Composites For Tissue Engineering Research Articles

Application of metal-organic frameworks-based functional composite scaffolds in tissue engineering.

With the rapid development of materials science and tissue engineering, a variety of biomaterials have been used to construct tissue engineering scaffolds. Due to the performance limitations of single materials, functional composite biomaterials have attracted great attention as tools to improve the effectiveness of biological scaffolds for tissue repair. In recent years, metal-organic frameworks (MOFs) have shown great promise for application in tissue engineering because of their high specific surface area, high porosity, high biocompatibility, appropriate environmental sensitivities and other advantages. This review introduces methods for the construction of MOFs-based functional composite scaffolds and describes the specific functions and mechanisms of MOFs in repairing damaged tissue. The latest MOFs-based functional composites and their applications in different tissues are discussed. Finally, the challenges and future prospects of using MOFs-based composites in tissue engineering are summarized. The aim of this review is to show the great potential of MOFs-based functional composite materials in the field of tissue engineering and to stimulate further innovation in this promising area.

Structures, Properties, and Bioengineering Applications of Alginates and Hyaluronic Acid.

In recent years, polymeric materials have been used in a wide range of applications in a variety of fields. In particular, in the field of bioengineering, the use of natural biomaterials offers a possible new avenue for the development of products with better biocompatibility, biodegradability, and non-toxicity. This paper reviews the structural and physicochemical properties of alginate and hyaluronic acid, as well as the applications of the modified cross-linked derivatives in tissue engineering and drug delivery. This paper summarizes the application of alginate and hyaluronic acid in bone tissue engineering, wound dressings, and drug carriers. We provide some ideas on how to replace or combine alginate-based composites with hyaluronic-acid-based composites in tissue engineering and drug delivery to achieve better eco-economic value.

Biopolymer-based composites for tissue engineering applications: A basis for future opportunities

Biomimetic scaffolds supporting tissue regeneration are complex materials with multifunctional characteristics. The unique biocompatibility and biodegradability of biopolymers make them excellent candidates for tissue engineering and regenerative medicine. Biopolymers, which have a wide range of properties, can be obtained from different natural sources. Depending on the target tissue, biopolymers can be engineered to meet a series of specific functions. We review different types of biopolymers and their composites, besides their interactions with specific cells and tissues. Specific cellular mechanisms in tissue regeneration are also considered to elucidate the effects of biopolymers on controlling cellular mechanisms given their advantages and challenging aspects. Furthermore, the modifications required to mimic the properties of neural, cardiac, bone, and skin tissues are discussed. Utilization of biopolymer-based composites in tissue engineering requires additional improvements, where several challenges should be overcome. This work is mainly focused on biopolymers used in tissue engineering, providing support for engineering of future biocomposites for the same purpose. Some examples of biocomposites are also provided, a general guide for selection of biopolymers and the secondary component (biopolymers as complements, additives, or nano-scale biomaterials) to develop biocomposites.

Effects of Mangosteen Peel Phenolic Compounds on Tilapia Skin Collagen-Based Mineralized Scaffold Properties.

A proper valorization of biological waste sources for an effective conversion into composites for tissue engineering is discussed in this study. Hence, the collagen and the phenolic compound applied in this investigation were extracted from waste sources, respectively, fish industry rejects and the peels of the mangosteen fruit. Porous scaffolds were prepared by combining both components at different compositions and mineralized at different temperatures to evaluate the modifications in the biomimetic formation of apatite. The inclusion of mangosteen extract showed the advantage of increasing the collagen denaturation temperature, improving the stability of its triple helix. Moreover, the extract provided antioxidant activity due to its phenolic composition, as confirmed by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant assays. Mineralization was successfully achieved as indicated by thermogravimetry and scanning electron microscopy. A higher temperature and a lower extract concentration reduced the calcium phosphate deposits. The extract also affected the pore size, particularly at a lower concentration. The X-ray diffraction pattern identified a low degree of crystallization. A high mineralization temperature induced the formation of smaller crystallites ranging from 18.9 to 25.4 nm. Although the deposited hydroxyapatite showed low crystallinity, the scaffolds are suitable for bone tissue applications and may be effective in controlling the resorbability rate in tissue regeneration.

A Reliable Porcine Fascio-Cutaneous Flap Model for Vascularized Composite Allografts Bioengineering Studies.

