New semi-IPN scaffolds based on HEMA and collagen modified with itaconic anhydride

Porous semi-IPN scaffolds were synthesized via free radical copolymerization of collagen modified with itaconic anhydride and 2-hydroxyethyl methacrylate, using ammonium persulfate and N,N,N′,N′-tetramethylethylenediamine as redox initiator system, with the aim of overcoming the high enzymatic degradation rate of native collagen scaffolds. The chemical modification of collagen was confirmed by ¹H NMR and FT-IR spectroscopy. The physico-chemical properties of the resulted matrices were investigated by elemental analysis, SEM, enzymatic degradation and water retention studies. The synthesized scaffolds, obtained through an innovative process, have fine microstructures, controlled water retention degree and enhanced stability against enzymatic digestion compared to native collagen. This may broaden the use of collagen-based scaffolds in tissue engineering, particularly for wound dressings.     

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).     

Biomaterials affect cell-cell interactions in vitro in tissue engineering

The facts that most tissues or organs consist of a variety of cells suggest that interactions between different types of cells play critical roles in tissue or organ development.In tissue engineering,the effects of biomaterials on cell-cell interactions have recently attracted increasing attention for better elucidating the mechanisms through which biomaterials promote tissue regeneration.Numerous studies have focused on these effects of biomaterials on cell-cell interactions.In this review,comprehensive information was provided about the existing cell co-culture technologies and the main behavioral modes of cell-cell interactions.The effects of biomaterials on the cell-cell interactions in various types of tissue regeneration have been summarized and discussed.In the end,the existing problems and future perspectives that would help promote the research of biomaterials in tissue engineering have been proposed.This article can help researchers to understand the progress and importance of studying the effects of biomaterials on cell-cell interactions in tissue engineering and to choose the optimal cell-cell co-culture models for designing experiments.     

Inside Front Cover: Tailoring Cell Adhesion Using Surface‐Grafted Polymer Gradient Assemblies (Adv. Mater. 23/2005)

A three‐step approach to tailor cell adhesion via surface‐grafted polymer gradients is shown in this image from the work of Genzer and co‐workers on p. 2802. Surface‐anchored polymer assemblies with gradients in polymer molecular weight and/or grafting density are first employed to tailor adsorption of the protein, which in turn governs the number density as well as the extent of spreading of osteoblastic cells. Increasing the surface coverage of the polymer results in a decrease in the amount of protein adsorbed, which causes a decrease in the number of cells adhered and a change in cell morphology.     

Nanostructured 3-D collagen/nanotube biocomposites for future bone regeneration scaffolds

The field of bionanotechnology has been rapidly growing during the last few years and we can now envision a controllable integration between biological and artificial matter, where new biomimetic structures with a wide range of chemical and physical properties will promote the development of a novel generation of medical devices. In this work we describe a collagen/carbon nanotube composite which has the potential to be used as a scaffold for tissue regeneration. Because this biocomposite incorporates the advantageous properties of both collagen and carbon nanotubes, it has most of the characteristics that an ideal biomaterial requires in order to be used as an osteoinductive agent. This biocomposite is bioresorbable and biodegradable and has the desired mechanical rigidity while maintaining a three-dimensional(3-D) nanostructured surface. Tuned stability and swelling were achieved under fluid environments by varying the amount of carbon nanotubes (CNTs) incorporated into the composite. These variations can dictate the degree of interaction between fibroblastic cells and the biomaterials. Proof-of-concept was shown by performing an in vitro induced mineralization of hydroxylapatite crystals under physiological conditions. Furthermore, the ability to attach biofunctional groups to the CNT walls can open a new road for tissue regeneration since the combination of CNTs with specific growth factors or cellular ligands can create an environment capable of signaling and influencing specific cell functions. Our observations suggest that collagen/carbon nanotube biocomposites will have important uses in a wide range of biotechnological areas. Electronic Supplementary Material  Supplementary material is available for this article at and is accessible for authorized users.     

Preliminary study on the adhesion and proliferation of human osteoblasts on starch-based scaffolds

Up to today, several techniques have been used to produce biodegradable porous scaffolds for tissue engineering. In this work, a new technique based on extrusion by using blowing agents in combination with a 50:50 (wt.%) blend of starch/cellulose acetate (SCA) was studied. The results show that by using this technique it was possible to obtain scaffolds with 70% of porosity and a fully interconnected network of pores, with sizes ranging from 200 to 500 μm. After their production, the mechanical properties of these scaffolds were tested, presenting a compressive modulus of 124.6±27.2 MPa and a compressive strength of 8.0±0.9 MPa. These values are within the best found in the literature and show that by using this technique, it is possible to produce scaffolds that, from a mechanical standpoint, may be suitable for bone tissue engineering. Cell culturing experiments showed that cells were viable and that there were no signs of cellular death after 3 weeks of culture. Finally, biochemical assays demonstrate that cells maintained the osteogenic phenotype throughout the experiment and deposition of mineralized extracellular matrix could be detected.     

