可注射的壳聚糖水凝胶的制备及应用进展

可注射的水凝胶由于其独特的性质在生物医学领域中备受关注。壳聚糖是自然界中唯一的一种阳离子多糖,具有含量丰富、价格低廉、生物相容性和生物可降解性良好等优点,经常被用来制备可注射的水凝胶。近年来,随着研究的进一步深入,通过采用各种化学或物理改性和修饰方法、引入各种生物功能分子或采用各种交联方法,具有优异性能的可注射的壳聚糖水凝胶不断涌现,其应用范围不断扩展,在实际应用中发挥了越来越重要的作用。本文主要介绍了常见的化学交联的和物理交联的可注射的壳聚糖水凝胶的制备方法,综述了其在药物载体、基因载体、细胞支架和伤口修复等生物医学领域中的应用进展,对其存在的问题及发展趋势进行了分析和展望,为可注射的壳聚糖水凝胶的进一步发展提供指导和借鉴。     

壳聚糖基智能水凝胶的研究进展

壳聚糖是一种天然高分子,含有氨基和羟基等特征基团;水凝胶是一种高分子交联网络体系,具有亲水性,在水中能够溶胀并保持大量水分而不溶解;“智能化”是自发地对外界环境刺激产生响应的一种特性.壳聚糖基智能水凝胶具有良好的生物相容性和可降解性,正倍受广大研究学者的关注.文章综述了近年来关于pH敏感型、温度敏感型以及pH/温度双重敏感型壳聚糖基智能水凝胶的研究概况,介绍了壳聚糖基水凝胶在医学领域如组织工程、药物释放方面的应用并对其未来的发展方向进行了探讨.     

壳聚糖基抗菌水凝胶的应用及研究进展

抗菌生物材料因其能够有效抑制细菌感染而被公认为是重要的抗生素替代品。其中抗菌水凝胶因制备工艺简单,结构多样,具有易负载和可控药物释放性、良好的生物相容性和抗菌性等多种特殊功能而受到越来越多的关注。壳聚糖及其衍生物具有高抗菌性、低毒性、生物相容性和降解性等优点被广泛用作抗菌水凝胶材料。本文根据壳聚糖基抗菌水凝胶的性能和抗菌机理,综述了近年来在固有抗菌水凝胶、光响应性抗菌水凝胶、荧光抗菌水凝胶、负载抗菌药物水凝胶和协同抗菌水凝胶等方面的研究进展,探讨了壳聚糖基抗菌水凝胶目前所面临的挑战,并对其未来发展作了展望。     

聚L-谷氨酸可注射水凝胶的制备及性能

通过活化改性聚L-谷氨酸（PLGA）制备酰肼化PLGA（PLGA-ADH）和3-氨基-1,2-丙二醇改性的PLGA（PLGA-OH）,PLGA-OH经高碘酸钠氧化制得醛基化PLGA（PLGA-CHO）,以PLGA-ADH和PLGA-CHO为前驱体,通过席夫碱交联反应构建了PLGA可注射水凝胶.研究了酰肼化和醛基化改性前后PLGA的结构变化,考察了固含量对水凝胶成胶时间、溶胀行为、机械性能、体外降解性能、药物释放行为及微观形貌等的影响,并进行了初步的细胞培养实验及裸鼠皮下注射成胶实验.结果表明,该PLGA可注射水凝胶在组织工程领域具有良好的应用前景.     

壳聚糖基智能凝胶材料及其应用

壳聚糖是一种通过超分子作用形成凝胶的氨基多糖,可形成配合物,如聚电解质配合物,共价配合物和自组装配合物等。壳聚糖基智能凝胶在控制释放载体、分离膜、固定化基质、人工细胞外基质和场响应材料等方面应用前景广阔。     

硫酸软骨素类可注射水凝胶体系及其凝胶化机制

硫酸软骨素是一种硫酸化糖胺聚糖类天然多糖,广泛分布于动物组织的细胞外基质和细胞表面,具有促进软骨生长、调控生长因子、加快伤口愈合等多种生物功能.近年来,基于硫酸软骨素良好的生物活性、生物相容性和生物降解性,硫酸软骨素类可注射水凝胶作为一种新型生物材料受到了广泛关注,尤其是在组织工程、药物输送和细胞治疗等生物医用领域的应...     

