Surface Chemical Modification of Cellulose Nanocrystals and Its Application in Biomaterials

Cellulose nanocrystals(CNCs) have been widely applied in biomaterials and show great biocompatibility and mechanical strength. In this review, the chemical reactions applied in CNC surface modification and their application in CNC based biomaterials are introduced. Furthermore, the conjugation of different functional molecules and nanostructures to the surface of CNCs are discussed, with focus on the binding modes, reaction conditions, and reaction mechanisms. With this introduction, we hope to provide a clear view of the strategies for surface modification of CNCs and their application in biomaterials, thus providing an overall picture of promising CNC-based biomaterials and their production.

Surface patterning and modification of polyurethane biomaterials using silsesquioxane-gelatin additives for improved endothelial affinity

Polyurethanes(PUs) are well-known for their biocompatibility but their intrinsic inert property hampers cell-matrix interactions. Surface modifications are thus necessary to widen their use for biomedical applications. In this work, surface modifications of PU were achieved first by incorporating polyhedral oligomeric silsesquioxane(POSS), followed by alteration of the surface topography via the breath figures method. Subsequently, surface chemistry was also modified by immobilization of gelatin molecules through grafting, for the enhancement of the surface cytocompatibility. Scanning electron microscopy(SEM) was used to verify the formation of highly ordered microstructures while static contact angle, FTIR and XPS confirmed the successful grafting of gelatin molecules onto the surfaces. In vitro culture of human umbilical vein endothelial cells(HUVECs) revealed that endothelial cell adhesion and proliferation were significantly enhanced on the gelatin-modified surfaces, as shown by live/dead staining and WST-1 proliferation assay. The results indicated that the combination of the strategies yielded an interface that improves cell attachment and subsequent growth. This enhancement is important for the development of higher quality biomedical implants such as vascular grafts.

Surface modification of biomaterials by photochemical immobilization and photograft polymerization to improve hemocompatibility

Thrombus formation and blood coagulation are serious problems associated with blood contacting products,such as catheters,vascular grafts,artificial hearts,and heart valves.Recent progresses and strategies to improve the hemocompatibility of biomaterials by surface modification using photochemical immobilization and photograft polymerization are reviewed in this paper.Three approaches to modify biomaterial surfaces for improving the hemocompatibility,i.e.,bioinert surfaces,immobilization of anticoagulative substances and biomimetic surfaces,are introduced.The biomimetic amphiphilic phosphorylcholine and Arg-Gly-Asp(RGD)sequence are the most effective and most often employed biomolecules and peptide sequence for improving hemocompatibility of material surfaces.The RGD sequence can enhance adhesion and growth of endothelial cells(ECs)on material surfaces and increase the retention of ECs under flow shear stress conditions.This surface modification is a promising strategy for biomaterials especially for cardiovascular grafts and functional tissue engineered blood vessels.

Surface Modification of Hydroxyapatite by Using γ-aminopropyl Silane

Surface modification of hydroxyapatite(HA)powder was performedwith r-aminopropyl silane in toluent solvent. The modificationeffects were characterized by using XPS and FT-IR methods. Theresults indi- cated that the P2p electron binding energy of themodified HA decrease 0.4 eV compared to that of HA. Further- more, anew peak, 998 cm^-1 absorption appeared in IR differential spectra ofmodified HA and HA, which is due to a stretching vibration ofstructure P-O-Si, meaning that a direct covalent bonding betweenhydroxyl group on HA surface and the organic silane molecule wasrealized after modification, and the chemical bonding type was P-O-Si.

Surface Modification of NiTi Alloy via Cathodic Plasma Electrolytic Deposition and its Effect on Ni Ion Release and Osteoblast Behaviors

To reduce Ni ion release and improve biocompatibility of NiTi alloy, the cathodic plasma electrolytic deposition （CPED） technique was used to fabricate ceramic coating onto a NiTi alloy surface. The formation of a coating with a rough and micro-textured surface was confirmed by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy, re- spectively. An inductively coupled plasma mass spectrometry test showed that the formed coating significantly reduced the release of Ni ions from the NiTi alloy in simulated body fluid. The in- fluence of CPED treated NiTi substrates on the biological behaviors of osteoblasts, including cell adhesion, cell viability, and osteogenic differentiation function （alkaline phosphatase）, was inves- tigated in vitro. Immunofluorescence staining of nuclei revealed that the CPED treated NiTi alloy was favorable for cell growth. Osteoblasts on CPED modified NiTi alloy showed greater cell viability than those for the native NiTi substrate after 4 and 7 days cultures. More importantly, osteoblasts cultured onto a modified NiTi sample displayed significantly higher differentiation lev-els of alkaline phosphatase. The results suggested that surface functionalization of NiTi alloy with ceramic coating via the CPED technique was beneficial for cell proliferation and differentiation. The approach presented here is useful for NiTi implants to enhance bone osseointegration and reduce Ni ion release in vitro.

