Advances in targeted nanotherapeutics: From bioconjugation to biomimicry

Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles (NPs) that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as “foreign”, resulting in their clearance by the mononuclear phagocytic system (MPS). To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPS. These biomimetic NPs fall into two distinct categories: synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall, bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery, and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.     

Hierarchical porous materials for tissue engineering

Biological organisms have evolved to produce hierarchical three-dimensional structures with dimensions ranging from nanometres to metres. Replicating these complex living hierarchical structures for the purpose of repair or replacement of degenerating tissues is one of the great challenges of chemistry, physics, biology and materials science. This paper describes how the use of hierarchical porous materials in tissue engineering applications has the potential to shift treatments from tissue replacement to tissue regeneration. The criteria that a porous material must fulfil to be considered ideal for bone tissue engineering applications are listed. Bioactive glass foam scaffolds have the potential to fulfil all the criteria, as they have a hierarchical porous structure similar to that of trabecular bone, they can bond to bone and soft tissue and they release silicon and calcium ions that have been found to up-regulate seven families of genes in osteogenic cells. Their hierarchical structure can be tailored for the required rate of tissue bonding, resorption and delivery of dissolution products. This paper describes how the structure and properties of the scaffolds are being optimized with respect to cell response and that tissue culture techniques must be optimized to enable growth of new bone in vitro.     

Nanostructured materials for cardiovascular tissue engineering

Substantial progress has been made in the field of cardiovascular tissue engineering with an ever increasing number of clinically viable implants being reported. However, poor cellular integration of constructs remains a major problem. Limitations in our knowledge of cell/substrate interactions and their impact upon cell proliferation, survival and phenotype are proving to be a major hindrance. Advances in nanotechnology have allowed researchers to fabricate scaffolds which mimic the natural cell environment to a greater extent; allowing the elucidation of appropriate physical cues which influence cell behaviour. The ability to manipulate cell/substrate interactions at the micro/nano scale may help to create a viable cellular environment which can integrate effectively with the host tissue. This review summarises the influence of nanotopographical features on cell behaviour and provides details of some popular fabricating techniques to manufacture 3D scaffolds for tissue engineering. Recent examples of the translation of this research into fabricating clinically viable implants for the regeneration of cardiovascular tissues are also provided.     

Biomimetic material strategies for cardiac tissue engineering

Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.     

Cellular materials as porous scaffolds for tissue engineering

A major goal of tissue engineering is to synthesize or regenerate tissues and organs. Today, this is done by providing a synthetic porous scaffold, or matrix, which mimics the body's own extracellular matrix, onto which cells attach, multiply, migrate and function. Porous scaffolds are currently being developed for regeneration of skin, cartilage, bone, nerve and liver. The microstructures of many porous scaffolds ressemble that of an engineering foam. In this paper, we describe the microstructural requirements for porous scaffolds, review several processes for making them and show typical microstructures. Clinical studies have found that a collagen-based scaffold for skin regeneration reduces wound contraction during the healing process, reducing scar formation. The process of wound contraction is not well understood. Here, we describe the measurement of contraction of collagen-based scaffolds by fibroblasts in vitro using a cell force monitor.     

Accordion-like honeycombs for tissue engineering of cardiac anisotropy

Tissue-engineered grafts may be useful in myocardial repair; however, previous scaffolds have been structurally incompatible with recapitulating cardiac anisotropy. Here, we use microfabrication techniques to create an accordion-like honeycomb microstructure in poly(glycerol sebacate), which yields porous, elastomeric three-dimensional (3D) scaffolds with controllable stiffness and anisotropy. Accordion-like honeycomb scaffolds with cultured neonatal rat heart cells demonstrated utility through: (1) closely matched mechanical properties compared to native adult rat right ventricular myocardium, with stiffnesses controlled by polymer curing time; (2) heart cell contractility inducible by electric field stimulation with directionally dependent electrical excitation thresholds (p<0.05); and (3) greater heart cell alignment (p<0.0001) than isotropic control scaffolds. Prototype bilaminar scaffolds with 3D interconnected pore networks yielded electrically excitable grafts with multi-layered neonatal rat heart cells. Accordion-like honeycombs can thus overcome principal structural-mechanical limitations of previous scaffolds, promoting the formation of grafts with aligned heart cells and mechanical properties more closely resembling native myocardium.     

Stem cells and biomimetic materials strategies for tissue engineering

Stem cells have been recognized as a promising alternative to somatic cells in the application of cell therapy owing to their potential to renew themselves through cell division and to differentiate into a wide range of specialized cell types. In order to maintain the phenotype expression and differentiated functions of stem cells, the simulated natural environment of the biomimetic material support has to provide the appropriate signals to the attached cells. Scaffolds with biomimetic components and nanotexture can provide chemical, physical as well as spatial cues that are essential to mimic natural tissue growth. Moreover, the plasticity of stem cells provides the basic possibility for multiple-tissue engineering using a certain type of stem cells. Progress in the understanding of self-renewal and directed differentiation of stem cells on biomimetic materials will lead scientists to propose the possibility of cell-based therapies to treat diseases, including the use of stem cells in tissue engineering. In this review paper, we will discuss the current state of the art and future perspectives on stem cells and biomimetic materials strategies for tissue engineering.     

