Scaffolds For Regenerative Medicine Research Articles

Recent advances in nano-scaffolds for tissue engineering applications: Toward natural therapeutics.

Among the promising methods for repairing or replacing tissue defects in the human body and the hottest research topics in medical science today are regenerative medicine and tissue engineering. On the other hand, nanotechnology has been expanded into different areas of regenerative medicine and tissue engineering due to its essential benefits in improving performance in various fields. Nanotechnology, a helpful strategy in tissue engineering, offers new solutions to unsolved problems. Especially considering the excellent physicochemical properties of nanoscale structures, their application in regenerative medicine has been gradually developed, and a lot of research has been conducted in this field. In this regard, various nanoscale structures, including nanofibers, nanosheets, nanofilms, nano-clays, hollow spheres, and different nanoparticles, have been developed to advance nanotechnology strategies with tissue repair goals. Here, we comprehensively review the application of the mentioned nanostructures in constructing nanocomposite scaffolds for regenerative medicine and tissue engineering. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Diagnostic Tools > Biosensing.

Tissue engineering of decellularized pancreas scaffolds for regenerative medicine in diabetes.

Diabetes mellitus is a global disease requiring long-term treatment and monitoring. At present, pancreas or islet transplantation is the only reliable treatment for achieving stable euglycemia in Type I diabetes patients. However, the shortage of viable pancreata for transplantation limits the use of this therapy for the majority of patients. Organ decellularization and recellularization is emerging as a promising solution to overcome the shortage of viable organs for transplantation by providing a potential alternative source of donor organs. Several studies on decellularization and recellularization of rodent, porcine, and human pancreata have been performed, and show promise for generating usable decellularized pancreas scaffolds for subsequent recellularization and transplantation. In this state-of-the-art review, we provide an overview of the latest advances in pancreas decellularization, recellularization, and revascularization. We also discuss clinical considerations such as potential transplantation sites, donor source, and immune considerations. We conclude with an outlook on the remaining work that needs to be done in order to realize the goal of using this technology to create bioengineered pancreata for transplantation in diabetes patients. STATEMENT OF SIGNIFICANCE: Pancreas or islet transplantation is a means of providing insulin-independence in diabetes patients. However, due to the shortage of viable pancreata, whole-organ decellularization and recellularization is emerging as a promising solution to overcome organ shortage for transplantation. Several studies on decellularization and recellularization of rodent, porcine, and human pancreata have shown promise for generating usable decellularized pancreas scaffolds for subsequent recellularization and transplantation. In this state-of-the-art review, we highlight the latest advances in pancreas decellularization, recellularization, and revascularization. We also discuss clinical considerations such as potential transplantation sites, donor source, and immune considerations. We conclude with future work that needs to be done in order to realize clinical translation of bioengineered pancreata for transplantation in diabetes patients.

3D printed mesoporous bioactive glass, bioglass 45S5, and β-TCP scaffolds for regenerative medicine: A comparative invitro study.

While autografts to date remain the "gold standard" for bone void fillers, synthetic bone grafts have garnered attention due to their favorable advantages such as ability to be tailored in terms of their physical and chemical properties. Bioactive glass (BG), an inorganic material, has the capacity to form a strong bond with bone by forming a bone-like apatite surface, enhancing osteogenesis. Coupled with additive manufacturing (3D printing) it is possible to maximize bone regenerative properties of the BG. The objective of this study was to synthesize and characterize 3D printed mesoporous bioactive glass (MBG), BG 45S5, and compare to β-Tricalcium phosphate (β-TCP) based scaffolds; test cell viability and osteogenic differentiation on human osteoprogenitor cells invitro. MBG, BG 45S5, and β-TCP were fabricated into colloidal gel suspensions, tested with a rheometer, and manufactured into scaffolds using a 3D direct-write micro-printer. The materials were characterized in terms of microstructure and composition with Thermogravimetric Analyzer/Differential Scanning Calorimeter (TGA/DSC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Micro-Computed Tomography (μ-CT), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Mattauch-Herzog-Inductively Coupled Plasma-Mass Spectrometry (MH-ICP-MS). Scaffolds were tested for cell proliferation and osteogenic differentiation using human osteoprogenitor cells. Osteogenic media was used for differentiation, and immunocytochemistry for osteogenic markers Runx-2, Collagen-I, and Osteocalcin. The cell viability results after 7 days of culture yielded significantly higher (p < 0.05) results in β-TCP scaffolds compared to BG 45S5 and MBG groups. All materials expressed osteogenic markers after 21 days of culture in expansion and osteogenic media.

