Designer self-assembling peptide scaffolds for 3-d tissue cell cultures and regenerative medicine

Biomaterial science has made enormous progress in the last few decades. Nonetheless, innovative biomaterials are still urgently needed to provide in vitro cell-culture models that more closely resemble three-dimensional (3-D) cell interactions and cyto-architectures in bodies and tissues. In this review, the recent advances toward this goal through molecular engineering of various designer self-assembling peptide scaffolds are discussed. These peptide scaffolds can be commercially and custom-tailor synthesized materials with high purity and may be not only useful for specific 3-D tissue cell cultures but also for tissue repair and regenerative therapies. Furthermore, these designer self-assembling peptide scaffolds have recently become powerful tools for regenerative medicine to repair nervous tissue, to stop bleeding in seconds, to repair infarctuated myocardia, as well as being useful medical devices for slow drug release.     

Three‐Dimensional Scaffolds of Carbonized Polyacrylonitrile for Bone Tissue Regeneration

Carbon‐based materials have been extensively studied for stem cell culture. However, difficulties associated with engineering pure carbon materials into 3D scaffolds have hampered applications in tissue engineering and regenerative medicine. Carbonized polyacrylonitrile (cPAN) could be a promising alternative, as cPAN is a highly ordered carbon isomorph that resembles the graphitic structure and can be easily processed into 3D scaffolds. Despite the notable features of cPAN, application of cPAN in tissue engineering and regenerative medicine have not been explored. This study, for the first time, demonstrates the fabrication of microporous 3D scaffolds of cPAN and excellent osteoinductivity of cPAN, suggesting utility of 3D cPAN scaffolds as synthetic bone graft materials. The combination of excellent processability and unique bioactive properties of cPAN may lead to future applications in orthopedic regenerative medicine.     

Controllable synthesis and characterization of porous polyvinyl alcohol/hydroxyapatite nanocomposite scaffolds via an in situ colloidal technique

During the last decades, there have been several attempts to combine bioactive materials with biocompatible and biodegradable polymers to create nanocomposite scaffolds with excellent biocompatibility, bioactivity, biodegradability and mechanical properties. In this research, the nanocomposite scaffolds with compositions based on PVA and HAp nanoparticles were successfully prepared using colloidal HAp nanoparticles combined with freeze-drying technique for tissue engineering applications. In addition, the effect of the pH value of the reactive solution and different percentages of PVA and HAp on the synthesis of PVA/HAp nanocomposites were investigated. The SEM observations revealed that the prepared scaffolds were porous with three dimensional microstructures, and in vitro experiments with osteoblast cells indicated an appropriate penetration of the cells into the scaffold's pores, and also the continuous increase in cell aggregation on the scaffolds with increase in the incubation time demonstrated the ability of the scaffolds to support cell growth. According to the obtained results, the nanocomposite scaffolds could be considered as highly bioactive and potential bone tissue engineering implants.     

骨组织工程支架材料研究进展*

骨在组织工程中得到了非常广泛、深入的研究.支架材料与许多可降解材料一起也在进行探索性研究.用于骨组织工程的生物材料可以是三维多孔的刚硬材料,也可以是可注射材料.本文从聚合物角度综述了骨组织工程对支架材料的基本要求,用于骨组织工程的可降解生物材料、支架材料的设计和制备技术以及支架材料的表面修饰等方面的研究进展.     

Complicity of degradable polymers in health-care applications

Polymeric biomaterials have revolutionized biomedical technology and related fields as biomaterials for health-care applications. Recent trend in polymeric medical technology has adapted a tendency to substitute degradable polymers instead of non-degradable synthetic polymers for the advancement of various health-care modalities. They have got considerable attention for their potential in various interdisciplinary arenas, which implies tissue engineering scaffolds, sustainable drug release, delivery agents, regenerative medicine, and development of life-saving devices, implants, dental products as well as in food technology. Various types of degradable polymers are been developed to date having stringent features applicable for various aspects in modern science. Thus, being the most renovative field of biomedicine and biomedical technology degradable polymers has gained substantial acceptance and appreciation recent times. This review critically underlines various degradative polymers and their subtypes, potential applications, types of degradation, and their possible effects in the biological system. Assessment of possible toxicological risks behind is an important criterion to be focused before validating any biomaterial safe for biomedical applications. Therefore various toxicological assessment strategies and their impact in biomedicine and technology were also included. In addition, the risk versus benefit assessment is also critically summarized.     

