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Advanced Healthcare Materials · 2022 ·Vol. 11 ·期 21 ·2201457 · IF 11.092

Physiology-Inspired Multilayer Nanofibrous Membranes Modulating Endogenous Stem Cell Recruitment and Osteo-Differentiation for Staged Bone Regeneration

Yingji Mao,Yu Chen,Weifeng Li,Ying Wang,Jingjing Qiu,Yingxiao Fu,Jianzhong Guan,Pinghui Zhou

Bone regeneration involves a cascade of sophisticated, multiple-staged cellular and molecular events, where early-phase stem cell recruitment mediated by chemokines and late-phase osteo-differentiation induced by pro-osteogenic factors play the crucial roles. Herein, enlightened by a bone physiological and regenerative mechanism, the multilayer nanofibrous membranes (PLLA@SDF-1 α @MT01) consisting of PLLA/MT01 micro-sol electrospun nanofibers as intima and PLLA/PEG/SDF-1 α electrospun nanofibers as adventitia are fabricated through micro-sol electrospinning and manual multi-layer stacking technologies. In vitro releasing profiles show that PLLA@SDF-1 α @MT01 represents the rapid release of stromal cell-derived SDF-1 α (SDF-1 α ) in the outer layers, while with long-term sustained release of MT01 in the inner layer. Owing to interconnected porosity like the natural bone extracellular matrix and improved hydrophilia, PLLA@SDF-1 α @MT01 manifests good biocompatibility both in vitro and in vivo. Furthermore, PLLA@SDF-1 α @MT01 can promote bone marrow mesenchymal stem cells (BMSCs) migration by amplifying the SDF-1 α /CXCR4 axis and stimulating BMSCs osteo-differentiation via activating the MAPK pathway in vitro. PLLA@SDF-1 α @MT01, with a programmed dual-delivery system, exhibits the synergetic promotion of bone regeneration and vascularization by emulating key characteristics of the staged bone repair in vivo. Overall, PLLA@SDF-1 α @MT01 that mimics the endogenous cascades of bone regeneration can enrich the physiology-mimetic staged regenerative strategy and represent a promising tissue-engineered scaffold for the bone defect.

研究领域: 组织工程 · 再生医学 · 生物材料 · 干细胞生物学 · 骨科 · 生物医学工程
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Bioactive Materials · 2021 · IF 14.593

Incorporating redox-sensitive nanogels into bioabsorbable nanofibrous membrane to acquire ROS-balance capacity for skin regeneration

Shihao Zhang,Yamin Li,Xiaofeng Qiu,Anqi Jiao,Wei Luo,Xiajie Lin,Xiaohui Zhang,Zeren Zhang,Jiachan Hong,Peihao Cai,Yuhong Zhang,Yan Wu,Jie Gao,Changsheng Liu,Yulin Li

Facing the high incidence of skin diseases, it is urgent to develop functional materials with high bioactivity for wound healing, where reactive oxygen species (ROS) play an important role in the wound healing process mainly via adjustment of immune response and neovasculation. In this study, we developed a kind of bioabsorbable materials with ROS-mediation capacity for skin disease therapy. Firstly, redox-sensitive poly(N-isopropylacrylamide-acrylic acid) (PNA) nanogels were synthesized by radical emulsion polymerization method using a disulfide molecule as crosslinker. The resulting nanogels were then incorporated into the nanofibrous membrane of poly( l -lactic acid) (PLLA) via airbrushing approach to offer bioabsorbable membrane with redox-sensitive ROS-balance capacity. In vitro biological evaluation indicated that the PNA-contained bioabsorbable membrane improved cell adhesion and proliferation compared to the native PLLA membrane. In vivo study using mouse wound skin model demonstrated that PNA-doped nanofibrous membranes could promote the wound healing process, where the disulfide bonds in them were able to adjust the ROS level in the wound skin for mediation of redox potential to achieve higher wound healing efficacy.

CAS / MDL: 79-10-7
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 伤口愈合
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MACROMOLECULAR BIOSCIENCE · 2022 ·Vol. 22 ·期 9 ·2200179 · IF 5.859

3D Contour Printing of Anatomically Mimetic Cartilage Grafts with Microfiber-Reinforced Double-Network Bioink

Meng Wang,Jianping Zhao,Yixuan Luo,Qianyi Liang,Yisi Liu,Gang Zhong,Yin Yu,Fei Chen

Bioprinting is an emerging technology for fabricating cell-laden scaffolds with custom shapes that resemble the complex architecture of human tissues, however, construction of mechanically competent tissue grafts which mimic irregular cartilage defect is still a big challenge. Here, 3D printing of short fiber-reinforced double-network bioink to generate anatomically accurate and mechanical tunable scaffold for cartilage regeneration is reported. Poly(lactic acid) (PLLA) short fibers are first prepared by electrospinning and then fragmented through aminolysis reaction. Composite inks are constructed with an incorporation of fragmented microfibers with varied amounts and lengths into oxidized alginate bioink. The results show that incorporation of PLLA short fibers not only improves the printing fidelity but also facilitates in generating mechanically strong constructs. By incorporating gelatin methacryloyl (GelMA) and optimizing the bioink composition, the fabricated constructs with a compressive stress of ≈150 kPa even after 100 cyclical compression loading (up to 40% of strain) are achieved. In addition, this mechanically reinforced alginate/GelMA double-network bioink displays good biocompatibility and supports bone marrow-derived stromal cell chondrogenesis in vitro. Collectively, these findings demonstrate this approach is capable of printing engineered grafts which resemble the irregular size and mechanical properties of cartilage and thus hold potential for functional tissue regeneration.