Sustainable Vegetable Oil-Based Biomaterials: Synthesis and Biomedical Applications.

One of the main criteria for ecological sustainability is that the materials produced for common use are green. This can include the use of biomaterials and materials that are environmentally friendly, biodegradable and produced at low cost. The exploration of natural resources as sustainable precursors leads to the production of biopolymers that are useful for 3D printing technology. Recently, waste vegetable oils have been found to be a good alternative source for the production of biopolymers in various applications from the engineering to the biomedicine. In this review, the processes for the synthesis of vegetable oil-based biomaterials are described in detail. Moreover, the functionalization strategies to improve the mechanical properties of these materials and the cell-material interaction for their potential use as micro-structured scaffolds in regenerative medicine are discussed.

Structural and biofunctional evaluation of decellularized jellyfish matrices.

Extracellular matrices decellularized from marine animal tissues are emerging scaffolds in tissue engineering. Jellyfish tissues are suitable for making functional and safe decellularized matrices in part due to their simple structure, high water content, and low risk of pathogen transmission to humans. Jellyfish are some of the most prevalent marine animals, but their decellularized matrices have remained largely undeveloped. Here we evaluated the structures and functions of the jellyfish (Rhopilema esculentum) matrices decellularized with seven different detergents. All of them showed effectiveness in removing the cellular components. Scanning electron microscopy and mechanical testing revealed that the decellularized matrices mostly retained the native microstructures, whereas only SDS and SNL distorted the matrices' multilayered and fibrous architecture. The collagen hybridizing peptide fluorescence staining showed that SDS, SNL, Triton X-100, IGEPAL, and Tween-20 denatured the jellyfish collagen molecules to varying degrees while CHAPS and SD protected the collagen's triple-helix conformation. We demonstrated that the decellularized jellyfish matrices showed similarity to different types of mammalian collagen and supported the adhesion and proliferation of human dermal and corneal fibroblasts and mouse chondrocytes in 3D culture. Importantly, the decellularized jellyfish matrix also facilitated wound healing in vivo by reducing inflammation while promoting angiogenesis and tissue remodeling. Taken together, our study demonstrated that the decellularized jellyfish matrices are an easy-to-prepare, biocompatible, and potentially widely applicable scaffold for regenerative medicine.

Bioinspired Electropun Fibrous Materials Based on Poly-3-Hydroxybutyrate and Hemin: Preparation, Physicochemical Properties, and Weathering.

The development of innovative fibrous materials with valuable multifunctional properties based on biodegradable polymers and modifying additives presents a challenging direction for modern materials science and environmental safety. In this work, high-performance composite fibrous materials based on semicrystalline biodegradable poly-3-hydroxybutyrate (PHB) and natural iron-containing porphyrin, hemin (Hmi) were prepared by electrospinning. The addition of Hmi to the feed PHB mixture (at concentrations above 3 wt.%) is shown to facilitate the electrospinning process and improve the quality of the electrospun PHB/Hmi materials: the fibers become uniform, their average diameter decreases down to 1.77 µm, and porosity increases to 94%. Structural morphology, phase composition, and physicochemical properties of the Hmi/PHB fibrous materials were studied by diverse physicochemical methods, including electronic paramagnetic resonance, optical microscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy, elemental analysis, differential scanning calorimetry, Fourier-transformed infrared spectroscopy, mechanical analysis, etc. The proposed nonwoven Hmi/PHB composites with high porosity, good mechanical properties, and retarded biodegradation due to high antibacterial potential can be used as high-performance and robust materials for biomedical applications, including breathable materials for wound disinfection and accelerated healing, scaffolds for regenerative medicine and tissue engineering.

An Effective Method for Decellularization of Human Foreskin: Implications for Skin Regeneration in Small Wounds.