A Nanocage for Nanomedicine: Polyhedral Oligomeric Silsesquioxane (POSS)

Ground‐breaking advances in nanomedicine (defined as the application of nanotechnology in medicine) have proposed novel therapeutics and diagnostics, which can potentially revolutionize current medical practice. Polyhedral oligomeric silsesquioxane (POSS) with a distinctive nanocage structure consisting of an inner inorganic framework of silicon and oxygen atoms, and an outer shell of organic functional groups is one of the most promising nanomaterials for medical applications. Enhanced biocompatibility and physicochemical (material bulk and surface) properties have resulted in the development of a wide range of nanocomposite POSS copolymers for biomedical applications, such as the development of biomedical devices, tissue engineering scaffolds, drug delivery systems, dental applications, and biological sensors. The application of POSS nanocomposites in combination with other nanostructures has also been investigated including silver nanoparticles and quantum dot nanocrystals. Chemical functionalization confers antimicrobial efficacy to POSS, and the use of polymer nanocomposites provides a biocompatible surface coating for quantum dot nanocrystals to enhance the efficacy of the materials for different biomedical and biotechnological applications. Interestingly, a family of POSS‐containing nanocomposite materials can be engineered either as completely non‐biodegradable materials or as biodegradable materials with tuneable degradation rates required for tissue engineering applications. These highly versatile POSS derivatives have created new horizons for the field of biomaterials research and beyond. Currently, the application of POSS‐containing polymers in various fields of nanomedicine is under intensive investigation with expectedly encouraging outcomes.

     

The rheological and structural properties of Fmoc-peptide-based hydrogels: the effect of aromatic molecular architecture on self-assembly and physical characteristics

Biocompatible hydrogels are of high interest as a class of biomaterials for tissue engineering, regenerative medicine, and controlled drug delivery. These materials offer three-dimensional scaffolds to support the growth of cells and development of hierarchical tissue structures. Fmoc-peptides were previously demonstrated as attractive building blocks for biocompatible hydrogels. Here, we further investigate the biophysical properties of Fmoc-peptide-based hydrogels for medical applications. We describe the structural and thermal properties of these Fmoc-peptides, as well as their self-assembly process. Additionally, we study the role of interactions between aromatic moieties in the self-assembly process and on the physical and structural properties of the hydrogels.     

生物材料表面性能调控骨髓间充质干细胞分化

结合细胞和生物可降解支架的组织工程和再生医学技术为组织、器官的修复和再生提供了一种新途径。骨髓间充质干细胞(BMSCs)具有多向分化潜能,因其取材简单、来源广泛、增殖能力强,无伦理争议,免疫排斥反应小而备受关注。BMSCs在特定区域定向分化成为靶细胞是干细胞治疗的一个重要前提,尤其受到生物材料表面正负电荷、亲疏水和不同的拓扑结构的影响。材料表面涂层蛋白或接枝多肽能够促进BMSCs的分化能力,而生物材料不同的机械性能、几何形状也会影响BMSCs的分化方向。本文综述了近期生物材料调控BMSCs分化的研究结果,为基于BMSCs的组织工程和再生医学材料的设计提供借鉴和指导。     

Scaffold Design for Tissue Engineering

Tissue engineering has emerged as a promising alternative approach in the treatment of malfunctioning or lost organs. In this approach, a temporary scaffold is needed to serve as an adhesive substrate for the implanted cells and a physical support to guide the formation of the new organs. In addition to facilitating cell adhesion, promoting cell growth, and allowing the retention of differentiated cell functions, the scaffold should be biocompatible, biodegradable, highly porous with a large surface/volume ratio, mechanically strong, and malleable. A number of three‐dimensional porous scaffolds fabricated from various kinds of biodegradable materials have been developed. This paper reviews some of the advances in scaffold design focusing on the hybrid scaffolds recently developed in the authors' laboratory.     