可注射水凝胶在伤口敷料中的研究进展

目前,在伤口治疗中对伤口敷料的选择越来越严格。传统的伤口敷料如纱布、绷带、海绵等在伤口愈合过程中容易诱发细菌感染,延缓伤口愈合,甚至引发慢性并发症。可注射水凝胶具备良好的生物相容性,能够适应伤口的形状以填充伤口,且具备一定的抗菌活性,从而避免伤口感染,相比传统的水凝胶伤口敷料更具备医疗优势,因此在生物医药领域得到广泛关注。本文对天然型可注射水凝胶和复合型可注射水凝胶在伤口愈合中的研究进展进行了综述;也对可注射水凝胶的未来发展趋势进行了展望。     

可注射水凝胶的制备与应用

可注射水凝胶在再生医学和药物控释等方面有着广泛的用途,是近年来生物医用材料领域新的研究方向.本文综述了近年来人们在可注射水凝胶制备和应用方面的研究进展,最后展望了其发展前景.     

ε－聚赖氨酸增强的可注射白蛋白水凝胶

牛血清白蛋白水凝胶拥有优异的生物相容性及生物降解性,被广泛应用于组织工程领域中.目前已经成功制备了可注射牛血清白蛋白水凝胶,但其力学性能仍有待提高.本文利用一种简单的方法提高了该可注射白蛋白水凝胶的力学性能.以尿素为变性剂,谷胱甘肽为还原剂制备由氢键及二硫键协同作用的白蛋白凝胶网络,并在牛血清白蛋白完全解旋后在体系中物...     

可注射温敏性聚合物的研究进展

可注射温敏性聚合物广泛用于药物释放载体及组织工程支架,本文综述了一些可溶胶一凝胶转变的温敏性聚合物的最新研究进展,包括天然及改性的天然高分子、异丙基丙烯酰胺共聚物和聚乙二醇,聚(D,L乳酸-co-乙醇酸)共聚物等体系,并简要介绍了它们在医学领域的应用。     

N-异丙基甲基丙烯酰胺共聚热缩温敏水凝胶

从甲基丙烯腈与异丙醇反应制备了N-异丙基甲基丙烯酰胺(NIPM),研究了其以N,N′-亚甲基双丙烯酰胺(MBA)为交联剂在不同溶剂体系的聚合及所形成的水凝胶的性质。表明NIPM-MBA凝胶具有热缩温敏性。在NIPM-MBA体系引入丙烯酸钠、甲基丙烯酸钠等负离子单体时,凝胶的溶胀比明显增加,MBA所占比例较少的体系,具有热缩、热胀双重性。     

Injectable in situ Physically and Chemically Crosslinkable Gellan Hydrogel

An injectable, in situ physically and chemically crosslinkable gellan hydrogel is synthesized via gellan thiolation. The thiolation does not alter the gellan's unique 3‐D conformation, but leads to a lower phase transition temperature under physiological conditions and stable chemical crosslinking. The synthesis and hydrogels are characterized by ¹H NMR, FT‐IR, CD, or rheology measurements. The injectability and the tissue culture cell viability is also tested. The thiolated gellan hydrogel exhibits merits, such as ease for injection, quick gelation, lower gelling temperature, stable structure, and nontoxicity, which make it promising in biomedicine and bioengineering as an injectable hydrogel.

     

负载顺铂的泊洛沙姆温敏凝胶用于小鼠宫颈癌的局部化疗

为了探讨载有顺铂的温敏凝胶对小鼠宫颈癌的局部化疗作用,制备了载有顺铂的泊洛沙姆温敏凝胶,并通过流变学、体外溶蚀、体外释放等技术手段表征其结构和性能,采用鼠源宫颈癌U14细胞制备了原位宫颈/阴道癌模型,将载药凝胶灌注入荷瘤鼠阴道,评价载药凝胶对小鼠宫颈/阴道癌的抑制作用。结果表明,载有顺铂的泊洛沙姆温敏凝胶经阴道给药后对小鼠宫颈/阴道癌的抑瘤率可达到63.1%,可有效抑制小鼠宫颈癌的生长,而系统安全性则远远高于静脉注射顺铂。因此,载有顺铂的温敏凝胶有可能成为一种新型的宫颈癌治疗剂型。     

