered multi-functional membrane (MFM), with each layer serving a specific release profile and function. These layers consist of Qk peptide, strontium (Sr), and vancomycin (Van) for angiogenesis, bone growth, and infection control. The MFM was meticulously designed to ensure sustained drug release kinetics and improved bone regeneration. The membrane morphology was analyzed via SEM, and its mechanical properties were measured via stress–strain curves. In vitro studies confirmed the controlled release of the agents for 21 days. These findings indicate significant enhancements needed for GBR, as supported by in vitro results. The synergy of the membrane's components contributes to a greater therapeutic impact. Furthermore, in vivo results further supported the exceptional performance of MFM in GBR. Within 5 days of implantation, notable improvements in revascularization were observed. After 1 month, micro-CT scans displayed accelerated bone regeneration, while the membrane effectively prevented bacterial growth within 3 days. The MFM/Van-Sr-Qk membrane shows excellent potential for advancing bone regeneration and GBR therapies, warranting further research and development in this promising field.

CAS / MDL: 47165-04-8
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 药学 · 骨科
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