Smart Porous Multi-Stimulus Polysaccharide-Based Biomaterials for Tissue Engineering

Recently, tissue engineering and regenerative medicine studies have evaluated smart biomaterials as implantable scaffolds and their interaction with cells for biomedical applications. Porous materials have been used in tissue engineering as synthetic extracellular matrices, promoting the attachment and migration of host cells to induce the in vitro regeneration of different tissues. Biomimetic 3D scaffold systems allow control over biophysical and biochemical cues, modulating the extracellular environment through mechanical, electrical, and biochemical stimulation of cells, driving their molecular reprogramming. In this review, first we outline the main advantages of using polysaccharides as raw materials for porous scaffolds, as well as the most common processing pathways to obtain the adequate textural properties, allowing the integration and attachment of cells. The second approach focuses on the tunable characteristics of the synthetic matrix, emphasizing the effect of their mechanical properties and the modification with conducting polymers in the cell response. The use and influence of polysaccharide-based porous materials as drug delivery systems for biochemical stimulation of cells is also described. Overall, engineered biomaterials are proposed as an effective strategy to improve in vitro tissue regeneration and future research directions of modified polysaccharide-based materials in the biomedical field are suggested.     

Particle-collision and porogen-leaching technique to fabricate polymeric porous scaffolds with microscale roughness of interior surfaces

A facile technique is herein reported to fabricate three-dimensional(3D) polymeric porous scaffolds with interior surfaces of a topographic microstructure favorable for cell adhesion.As demonstration,a well-known biodegradable polymer poly(lactide-co-glycolide)(PLGA) was employed as matrix.Under the porogen-leaching strategy,the large and soft porogens of paraffin were modified by colliding with small and hard salt particles,which generated micropits on the surfaces of paraffin spheres.The eventual PLGA scaffolds after leaching the modified porogens had thus interior surfaces of microscale roughness imprinted by those micropits.The microrough scaffolds were confirmed to benefit adhesion of bone marrow stromal cells(BMSCs) of rats and meanwhile not to hamper the proliferation and osteogenic differentiation of the cells.The insight and technique might be helpful for biomaterial designing in tissue engineering and regenerative medicine.     

An overview of nano-polymers for orthopedic applications

This review paper presents many exciting nanotechnology and tissue engineering approaches involving polymers that have enormous potential impact on human health care, particularly for orthopedic applications. As scaffolds play a vital role in tissue engineering, the feasibility of designing polymeric nano-featured scaffolds is reviewed. Although bone is a very diverse tissue providing different functions within the body, recent work has resulted in new biomaterials with promise to solve orthopedic problems. Significant advancements in orthopedic care are required since recent data highlight a less than 15 year lifetime of current hip implants. Nanotechnology (or the use of nanomaterials) is providing a wide range of new materials to improve the current short lifetimes of orthopedic implants.     

Vinylcarbonates and vinylcarbamates: Biocompatible monomers for radical photopolymerization

The last decade has seen a remarkable interest in the use of biocompatible and biodegradable polymers as scaffolds for tissue engineering. The fabrication of 3D scaffolds by lithography‐based additive manufacturing technology (AMT) represents an appealing approach. As poly(lactic acid), the state of the art biocompatible and biodegradable material, cannot be processed by these photopolymerization‐based techniques, it has so far been necessary to use selected (meth)acrylates. By developing new photopolymers based on vinyl carbonates and vinyl carbamates as a reactive group we have been able to avoid most of the disadvantages of classical (meth)acrylate‐based photopolymers. The new generation of biocompatible monomers show low cytotoxicity, have good storage stability, and are sufficiently photoreactive to be structured by lithography based AMT. The mechanical properties and rates of degradation of the polymers can be easily tuned over a broad range. Degradation results in the formation of nonacidic and nontoxic degradation products of low molecular weight that can be easily transported within the human body. Initial in vivo tests showed significant osseointegration of the 3D cellular scaffolds and no signs of implant rejection. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

3D打印技术制备生物医用高分子材料的研究进展

3D打印技术能够根据不同患者需要,快速精确制备适合不同患者的个性化生物医用高分子材料,并能同时对材料的微观结构进行精确控制.因此,这种新兴的医用高分子材料制备技术在未来生物医学应用(尤其是组织工程应用)中具有独特的优势.近年来,对于3D打印技术制备生物医用高分子材料的研究开发受到了越来越多的关注.不同的生物相容高分子原料被应用于3D打印技术,而这些3D成型高分子材料被用于体外细胞培养,或动物模型的软组织或硬组织修复中.本文主要介绍了近年来3D打印技术在生物医用高分子材料制备中的研究进展,并对该领域的未来应用和挑战进行了展望.     

