Biomaterials and tissue engineering scaffolds Research Papers (original) (raw)

Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cellladen hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine.

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- Mechanical Engineering, Biomaterials Engineering, Chemical Engineering, Chemistry

UBYTKÓW SKÓRY artykuł przeglądowy POLYMER BIOMATERIALS FOR SKIN REGENERATION A review Małgorzata Martowicz, Jadwiga Laska* 1 Państwowa Wyższa Szkoła Zawodowa w Tarnowie, Instytut Matematyczno-Przyrodniczy, ul. Mickiewicza 8, 33-100 Tarnów 2 Akademia Górniczo-Hutnicza, Wydział Inżynierii Materiałowej i Ceramiki, Katedra Biomateriałów, al. Mickiewicza 30, 30-059 Kraków 3 Państwowa Wyższa Szkoła Zawodowa w Tarnowie, Instytut Politechniczny, ul. Mickiewicza 8, 33-100 Tarnów * e-mail: jlaska@agh.edu.pl 1 State Higher Vocational School in Tarnow, Institute of Mathematical and Natural Science, ul. Mickiewicza 8, 33-100 Tarnów, Poland 2 AGH University of Science and Technology, Faculty Materials Science and Ceramics, Department of Biomaterials, al. Mickiewicza 30, 30-059 Kraków, Poland 3 State Higher Vocational School in Tarnow, The Polytechnic Institute, ul. Mickiewicza 8, 33-100 Tarnów, Poland * e-mail: jlaska@agh.edu.pl

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering.

- by Ayşegül Doğan and +3
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- Biomedical Engineering, Tissue Engineering, Scanning Electron Microscopy, Immunohistochemistry

Dermal scaffolds promote healing of debilitating skin injuries caused by burns and chronic skin conditions. Currently available products present disadvantages and therefore, there is still a clinical need for developing new dermal substitutes. This study aimed at comparing the viscoelastic,
physical and bio-degradable properties of two dermal scaffolds, the collagen-based and clinically well established Integra® and a novel fibrin-based dermal scaffold developed at our laboratory called Smart Matrix®, to further evaluate our previous published findings that suggested a higher influx of cells, reduced wound contraction and less scarring for Smart Matrix® when used in vivo. Rheological results showed that Integra® (G′ = 313.74 kPa) is mechanically stronger than Smart Matrix® (G′ = 8.26 kPa), due to the presence of the silicone backing layer in Integra®. Micro-pores were observed on both dermal scaffolds, although nano-pores as well as densely packed nanofibres
were only observed for Smart Matrix®. Average surface roughness was higher for Smart Matrix® (Sa = 114.776 nm) than for Integra® (Sa = 75.565 nm). Both scaffolds possess a highly porous structure (80–90%) and display a range of pore micro-sizes that represent the actual in vivo
scenario. In vitro proteolytic bio-degradation suggested that Smart Matrix® would degrade faster upon implantation in vivo than Integra®. For both scaffolds, the enzymatic digestion occurs via bulk degradation. These observed differences could affect cell behaviour on both scaffolds. Our results suggest that fine-tuning of scaffolds’ viscoelastic, physical and bio-degradable properties can maximise cell behaviour in terms of attachment, proliferation and infiltration, which are essential for
tissue repair.

- by Nimesha Patel and +1
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- Tissue Engineering, Surface Roughness, Rheological properties, Biomaterials and tissue engineering scaffolds

Nanocomposite hydrogel particles grasp considerable attention in nanotechnology and nanomedicine as one of the potential drug delivery platforms. However, prevail a coveted drug delivery strategy with sustain and stimulidrug release is still challenging. Herein, poly (N-(4-aminophenyl) methacrylamide))-carbon nano-onions (PAPMA-CNOs = f-CNOs)/diclofenac-complex integrated chitosan (CS) nanocomposite hydrogel nanoparticles (CNPs) were fabricated using an ionic gelation strategy. CNPs possess several conducive physicochemical properties, including spherical morphology and uniform particle distribution.In vitro drug release from CNPs was vetted in different pHs of gastrointestinal (GI) tract environment at a temperature range of 37− 55 • C and found dual (pH and thermo)-responsive controlled drug release. Under pH 7.4, CNPs exhibited the highest drug release at 55 • C in 15 days. The drug release results disclose that the structure of CNPs was disassembled at 55 • C to release the encapsulated drug molecules in a controlled fashion. The CNPs also displayed good cell viability against human fibroblast cells. Thus, all the results together unveil that CNPs would thrive as a promising pH and temperature-triggered drug delivery platform for the GI tract and colon targeted drug delivery.