Bioactive materials for tissue engineering, regeneration and repair

Tissue engineering is an interdisciplinary field which applies the principles of engineering and the life sciences to the design, construction, modification, growth and maintenance of living tissues [1, 2]. One of two approaches can be taken: (1) in vitro construction of bioartificial tissues from cells seeded onto a resorbable scaffold or (2) in vivo modification of cell growth and function to stimulate tissue regeneration [2, 3]. This concept represents a shift in emphasis from replacement to regeneration of diseased or damaged tissues, in which the development of bioactive materials has played a significant role.This paper will begin with an overview of the use of biomaterials as implants and their limitations, leading to the reasons for the dramatic shift in focus regarding the approach to repairing damaged tissues. The majority of the paper will discuss the ways in which biomaterials can be developed to implement the concept of tissue engineering. Finally, the implications of these developments for future treatment of damaged or diseased tissues will be considered.     

Electrospun nanofibrous materials for tissue engineering and drug delivery

Abstract

The electrospinning technique, which was invented about 100 years ago, has attracted more attention in recent years due to its possible biomedical applications. Electrospun fibers with high surface area to volume ratio and structures mimicking extracellular matrix (ECM) have shown great potential in tissue engineering and drug delivery. In order to develop electrospun fibers for these applications, different biocompatible materials have been used to fabricate fibers with different structures and morphologies, such as single fibers with different composition and structures (blending and core-shell composite fibers) and fiber assemblies (fiber bundles, membranes and scaffolds). This review summarizes the electrospinning techniques which control the composition and structures of the nanofibrous materials. It also outlines possible applications of these fibrous materials in skin, blood vessels, nervous system and bone tissue engineering, as well as in drug delivery.     

血管组织工程支架材料的研究进展

血管支架材料在组织工程血管构建过程中起着非常重要的作用.近年来已合成与制备了许多新型血管支架材料,并对材料进行了相关方面处理.本文对天然生物材料、合成高分子可降解材料和复合材料等血管组织工程支架材料进行了综述.     

Progress on materials and scaffold fabrications applied to esophageal tissue engineering

The mortality rate from esophageal disease like atresia, carcinoma, tracheoesophageal fistula, etc. is increasing rapidly all over the world. Traditional therapies such as surgery, radiotherapy or chemotherapy have been met with very limited success resulting in reduced survival rate and quality of patients' life. Tissue-engineered esophagus, a novel substitute possessing structure and function similar to native tissue, is believed to be an effective therapy and a promising replacement in the future. However, research on esophageal tissue engineering is still at an early stage. Considerable research has been focused on developing ideal scaffolds with optimal materials and methods of fabrication. This article gives a review of materials and scaffold fabrications currently applied in esophageal tissue engineering research.     

Stem cell homing-based tissue engineering using bioactive materials

Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.     

A review on biodegradable polymeric materials for bone tissue engineering applications

Biodegradable polymer scaffolds have played a significant role in wide range of tissue engineering application such as bone scaffolds since the last decade. The aim of this article is to provide the comprehensive overview of biocompatible and biodegradable polymer materials and composite materials with their advantages and drawbacks in the application of biomaterial scaffolds, furthermore the properties and degradation criteria of the biomaterials are discussed in this review.     

Biomaterials in cardiac tissue engineering: Ten years of research survey

Driven by enormous clinical need, myocardial tissue engineering has become a prime focus of research within the field of tissue engineering. Myocardial tissue engineering combines isolated functional cardiomyocytes and a biodegradable or nondegradable biomaterial to repair diseased heart muscle. The challenges in heart muscle engineering include cell related issues (such as scale up in a short timeframe, efficiency of cell seeding or cell survival rate, and immune rejection), the design and fabrication of myocardial tissue engineering substrates, and the engineering of tissue constructs in vitro and in vivo. Several approaches have been put forward, and a number of models combining various polymeric biomaterials, cell sources and bioreactors have been developed in the last 10 years for myocardial tissue engineering. This review provides a comprehensive update on the biomaterials, as well as cells and biomimetic systems, used in the engineering of the cardiac muscle. The article is organized as follows. A historic perspective of the evolution of cardiac medicine and emergence of cardiac tissue engineering is presented in the first section. Following a review on the cells used in myocardial tissue engineering (second section), the third section presents a review on biomaterials used in myocardial tissue engineering. This section starts with an overview of the development of tissue engineering substrates and goes on to discuss the selection of biomaterials and design of solid and porous substrates. Then the applications of a variety of biomaterials used in different approaches of myocardial tissue engineering are reviewed in great detail, and related issues and topics that remain challenges for the future progress of the field are identified at the end of each subsection. This is followed by a brief review on the development of bioreactors (fourth section), which is an important achievement in the field of myocardial tissue engineering, and which is also related to the biomaterials developed. At the end of this article, the major achievements and remaining challenges are summarized, and the most promising paradigm for the future of heart muscle tissue engineering is proposed (fifth section).     

Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.