Chemical Modification of Nanocellulose in Wood Adhesive: Review

Bio-based nanomaterial is more attractive, due to its abundance, eco-friendliness and sustainability, when compared to the non-renewable toxic petrochemicals used in the wood adhesive sector. Recent studies on the formaldehyde emission by petrochemical binders in wood adhesives have attracted scientists for the research in biomaterial-based binders. In this aspect nanocellulose (NC) is one such material which has reinforcing ability and has natural binding properties. Conventional wood adhesive uses petrochemical-based binders and additives. Inclusion of nanocellulose in wood adhesive could drastically reduce the dependency on non-renewable petroleum sources. Even though wood adhesive uses NC for improving mechanical properties of the adhesive, usage is restricted because of its inability to enhance tackiness and adhesion compared with petrochemicals. Availability of free hydroxyl groups and feasibility for modification can be a potential way for functionalization of this nanomaterial. To improve adhesion properties and to make nanocellulose act as a functional filler, the crosslinking approach can be a possible solution. Enhancement of thermal properties with improved thermal degradation, water barrier properties of crosslinked films and enhanced mechanical properties especially in crosslinked poly (vinyl alcohol) (PVA) matrix, which is one of the binders for wood adhesive discussed in this review paper proves the potential applicability of crosslinked NC. Hence by inclusion of NC in wood adhesive and crosslinking with the binder, both mechanical and performance properties are expected to enhance which will create a new world and possibilities for the bio-based eco-friendly wood adhesives. In this review paper, we have reviewed the crosslinking of nanocellulose to enhance the performance of wood adhesives.

Composite Biomaterials Based on Poly(L-Lactic Acid)and Functionalized Cellulose Nanocrystals

The biocomposite films were prepared from poly(L-lactic acid)and cellulose nanocrystals.To improve interfacial compatibility of hydrophilic cellulose nanocrystals with hydrophobic matrix polymer as well as to provide the osteoconductive properties,cellulose was functionalized with poly(glutamic acid).The modified cellulose nanocrystals were better distributed and less aggregated within the matrix,which was testified by scanning electron,optical and polarized light microscopy.According to mechanical tests,composites filled with nanocrystals modified with PGlu demonstrated higher values of Young’s modulus,elongation at break and tensile strength.Incubation of composite materials in model buffer solutions for 30 weeks followed with staining of Ca^(2+)deposits with Alizarin Red S assay testified better mineralization of materials containing PGlu-modified cellulose nanocrystals as filler.As the result of in vivo experiment,the developed composite materials showed less level of inflammation in comparison with pure polymer matrix and composites filled with non-functionalized cellulose nanocrystals.

Engineering multifunctional bioactive citrate-based biomaterials for tissue engineering

Developing bioactive biomaterials with highly controlled functions is crucial to enhancing their applications in regenerative medicine.Citrate-based polymers are the few bioactive polymer biomaterials used in biomedicine because of their facile synthesis,controllable structure,biocompatibility,biomimetic viscoelastic mechanical behavior,and functional groups available for modification.In recent years,various multifunctional designs and biomedical applications,including cardiovascular,orthopedic,muscle tissue,skin tissue,nerve and spinal cord,bioimaging,and drug or gene delivery based on citrate-based polymers,have been extensively studied,and many of them have good clinical application potential.In this review,we summarize recent progress in the multifunctional design and biomedical applications of citrate-based polymers.We also discuss the further development of multifunctional citrate-based polymers with tailored properties to meet the requirements of various biomedical applications.

Chemical Modification of Silk Proteins: Current Status and Future Prospects

Silk extracted from the cocoon of silkworm has been used as textile materials for thousands of years.Recently,silk has been redefined as a protein-based biomaterial with great potential in biomedical applications owing to its excellent mechanical properties,biocompatibility,and biodegradability.With the advances in silk processing technologies,a broad range of intriguing silk-based functional biomaterials have been made and applied for various biomedical uses.However,most of these materials are based on natural silk proteins without chemical modification,leading to limited control of properties and functions(e.g.,biodegradability and bioactivity).A chemical toolbox for modifying the silk proteins is required to achieve versatile silk-based materials with precisely designed properties or functions for different applications.Furthermore,inspired by the traditional fine chemical industry based on synthetic chemistry,developing silk-based fine chemicals with special functions can significantly extend the applications of silk materials,particularly in biomedical fields.This review summarizes the recent progress on chemical modification of silk proteins,focusing on the methodologies and applications.We also discuss the challenges and opportunities of these chemically modified silk proteins.