The use of decellularised matrices as scaffolds offers the advantage of great similarity with the tissue to be replaced. Moreover, decellularised tissues and organs can be repopulated with the patient’s own cells to produce bespoke therapies. Great progress has been made in research and development of decellularised scaffolds, and more recently, these materials are being used in exciting new areas like hydrogels and bioinks. However, much effort is still needed towards preserving the original extracellular matrix composition, especially its minor components, assessing its functionality and scaling up for large tissues and organs. Emphasis should also be placed on developing new decellularisation methods and establishing minimal criteria for assessing the success of the decellularisation process. The aim of this review is to critically review the existing literature on decellularised scaffolds, especially on the preparation of these matrices, and point out areas for improvement, fini...

In this study, using Harfang Code 32 device, the slag catcher pipelines in one of the South Pars phases were tested. In radiography method of these lines, no clear defect was observed in radiographic films due to the high thickness of 40 mm. However, marvelous results were obtained using advanced ultrasonic. Review and analysis of the results will result in high potential of three-dimensional ultrasonic method in identifying defects in pipelines with high thicknesses and preventing financial and life-threatening risks during the use of these refineries in the future.

A Perspective on Bioprinting Ethics (Invited Editorial)

3D porous scaffold fabrication which include Bioglass and copper nanoparticle

Elektrospin Nanofiberlerin Mekanik Özellikleri ve Scaffold Uygulamaları

- by muhammet ali şenyurt
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- Biomedical Engineering, Biomechanics, Nanocomposites, Nanomaterials

Droplet-based bioprinting (DBB) offers greater advantages due to its simplicity and agility with precise control on deposition of biologics including cells, growth factors, genes, drugs and biomaterials, and has been a prominent technology in the bioprinting community. Due to its immense versatility, DBB technology has been adopted by various application areas, including but not limited to, tissue engineering and regenerative medicine, transplantation and clinics, pharmaceutics and high-throughput screening, and cancer research. Despite the great benefits, the technology currently faces several challenges such as a narrow range of available bioink materials, bioprinting-induced cell damage at substantial levels, limited mechanical and structural integrity of bioprinted constructs, and restrictions on the size of constructs due to lack of vascularization and porosity. This paper presents a first-time review of DBB and comprehensively covers the existing DBB modalities including inkjet, electrohydrodynamic, acoustic, and micro-valve bioprinting. The recent notable studies are highlighted, the relevant bioink biomaterials and bioprinters are expounded, the application areas are presented, and the future prospects are provided to the reader.

- by Ibrahim Tarik Ozbolat
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- Biomaterials Engineering, Biomaterials, Tissue Engineering, Stem Cells

The institution offers under graduate courses in ten branches and post graduate courses in twenty one disciplines of science, engineering andtechnology besides M.S. (by Research) and Ph.D. in all the departments. The faculty is inducted through a process of open advertisement throughout the country. The institute is an example of cultural unity with students drawn from most of the states in the country.

- by Magapu S
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- Biomaterials and tissue engineering scaffolds
- by Alireza Nouri
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- Biomaterials, Titanium, Dental Implants, Orthopaedics

Neurodegeneration is a general term for the progressive loss of structure and/ or function of neurons, gives rise to dysfunction or death of neurons. Neurodegenerative diseases including Alzheimer´s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinal cord injury (SCI) and brain ischemia (BI) occur as a result of neurodegenerative processes leading to different degrees of paralysis and loss of sensation and cognition in the patients. Unfortunately, no successful cure for neurodegenerative disorders has been developed so far, and most of the currently available pharmacological therapies are mainly palliative. In recent years, stem cells have provided a great opportunity to develop potentially powerful innovative strategies to cure neurodegenerative diseases. Stem cells transplantation is capable of restoring injured neuronal tissue by replacement of the damaged cells via using directly differentiated cells or by protecting of existing healthy neurons and glial cells from further damage, or by repairing through providing a conductive environment in favor of regeneration. Here we have brought together some of these examples, discuss possible therapeutic means using different types of stem cells, mainly adult stem cells (ASCs), to treat neurodegenerative diseases.

