抗菌水凝胶在生物医学领域的研究进展

细菌感染是阻碍伤口愈合的重要因素之一,同时也是生物医学领域面临的一个重要问题。目前的抗菌水凝胶有着高抗菌活性、生物相容性以及可注射性等性能,并且其物理化学性质与生物组织相似,使得越来越多新型的抗菌水凝胶材料被用于治疗细菌感染。综述了近几年抗菌水凝胶的研究进展,归纳总结了几种不同类型的抗菌水凝胶的制备方法,抗菌活性和生物相容性等。重点阐述了抗菌水凝胶在伤口敷料、药物负载和传递以及组织工程等生物医学领域中的应用前景。     

组织工程用水凝胶制备方法研究进展

高分子水凝胶作为-类重要的生物材料被广泛应用于生物医药和组织工程领域.本文综述了基于化学交联和物理交联的有关组织工程用水凝胶的设计方法,重点介绍了通过自由基共聚、结构互补基团间的化学反应、高能辐射和酶交联的化学交联型水凝胶以及通过离子间的相互作用,结晶作用、氢键及疏水性相互作用形成的物理交联型水凝胶的研究进展,对比了各种交联机制的优缺点,并对水凝胶在组织工程领域中的进-步应用进行了展望.     

N-琥珀酰壳聚糖/氧化硫酸软骨素水凝胶的制备

采用N-琥珀酰壳聚糖(NCS)与氧化硫酸软骨素(OCS)进行复合,制备NCS/OCS复合水凝胶.考察了OCS与NCS不同质量比对复合水凝胶的凝胶化时间、压缩强度、平衡溶胀以及体外降解等物理化学性能的影响.结果表明:当m(NCS):m(OCS)为7:3时复合水凝胶能满足临床要求,此时复合水凝胶在37 ℃条件下的凝胶时间约为16 min,压缩强度为(5.82±0.5) kPa,30d后,复合水凝胶的剩余质量分数约为40％.通过氧化硫酸软骨素与N-琥珀酰壳聚糖进行复合,可注射水凝胶的凝胶强度和降解性能得到明显改善,该材料有望在软骨组织工程支架方面得到应用.     

可注射用合成水凝胶在手术患者伤口的应用与护理探讨

为探究可注射水凝胶在肝移植手术患者创面应用的效果,采用随机分配的原则将患者分为A、B、C组,A组注射可注射水凝胶,B组注射0.9%氯化钠注射液,C组注射纤维蛋白胶,观察患者的出血量和出血时间、7 d后的血常规、体质量及凝血等指标。结果表明,采用的可注射水凝胶组的平均出血时间是(34.8±1.30) s,显著缩短(P<0.01);术后7 d的血常规、体质量及凝血等指标基本一致,只有在PLT、HCT二项指标上的差异显著,其中可注射水凝胶组的PLT水平最高;在腹腔内粘连程度方面,各组间无统计学意义(P>0.05)。采用可注射水凝胶的止血效果大致等同于纤维蛋白胶,但出血时间和出血量优势明显。     

SA-Zn水凝胶的性能特点及应用

水凝胶可以用于组织工程的支架、药物输送的载体,光学和流体学的致动器,以及用于生物学研究的细胞外基质模型.其中,可伸缩离子导电水凝胶由于其特性,在运动监测仪器中广泛运用.本文主要综述了一种超拉伸可回收离子导电水凝胶SA-Zn的结构与特性和SA-Zn水凝胶的机械性能以及作为传感器在人体运动检测的应用.     

生物医用高强度水凝胶的研究进展

水凝胶是一种高含水量的三维网状聚合物,广泛应用于各个领域,但力学性能较差的特点限制了其在生物医用领域的应用。因此,如何提高水凝胶的力学强度成为国内外专家学者研究的重点。本文主要介绍了几种新型高强度水凝胶的合成及研究进展,包括滑动水凝胶、双网络水凝胶、复合水凝胶以及其它水凝胶,详细分析了影响这些水凝胶力学性能的因素。指出研制具有生物相容性、可生物降解、可注射、可负载活性因子并且具备良好的力学性能水凝胶是今后的研究方向。     

壳聚糖温敏水凝胶研究进展

温敏性水凝胶是一种智能型高分子水凝胶,能在应答外界温度刺激时发生自身相变,具有良好的生物相容性与力学性能,被广泛应用于组织工程、细胞包封、药物传递等方面。壳聚糖是一种在自然界中大量存在的多糖,因具有低细胞毒性与生物相容性,常作为药物缓释体被广泛应用。重点对近几年壳聚糖温敏水凝胶的相关研究进行综述。     