Vascularized Composite Allografts (VCA) such as hand, face, or penile transplant represents the cutting-edge treatment for devastating skin defects, failed by the first steps of the reconstructive ladder. Despite promising aesthetic and functional outcomes, the main limiting factor remains the need for a drastically applied lifelong immunosuppression and its well-known medical risks, preventing broader indications. Therefore, lifting the immune barrier in VCA is essential to tip the ethical scale and improve patients' quality of life using the most advanced surgical techniques. De novo creation of a patient-specific graft is the upcoming breakthrough in reconstructive transplantation. Using tissue engineering techniques, VCAs can be freed of donor cells and customized for the recipient through perfusion-decellularization-recellularization. To develop these new technologies, a large-scale animal VCA model is necessary. Hence, swine fascio-cutaneous flaps, composed of skin, fat, fascia, and vessels, represent an ideal model for preliminary studies in VCA. Nevertheless, most VCA models described in the literature include muscle and bone. This work reportsa reliable and reproducible technique for saphenous fascio-cutaneous flap harvest in swine, a practical tool for various research fields, especially vascularized composite tissue engineering.

Controlled metoprolol tartrate release from poly(ε-caprolactone)-poly(ε-caprolactone)/polyethylene oxide/metoprolol tartrate composites with alternating multi-layered structures prepared through layer-multiplying co-extrusion

Multi-layered structure design has provided a promising and powerful strategy for the fabrication of controlled-release dosage forms. However, a convenient and effective preparation technology is still urgently needed. Herein, we applied layer-multiplying co-extrusion (LMCE) technology to construct poly(ε-caprolactone)-poly(ε-caprolactone)/polyethylene oxide/metoprolol tartrate (PCL-PCL/PEO/MPT) composites with alternating multi-layered structures in one step. The layer number could be doubled by an addition of layer-multiplying element. The degradation analysis indicated that fewer PCL layers were beneficial to the dissolution of PEO and increased the pore size in the matrix. The in vitro release results suggested the MPT encapsulated in PEO aggregates was released gradually in a layer-by-layer manner, and the MPT release was flexibly modulated by the number of PCL layer and PEO content. Additionally, methyl thiazolyl tetrazolium assay presented a potential application of PCL-PCL/PEO/MPT composites in tissue engineering. The LMCE technology should have great potential for the preparation of controlled-release dosage forms.

Preparation, Properties, and Application of Graphene-Based Materials in Tissue Engineering Scaffolds.

Tissue engineering has a great application prospect as an effective treatment for tissue and organ injury, functional reduction, or loss. Bioactive tissues are reconstructed and damaged organs are repaired by the three elements, including cells, scaffold materials, and growth factors. Graphene-based composites can be used as reinforcing auxiliary materials for tissue scaffold preparation because of their large specific surface area, and good mechanical support. Tissue engineering scaffolds with graphene-based composites have been widely studied. Part of research have focused on the application of graphene-based composites in single tissue engineering. The basic principles of graphene materials used in tissue engineering are summarized in some research. Some studies emphasized the key problems and solutions urgently needed to be solved in the development of tissue engineering and discussed their application prospect. Some related studies mainly focused on the conductivity of graphene and discussed the application of electroactive scaffolds in tissue engineering. In this review, the composite materials for preparing tissue engineering scaffolds are briefly described, which emphasizes the preparation methods, biological properties, and practical applications of graphene-based composite scaffolds. The synthetic techniques, with stressing solvent casting, electrospinning, and three-dimensional printing, are introduced in detail. The mechanical, cell-oriented, and biocompatible properties of graphene-based composite scaffolds in tissue engineering are analyzed and summarized. Their applications in bone tissue engineering, nerve tissue engineering, cardiovascular tissue engineering, and other tissue engineering are summarized systematically. In addition, this work also looks forward to the difficulties and challenges in the future research, providing some references for the follow-up research of graphene-based composites in tissue engineering scaffolds. Impact statement Regeneration and repair of tissue and organ injury has become a new research hotspot in recent years. Tissue engineering scaffolds prepared with graphene-based materials have good biocompatibility, excellent mechanical properties, and strong cell orientation, which can fully induce the proliferation and differentiation of seed cells. This review briefly describes the basic materials for the preparation of tissue engineering scaffolds, and focuses on the preparation, performance, and application of graphene-based materials in tissue engineering, providing sufficient understanding of graphene applied in regenerative medicine.