- by Hojjat Naderi-Meshkin
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- Bioinformatics, Neuroscience, Medical Sciences, Neurology

Electrospinning is a versatile technique for generating a mat of continuous fibers with diameters from a few nanometers to several micrometers. The diversity of electrospinnable materials, and the unique features associated with electro-spun fibers make this technique and its resultant structures attractive for applications in the biomedical field. This article presents an overview of this technique focusing on its application for tissue engineering. In particular, the advantages and disadvantages of using an electrospinning mat for biomedical applications are discussed. It reviews the different available electrospinning configurations, detailing how the different process variables and material types determine the obtained fibers characteristics. Then a description of how nanofiber based scaffolds offer great promise in the regener-ation or function restoration of damaged or diseased bones, muscles or nervous tissue is reported. Different methods for incorporating active agents on nanofibers and controlling their release mechanisms are also reviewed. The review concludes with some personal perspectives on the future work to be done in order to include electrospinning technique in the industrial development of biomedical materials.

- by Laura Ribba
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- Nanofibers, Osseointegration, Drug delivery, Electrospinning

The chemical and structural similarities of calcium orthophosphates (abbreviated as CaPO4) to the mineral composition of natural bones and teeth have made them a good candidate for bone tissue engineering applications. Nowadays, a variety of natural or synthetic CaPO4-based biomaterials is produced and has been extensively used for dental and orthopedic applications. Despite their inherent brittleness, CaPO4 materials possess several appealing characteristics as scaffold materials. Namely, their biocompatibility and variable stoichiometry, thus surface charge density, functionality and dissolution properties, make them suitable for both drug and growth factor delivery. Therefore, CaPO4, especially hydroxyapatite (HA) and tricalcium phosphates (TCPs), have attracted a significant interest in simultaneous use as bone grafts and drug delivery vehicles.

Since most starting materials for tissue engineering are in powder form, using powder-based additive manufacturing methods is attractive and practical. The principal point of employing additive manufacturing (AM) systems is to fabricate parts with arbitrary geometrical complexity with relatively minimal tooling cost and time. Selective laser sintering (SLS) and inkjet 3D printing (3DP) are two powerful and versatile AM techniques which are applicable to powderbased material systems. Hence, the latest state of knowledge available on the use of AM powderbased techniques in tissue engineering and their effect on mechanical and biological properties of fabricated tissues and scaffolds must be updated. Determining the effective setup of parameters, developing improved biocompatible/bioactive materials, and improving the mechanical/ biological properties of laser sintered and 3D printed tissues are the three main concerns which have been investigated in this article.

- by Hooman Yarmand
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- Materials Engineering, Biomaterials, Tissue Engineering, Nanocomposites
- by Alireza Nouri
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- Biomaterials, Bone Healing, Titanium, Dental Materials

Developing cartilage constructs with injectability, appropriate matrix composition, and persistent cartilaginous phenotype remains an enduring challenge in cartilage repair. Fourteen patients with minor contour deformity were treated with fluid cartilage filler gently injected as autologous fluid graft in deep planes of defect of the nose that were close to the bone or the cartilage. A computerized tomographic scan control was performed after 12 months. Pearson's Chi-square test was used to investigate differences in cartilage density between native and newly formed cartilages. The endpoints were the possibility of using fluid cartilage as filler with aesthetic and functional improvement and versatility. Patients were followed up for two years. The constructs of fluid cartilage graft that were injected in the deep plane resulted in a persistent cartilage tissue with appropriate morphology, adequate central nutritional perfusion without central necrosis or ossification, and further augmented nasal dorsum without obvious contraction and deformation. This report demonstrated that fluid cartilage grafts are useful for cartilage regeneration in patients with outcomes of rhinoplasty, internal nasal valve collapse, and minor congenital nose aesthetics deformity

Bioprinting is an emerging technology to fabricate artificial tissues and organs through additive manufacturing of living cells in a tissues-specific pattern by stacking them layer by layer. Two major approaches have been proposed in the literature: bioprinting cells in a scaffold matrix to support cell proliferation and growth, and bioprinting cells without using a scaffold structure. Despite great progress, particularly in scaffold-based approaches along with recent significant attempts, printing large-scale tissues and organs is still elusive. This paper demonstrates recent significant attempts in scaffoldbased and scaffold-free tissue printing approaches, discusses the advantages and limitations of both approaches, and presents a conceptual framework for bioprinting of scale-up tissue by complementing the benefits of these approaches.