双网络水凝胶的研究进展

双网络水凝胶在保持高吸水性等性能的基础上改善了传统水凝胶机械性能差、不稳定等缺点。重点介绍了双网络水凝胶及其在组织工程、伤口敷料、离子吸附、农林业等方面的应用。当在组织工程、导电和伤口敷料等医学领域应用时,水凝胶的生物相容性及力学性能成为研究重点;当应用在林业和吸附染料、离子方面时,水凝胶的溶胀性能较为重要。     

蛋白基水凝胶及其应用

近年来,蛋白基水凝胶因具有来源丰富、可生物降解和良好的生物相容性等优点受到人们的关注.在阐述蛋白基水凝胶交联机理的基础上,介绍了波谱、热分析和显微镜等方法在蛋白质凝胶结构研究方面的应用,并综述了国内外蛋白质凝胶在吸水凝胶、智能凝胶及组织工程方面的应用,指出了蛋白基水凝胶研究中存在的问题及发展方向.     

医用水凝胶的制备和应用研究进展

综述了均聚物水凝胶、共聚物水凝胶、半互穿网络结构水凝胶、互穿网络结构水凝胶等4种医用水凝胶制备方法的研究进展,对医用水凝胶在医学领域中的应用研究状况,例如作为伤口修复功能材料、药物缓释载体、组织工程支架、口腔应用材料等进行了介绍,为开发新型医用水凝胶类产品和转化应用提供参考。水凝胶在医学领域具有广阔的应用前景,对新型医用水凝胶的发展进行了展望,针对目前医用水凝胶存在的不足,提出了未来可进一步研究的方向。     

Application of minimally invasive injectable conductive hydrogels as stimulating scaffolds for myocardial tissue engineering

So far, several methods for myocardial tissue engineering have been developed to regenerate myocardium and even create contractile heart muscles. Among these approaches, hydrogel based methods have attracted much attention due to their ability to mimic the architecture of native extracellular matrix. Injectable hydrogels are a specific class of hydrogels which can be formed in situ by physical and/or chemical crosslinking. Generally, using these hydrogels is more advantageous because they are minimally (less) invasive in comparison with open surgery. Moreover, with respect to the fact that ‘myocardium is a conductive tissue’, utilization of conductive polymers for myocardial tissue engineering has demonstrated promising results. Both the injectable hydrogels and conductive polymers have some merits and demerits, but studies show that using a combination of them has prominently enhanced regeneration of the myocardium. In this review, the focus is on injectable hydrogels, conductive polymers and injectable conductive hydrogels for myocardial tissue engineering. © 2018 Society of Chemical Industry     

Tunable Engineering of Heparinized Injectable Hydrogels for Affinity‐Based Sustained Delivery of Bioactive Factors

Here, the design of an in situ‐forming injectable hydrogel is reported based on pH‐ and temperature‐responsive copolymers finely engineered with heparin for the sustained delivery of bioactive factors. In order to develop such heparinized injectable hydrogels, pH‐ and temperature‐responsive copolymers based on poly(ethylene glycol) and poly(urethane sulfamethazine) (PEG‐PUSSM) are synthesized and acrylated, and subsequently coupled with thiolated heparin through Michael‐addition reaction. The content of heparin in the bioconjugates (Hep‐PUSSM) is finely tuned to control the release of heparin‐binding bioactive factors. The free‐flowing bioconjugate sols at room temperature transform to stable viscoelastic gel in physiological conditions, indicating that heparin modification does not affect the sol–gel transition. The subcutaneous administration of bioconjugate sols to the dorsal‐region of Sprague‐Dawley rats forms a hydrogel depot and shows controlled degradation. The bioconjugates effectively bind with bioactive factors (VEGF) through simple mixing, and the release is controlled over a period of 4 weeks without an initial burst. As a result, the implantation of VEGF‐loaded bioconjugate gel induces angiogenesis throughout the hydrogel network. The tunable engineering of the injectable hydrogel by heparinization with independent controllable physical properties sustains the release of bioactive factors, indicating that it may be a promising platform for the delivery of bioactive factors.     