An Injectable and Antifouling Supramolecular Polymer Hydrogel with Microenvironment-Regulatory Function to Prevent Peritendinous Adhesion and Promote Tendon Repair

The imbalance of extrinsic and intrinsic healing of tendon is thought to be the main cause of peritendinous adhesions. In this work, an injectable supramolecular poly(N-(2-hydroxypropyl) acrylamide) (PHPAm) hydrogel is prepared merely via side chain hydrogen-bonding crosslinks. This PHPAm exhibits good antifouling and self-healing properties. The supramolecular hydrogel simultaneously loaded with Prussian blue (PB) nanoparticles and platelet lysate (PL) is explored as a functional physical barrier, which can significantly resist the adhesion of fibrin and fibroblasts, attenuate the local inflammatory response, and enhance the tenocytes activity, thus balancing extrinsic and intrinsic healing. The PHPAm hydrogel is shown to prevent peritendinous adhesions considerably by inhibiting NF-κB inflammatory pathway and TGF-β1/Smad3-mediated fibrosis pathway, thereby significantly improving tendon repair by releasing bioactive factors to regulate the tenocytes behavior. This work provides a new strategy for developing physical barriers to prevent peritendinous adhesions and promote tissue repair effectively.     

Use of 5‐Fluorouracil Loaded Micelles and Cisplatin in Thermosensitive Chitosan Hydrogel as an Efficient Therapy against Colorectal Peritoneal Carcinomatosis

Colorectal peritoneal carcinomatosis (CRPC) is a common systemic metastasis of intra‐abdominal cancers. Intraperitoneal chemotherapy against CRPC is at present the preferred treatment. The aim of this study is to develop a novel hydrogel drug delivery system through the combination of 5‐fluorouracil (5‐FU) loaded polymeric micelles and cisplatin (DDP) in biodegradable thermosensitive chitosan (CS) hydrogel. The prepared CS hydrogel drug is a free‐flowing solution at room temperature and forms a stationary gel at body temperature. Therefore, a CRPC mouse model is established to investigate the antitumor activity of CS hydrogel drug system. The results suggest that intraperitoneal administration of CS hydrogel drug can inhibit tumor growth and metastasis, and prolong survival time compared with other groups, thus improving the chemotherapeutic effect. Ki‐67 immunohistochemical analysis reveals that tumors in the CS hydrogel drug group has lower cell proliferation in contrast to other groups (P < 0.001). Furthermore, hematoxylin‐eosin staining of liver and lung tissue indicates that the CS hydrogel drug has also a certain inhibitory effect on colorectal cancer metastasis to the liver and lung. Hence, the work highlights the potential clinical applications of the CS hydrogel drug.

     

Development and In Vivo Assessment of an Injectable Cross-Linked Cartilage Acellular Matrix-PEG Hydrogel Scaffold Derived from Porcine Cartilage for Tissue Engineering

The cartilage acellular matrix (CAM) derived from porcine cartilage, which does not induce significant inflammation and provides an environment conducive for cell growth and differentiation, is a promising biomaterial candidate for scaffold fabrication. However, the CAM has a short period in vivo, and the in vivo maintenance is not controlled. Therefore, this study is aimed at developing an injectable hydrogel scaffold using a CAM. The CAM is cross-linked with a biocompatible polyethylene glycol (PEG) cross-linker to replace typically used glutaraldehyde (GA) cross-linker. The cross-linking degree of cross-linked CAM by PEG cross-linker (Cx-CAM-PEG) according to the ratios of the CAM and PEG cross-linker is confirmed by contact angle and heat capacities measured by differential scanning calorimetry. The injectable Cx-CAM-PEG suspension exhibits controllable rheological properties and injectability. Additionally, injectable Cx-CAM-PEG suspensions with no free aldehyde group are formed in the in vivo hydrogel scaffold almost simultaneously with injection. In vivo maintenance of Cx-CAM-PEG is realized by the cross-linking ratio. The in vivo formed Cx-CAM-PEG hydrogel scaffold exhibits certain host–cell infiltration and negligible inflammation within and near the transplanted Cx-CAM-PEG hydrogel scaffold. These results suggest that injectable Cx-CAM-PEG suspensions, which are safe and biocompatible in vivo, represent potential candidates for (pre-)clinical scaffolds.     