Objective Acellular matrices of different allogeneic or xenogeneic origins are widely used as structural scaffolds in regenerative medicine. The main goal of this research was to optimize a method for decellularization of foreskin for skin regeneration in small wounds. Materials and Methods In this experimental study, the dermal layers of foreskin were divided into two sections and subjected to two different decellularization methods: the sodium dodecyl sulfate method (SDS-M), and our optimized foreskin decellularization method (OFD-M). A combination of non-ionic detergents and SDS were used to decellularize the foreskin in OFD-M. The histological, morphological, and biomechanical properties of both methods were compared. In addition, human umbilical cord mesenchymal stem cells (hucMSCs) were isolated, and the biocompatibility and recellularization of both scaffolds by hucMSC were subsequently determined. Results We observed that OFD-M is an appropriate approach for successful removal of cellular components from the foreskin tissue, without physical disturbance to the acellular matrix. In comparison to SDS-M, this new bioscaffold possesses a fine network containing a high amount of collagen fibers and glycosaminoglycans (GAG) (P≤0.03), is biocompatible and harmless for hucMSC (viability 91.7%), and exhibits a relatively high tensile strength. ConclusionWe found that the extracellular matrix (ECM) structural integrity, the main ECM components, and the mechanical properties of the foreskin are well maintained after applying the OFD-M decellularization technique, indicating that the resulting scaffold would be a suitable platform for culturing MSC for skin grafting in small wounds.

Scaffolds in the microbial resistant era: Fabrication, materials, properties and tissue engineering applications.

Due to microbial infections dramatically affect cell survival and increase the risk of implant failure, scaffolds produced with antimicrobial materials are now much more likely to be successful. Multidrug-resistant infections without suitable prevention strategies are increasing at an alarming rate. The ability of cells to organize, develop, differentiate, produce a functioning extracellular matrix (ECM) and create new functional tissue can all be controlled by careful control of the extracellular microenvironment. This review covers the present state of advanced strategies to develop scaffolds with antimicrobial properties for bone, oral tissue, skin, muscle, nerve, trachea, cardiac and other tissue engineering applications. The review focuses on the development of antimicrobial scaffolds against bacteria and fungi using a wide range of materials, including polymers, biopolymers, glass, ceramics and antimicrobials agents such as antibiotics, antiseptics, antimicrobial polymers, peptides, metals, carbon nanomaterials, combinatorial strategies, and includes discussions on the antimicrobial mechanisms involved in these antimicrobial approaches. The toxicological aspects of these advanced scaffolds are also analyzed to ensure future technological transfer to clinics. The main antimicrobial methods of characterizing scaffolds’ antimicrobial and antibiofilm properties are described. The production methods of these porous supports, such as electrospinning, phase separation, gas foaming, the porogen method, polymerization in solution, fiber mesh coating, self-assembly, membrane lamination, freeze drying, 3D printing and bioprinting, among others, are also included in this article. These important advances in antimicrobial materials-based scaffolds for regenerative medicine offer many new promising avenues to the material design and tissue-engineering communities.

Mucoadhesive and Antimicrobial Allantoin/β Cyclodextrins-Loaded Carbopol Gels as Scaffolds for Regenerative Medicine.

Allantoin and its β-cyclodextrin and hydroxypropyl-β-cyclodextrin inclusion complexes 1:1 have been used to prepare carbopol-based mucoadhesive gels. The gelation process occurred by adjustment with glycerol 10% in the presence of triethanolamine. The structural features induced by the presence of allantoin and the corresponding β-cyclodextrins inclusion complexes have been first investigated by infrared spectroscopy highlighting strong interactions within the gels network and ideal crosslinks for the self-healing behavior. The hydrophilicity of the gels was investigated by the determination of the surface tension parameters and the free energy of hydration. The interfacial free energy values indicated prolonged biocompatibility with blood. The gels-water molecule interactions in terms of sorption, permeability, and diffusion coefficients were evaluated by dynamic vapor sorption analysis. The self-assembly process through intermolecular H-bonding, the high hydrophilicity, the mechanical performance, the hydrolytic stability in simulated biological media, the biocompatibility with normal human dermal fibroblast (NHDF) cells, the mucoadhesivity and antimicrobial activity on selected microorganism species (S. Aureus and C. albicans) of the allantoin-based gels recommend them as promising scaffold alternatives in regenerative medicine.