Proteomics as a tool to gain next level insights into photo-crosslinkable biopolymer modifications

The distribution of photo-crosslinkable moieties onto a protein backbone can affect a biomaterial’s crosslinking behavior, and therefore also its mechanical and biological properties. A profound insight in this respect is essential for biomaterials exploited in tissue engineering and regenerative medicine. In the present work, photo-crosslinkable moieties have been introduced on the primary amine groups of: (i) a recombinant collagen peptide (RCPhC1) with a known amino acid (AA) sequence, and (ii) bovine skin collagen (COL BS) with an unknown AA sequence. The degree of substitution (DS) was quantified with two conventional techniques: an ortho-phthalic dialdehyde (OPA) assay and ^(1)H NMR spectroscopy. However, neither of both provides information on the exact type and location of the modified AAs. Therefore, for the first time, proteomic analysis was evaluated herein as a tool to identify functionalized AAs as well as the exact position of photo-crosslinkable moieties along the AA sequence, thereby enabling an in-depth, unprecedented characterization of functionalized photo-crosslinkable biopolymers. Moreover, our strategy enabled to visualize the spatial distribution of the modifications within the overall structure of the protein. Proteomics has proven to provide unprecedented insight in the distribution of photo-crosslinkable moieties along the protein backbone, undoubtedly contributing to superior functional biomaterial design to serve regenerative medicine.

Recent Advances on Surface-modified Biomaterials Promoting Selective Adhesion and Directional Migration of Cells

The surfaces and interfaces of biomaterials interact with the biological systems in multi-scale levels,and thereby influence the biological functions and comprehensive performance in vitro and in vivo.In particular,a surface promoting the selective adhesion and directional migration of desired types of cells in complex environment is extremely important in the repair and regeneration of tissues such as peripheral nerve and blood vessel,and long-term application of intracorporal devices such as intravascular implants.Therefore,surface modification of biomaterials is a facile and effective method to achieve the desired cell-biomaterials interactions.In this short review,recent advances on the surface modification of biomaterials to regulate selective cell adhesion and migration are briefly summarized.In particular,the surface properties of biomaterials are manipulated via the convenient introduction of amino groups to the ester-based polymers,the formation of polyelectrolyte multilayers,and the fabrication of topology and gradient cues,etc.,followed by the association of chemical and biological signals such as collagen,heparin,hyaluronic acid,peptides and cell growth factors.The selective adhesion and directional migration of various types of cells such as endothelial cells(ECs),smooth muscle cells(SMCs),hepatocytes and Schwann cells(SCs)are achieved over the competitive counterpart cells by the use of cell-resisting substances and cell-selective motifs on gradient substrates in most cases.Recent advances on cell behaviors in three-dimensional(3D)ceH-extracellular matrix(ECM)-mimicking substrates are also reviewed.

Osteoimmunomodulatory effects of biomaterial modification strategies on macrophage polarization and bone regeneration

Biomaterials as bone substitutes are always considered as foreign bodies that can trigger host immune responses.Traditional designing principles have been always aimed at minimizing the immune reactions by fabricating inert biomaterials.However,clinical evidence revealed that those methods still have limitations and many of which were only feasible in the laboratory.Currently,osteoimmunology,the very pioneering concept is drawing more and more attention-it does not simply regard the immune response as an obstacle during bone healing but emphasizes the intimate relationship of the immune and skeletal system,which includes diverse cells,cytokines,and signaling pathways.Properties of biomaterials like topography,wettability,surface charge,the release of cytokines,mediators,ions and other bioactive molecules can impose effects on immune responses to interfere with the skeletal system.Based on the bone formation mechanisms,the designing methods of the biomaterials change from immune evasive to immune reprogramming.Here,we discuss the osteoimmunomodulatory effects of the new modification strategies—adjusting properties of bone biomaterials to induce a favorable osteoimmune environment.Such strategies showed potential to benefit the development of bone materials and lay a solid foundation for the future clinical application.