Any significant loss of vision or blindness caused by corneal damages is referred to as corneal blindness. Corneal blindness is the fourth most common cause of blindness worldwide, representing more than 5% of the total blind population. Currently, corneal transplantation is used to treat many corneal diseases. In some cases, implantation of artificial cornea (keratoprosthesis) is suggested after a patient has had a donor corneal transplant failure. The shortage of donors and the side effects of keratoprosthesis are limiting these approaches. Recently, researchers have been actively pursuing new approaches for corneal regeneration because of these limitations. Nowadays, tissue engineering of different corneal layers (epithelium, stroma, endothelium, or full thickness tissue) is a promising approach that has attracted a great deal of interest from researchers and focuses on regenerative strategies using different cell sources and biomaterials. Various sources of corneal and non-corneal stem cells have shown significant advantages for corneal epithelium regeneration applications. Pluripotent stem cells (embryonic stem cells and iPS cells), epithelial stem cells (derived from oral mucus, amniotic membrane, epidermis and hair follicle), mesenchymal stem cells (bone marrow, adipose-derived, amniotic membrane, placenta, umbilical cord), and neural crest origin stem cells (dental pulp stem cells) are the most promising sources in this regard. These cells could also be used in combination with natural or synthetic scaffolds to improve the efficacy of the therapeutic approach. As the ocular surface is exposed to external damage, the number of studies on regeneration of the corneal epithelium is rising. In this paper, we reviewed the stem cell-based strategies for corneal epithelium regeneration.

- by Hamed Nosrati and +1
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- Biomaterials, Tissue Engineering, Biomechanics, Regeneration

This review focuses on low-pressure plasma modification methods to produce hydrophobic coatings and surface modifications on biomaterials. Plasma-deposited fluoropolymer, siloxane, and diamond-like carbon (DLC) coatings are reviewed in terms of process developments, monomers used, stability and aging properties, and their behavior in adsorption of proteins, cell attachment, and bacterial adhesion. These hydrophobic coatings are stable with correct selection of monomers and process conditions, but the plasma polymerized siloxane and fluorocarbons have been mainly applied in biochip and test kits rather than in blood-contact applications. Similarly, the surface characteristics and interfacial bonding of DLC coatings play a crucial role in their successful implementation

- by Kim S Siow
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- Biomaterials Engineering, Plasma Physics, Biomedical Engineering, Biomaterials

The use of bioprinting as a powerful tool for tissue and organ fabrication has been a promising development in the field of biomedicine, offering unprecedented versatility in the fabrication of biologically and physiologically relevant constructs. Even though there are a plethora of commercial bioprinters available in the market, most of them are overly expensive. Thus, university facilities and independent research groups often find it difficult, if not impossible, to equip themselves with such machinery. In this Review, we analyze affordable alternatives to commercial bioprinters, which are presented by the Do-it-Yourself (DiY) community. First, we discuss the current state of these low-cost technologies, and the advances made to bridge the divergence between marketed bioprinters and DiY devices. Afterwards, the different bioprinting technologies that are most commonplace for these low-cost devices are examined. Additionally, an overview of the pioneering DiY bioprinters takes place, as well as the open-source software alternatives to control these bioprinters. Next, we analyze the different factors to take into consideration during the bioprinting workflow, such as bioinks, computer-aided models, and bioprinting parameters. Finally, we conclude with a brief assessment of current limitations and potential solutions, as well as future developments in the arena of bioprinting.

- by Prajwal Agrawal
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- Biomaterials Engineering, Biomaterials, Tissue Engineering, 3D printing