研究领域: 生物打印 · 组织工程 · 生物材料 · 再生医学
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Bioactive Materials · 2021 · IF 14.593

Construction of nanofibrous scaffolds with interconnected perfusable microchannel networks for engineering of vascularized bone tissue

Jiani Gu,Qianqian Zhang,Mengru Geng,Weizhong Wang,Jin Yang,Atta ur Rehman Khan,Haibo Du,Zhou Sha,Xiaojun Zhou,Chuanglong He

Vascularization and bone regeneration are two closely related processes during bone reconstruction. A three-dimensional (3D) scaffold with porous architecture provides a suitable microenvironment for vascular growth and bone formation. Here, we present a simple and general strategy to construct a nanofibrous poly( l -lactide)/poly(ε-caprolactone) (PLLA/PCL) scaffold with interconnected perfusable microchannel networks (IPMs) based on 3D printing technology by combining the phase separation and sacrificial template methods. The regular and customizable microchannel patterns within the scaffolds (spacings: 0.4 mm, 0.5 mm, and 0.6 mm; diameters: 0.8 mm, 1 mm, and 1.2 mm) were made to investigate the effect of microchannel structure on angiogenesis and osteogenesis. The results of subcutaneous embedding experiment showed that 0.5/0.8-IPMs (spacing/diameter = 0.5/0.8) and 0.5/1-IPMs (spacing/diameter = 0.5/1) scaffolds exhibited more vascular network formation as compared with other counterparts. After loading with vascular endothelial growth factor (VEGF), [email protected] /0.8 scaffold prompted better human umbilical vein endothelial cells (HUVECs) migration and neo-blood vessel formation, as determined by Transwell migration, scratch wound healing, and chorioallantoic membrane (CAM) assays. Furthermore, the microangiography and rat cranial bone defects experiments demonstrated that [email protected] /0.8 scaffold exhibited better performance in vascular network formation and new bone formation compared to [email protected] /1 scaffold. In summary, our results suggested that the microchannel structure within the scaffolds could be tailored by an adjustable caramel-based template strategy, and the combination of interconnected perfusion microchannel networks and angiogenic factors could significantly enhance vascularization and bone regeneration.

CAS / MDL: 57-50-1
研究领域: 组织工程 · 生物材料 · 生物医学工程 · 再生医学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2019 · IF 3.973

Nanofibrous vascular scaffold prepared from miscible polymer blend with heparin/stromal cell-derived factor-1 alpha for enhancing anticoagulation and endothelialization

Weizhong Wang,Dinghua Liu,Dejian Li,Haibo Du,Jingtian Zhang,Zhengwei You,Maoquan Li,Chuanglong He

There is an urgent clinical demand to develop a functional small diameter vascular graft with long-term patency, which mainly relies on the anticoagulation and endothelialization of the vascular graft. In addition, improved degradation of vascular graft provides more space for cell infiltration and facilitates remodeling of blood vessel. In this study, an elastic and biomimetic nanofibrous vascular scaffold with improved degradability was prepared by adding poly(lactic-co-glycolic acid) (PLGA) into the poly(L-lactic acid) (PLLA)/poly(L-lactide-co-ε-caprolactone) (PLCL) blend using thermally induced phase separation (TIPS) technique. The incorporation of PLGA also improved the hydrophilicity of the composite scaffold. Then the vascular scaffold was surface modified by combination of heparin and stromal cell-derived factor-1 alpha (SDF-1α). The results of whole blood clotting kinetics and plasma recalcification profiles indicated that heparinized modification significantly enhanced the anticoagulation of vascular scaffold. In vitro cell culture assays demonstrated the immobilized SDF-1α facilitated recruitment of endothelial progenitor cells (EPCs), migration and proliferation of mature endothelial cells, human umbilical vein endothelial cells (HUVECs), and expression of VE-cadherin/CD144 and endothelial nitric oxide synthase (eNOS) genes in HUVECs, thereby accelerating the endothelialization of the modified vascular scaffold. Besides, the nanofibrous vascular scaffold modified with heparin and SDF-1α inhibited the proliferation of human vascular smooth muscle cells (HVSMCs). Therefore, the phase separated nanofibrous vascular scaffold modified with heparin and SDF-1α shows the promising in vitro performance as a functional small diameter vascular graft.

研究领域: 生物材料 · 组织工程 · 血管移植物 · 生物医学工程
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JOURNAL OF CONTROLLED RELEASE · 2024 · IF 10.5

Uni-directional release of ibuprofen from an asymmetric fibrous membrane enables effective peritendinous anti-adhesion

Jixia Deng,Zhixiao Yao,Shikun Wang,Xinyu Zhang,Lei Zhan,Tongyu Wang,Wenhua Yu,Jiamei Zeng,Jinglei Wu,Shaoju Fu,Shihao Wu,Yuanming Ouyang,Chen Huang

Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.

CAS / MDL: 75-05-8 15687-27-1
研究领域: 生物医学工程 · 药剂学 · 组织工程 · 材料科学
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