Interaction-Induced Structural Transformations in Polysaccharide and Protein-Polysaccharide Gels as Functional Basis for Novel Soft-Matter: A Case of Carrageenans.

Biocompatible, nontoxic, and biodegradable polysaccharides are considered as a promising base for bio-inspired materials, applicable as scaffolds in regenerative medicine, coatings in drug delivery systems, etc. The tunable macroscopic properties of gels should meet case-dependent requirements. The admixture of proteins to polysaccharides and their coupling in more sophisticated structures opens an avenue for gel property tuning via physical cross-linking of components and the modification of gel network structure. In this review recent success in the conformational studies of binary protein–polysaccharide gels is summarized with the main focus upon carrageenans. Future perspectives and challenges in rational design of novel polysaccharide-based materials are outlined.

Biodegradable polyurethane scaffolds in regenerative medicine: Clinical translation review.

Early explorations of tissue engineering and regenerative medicine concepts commonly utilized simple polyesters such as polyglycolide, polylactide, and their copolymers as scaffolds. These biomaterials were deemed clinically acceptable, readily accessible, and provided processability and a generally known biological response. With experience and refinement of approaches, greater control of material properties and integrated bioactivity has received emphasis and a broadened palette of synthetic biomaterials has been employed. Biodegradable polyurethanes (PUs) have emerged as an attractive option for synthetic scaffolds in a variety of tissue applications because of their flexibility in molecular design and ability to fulfill mechanical property objectives, particularly in soft tissue applications. Biodegradable PUs are highly customizable based on their composition and processability to impart tailored mechanical and degradation behavior. Additionally, bioactive agents can be readily incorporated into these scaffolds to drive a desired biological response. Enthusiasm for biodegradable PU scaffolds has soared in recent years, leading to rapid growth in the literature documenting novel PU chemistries, scaffold designs, mechanical properties, and aspects of biocompatibility. Despite the enthusiasm in the field, there are still few examples of biodegradable PU scaffolds that have achieved regulatory approval and routine clinical use. However, there is a growing literature where biodegradable PU scaffolds are being specifically developed for a wide range of pathologies and where relevant pre-clinical models are being employed. The purpose of this review is first to highlight examples of clinically used biodegradable PU scaffolds, and then to summarize the growing body of reports on pre-clinical applications of biodegradable PU scaffolds.

Sustainable Applications of Animal Waste Proteins.

Currently, the growth of the global population leads to an increase in demand for agricultural products. Expanding the obtaining and consumption of food products results in a scale up in the amount of by-products formed, the development of processing methods for which is becoming an urgent task of modern science. Collagen and keratin make up a significant part of the animal origin protein waste, and the potential for their biotechnological application is almost inexhaustible. The specific fibrillar structure allows collagen and keratin to be in demand in bioengineering in various forms and formats, as a basis for obtaining hydrogels, nanoparticles and scaffolds for regenerative medicine and targeted drug delivery, films for the development of biodegradable packaging materials, etc. This review describes the variety of sustainable sources of collagen and keratin and the beneficial application multiformity of these proteins.

Kirigami-Inspired Biodesign for Applications in Healthcare.

Mechanically flexible and conformable materials and integrated devices have found diverse applications in personalized healthcare as diagnostics and therapeutics, tissue engineering and regenerative medicine constructs, surgical tools, secure systems, and assistive technologies. In order to impart optimal mechanical properties to the (bio)materials used in these applications, various strategies have been explored-from composites to structural engineering. In recent years, geometric cuts inspired by the art of paper-cutting, referred to as kirigami, have provided innovative opportunities for conferring precise mechanical properties via material removal. Kirigami-based approaches have been used for device design in areas ranging from soft bioelectronics to energy storage. In this review, the principles of kirigami-inspired engineering specifically for biomedical applications are discussed. Factors pertinent to their design, including cut geometry, materials, and fabrication, and the effect these parameters have on their properties and configurations are covered. Examples of kirigami designs in healthcare are presented, such as, various form factors of sensors (on skin, wearable), implantable devices, therapeutics, surgical procedures, and cellular scaffolds for regenerative medicine. Finally, the challenges and future scope for the successful translation of these biodesign concepts to broader deployment are discussed.