电化学沉积时间对碱预处理钛合金表面HA涂层的影响

采用碱预处理钛合金表面再电化学沉积的方法,研究了电化学沉积时间对羟基磷灰石(HA)涂层物相、形貌、生物活性及其与钛合金基体间结合强度的影响。结果表明,碱预处理钛合金表面制备的电化学沉积涂层主要由片状HA相组成,电化学沉积时间对涂层物相组成没有影响,但会影响涂层厚度;沉积时间60 min时得到的HA涂层较致密,与基体的结合强度达17.85 MPa。各沉积时间下得到的HA涂层均具有较好的生物活性,在模拟体液(SBF)中,CO_(3)^(2-)置换HA中的PO_(4)^(3-)进入磷灰石中形成类骨磷灰石CHA,呈馒头状,直径7~8μm,且在SBF中浸泡3 d,CHA可铺满HA表面。

提高间充质干细胞治疗皮瓣缺血再灌注损伤的策略

背景:间充质干细胞在治疗皮瓣缺血再灌注损伤方面潜力巨大,然而其自身的缺陷及在治疗皮瓣缺血再灌注损伤中的作用下降等原因限制了其广泛应用。目的:综述提高间充质干细胞治疗皮瓣缺血再灌注损伤的策略,为其进一步理论研究和临床应用提供参考。方法:检索中国知网、万方和PubMed数据库收录的相关文献。中文检索词为“间充质干细胞,皮瓣缺血再灌注损伤,间充质基质细胞,干细胞,皮瓣,缺血再灌注损伤,预处理,基因修饰,生物材料封装,联合运用”。英文检索词为“mesenchymal stem cell,Ischemia-reperfusion injury of skin flap,Mesenchymal stromal cells,Stem cells,skin flap,Ischemia-reperfusion injury,Pretreatment,Gene modification,Biomaterial packaging,Joint application”。检索2007年以来发表的相关文献,通过阅读文章剔除研究内容与文章主题关系不大、质量较差及内容陈旧的文献,最终纳入75篇文献进行归纳总结。结果与结论:①间充质干细胞具有抑制炎症反应、抗氧化应激以及诱导血管新生等显著作用,在治疗皮瓣缺血再灌注损伤中蕴含着巨大潜力。②尽管间充质干细胞在治疗皮瓣缺血再灌注损伤中显示出了巨大潜力,但其在治疗上存在的缺陷限制了在临床上的广泛运用,通过预处理(细胞因子、低氧、药物及其他预处理间充质干细胞)、基因修饰间充质干细胞、生物材料封装间充质干细胞以及间充质干细胞和其他药物或治疗方法联合运用等,这些方法不仅可以克服间充质干细胞在治疗上的缺陷,还提高了其在皮瓣缺血再灌注损伤方面的治疗效果。③因此,在未来进一步提高间充质干细胞治疗皮瓣缺血再灌注损伤的效果,挖掘其治疗潜力,对于间充质干细胞的研究和皮瓣缺血再灌注损伤的治疗都具有非常重要的意义。

骨组织工程中促血管支架应用的可视化分析

背景:对于支架物理性质的研究始终是组织工程研究领域的热点,但对于促血管支架来说,除了要满足支架的基本性能外,还需要通过其他方法来促进血管在支架内的再生过程,以达到修复骨组织的最终目的。目的:对国内外发表的骨组织工程下促血管支架的文献进行可视化分析,探究该领域的研究热点及研究现状,为后续研究提供参考。方法:以中国知网及Web of Science核心集数据库为检索库,检索骨组织工程下促血管支架的相关文献,去除不符合纳入标准的文献,随后导入CiteSpace 6.1.R2软件,对研究领域的作者、国家机构及关键词进行可视化分析。结果与结论:①骨组织工程下促血管支架应用的研究中,发文量最多的前3个国家分别为中国、美国和德国。②中国知网数据库机构该领域研究发文量排名前3位分别为南方医科大学、华中科技大学、东华大学;Web of Science核心集数据库中机构发文量排名前3位分别为上海交通大学、四川大学、中国科学院。③中国知网数据库关键词频次排名前3位为“组织工程、血管化、血管生成”,Web of Science核心集数据库关键词频次排名前3位为“mesenchymal stem cell(间充质干细胞),scaffold(支架),vascularization(血管化)”。④参考文献共被引情况和高被引文献分析显示,该领域的血管化策略研究热点为支架设计、血管生成因子的输送、体外共培养和体内预血管化;技术方面研究热点为3D打印、静电纺丝、血管移植及血管融合;机制方面研究热点为免疫调节和巨噬细胞、药物/生长因子输送、内皮细胞和成骨细胞之间的关系、骨细胞和内皮细胞之间旁分泌关系及信号分子通路、血管生成和抗血管生成分子。⑤国内外骨组织工程下促血管支架应用研究均十分重视干细胞和3D打印技术的运用,而目前的研究热点主要为生物3D打印技术、支架改性修饰的方法以及基于骨修复机制智能生物材料的开发应用。

