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COMPOSITES PART B-ENGINEERING · 2024 · IF 12.7

Injectable, stretchable, and conductance-stable fiber for myocardial infarction repair

Yimeng Li,Chaofu Li,Mengqi Shan,Leqian Wei,Lizhen Lan,Xiaoli Liu,Lamei Guo,Fujun Wang,Ze Zhang,Lu Wang,Li Shen,Jifu Mao

Injecting electroactive biomaterials into infarcted myocardium to restore blocked electrical signal pathways is an effective way for repairing myocardial infarction. However, re-establishing stable and anisotropic conductive pathways during the constant contraction and relaxation of the heart remains a challenge. Herein, inspired by the myocardial fibers with striated surfaces, a super-elastic and conductance-stable polyurethane fiber with buckled polypyrrole coating (PU 150 % @PPy) was designed. The bionic composite fiber exhibited excellent stretchability (>450 %), electrical stability under large strains (Δ R / R 0 of only 0.04 at 100 % strain), and long-term durability (>1000000 cycles), enabling stable transmission of electrical signals in a beating heart. Specifically, the composite fibers could be injected into the infarct area in minimally invasive manner and aligned with the myocardial fibers to provide anisotropic conductive pathways. After injecting the PU@PPy fibers into the infarcted heart, the cardiac function was improved (33.19 % increase in fractional shortening and 38.80 % increase in ejection fraction) and the myocardial remodeling was decreased (40.30 % reduction in infarct size and 92.77 % increase in myocardial wall thickness) by re-establishing the electrical communication of the electrically separated cardiomyocytes in the infarct area as well as by providing mechanical support. The injectable, stretchable, and conductance-stable fiber offers a promising strategy for reconstructing infarcted myocardium.

研究领域: 生物医学工程 · 材料科学 · 心脏病学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Injectable, Hierarchically Degraded Bioactive Scaffold for Bone Regeneration

Jixing Ye,Ningyuan Liu,Zongxin Li,Liehua Liu,Ming Zheng,Xueping Wen,Nan Wang,Yanqin Xu,Biemin Sun,Qiang Zhou

Bioactive materials play vital roles in the repair of critical bone defects. However, bone tissue engineering and regenerative medicine are still challenged by the need to repair bone defects evenly and completely. In this study, we functionally simulated the natural creeping substitution process of autologous bone repair by constructing an injectable, hierarchically degradable bioactive scaffold with a composite hydrogel, decalcified bone matrix (DBM) particles, and bone morphogenetic protein 2. This composite scaffold exhibited superior mechanical properties. The scaffold promoted cell proliferation and osteogenic differentiation through multiple signaling pathways. The hierarchical degradation rates of the crosslinked hydrogel and DBM particles accelerated tissue ingrowth and bone formation with a naturally woven bone-like structure in vivo. In the rat calvarial critical defect repair model, the composite scaffold provided even and complete repair of the entire defect area while also integrating the new and host bone effectively. Our results indicate that this injectable, hierarchically degradable bioactive scaffold promotes bone regeneration and provides a promising strategy for evenly and completely repairing the bone defects.

CAS / MDL: 85073-19-4
研究领域: 组织工程 · 再生医学 · 生物材料 · 骨科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMATERIALS · 2021 · IF 12.479

Injectable Mussel‐Inspired highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration

Fang-Xue Zhang,Peng Liu,Wang Ding,Qing-Bing Meng,Di-Han Su,Qi-Chen Zhang,Rui-Xian Lian,Bao-Qing Yu,Ming-Dong Zhao,Jian Dong,Yu-Lin Li,Li-Bo Jiang

In the early stage of osteoarthritis (OA), cartilage degradation in the surface region leads to superficial cartilage defect. However, enhancing the regeneration of cartilage defect remains a great challenge for existing hydrogel technology because of the weak adhesion to wet tissue. In the present study, an injectable mussel-inspired highly adhesive hydrogel with exosomes was investigated for endogenous cell recruitment and cartilage defect regeneration. The hydrogel with high bonding strength to the wet surface was prepared using a crosslinked network of alginate-dopamine, chondroitin sulfate , and regenerated silk fibroin (AD/CS/RSF). Compared with commercial enbucrilate tissue adhesive, the AD/CS/RSF hydrogel provided a comparative lap shear strength of 120 kPa, with a similar gelation time and a higher capacity for maintaining adhesive strength. The AD/CS/RSF/EXO hydrogel with encapsulated exosomes recruited BMSCs migration and inflation, promoted BMSCs proliferation and differentiation. Most importantly, the AD/CS/RSF/EXO hydrogel accelerated cartilage defect regeneration in situ, and extracellular matrix remodeling after injection in rat patellar grooves. The exosomes released by the hydrogels could recruit BMSCs into the hydrogel and neo-cartilage via the chemokine signaling pathway . Our findings reveal an injectable and adhesive hydrogel for superficial cartilage regeneration, which is a promising approach for minimally treating cartilage defect with arthroscopic assistance.

