Browsing by Author "Wang, Xiumei"

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    A high-strength mineralized collagen bone scaffold for large-sized cranial bone defect repair in sheep
    (Oxford University Press, 2018) Wang, Shuo; Zhao, Zhijun; Yang, Yongdong; Mikos, Antonios G.; Qiu, Zhiye; Song, Tianxi; Cui, Fuzhai; Wang, Xiumei; Zhang, Chunyang
    Large-sized cranial bone defect repair presents a great challenge in the clinic. The ideal cranioplasty materials to realize the functional and cosmetic recovery of the defect must have sufficient mechanical support, excellent biocompatibility, good osseointegration and biodegradability as well. In this study, a high-strength mineralized collagen (MC) bone scaffold was developed with biomimetic composition, microstructure and mechanical properties for the repair of sheep large-sized cranial bone defects in comparison with two traditional cranioplasty materials, polymethyl methacrylate and titanium mesh. The compact MC scaffold showed no distinct pore structure and therefore possessed good mechanical properties. The strength and elastic modulus of the scaffold were much higher than those of natural cancellous bone and slightly lower than those of natural compact bone. In vitro cytocompatibility evaluation revealed that the human bone marrow mesenchymal stem cells (hBMSC) had good viability, attachment and proliferation on the compact MC scaffold indicating its excellent biocompatibility. An adult sheep cranial bone defect model was constructed to evaluate the performances of these cranioplasty materials in repairing the cranial bone defects. The results were investigated by gross observation, computed tomography scanning as well as histological assessments. The in vivo evaluations indicated that compact MC scaffold showed notable osteoconductivity and osseointegration with surrounding cranial bone tissues by promoting bone regeneration. Our results suggested that the compact MC scaffold has a promising potential for large-sized cranial bone defect repair.
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    Hierarchically Engineered Artificial Lamellar Bone with High Strength and Toughness
    (Wiley, 2023) Zhao, Yonggang; Zheng, Jingchuan; Xiong, Yang; Wang, Hetong; Yang, Shuhui; Sun, Xiaodan; Zhao, Lingyun; Mikos, Antonios G.; Wang, Xiumei
    Complex hierarchical architectures are ubiquitous in natural hard tissues, which comprise an elaborate assembly of hard and soft phases spanning from the nanoscale to the macroscale. The elegant architectures grant unique performance in terms of strength and toughness, but the biomimetic fabrication of synthetic materials with highly consistent structural and mechanical characteristics with natural counterparts remains a great challenge. Here, a centimeter-size artificial lamellar bone is successfully fabricated for the first time via a well-orchestrated “multiscale cascade regulation” strategy combining multiple techniques of molecular self-assembly, electrospinning, and pressure-driven fusion from molecular to macroscopic levels. The bulk artificial lamellar bone that is composed of hierarchically assembled mineralized collagen fibrils with a waiver of any synthetic polymer highly resembles the chemical composition, multiscale structural organization, and rotated plywood-like structure of natural lamellae, thus achieving a good combination of lightweight and high-stiffness (Ey ≈ 15.2 GPa), -strength (σf ≈ 118.4 MPa), and -toughness (KJC ≈ 9.3 MPa m1/2). This multiscale cascade regulation strategy can break through the limitations of a single technique and enable the construction of elaborate composite materials with multiscale step-by-step regulations of hierarchically structural organizations for unique mechanical properties.
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    Increased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regeneration
    (Ivyspring, 2018) Lu, Jiaju; Shen, Xuezhen; Sun, Xun; Yin, Heyong; Yang, Shuhui; Lu, Changfeng; Wang, Yu; Liu, Yifan; Huang, Yingqi; Yang, Zijin; Dong, Xianqi; Wang, Chenhao; Guo, Quanyi; Zhao, Lingyun; Sun, Xiaodan; Lu, Shibi; Mikos, Antonios G.; Peng, Jiang; Wang, Xiumei
    Even small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP). We hypothesized that increased recruitment of endogenous stem cells by the composite scaffold could enhance cartilage regeneration. Methods: To test our hypothesis, in vitro proliferation, attachment and chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) were tested to confirm the bioactivities of the functionalized peptide hydrogel. The composite scaffold was then implanted into full-thickness cartilage defects on rabbit knee joints for cartilage repair, in comparison with microfracture or other sample groups. Stem cell recruitment was monitored by dual labeling with CD29 and CD90 under confocal microcopy at 1 week after implantation, followed by chondrogenic differentiation examined by qRT-PCR. Repaired tissue of the cartilage defects was evaluated by histological and immunohistochemistry staining, microcomputed tomography (micro-CT) and magnetic resonance imaging (MRI) at 3 and 6 months post-surgery. Macroscopic and histological scoring was done to evaluate the optimal in vivo repair outcomes of this composite scaffold. Results: The functionalized SAP hydrogels could stimulate rabbit MSC proliferation, attachment and chondrogenic differentiation during in vitro culture. At 7 days after implantation, increased recruitment of MSCs based on CD29+ /CD90+ double-positive cells was found in vivo in the composite hydrogel scaffold, as well as upregulation of cartilage-associated genes (aggrecan, Sox9 and type II collagen). After 3 and 6 months post-surgery, the articular cartilage defect in the composite scaffold-treated group was fully covered with cartilage-like tissue with a smooth surface, which was similar to the surrounding native cartilage, according to the results of histological and immunohistochemistry staining, micro-CT and MRI analysis. Macroscopic and histological scoring confirmed that the quality of cartilage repair was significantly improved with implantation of the composite scaffold at each timepoint, in comparison with microfracture or other sample groups. Conclusion: Our findings demonstrated that the composite scaffold could enhance endogenous stem cell homing and chondrogenic differentiation and significantly improve the therapeutic outcome of chondral defects. The present study provides a promising approach for in vivo cartilage repair without cell transplantation. Optimization of this strategy may offer great potential and benefits for clinical application in the future.
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    Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model
    (AAAS, 2022) Zhu, Jinjin; Yang, Shuhui; Qi, Yadong; Gong, Zhe; Zhang, Haitao; Liang, Kaiyu; Shen, Panyang; Huang, Yin-Yuan; Zhang, Zhe; Ye, Weilong; Yue, Lei; Fan, Shunwu; Shen, Shuying; Mikos, Antonios G.; Wang, Xiumei; Fang, Xiangqian
    Osteoarthritis (OA) is a common joint disease characterized by progressive loss of cartilage and reduction in lubricating synovial fluid, which lacks effective treatments currently. Here, we propose a hydrogel-based miRNA delivery strategy to rejuvenate impaired cartilage by creating a regenerative microenvironment to mitigate chondrocyte senescence that mainly contributes to cartilage breakdown during OA development. An aging-related miRNA, miR-29b-5p, was first found to be markedly down-regulated in OA cartilage, and their up-regulation suppressed the expression of matrix metalloproteinases and senescence-associated genes (P16INK4a/P21) via ten-eleven-translocation enzyme 1 (TET1). An injectable bioactive self-assembling peptide nanofiber hydrogel was applied to deliver agomir-29b-5p, which was functionalized by conjugating a stem cell–homing peptide SKPPGTSS for endogenous synovial stem cell recruitment simultaneously. Sustained miR-29b-5p delivery and recruitment of synovial stem cells and their subsequent differentiation into chondrocytes led to successful cartilage repair and chondrocyte rejuvenation. This strategy enables miRNA-based therapeutic modality to become a viable alternative for surgery in OA treatment.