In vitro cellular response to hydroxyapatite scaffolds with oriented pore architectures

The objective of the present work was to evaluate the in vitro cellular response to hydroxyapatite (HA) scaffolds with oriented pore architectures. Hydroxyapatite scaffolds with approximately the same porosity (65–70%) but two different oriented microstructures, described as ‘columnar’ (pore diameter = 90–110 μm) and ‘lamellar’ (pore width = 20–30 μm), were prepared by unidirectional freezing of suspensions. The response of murine MLO-A5 cells, an osteogenic cell line, to these scaffolds was evaluated using assays of MTT hydrolysis, alkaline phosphatase (ALP) activity, and alizarin red staining. While the cellular response to both groups of scaffolds was better than control wells, the columnar scaffolds with the larger pore width provided the most favorable substrate for cell proliferation and function. These results indicate that HA scaffolds with the columnar microstructure could be used for bone repair applications in vivo.     

Controlling Stem Cell Fate with Material Design

Advances in our understanding of stem cell interactions with their environment are leading to the development of new materials‐based approaches to control stem cell behavior toward cellular culture and tissue regeneration applications. Materials can provide cues based on chemistry, mechanics, structure, and molecule delivery that control stem cell fate decisions and matrix formation. These approaches are helping to advance clinical translation of a range of stem cell types through better expansion techniques and scaffolding for use in tissue engineering approaches for the regeneration of many tissues. With this in mind, this progress report covers basic concepts and recent advances in the use of materials for manipulating stem cells.     

Characterisation of vascularisation of scaffolds for tissue engineering

Abstract

Vascularisation of scaffolds is now recognised as a crucial requirement for the success of tissue engineering strategies. This review summarises the state-of-the-art in the techniques available for the in vivo assessment of vascularisation of scaffolds with focus on growth factor delivering scaffolds, microfabrication technologies and in vivo characterisation methods based on the arteriovenous loop model to create three dimensionally vascularised tissue replacements.     

Multiple Functionalities of Polyelectrolyte Multilayer Films: New Biomedical Applications

The design of advanced functional materials with nanometer‐ and micrometer‐scale control over their properties is of considerable interest for both fundamental and applied studies because of the many potential applications for these materials in the fields of biomedical materials, tissue engineering, and regenerative medicine. The layer‐by‐layer deposition technique introduced in the early 1990s by Decher, Moehwald, and Lvov is a versatile technique, which has attracted an increasing number of researchers in recent years due to its wide range of advantages for biomedical applications: ease of preparation under “mild” conditions compatible with physiological media, capability of incorporating bioactive molecules, extra‐cellular matrix components and biopolymers in the films, tunable mechanical properties, and spatio‐temporal control over film organization. The last few years have seen a significant increase in reports exploring the possibilities offered by diffusing molecules into films to control their internal structures or design “reservoirs,” as well as control their mechanical properties. Such properties, associated with the chemical properties of films, are particularly important for designing biomedical devices that contain bioactive molecules. In this review, we highlight recent work on designing and controlling film properties at the nanometer and micrometer scales with a view to developing new biomaterial coatings, tissue engineered constructs that could mimic in vivo cellular microenvironments, and stem cell “niches.”     

Characterization of TEMPO-oxidized bacterial cellulose scaffolds for tissue engineering applications

Introduction of active groups on the surface of bacterial cellulose (BC) nanofibers is one of the promising routes of tailoring the performance of BC scaffolds for tissue engineering. This paper reported the introduction of aldehyde groups to BC nanofibers by 2,2,6,6-tetramethylpyperidine-1-oxy radical (TEMPO)-mediated oxidation and evaluation of the potential of the TEMPO-oxidized BC as tissue engineering scaffolds. Periodate oxidation was also conducted for comparison. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses were carried out to determine the existence of aldehyde groups on BC nanofibers and the crystallinity. In addition, properties relevant to scaffold applications such as morphology, fiber diameter, mechanical properties, and in vitro degradation were characterized. The results indicated that periodate oxidation could introduce free aldehyde to BC nanofibers and the free aldehyde groups on the TEMPO-oxidized BC tended to transfer to acetal groups. It was also found that the advantageous 3D structure of BC scaffolds remained unchanged and that no significant changes in morphology, fiber diameter, tensile structure and in vitro degradation were found after TEMPO-mediated oxidation while significant differences were observed upon periodate oxidation. The present study revealed that TEMPO-oxidation could impart BC scaffolds with new functions while did not degrade their intrinsic advantages.     

Responsive Polymers at the Biology/Materials Science Interface

Synthetic polymers can be prepared with features that combine many of the advantageous properties of natural materials, including environmental response. This Research News article considers the different types of response that can be ‘programmed in' to polymers and the applications that are developing as a consequence of the designed responses. In particular, we focus on two key applications at the biology/materials science interface: responsive drug delivery systems and ‘smart' surfaces for cell culture and regenerative medicine.