In addition to be the second most abundant natural polymer
in nature, a renown has a great potential as a biomaterial in the
area of biotechnology, because it is biocompatible, bio reactive and
biodegradable [1,2]. Such characteristics, diverse applications in
areas such as agriculture, food, environmental, and as two areas
with greater focus: pharmaceutical and health [3,4]. Its structure
consists of N-acetyl-d-glucosamine units with β- (1,4) bonds, having
as main characteristic the insolubility in water and some organic
acids [5]. Chitin belongs to the group of structural polysaccharides,
together with cellulose, the second polymer being more abundant
in the biosphere [6-9]. Due to its structural nature, a product
release system was not found in any of the arthropod exoskeleton,
in the structures of molluscs [10], in the cell wall of fungi [11,12],
protozoa and bacteria, egg shells of nematodes [13,14], the shrimp
fishery residue being the most widely used source [15].Throughout
the decades of research and handling of this polymer, many methods
of extraction have been developed, being the chemical method most
found in the literature, being also used in the means of production
of industrial chitin.
The USA, Japan, India, Canada, China, South Korea, Russia
and Norway generally use the reject of crustacean fishing for
production. The use of strong acids and bases in the chitin
extraction process generates critical points to the process, such as:
high cost of the materials involved, generation of chemical effluent
and final product with low levels of purity [16,17]. Biological
processes become more attractive because they have an affordable
cost of production, do not generate high risk effluent (such as the
chemical process) and high-quality final product [18,19]. All the
processes found in the literature are an objective: to obtain chitin
by separating the proteins and minerals from the raw material used
[20]. Chitin, besides having great biotechnological value, generates
by-products (such as chitosan) that also have added value and even
more relevant properties. In this paper we discuss the already
known processes of obtaining chitin known and registered in the
literature of 2010 up to the present moment: Chemical, enzymatic
and biological processes relating the different methods of obtaining
and with the objective to identify the particularities of each process
regarding the industrial viability and economically balancing them
so that the reader concludes the best process for their research,
also the possibility of executing quality improvements in these
processes.
We will also discuss the polymorphic structures of α- and
β-chitin and the different methods of obtaining each, since different
processes are required in each of them due to their structures,
properties and reactivity. The main objective of this review is to be
able to relate the different processes of obtaining chitin with the
most suitable applications for the method, based on such relation in
aspects such as degree of purity and economic applicability.

The qualities of polymer based biomaterials in facilitating bone regeneration process through tissue engi-neering have attracted the attention of researchers. Biomaterials with properties that can be manipulatedto mimic the three-dimensional architecture of extracellular matrix (ECM) of the native bone tissues, withmechanical properties required for scaffold, biodegradability, excellent biocompatibility and non-toxicityare required. The unique qualities of bacterial cellulose (BC) including biocompatibility, good mechanicalstrength, microporosity and biodegradability with its unique surface chemistry make it ideally suitablefor bone regeneration applications. The ease of being manipulated to mimic any form and structure makeit good scaffold biomaterial to incorporate other nanoparticles for cell proliferation and differentiationfor timely osseointegration and bone ingrowth. This review detailed requirements of scaffold materialsfor bone tissue engineering, provides comprehensive knowledge and highlights of current research onbacterial cellulose composites used for tissue engineering and the potentials of bacterial cellulose forbone regeneration including other nanoparticles incorporated.

- by Selorm Torgbo
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- Nanocomposites, Cellulose, Bone Regeneration, Biopolymers

Analizując zagadnienia biomateriałów oraz dziedziny nauki jaką jest inżynieria tkankowa, należy zaznaczyć, iż jest ona dziedziną interdyscyplinarną, która łączy w sobie wiedzę z zakresu zarówno biologii komórek, medycyny klinicznej, a także nauk ściśle technicznych (biofizyka, biochemia, biomechanika, inżynieria materiałowa oraz biomedyczna) 1. Do podstawowych celów tej dziedziny nauki należy zaliczyć przede wszystkim regenerację uszkodzonych tkanek, narządów wewnętrznych, a także tworzenie nowych tkanek. Z kolei do podstawowych elementów inżynierii tkankowej zalicza się komórki biologiczne, matrycę strukturalną, która umożliwia zasiedlenie komórek oraz czynniki odpowiedzialne za wzrost 2. Warto zaznaczyć również, iż sposób leczenia występujących ubytków tkanek przy wykorzystaniu inżynierii tkankowej zaliczany jest do nowych rozwiązań, w którym pokładane są wielkie nadzieje z zakresu medycyny regeneracyjnej. Dąży ona przede wszystkim do odtwarzania struktur, ale również funkcji tych struktur organizmu, które uległy zniszczeniu 3. Głównym założeniem inżynierii tkankowej jest wykorzystywanie macierzystych komórek pacjenta, które pozyskiwane są ze szpiku kostnego lub też z tkanki tłuszczowej. Następnie dochodzi do zasiedlenia nimi wytworzonego rusztowania oraz wszczepienia całej struktury w zmienione chorobowo miejsce lub w miejsce usuniętych tkanek. Wspomniane rusztowanie stanowi szkielet dla komórek, które ulegają namnażaniu. Proces ten obrazuje rysunek numer 1.