研究领域: 生物材料 · 组织工程 · 再生医学 · 骨科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Materials Today Bio · 2023 · IF 8.2

Injectable hyperbranched PEG crosslinked hyaluronan hydrogel microparticles containing mir-99a-3p modified subcutaneous ADSCs-derived exosomes was beneficial for long-term treatment of osteoarthritis

Zhaowei Yin,Chaoren Qin,Shaowei Pan,Chen Shi,Guanfu Wu,Yan Feng,Jing Zhang,Ziyi Yu,Bin Liang,Jianchao Gui

Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (Exos IPFP ) and ScAT stem cells (Exos ScAT ) in OA treatment. Results suggested that Exos IPFP significantly inhibit the degradation of cartilage extracellular matrix (ECM) than Exos ScAT , following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in Exos ScAT (Exos ScAT−99b−3p ), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in Exos ScAT would enable them to exhibit comparable or even superior effectiveness to Exos IPFP for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.

研究领域: 生物材料 · 干细胞治疗 · 基因治疗 · 骨科 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Advanced Healthcare Materials · 2023 · IF 10

Injectable Asymmetric Adhesive-Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention

Zhongming Zhao,Hong Sun,Chaojie Yu,Baijun Liu,Rui Liu,Qi Yang,Bingyan Guo,Xiuqiang Li,Mengmeng Yao,Fanglian Yao,Hong Zhang,Junjie Li

Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by “two-step” injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.

研究领域: 材料科学 · 生物医学工程 · 外科手术 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2024 · IF 9.4

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect

Lei Huang,Shihao Zhang,Mengxuan Bian,Xingdong Xiang,Lan Xiao,Jiayi Wang,Shunyi Lu,Weisin Chen,Cheng Zhang,Guokang Mo,Libo Jiang,Yulin Li,Jian Zhang

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and β-Tricalcium Phosphate (β-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo . Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. Statement of significance Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into β-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro . Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.

CAS / MDL: 1336-21-6
研究领域: 生物医学工程 · 材料科学 · 组织工程 · 骨科 · 生物材料
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Injectable alginate-based zwitterionic hydrogels promoting endometrial repair and restoring fertility

Sisi Zhang,Erna Jia,Weiqi Zhang,Zhiying Wang,Da Deng,Yixin Zhang,Xuefeng Huang,Qingquan Tian,Ying Tan,Bujun Wang,Feng Lin

The development of novel therapeutic approaches to facilitate endometrial repair and regeneration while preventing adhesion recurrence is a crucial research objective aimed at enhancing clinical outcomes for women with intrauterine adhesions (IUA). In this study, we introduced an injectable Alg-GMA/PTSB zwitterionic hydrogel, characterized by excellent biocompatibility, anti-protein adsorption properties, and biodegradability. In a rat model, the hydrogel significantly promoted the regeneration and angiogenesis of damaged endometrial tissue, leading to improved recovery of epithelial cells, glands, proliferation, and vascularization. Furthermore, it exhibited the ability to suppress cellular apoptosis and collagen deposition, thereby mitigating fibrosis. Additionally, the hydrogel restored the expression of estrogen/progesterone receptors and endometrial receptivity markers, contributing to enhanced embryo implantation and fertility. These findings underscore the potential of the hydrogel as a promising therapeutic strategy for addressing endometrial injury, reducing fibrosis, restoring fertility, and ultimately improving outcomes for women with IUA.

研究领域: 妇科学 · 生殖医学 · 生物材料 · 组织工程
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Injectable, Biodegradable, Thermosensitive Nanoparticles-Aggregated Hydrogel with Tumor-Specific Targeting, Penetration, and Release for Efficient Postsurgical Prevention of Tumor Recurrence

Huiming Liu,Xiaoguang Shi,Di Wu,Frewein Kahsay Khshen,Liandong Deng,Anjie Dong,Weiwei Wang,Jianhua Zhang

High locoregional recurrence of breast cancer after surgery remains a clinically appealing challenge. Local chemotherapy, especially sustainable delivery of chemotherapeutics at tumor sites by implantable hydrogels, has shown great potential to prevent cancer recurrence. However, the applications of conventional hydrogels are often limited by their intrinsic poor drug penetration into solid tumors and nonspecific drug accumulation in adjacent normal tissues. Herein, we developed a novel modular coassembly strategy to prepare a kind of pH-sensitive, tumor-specific targeting, and penetrating peptide (CRGDK)-modified doxorubicin-based prodrug nanoparticles (PDNPs), whose aqueous dispersion can undergo sol–gel transition after in vivo injection by thermo-induced self-aggregation to in situ form biodegradable hydrogel depot (PDNPs-gel), anchoring high amounts of PDNPs at tumor sites. Because of CRGDK-mediated targeting to overexpressed neuropilin-1 receptors on tumor vessels and tumor cells, PDNPs released from PDNPs-gel can effectively penetrate into tumor tissues, specifically enter tumor cells and finally realize intracellular acid-triggered drug release. In an in vivo incomplete resection of breast cancer model, a single peritumoral administration of PDNP-gel can achieve high inhibition efficacy against tumor recurrence. In addition, the administration of PDNP-gel only involves simple redispersion of PDNPs in water without any pretreatment for gelation, providing great convenience for storage, dosage, and prescription in practical use. Collectively, the reported multifunctional nanoparticles self-aggregated hydrogel system possesses great potential for efficient postsurgical prevention of tumor recurrence.

研究领域: 癌症研究 · 药学 · 纳米技术 · 生物材料 · 药物递送系统 · 生物医学工程
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