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颅骨再生
Materials Science & Engineering C-Materials for Biological Applications · 2019 · IF 4.959

Tuning pore features of mineralized collagen/PCL scaffolds for cranial bone regeneration in a rat model

Shuo Wang,Yongdong Yang,Gerry L. Koons,Antonios G. Mikos,Zhiye Qiu,Tianxi Song,Fuzhai Cui,Xiumei Wang

Porosity is indispensable for a bone tissue-engineered scaffold for facilitating endogenous cell migration and nascent bone ingrowth. In large-sized cranial bone defect repair, porous scaffolds meet great challenges to match cranial bone regeneration and provide sufficient protection with structural integrity. Therefore, the pore features of the scaffolds for cranial bone regeneration should differ from those typical porous scaffolds used in tubular bone repair and be finely tuned. In this study, a series of porous mineralized collagen/PCL scaffolds with different pore features were fabricated via freeze-drying and applied in a Sprague Dawley rat cranial bone calvarial defect model. The pore size for four groups increased from 10–45 μm to 40–130 μm. As scaffold porosity increased, the compressive strength decreased from 2.09 ± 0.12 MPa to 0.51 ± 0.04 MPa. The micro-computed tomography three-dimensional reconstruction images showed that as pore size and porosity increased, the amount of new bone formation had a maximum in group 3 (pore size: 20–100 μm, compressive strength: 1.06 ± 0.03 MPa). In addition, the histological and histomorphometric analyses showed a consistent tendency which confirmed the Micro-CT results. Meanwhile, histological findings including bony bridging, tissue response at the bone-implant interface and fibrous capsule thickness indicated that the dura mater pathway played the most important role in the regenerative process of this calvarial defect model.

CAS / MDL: 30525-89-4
研究领域: 生物材料学 · 组织工程学 · 医学
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BIOMATERIALS · 2022 · IF 15.304

Biomimetic glycopeptide hydrogel coated PCL/nHA scaffold for enhanced cranial bone regeneration via macrophage M2 polarization-induced osteo-immunomodulation

Yaping Wang,Jingrong Wang,Rui Gao,Xiang Liu,Zujian Feng,Chuangnian Zhang,Pingsheng Huang,Anjie Dong,Deling Kong,Weiwei Wang

The reconstruction of large cranial bone defects by bioactive materials without exogenous cells or growth factors remains a substantial clinical challenge. Here, synthetic fibrous glycopeptide hydrogel (GR gel ) self-assembled by β-sheet RADA16-grafted glucomannan was designed to mimic the glycoprotein composition and the fibrillar architecture of natural extracellular matrix (ECM), which was non-covalently composited with 3D-printed polycaprolactone/nano hydroxyapatite (PCL/nHA) scaffold for cranial bone regeneration . The glycopeptide hydrogel significantly promoted the proliferation, osteogenic differentiation of bone mesenchymal stem cells (BMSCs), which was further augmented by GR gel -induced macrophage M2-phonotype polarization and the effective M2 macrophage-BMSC crosstalk . The repair of critical-size skull bone defect in rat indicated a superior efficacy of PCL/ [email protected] gel implant on bone regeneration and osseointegration , with an average bone area of 83.3% throughout the defect location at 12 weeks post treatment. Furthermore, the osteo-immunomodulatory GR gel induced a reparative microenvironment similar with that in normal cranium, as characterized by an increased percentage of anti-inflammatory M2 macrophages and osteoblasts, and high-level vascularization . Collectively, the composite scaffold developed here with macrophage polarization-mediated osteo-immunomodulation may represent a promising implant for expediting in situ bone regeneration by providing biochemical and osteoinductive cues at the injured tissue.

研究领域: 生物材料学 · 组织工程学 · 再生医学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Divalent Anion-Induced Biohydrogels with High Strength, Anti-swelling, and Bioactive Capability for Enhanced Skull Bone Regeneration

Ziying You,Yue Yu,Tie Hua Wang,Chenglin Wang,Ding Xiong,Yu Shi,Zhenming Wang,Ling Ye

Increased intracranial pressure after traumatic brain injury (TBI) is an urgent problem in clinical practice. A pliable hydrogel is preferred for cranioplasty applications after TBI since it can protect brain tissue and promote bone healing. Nevertheless, biohydrogels for cranial bone regeneration still face challenges of poor mechanical properties, large swelling ratios, and low osteogenesis activity. Herein, inspired by Hofmeister effects, biopolymer hydrogels composed of protein and polysaccharides were treated with a Hofmeister series including a series of monovalent and divalent anions. Our results reveal that the divalent anion-cross-linked biohydrogels exhibit stronger mechanical properties and lower swelling ratios compared with monovalent-anion treated gels. Intriguingly, the divalent HPO42– anion induced biohybrid hydrogels with excellent mechanical behaviors (3.7 ± 0.58 MPa, 484 ± 76.7 kPa, and 148.3 ± 6.85 kJ/m3), anti-swelling capability (16.7%), and gradual degradation ability, significantly stimulating osteogenic differentiation and in vivo cranial bone regeneration. Overall, this study may provide new insights into the design of biomimetic hydrogels for treating cranial bone defects after TBI.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 再生医学
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Tricarboxylic Acid Cycle Metabolite-Coordinated Biohydrogels Augment Cranial Bone Regeneration Through Neutrophil-Stimulated Mesenchymal Stem Cell Recruitment and Histone Acetylation-Mediated Osteogenesis

Tingjun Liu,Ziying You,Fangyuan Shen,Puying Yang,Junyu Chen,Shuhuai Meng,Chenglin Wang,Ding Xiong,Chengjia You,Zhenming Wang,Yu Shi,Ling Ye

Cranial bone defects remain a major clinical challenge, increasing patients’ life burdens. Tricarboxylic acid (TCA) cycle metabolites play crucial roles in facilitating bone tissue regeneration. However, the development of TCA cycle metabolite-modified biomimetic grafts for skull bone regeneration still needs to be improved. The mechanism underlying the release of TCA cycle metabolites from biomaterials in regulating immune responses and mesenchymal stem cell (MSC) fate (migration and differentiation) remains unknown. Herein, this work constructs biomimetic hydrogels composed of gelatin and chitosan networks covalently cross-linked by genipin (CGG hydrogels). A series of TCA cycle metabolite-coordinated CGG hydrogels with strong mechanical and antiswelling performances are subsequently developed. Remarkably, the citrate (Na3Cit, Cit)-coordinated CGG hydrogels (CGG-Cit hydrogels) with the highest mechanical modulus and strength significantly promote skull bone regeneration in rat and murine cranial defects. Mechanistically, using a transgenic mouse model, bulk RNA sequencing, and single-cell RNA sequencing, this work demonstrates that CGG-Cit hydrogels promote Gli1+ MSC migration via neutrophil-secreted oncostatin M. Results also indicate that citrate improves osteogenesis via enhanced histone H3K9 acetylation on osteogenic master genes. Taken together, the immune microenvironment- and MSC fate-regulated CGG-Cit hydrogels represent a highly efficient and facile approach toward skull bone tissue regeneration with great potential for bench-to-bedside translation.

研究领域: 生物材料 · 再生医学 · 干细胞生物学 · 免疫学 · 分子生物学 · 骨组织工程
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