Biodegradable polymers exhibiting temperature-responsive sol–gel transition as injectable biomedical materials

Injectable biodegradable copolymer hydrogels, which exhibit temperature-responsive sol-to-gel transition, have recently drawn much attention as promising biomedical materials such as drug delivery, cell implantation, and tissue engineering. These injectable hydrogels can be implanted in the human body with minimal surgical invasion. Temperature-responsive gelling copolymers usually possess block- and/or branched architectures and amphiphilicity with a delicate hydrophobic/hydrophilic balance. Poly(ethylene glycol) (PEG) has typically been used as hydrophilic segments due to its biocompatibility and temperature-dependent dehydration nature. Aliphatic polyesters such as polylactide, poly(lactide-co-glycolide), poly(ε-caprolactone), and their modified copolymers have been used as hydrophobic segments based on their biodegradability and biocompatibility. Copolymers of PEG with other hydrophobic polymers such as polypeptides, polydepsipeptides have also been recently reported as injectable hydrogels. In this review, brief history and recent advances in injectable biodegradable polymer hydrogels are summarized especially focusing on the relationship between polymer architecture and their gelation properties. Moreover, the applications of these injectable polymer gels for biomedical use such as drug delivery and tissue engineering are also described.     

Thermosensitive PCL‐PEG‐PCL hydrogels: Synthesis,characterization, and delivery of proteins

In this work, a biodegradable and injectable in situ gel‐forming controlled drug delivery system based on thermosensitive poly(ε‐caprolactone)‐poly(ethylene glycol)‐poly(ε‐caprolactone) (PCL‐PEG‐PCL) hydrogels was studied. A series of PCL‐PEG‐PCL triblock copolymers were synthesized and characterized by ¹H‐NMR and gel permeation chromatography (GPC). Thermosensitivity of the PCL‐PEG‐PCL triblock copolymers was tested using the tube inversion method. The in vitro release behaviors of two model proteins, including bovine serum albumin (BSA) and horseradish peroxidase (HRP), from PCL‐PEG‐PCL hydrogels were studied in detail. The in vivo gel formation and degradation of the PCL‐PEG‐PCL triblock copolymers were also investigated in this study. The results showed that aqueous solutions of the synthesized PCL‐PEG‐PCL copolymers can form in situ gel rapidly after injection under physiological conditions. The PCL‐PEG‐PCL hydrogels showed the ability to control the release of incorporated BSA and HRP. The released HRP was confirmed to conserve its biological activity by specific enzymatic activity assay. The in vivo gel formation and degradation studies indicated that PCL‐PEG‐PCL copolymers hydrogels can sustain at least 45 days by subcutaneous injection. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PCL‐PEG‐PCL copolymers hydrogels show promise as an in situ gel‐forming controlled drug delivery system for therapeutic proteins. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Thermo-sensitive hydrogels formed from the photocrosslinkable polypseudorotaxanes consisting of <Emphasis Type="Italic">β</Emphasis>-cyclodextrin and Pluronic F68/PCL macromer

To create thermo-sensitive supramolecular hydrogels with high mechanical strength, viscous gel precursors were first formed via block-selected inclusion complexation between β-cyclodextrin (β-CD) and Pluronic F68/poly(ε-caprolactone) block copolymer terminated with acryloyl groups in aqueous media, and subsequently in situ photocrosslinking was employed in the presence of a photoinitiator. The supramolecular assembly in photocrosslinked hydrogels was revealed by wide-angle X-ray diffraction (WXRD) and thermogravimetric analysis (TGA). The rheological studies demonstrated that in situ photocrosslinking could greatly improve the mechanical strength of the gellike precursors. The swelling measurements showed that as-obtained hydrogel displayed a thermo-responsive property. The temperature dependence of the hydrogels decreased with the increase of the β-CD amounts introduced. The resultant hydrogels have the potential to use as carriers for drug delivery and tissue engineering scaffolds.     

Tyrosinase‐mediated in situ forming hydrogels from biodegradable chondroitin sulfate–tyramine conjugates

Tyrosinase‐mediated crosslinking of chondroitin sulfate–tyramine (CS‐TA) conjugates was successfully applied in the preparation of biodegradable in situ forming hydrogels under physiological conditions. Depending on the polymer concentration, the degree of substitution of TA residue and the tyrosinase concentration, the gelation times ranged from 2.3 to 129 min. Studies on the gel contents of CS‐TA hydrogels showed that their degrees of crosslinking could be controlled by varying the tyrosinase concentrations. CS‐TA hydrogels could be completely degraded by the chondroitinase ABC within a time range from 6 days to 11 weeks. CS‐TA hydrogels possessed highly elastic properties and their storage moduli varied from 120 to 1300 Pa, as determined by rheological analysis. Scanning electron microscopy observation confirmed that CS‐TA hydrogels contained a well‐interconnected pore structure. A live–dead assay demonstrated that NIH 3T3 fibroblasts incorporated in CS‐TA hydrogels retained their viability. In addition, in vitro release of methylene blue (a photodynamic therapy drug) from CS‐TA hydrogels could be effectively sustained by the drug encapsulation in the hydrogels. This study indicates that tyrosinase‐mediated in situ forming CS‐TA hydrogels are promising for biomedical applications including drug release and tissue engineering. © 2012 Society of Chemical Industry     