Recent patents on water-soluble polysaccharides for advanced drug delivery, tissue engineering and regenerative medicine.

Water-soluble polysaccharides have unique properties and have found wide application in the design of advanced drug-delivery systems and the biofabrication of tissue engineered scaffolds in regenerative medicine. This patent review provides a concise incursion into the mechanisms that define the key properties of water-soluble polysaccharides that have found embodiment within active patents recently granted (2020-2021). In addition, the relationship between their solubility and structural features such as molecular weight, ionic profile, degree of branching/crosslinking, side-chain flexibility and the presence/modification of functional groups that have been discusses. An assimilation of patents in which water-soluble polysaccharides are central to the design of therapeutic interventions applied to specialized treatments in oncology, infectious diseases and neuronal disorders is provided.

Curcumin loaded waste biomass resourced cellulosic nanofiber cloth as a potential scaffold for regenerative medicine: An in-vitro assessment.

This article demonstrates the development of nanofibrous cloths by electrospinning of renewable materials, i.e., curcumin-loaded 90% cellulose acetate (CA)/10% poly(ε-caprolactone) (PCL), for applications in regenerative medicine. The CA is derived from the biomass waste of the oil palm plantation (empty fruit bunch). The nanofiber scaffolds are characterized for the fiber morphology, microstructure, thermal properties, and wettability. The optimized smooth and bead-free electrospun fiber cloth contains 90% CA and 10% PCL in two curcumin compositions (0.5 and 1wt%). The role of curcumin is shown to be two-fold: the first is its function as a drug and the second is its role in lowering the water contact angle and increasing the hydrophilicity. The hydrophilicity enhancements are related to the hydrogen bonding between the components. The enhanced hydrophilicity contributed to improve the swelling behavior of the scaffolds; the CA/PCL/Cur (0.5%) and the CA/PCL/Cur (1.0%) showed swelling of ~700 and 950%, respectively, in phosphate-buffered saline (PBS). The drug-release studies revealed the highest cumulative drug release of 60% and 78% for CA/PCL/Cur (0.5%) and CA/PCL/Cur (1.0%) nanofibers, respectively. The in-vitro studies showed that CA/PCL/Cur (0.5wt%) and CA/PCL/Cur (1.0wt%) nanofiber scaffolds facilitate a higher proliferation and expression of actin in fibroblasts than those scaffolds without curcumin for wound healing applications.

Development of new filaments for 3D printing based on bio-inspired ceramics

3D printing allows the development of devices in a wide range of sectors, including the automotive industry, construction, aeronautics, food, textiles and also biomedical, among others. There are several technologies being the impression by molten deposition (FDM) one of the most widespread. In the particular case of biomedical engineering, three are the main application and research axes: (1) biomodels for the preparation of surgical interventions, (2) design and manufacture of customized biomedical devices and (3) porous scaffolds for regenerative medicine. The objective of the present study focuses on the development of a new filament for 3D-FDM printing composed of polylactic acid (PLA) and a biphasic crystalline bioceramic of marine origin (Biofast). Several filament formulations were obtained after extrusion of mixtures with variable proportions PLA / Biofast. The physical-chemical properties of both the filament and the printed pieces were studied by scanning electron microscopy, Raman and IR spectroscopy. The analyzes show that the bioceramic particles are evenly distributed in the polymer matrix and their incorporation can be controlled depending on the selected mixture. As for the crystal structure and links, manufacturing processes do not originate modifications that may affect the biocompatibility of the final device. Thus, these new filaments are shown as potential candidates for application in biomedical engineering.