Biodegradable elastomers for tissue engineering and cell-biomaterial interactions

Synthetic biomaterials serve as a cornerstone in the development of clinically focused regenerative medicine therapies that aim to reduce suffering and prolong life. Recent improvements in biodegradable elastomeric materials utilize natural extracellular matrix proteins as inspiration to yield a new class of materials with superior degradation kinetics, desirable biocompatibility profiles, and mechanical properties that closely match those of soft tissues. This review describes several classes of synthetic biodegradable elastomers and associated fabrication techniques that are relevant to scaffold development. The application of these materials to select tissue engineering models is also discussed.     

Polymers for medicobiological use

This review briefly summarizes the main approaches to the use of polymers as materials for designing implants; components of biologically active systems; and systems employed in cell, tissue, and gene engineering; as materials for sorption and membrane-separation devices and bioanalytical systems, and as artificial biocatalysts and general-purpose biodegradable materials.     

Degradation of Engineering Materials – Implications to Regenerative Medicine

Summary: Materials in general, to some degree are susceptible to environmental degradation. The degradation of biomaterials is one of the most relevant issues in the field of regenerative medicine. In industrial practice, the degradation is always a negative phenomenon. In bioengineering, the degradation may be undesirable (e.g. corrosion of metallic implants, wear of artificial joint implant) or desirable (biodegradable devices and tissue engineering). In both cases, the knowledge of the kinetics of degradation is crucial for safe use of biocomponents. The methods for predicting remaining life commonly used in industrial practice will be presented in the context of biomaterials. Non destructive techniques for monitoring degradation will be discussed and some ideas about their application to bio-environments proposed.     

生物降解聚合物的研究和产业化进展及展望

结合作者等近十年来在生物降解聚合物领域的研究和产业化工作,本文概述了聚乳酸、聚氨基酸、聚对二氧六环酮及其它生物降解聚合物的合成进展,综述了可生物降解温度敏感水凝胶、形状记忆高分子材料的研究概况,阐述了可生物降解聚合物在生物活性大分子控释体系、超细纤维组织工程支架上的应用研究,介绍了可生物降解聚合物在食品包装、纺织和汽车电子等方面的应用,总结了可生物降解聚合物、医疗器械、药物制剂和组织工程等领域产业化近况.最后展望了生物降解聚合物的研究、应用和产业化前景.     

Biomedical applications of biodegradable polymers

Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. Specifically, polymeric biomaterials that are biodegradable provide the significant advantage of being able to be broken down and removed after they have served their function. Applications are wide ranging with degradable polymers being used clinically as surgical sutures and implants. To fit functional demand, materials with desired physical, chemical, biological, biomechanical, and degradation properties must be selected. Fortunately, a wide range of natural and synthetic degradable polymers has been investigated for biomedical applications with novel materials constantly being developed to meet new challenges. This review summarizes the most recent advances in the field over the past 4 years, specifically highlighting new and interesting discoveries in tissue engineering and drug delivery applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Self-assembling peptide scaffolds for regenerative medicine

Biomaterials made from self-assembling, short peptides and peptide derivatives have great potential to generate powerful new therapies in regenerative medicine. The high signaling capacity and therapeutic efficacy of peptidic scaffolds has been established in several animal models, and the development of more complex, hierarchical structures based on peptide materials is underway. This highlight discusses several classes of self-assembling peptide-based materials, including peptide amphiphiles, Fmoc-peptides, self-complementary ionic peptides, hairpin peptides, and others. The self-assembly designs, bioactive signalling strategies, and cell signalling capabilities of these bioactive materials are reported. The future challenges of the field are also discussed, including short-term goals such as integration with biopolymers and traditional implants, and long term goals, such as immune system programming, subcellular targeting, and the development of highly integrated scaffold systems.