Collagen is the most frequently used protein in the fields of biomaterials and regenerative medicine. Within the skin, collagen type I and III are the most abundant, while collagen type VII is associated with pathologies of the dermal-epidermal junction. The focus of this review is mainly collagens I and III, with a brief overview of collagen VII. Currently, the majority of collagen is extracted from animal sources; however, animal-derived collagen has a number of shortcomings, including immunogenicity, batch-to-batch variation, and pathogenic contamination. Recombinant collagen is a potential solution to the aforementioned issues, although production of correctly post-translationally modified recombinant human collagen has not yet been performed at industrial scale. This review provides an overview of current collagen sources, associated shortcomings, and potential resolutions. Recombinant expression systems are discussed, as well as the issues associated with each method of expression.

5th International Conference of Advances in Materials Science and Engineering (MATE 2022) will an excellent international forum for sharing knowledge and results in theory, methodology and applications impacts and challenges of Materials Science and Engineering. The goal of this Conference is to bring together researchers and practitioners from academia and industry to focus on Materials Science and Engineering advancements, and establishing new collaborations in these areas. Original research papers, state-of-the-art reviews are invited for publication in all areas of Materials Science and Engineering.

Chitosan-beta glycerophosphate-hydroxyethyl cellulose (CH-GP-HEC) is a biocompatible and biodegradable scaffold exhibiting a sol-gel transition at 378C. Chondrogenic factors or mesenchymal stem cells (MSCs) can be included in the CH-GP-HEC, and injected into the site of injury to fill the cartilage tissue defects with minimal invasion and pain. The possible impact of the injectable CH-GP-HEC on the viability of the encapsulated MSCs was assessed by propidium iodide-fluorescein diacetate staining. Proliferation of the human and rat MSCs was also determined by MTS assay on days 0, 7, 14 and 28 after encapsulation. To investigate the potential application of CH-GP-HEC as a drug delivery device, the in vitro release profile of insulin was quantified by QuantiPro-BCA TM protein assay. Chondrogenic differentiation capacity of the encapsulated human MSCs (hMSCs) was also determined after induction of differentiation with transforming growth factor b3. MSCs have very good survival and proliferative rates within CH-GP-HEC hydrogel during the 28-day investigation. A sustained release of insulin occurred over 8 days. The CH-GP-HEC hydrogel also provided suitable conditions for chondrogenic differentiation of the encapsulated hMSCs. In conclusion, the high potential of CH-GP-HEC as an injectable hydrogel for cartilage tissue engineering is emphasised.

- by Hojjat Naderi-Meshkin and +1
- •
- Biochemistry, Clinical Psychology, Hydrogeology, Medical Sciences

The development of artificial organs and implants for replacement of injured and diseased hard tissues such as bones, teeth and joints is highly desired in orthopedic surgery. Orthopedic prostheses have shown an enormous success in restoring the function and offering high quality of life to millions of individuals each year. Therefore, it is pertinent for an engineer to set out new approaches to restore the normal function of impaired hard tissues. Over the last few decades, a large number of metals and applied materials have been developed with significant improvement in various properties in a wide range of medical applications. However, the traditional metallic bone implants are dense and often suffer from the problems of adverse reaction, biomechanical mismatch and lack of adequate space for new bone tissue to grow into the implant. Scientific advancements have been made to fabricate porous scaffolds that mimic the architecture and mechanical properties of natural bone. The porous structure provides necessary framework for the bone cells to grow into the pores and integrate with host tissue, known as osteointegration. The appropriate mechanical properties, in particular, the low elastic modulus mimicking that of bone may minimize or eliminate the stress-shielding problem. Another important approach is to develop biocompatible and corrosion resistant metallic materials to diminish or avoid adverse body reaction. Although numerous types of materials can be involved in this fast developing field, some of them are more widely used in medical applications. Amongst them, titanium and some of its alloys provide many advantages such as excellent biocompatibility, high strength-to-weight ratio, lower elastic modulus, and superior corrosion resistance, required for dental and orthopedic implants. Alloying elements, i.e. Zr, Nb, Ta, Sn, Mo and Si, would lead to superior improvement in properties of titanium for biomedical applications. New processes have recently been developed to synthesize biomimetic porous titanium scaffolds for bone replacement through powder metallurgy. In particular, the space holder sintering method is capable of adjusting the pore shape, the porosity, and the pore size distribution, notably within the range of 200 to 500 µm as required for osteoconductive applications. The present chapter provides a review on the characteristics of porous metal scaffolds used as bone replacement as well as fabrication processes of porous titanium (Ti)