EuF3-NaYF4纳米晶/PNIPAm三元复合凝胶的荧光温敏行为与影响机制

分别采用水热法制备EuF3与NaYF4纳米晶, 与N-异丙基丙烯酰胺（NIPAm）混合后进行自由基聚合, 一步法合成EuF3-NaYF4纳米晶/聚N-异丙基丙烯酰胺（PNIPAm）三元复合凝胶。 对纳米晶与复合凝胶的结构与荧光性能进行了表征。 重点研究了三元复合凝胶的荧光温敏行为, 并对其影响机制进行了探讨。 结果表明, EuF3与NaYF4纳米晶在PNIPAm凝胶基体中的体相掺杂, 同样产生了明显的能量传递。 两种纳米晶相对含量的变化, 对复合凝胶的荧光温敏性能有重要影响。     

Current Intelligent Injectable Hydrogels for In Situ Articular Cartilage Regeneration

Abstract

A high number of sport injuries result in damage to articular cartilage, a tissue type with poor self-healing capacity. Articular cartilage tissue is a sophisticated hydrogel, which contains 80% water and possesses strong mechanical properties. For this reason, synthetic hydrogels are thought to be an optimal material for cartilage regeneration. In the last decade, more than 2,000 research papers pertaining to “hydrogel and cartilage” have been published. Due to its biomimetic properties and user-friendly nature, especially in the field of minimal invasive surgery, intelligent injectable hydrogel have gradually become a focal point in cartilage research in recent years. In this review, we systematically summarize current “state-of-the-art” manufacture technologies of injectable hydrogels including ion-induced, thermo-induced, non-induced chemical, and light-induced crosslinking. We also review current strategies for designing intelligent injectable hydrogels, such as component-based, mechanical property-based and structure-based intelligent design to simulate the natural articular cartilage. Lastly, the applications of intelligent injectable hydrogels for cartilage regeneration are presented, and their outlooks for future clinical translation is dicussed.     

Injectable Enzyme‐Based Hydrogel Matrix with Precisely Oxidative Stress Defense for Promoting Dermal Repair of Burn Wound

Burn wound healing remains a challenging health problem worldwide due to the lack of efficient and precise therapy. Inherent oxidative stress following burn injury is importantly responsible for prolonged inflammation, fibrotic scar, and multiple organ failure. Herein, a bioinspired antioxidative defense system coupling with in situ forming hydrogel, namely, multiresponsive injectable catechol‐Fe³⁺ coordination hydrogel (MICH) matrix, is engineered to promote burn‐wound dermal repair by inhibiting tissue oxidative stress. This MICH matrix serves as the special traits of “Fe‐superoxide dismutases,” small molecular antioxidant (vitamin E), and extracellular matrix (ECM) in alleviating cellular oxidative damage, which demonstrates precise scavenging on reactive oxygen species (ROS) of different cellular locations, blocking lipid peroxidation and cell apoptosis. In in vivo burn‐wound treatment, this MICH promptly integrates with injured surrounding tissue to provide hydration microenvironment and physicochemical ECM for burn wounds. Importantly, the MICH matrix suppresses tissue ROS production, reducing the inflammatory response, prompting re‐epithelization and neoangiogenesis during wound healing. Meanwhile, the remodeling skin treated with MICH matrix demonstrates low collagen deposition and normal dermal collagen architecture. Overall, the MICH prevents burn wound progression and enhances skin regeneration, which might be a promising biomaterial for burn‐wound care and other disease therapy induced by oxidative stress.     

阳离子型温敏水凝胶的溶胀性能及其对表面活性剂的吸附行为

阳离子单体;温敏凝胶;阳离子型温敏水凝胶的溶胀性能及其对表面活性剂的吸附行为