In situ-forming injectable hydrogels for regenerative medicine

Regenerative medicine involves interdisciplinary biomimetic approaches for cell therapy and tissue regeneration, employing the triad of cells, signals, and/or scaffolds. Remarkably, the field of therapeutic cells has evolved from the use of embryonic and adult stem cells to the use of induced pluripotent stem cells. For application of these cells in regenerative medicine, cell fate needs to be carefully controlled via external signals, such as the physical properties of an artificial extracellular matrix (ECM) and biologically active molecules in the form of small molecules, peptides, and proteins. It is therefore crucial to develop biomimetic scaffolds, reflecting the nanoenvironment of three-dimensional (3D) ECM in the body. Here, we describe in situ-forming injectable hydrogel systems, prepared using a variety of chemical crosslinkers and/or physical interactions, for application in regenerative medicine. Selective and fast chemical reactions under physiological conditions are prerequisites for in situ formation of injectable hydrogels. These hydrogels are attractive for regenerative medicine because of their ease of administration, facile encapsulation of cells and biomolecules without severe toxic effects, minimally invasive treatment, and possibly enhanced patient compliance. Recently, the Michael addition reaction between thiol and vinyl groups, the click reaction between bis(yne) molecules and multiarm azides, and the Schiff base reaction have been investigated for generation of injectable hydrogels, due to the high selectivity and biocompatibility of these reactions. Noncovalent physical interactions have also been proposed as crosslinking mechanisms for in situ forming injectable hydrogels. Hydrophobic interactions, ionic interactions, stereocomplex formation, complementary pair formation, and host–guest interactions drive the formation of 3D polymeric networks. In particular, supramolecular hydrogels have been developed using the host–guest chemistry of cyclodextrin (CD) and cucurbituril (CB), which allows highly selective, simple, and biocompatible crosslinking. Molecular recognition and complex formation of supramolecules, without the need for additional additives, have been successfully applied to the 3D network formation of polymer chains. Finally, we review the current state of the art of injectable hydrogel systems for application in regenerative medicine, including cell therapy and tissue regeneration.     

Injectable Human Hair Keratin–Fibrinogen Hydrogels for Engineering 3D Microenvironments to Accelerate Oral Tissue Regeneration

Traumatic injury of the oral cavity is atypical and often accompanied by uncontrolled bleeding and inflammation. Injectable hydrogels have been considered to be promising candidates for the treatment of oral injuries because of their simple formulation, minimally invasive application technique, and site-specific delivery. Fibrinogen-based hydrogels have been widely explored as effective materials for wound healing in tissue engineering due to their uniqueness. Recently, an injectable foam has taken the spotlight. However, the fibrin component of this biomaterial is relatively stiff. To address these challenges, we created keratin-conjugated fibrinogen (KRT-FIB). This study aimed to develop a novel keratin biomaterial and assess cell–biomaterial interactions. Consequently, a novel injectable KRT-FIB hydrogel was optimized through rheological measurements, and its injection performance, swelling behavior, and surface morphology were investigated. We observed an excellent cell viability, proliferation, and migration/cell–cell interaction, indicating that the novel KRT-FIB-injectable hydrogel is a promising platform for oral tissue regeneration with a high clinical applicability.     

Strategy for Preparing Mechanically Strong Hyaluronic Acid–Silica Nanohybrid Hydrogels via In Situ Sol–Gel Process

A hybridization method to prepare a hyaluronic acid (HA)‐based nanohybrid hydrogel is proposed that introduces an additional inorganic silica network via an in situ sol–gel process. HA hydrogels have been extensively studied because of their excellent biocompatibility and biological functions; however, their poor mechanical strength hinders their use in tissue engineering applications. In the present work, the sol–gel technique is employed to achieve the formation of a structurally organized silica network in the HA hydrogel matrix rather than mixing of discrete particles with the HA polymer matrix. Importantly, the silica densification process results in significant enhancement of the mechanical properties. In addition, the nanohybrid hydrogels exhibit great degradation resistance and bioactivity on both fibroblast and pre‐osteoblast cells. Moreover, the physical characteristics and biological properties can be modulated by varying the silica content; these materials thus show great potential for a wide range of applications for soft and hard tissues.