Since the dissolution of polyolefins is a chronic problem, melt processing has been tacitly accepted as an obligation. In this work, polypropylene (PP) was modified on molecular level incorporating poly(ethylene glycol) (PEG) as graft segment (PP-g-PEG) in a range of 6 to 9 mol%. Gold nanoparticles were nucleated in the presence of the copolymer chains via redox reaction. The dissolution of the amphiphilic comb-type graft copolymers containing gold nanoparticles (80 nm in diameter) was achieved in toluene and successfully electrospun from its solution. The diameter of composite fibers was in the range from 0.3 to 2.5 µm. The design of the structurally organized copolymer fiber mats provided a support medium for the nanoparticles enhancing the active surface area for the catalytic applications. The resulting composite fibers exhibited rapid catalytic reduction of methylene blue (MB) dye in the presence of sodium borohydride (NaBH 4) compared to corresponding composite cast film.

A huge family of biodegradable biomaterials could be obtained using key α-amino acid based bis-nucleophilic monomers diamine-diesters, that comprise both: two hydrolysable ester bonds which contribute to biodegradability of the corresponding polymers with reasonable rates, and two terminal amino groups, which are used for a subsequent chain propagation and provide hydrophilic NH-CO (amide, urethane, and urea) links in the polymeric backbones, promoting tissue compatibility. Regular diamine-diesters on the basis of hydrophobic amino acids along with functional diamine-diesters containing orthogonal protected groups were obtained. Accordingly, regular and functional biodegradable polymers were synthesized based on these diamine-diester monomers. Depending on the nature of bis-electrophilic monomers, used as counter-partners of diamine-diester monomers in the chain-propagation reactions, three classes of ester polymers were obtained: poly(ester amide)s, poly(ester urethane)s, and poly(ester urea)s. A usage of these three classes of polymers, along with a huge variety of bis-nucleophilicand bis-electrophilic monomers utilized for their construction, allow to tune chemical, physical-chemical, biochemical, mechanical and other material properties of amino acid based biodegradable ester polymers in the widest range. The polymers already have revealed several obvious advantages compared to another family of biodegradable polymers – aliphatic polyesters, and look very promising for a wide range of applications in reconstructive medicine.

Novel findings on fabrication techniques for bioactive materials, discovering further basic knowledge about wound healing process, and availability of stem cells as alternative candidate for differentiated cells have highly encouraged scientists for developing new bioengineered skin substitutes (BSS) that offer an effective remedy for a specific wound type. However, technical, clinical, legislative and economic reasons hamper widespread commercialization and clinical translation of BSS. Among the various types of strategies that target skin repair and regeneration, tissue engineering with stem cells is most promising route. Tissue engineering by cooperation of several disciplines forms a context on which the commercial development of BSS is possible to provide benefits for patients who currently have limited or no cure options. The principles of tissue engineering are to initiate cell cultures in vitro, grow them in monolayer or on porous scaffolds and transplant the composite into a patient with a specific wound indication in vivo. The potential for creating of custom-designed biomaterials and availability of stem cells from either autologous or allogenic sources have helped to produce novel innovative BSS. Currently, wide range of skin substitutes are already being fabricated for clinical use in different wound indications but not yet definitively established. Therefore, many novel engineered constructs might be fabricated in the future. In this review, we describe the progress that has been made to date in the field of skin substitutes and the critical issues that are still hindering successful production and bench to bedside translation of BSS and restricting the availability of these innovative therapeutic constructs. Integrity of the science and technology, interdisciplinary expertise collaborations, and early interaction with regulatory entities such as Food and Drug Administration (FDA) and European Medicines Agency (EMA), together with other critical determinants, is vital to the successful commercialization of tissue engineering products into the marketplace/clinic.