Enhanced wound healing properties of guar gum/curcumin-stabilized silver nanoparticle hydrogels

Biocompatible materials that act as scaffolds for regenerative medicine are of enormous interest. Hydrogel-nanoparticle composites have great potential in this regard, however evaluations of their wound healing and safety in vivo in animal studies are scarce. Here we demonstrate that a guar gum/curcumin-stabilized silver nanoparticle hydrogel composite is an injectable material with exceptional wound healing and antibacterial properties. We show that the curcumin-bound silver nanoparticles themselves exhibit low cytotoxicity and enhance proliferation, migration, and collagen production in in vitro studies of human dermal fibroblasts. We then show that the hydrogel-nanoparticle composite promotes wound healing in in vivo studies on rats, accelerating wound closure by > 40% and reducing bacterial counts by 60% compared to commercial antibacterial gels. Histopathology indicates that the hydrogel composite enhances transition from the inflammation to proliferation stage of healing, promoting the formation of fibroblasts and new blood vessels, while target gene expression studies confirm that the accelerated tissue remodeling occurs along the normal pathways. As such these hydrogel composites show great promise as wound dressing materials with high antibacterial capacity.

Modulation of Conductivity of Alginate Hydrogels Containing Reduced Graphene Oxide through the Addition of Proteins.

Modifying hydrogels in order to enhance their conductivity is an exciting field with applications in cardio and neuro-regenerative medicine. Therefore, we have designed hybrid alginate hydrogels containing uncoated and protein-coated reduced graphene oxide (rGO). We specifically studied the adsorption of three different proteins, BSA, elastin, and collagen, and the outcomes when these protein-coated rGO nanocomposites are embedded within the hydrogels. Our results demonstrate that BSA, elastin, and collagen are adsorbed onto the rGO surface, through a non-spontaneous phenomenon that fits Langmuir and pseudo-second-order adsorption models. Protein-coated rGOs are able to preclude further adsorption of erythropoietin, but not insulin. Collagen showed better adsorption capacity than BSA and elastin due to its hydrophobic nature, although requiring more energy. Moreover, collagen-coated rGO hybrid alginate hydrogels showed an enhancement in conductivity, showing that it could be a promising conductive scaffold for regenerative medicine.

3D Printing of Black Bioceramic Scaffolds with Micro/Nanostructure for Bone Tumor-Induced Tissue Therapy.

It is common to improve the relevant performance in the field of energy storage materials or catalytic materials by regulating the number of defects. However, there are few studies on the biomaterials containing defects for tissue engineering. Herein, a new type of defect-rich scaffolds, black akermanite (B-AKT) bioceramic scaffolds with micro/nanostructure, the thickness of which is from 0.14 to 1.94µm, is fabricated through introducing defects on the surface of bioceramic scaffolds. The B-AKT scaffolds have advantages on the degradation rate and the osteogenic capacity over the AKT (Ca2 MgSi2 O7 ) scaffolds due to the surface defects which stimulate the osteogenic differentiation of rabbit bone mesenchymal stem cells via activating bone morphogenetic protein 2 （BMP2） signaling pathway and further promote bone formation in vivo. In addition, the prepared B-AKT scaffolds, the temperature of which can be over 100°C under the near infrared （NIR） irradiation (0.66 Wcm-2 ), possess excellent performance on photothermal and antitumor effects. The work develops an introducing-defect strategy for regulating the biological performance of bioceramic scaffolds, which is expected to be applied in the next generation of bioceramic scaffolds for regenerative medicine.

Mechanical characterization of rose bengal and green light crosslinked collagen scaffolds for regenerative medicine.

Collagen is one of the most important biomaterials for tissue engineering approaches. Despite its excellent biocompatibility, it shows the non-negligible disadvantage of poor mechanical stability. Photochemical crosslinking with rose bengal and green light (RGX) is an appropriate method to improve this property. The development of collagen laminates is helpful for further adjustment of the mechanical properties as well as the controlled release of incorporated substances. In this study, we investigate the impact of crosslinking and layering of two different collagen scaffolds on the swelling behavior and mechanical behavior in micro tensile tests to obtain information on its wearing comfort (stiffness, strength and ductility). The mechanical stability of the collagen material after degradation due to cell contact is examined using thickness measurements. There is no linear increase or decrease due to layering homologous laminates. Unexpectedly, a decrease in elongation at break, Young’s modulus and ultimate tensile strength are measured when the untreated monolayer is compared to the crosslinked one. Furthermore, we can detect a connection between stability and cell proliferation. The results show that with variation in number and type of layers, collagen scaffolds with tailored mechanical properties can be produced. Such a multi-layered structure enables the release of biomolecules into inner or outer layers for biomedical applications.