聚砜膜亲水力学性能提升改进及血液透析实际应用

针对传统血液透析膜通透效果及对毒素分子清除效果差的问题。试验对改性膜的制备配比进行优化,对其基础性能及生物性能进行研究,对其临床应用效果进行考察。结果表明,在季胺化聚三氟苯乙烯质量分数为4%,聚乙烯吡咯烷酮质量分数为3%制备的改性聚砜膜水接触角为64.3°,水通量为82.4 L/(m^(2)·h),牛血清蛋白截留率为95.7%,Zeta电位为41.3 mV,断裂强度为5.4 MPa,断裂伸长率为6.1%。与血液接触后,改性聚砜膜上血小板粘附率仅为1.7%,细胞变形率仅为4.47%,60 d对DPPH自由基清除率和ABTS+自由基清除率分别为87.7%和98.5%,满足血液透析的相关要求。将其用于临床血液透析,确定改性聚砜膜优于传统医用透析膜。

人工血管的研发进展及应用现状

心血管疾病是威胁人类健康的重大疾病,是全球面临的重大公共卫生问题。人工血管置换术已成为多种血管类疾病治疗的主要方法,但仍会面临移植失败的风险。本综述主要从小口径人工血管的研发困境、人工血管的研发进展以及人工血管的产业化进程等目前的热点研究方向做一简要综述,以期为研究人员提供新的思路。

基于软光刻的高分子生物材料表面图案化及改性研究进展

生物材料表面的微形貌通过模仿细胞外基质,对细胞的行为具有调控作用。本文基于聚二甲基硅氧烷软光刻技术,分析热塑性和非热塑性材料的理化和生物特性,阐述如何分别采用熔融浇铸和溶液浇注的方法进行单一或复合表面图案化制备,探讨如何通过图案特性对组织工程细胞生物学行为产生影响。此外借鉴热塑性材料改性方法(表面化学修饰、表面微纳米级形貌修饰、表面生物涂层修饰)探讨如何在热塑性图案化结构的基础上赋予材料新的生物功能,为高分子生物材料表面的图案化和改性研究提供参考。

生物炭改性方法及其对水体磷酸盐吸附性能的研究

去除水体磷酸盐对于控制富营养化现象具有重要作用,吸附法因其效率高、成本低、易操作及污染小等优点而被广泛应用,且改性生物炭对磷酸盐具有更强吸附能力。本综述基于国内外关于改性生物炭吸附水体磷酸盐的研究,总结了常见生物炭制备方法,及对经物理法、化学法、生物法改性后的生物炭性能比较,揭示了不同方法制备改性生物炭在吸附水体磷酸盐实验中的实际效果差异特征。最后针对性的介绍了以藻类、木质素与秸秆三类代表性生物材料制备生物炭采用的最佳改性方案,以期为后续研究及应用提供方向与理论支撑。

GRAFTING OF SULFOBETAINE ONTO A POLYURETHANE SURFACE TO IMPROVE BLOOD COMPATIBILITY

On the molecular level, it is believed that polymers containing zwitterionic structures should be compatible withblood. In this work polyurethane films were grafted with sulfobetaine by a three-step procedure. In the first step, the films'surfaces were treated with hexamethylene diisocyanate (HDI) in toluene at 50℃ in the presence of di-n-butyl tin dilaurate(DBTDL) as a catalyst. The extent of the reaction was monitored by ATR-IR spectra; a maximum number of free NCOgroups was obtained after a reaction time of 90 min. In the second step, the hydroxyl groups of N,N-dimethylethylethanolamine (DMEA) were allowed to react in toluene with NCO groups bound on the surface. In the thirdstep, sulfobetaines were formed on the surface through the ring-opening reaction between tertiary amine of DMEA and 1,3-propanesultone (PS). The surfaces of the films were characterized by ATR-IR and XPS showing that the grafted surfaceswere composed of sulfobetaine. The results of the contact angle measurement show that the surface was strongly hydrophilic.The platelet adhesion test demonstrated that the films grafted with sulfobetaine have excellent blood compatibility.