- by Hojjat Naderi-Meshkin and +1
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- Medical Sciences, Biomedical Engineering, Biomaterials, Tissue Engineering

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

The qualities of polymer based biomaterials in facilitating bone regeneration process through tissue engineering have attracted the attention of researchers. Biomaterials with properties that can be manipulated to mimic the three-dimensional architecture of extracellular matrix (ECM) of the native bone tissues, with mechanical properties required for scaffold, biodegradability, excellent biocompatibility and non-toxicity are required. The unique qualities of bacterial cellulose (BC) including biocompatibility, good mechanical strength, microporosity and biodegradability with its unique surface chemistry make it ideally suitable for bone regeneration applications. The ease of being manipulated to mimic any form and structure make it good scaffold biomaterial to incorporate other nanoparticles for cell proliferation and differentiation for timely osseointegration and bone ingrowth. This review detailed requirements of scaffold materials for bone tissue engineering, provides comprehensive knowledge and highlights of current research on bacterial cellulose composites used for tissue engineering and the potentials of bacterial cellulose for bone regeneration including other nanoparticles incorporated.

- by Prakit Sukyai and +1
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- Biomaterials and tissue engineering scaffolds

We report the design of electrospun poly caprolactone (PCL) nano fibrous mat containing ethyl acetate extract of medicinal plant Clerodendrum phlomidis L.F (CP). Non polar solvent extract of Clerodendrum phlomidis leaf analyzed for their phytochemical components and chemical identification by GC-MS analysis. More than 40 phyto constituents were identified and the major components found to be terpenoids, flavonoids, phytol, hexadecanoic acid and palmitic acid. SEM images revealed there was a substantial decrease in PCL fiber diameter from 400 to 300 nm upon CP addition. HRTEM analysis corroborates well with the SEM results obtained. Xray diffraction (XRD), UV-visible spectroscopy (UV-vis), and Fourier transform infrared (FTIR) spectroscopy confirmed the CP incorporation into the matrix. Water contact angle measurement showed with the addition of CP, there was an increase in wettability of the PCL fibers without affecting their mechanical properties. TGA studies showed the as spun mats were thermally stable. Antibacterial studies was investigated against the predominant pathogenic gram positive and gram negative bacteria: Staphylococctus aureus, Pseudomonas aeruginosa, Salmonella

Piezoelectric materials that generate electrical signals in response to mechanical strain can be used in tissue engineering to stimulate cell proliferation. Poly (vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)), a piezoelectric polymer, is widely used in biomaterial applications. We hypothesized that incorporation of zinc oxide (ZnO) nanoparticles into the P(VDF-TrFE) matrix could promote adhesion, migration, and proliferation of cells, as well as blood vessel formation (angiogenesis). In this study, we fabricated and comprehensively characterized a novel electrospun P(VDF-TrFE)/ZnO nanocomposite tissue engineering scaffold. We analyzed the morphological features of the polymeric matrix by scanning electron microscopy, and utilized Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry to examine changes in the crystalline phases of the copolymer due to addition of the nanoparticles. We detected no or minimal adverse effects of the biomaterials with regard to blood compatibility in vitro, biocompatibility, and cytotoxicity, indicating that P(VDF-TrFE)/ZnO nanocomposite scaffolds are suitable for tissue engineering applications. Interestingly, human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells cultured on the nanocomposite scaffolds exhibited higher cell viability, adhesion, and proliferation compared to cells cultured on tissue culture plates or neat P(VDF-TrFE) scaffolds. Nanocomposite scaffolds implanted into rats with or without hMSCs did not elicit immunological responses, as assessed by macroscopic analysis and histology. Importantly, nanocomposite scaffolds promoted angiogenesis, which was increased in scaffolds pre-seeded with hMSCs. Overall, our results highlight the potential of these novel P(VDF-TrFE)/ZnO nanocomposites for use in tissue engineering, due to their biocompatibility and ability to promote cell adhesion and angiogenesis.

The purpose of this study is to demonstrate the ability of additive manufacturing, also known as 3D printing, to produce effective drug delivery devices and implants that are both identifiable, as well as traceable. Drug delivery devices can potentially be used for drug release in the direct vicinity of target tissues or the selected medication route in a patient-specific manner as required. The identification and traceability of additively manufactured implants can be administered through radiofrequency identification systems. The focus of this study is to explore how embedded medication and sensors can be added in different additive manufacturing processes. The concept is extended to biomaterials with the help of the literature. As a result of this study, a patient-specific drug delivery device can be custom-designed and additively manufactured in the form of an implant that can identify, trace, and dispense a drug to the vicinity of a selected target tissue as a patient-specific function of time for bodily treatment and restoration.

- by Mika Salmi
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- Biomaterials Engineering, Biomedical Engineering, Drugs And Addiction, Biomaterials