“Postulating Penis: What Influences the Interest of Transmasculine Patients in Gender Affirming Penile Reconstruction Techniques?”

The limitations of metoidioplasty and phalloplasty have been reported as deterrents for transgender and other gender expansive individuals (T/GE) desiring gender affirming surgery, and thus penile transplantation, epithesis, and composite tissue engineering (CTE) are being explored as alternative interventions. We aim to understand the acceptability of novel techniques and factors that may influence patient preferences in surgery to best treat this diverse population. Descriptions of metoidioplasty, phalloplasty, epithesis, CTE, and penile transplant were delivered via online survey from January 2020 to May 2020. Respondents provided ordinal ranking of interest in each intervention from 1 to 5, with 1 representing greatest personal interest. Demographics found to be significant on univariable analysis underwent multivariable ordinal logistic regression to determine independent predictors of interest. Sexual orientation, gender, and age were independent predictors of interest in interventions. There were 965 qualifying respondents. Gay respondents were less likely to be interested in epithesis (OR: 2.282; P = .001) compared to other sexual orientations. Straight individuals were the least likely to be interested in metoidioplasty (OR 3.251; P = .001), and most interested in penile transplantation (OR 0.382; P = .005) and phalloplasty (OR 0.288, P < .001) as potential interventions. Gay and queer respondents showed a significant interest in phalloplasty (Gay: OR 0.472; P = .004; Queer: OR 0.594; P = .017). Those who identify as men were more interested in phalloplasty (OR 0.552; P < .001) than those with differing gender identities. Older age was the only variable associated with a decreased interest in phalloplasty (OR 1.033; P = .001). No demographic analyzed was an independent predictor of interest in CTE. A thorough understanding of patient gender identity, sexual orientation, and sexual behavior should be obtained during consultation for gender affirming penile reconstruction, as these factors influence patient preferences for surgical interventions. This study used an anonymous online survey that was distributed through community channels and allowed for the collection of a high quantity of responses throughout the T/GE population that would otherwise be impossible through single-center or in-person means. The community-based methodology minimized barriers to honesty, such as courtesy bias. The survey was only available in English and respondents skewed young and White. Despite previously reported concerns about the limitations of metoidioplasty, participants ranked it highly, along with CTE, in terms of personal interest, with sexual orientation, gender, and age independently influencing patient preferences, emphasizing their relevance in patient-surgeon consultations.

Immune Response to Silk Sericin-Fibroin Composites: Potential Immunogenic Elements and Alternatives for Immunomodulation.

The unique properties of silk proteins (SPs), particularly silk sericin (SS) and silk fibroin (SF), have attracted attention in the design of scaffolds for tissue engineering over the past decades. Since SF has good mechanical properties, while SS displays bioactivity, scaffolds combining both proteins should exhibit complementary properties enhancing the potential of these materials. Unfortunately, SS-SF composites can generate chronic immune responses and their immunogenic element is not completely clear. The potential of SS-SF composites in tissue engineering, elements which may contribute to their immunogenicity, and alternatives for their preparation and design, to modulate the immune response and take advantage of their useful properties, are discussed in this review. It is known that SS can enhance β-sheet formation in SF, which may act as hydrophobic regions with a strong affinity for adsorption proteins inducing the chronic recruitment of inflammatory cells. Therefore, tailoring the exposure of hydrophobic regions at the scaffold surface should represent a viable strategy to modulate the immune response. This can be achieved by coating SS-SF composites with SS or other hydrophilic polymers, to take advantage of their antibiofouling properties. Research is still needed to realize the full potential of these composites for tissue engineering.

In-vitro and antibacterial activities of novel POT/TiO2/PCL composites for tissue engineering and biomedical applications

In-vitro and antibacterial activities of novel POT/TiO2/PCL composites for tissue engineering and biomedical applications

Engineering Vascularized Composite Tissues by Perfusion Decellularization/Recellularization: Review

In the field of tissue engineering, the “perfusion decellularization and recellularization” emerged over the last decade. This technique is generating a complex and perfusable acellular scaffolds (e.g., solid organ) from discarded living tissue. The present work aims to describe all studies in which this technique was applied to complex composite tissues, or one of their elementary tissues. A total of 25 experimental publications were found between 2009 and 2020. Studies interested skin/adipose, muscle and nerve flaps for elementary tissues, and larynx, ears, face, upper limbs, uterus, and penis grafts for complex tissue associations. Rat and human models were the most represented. This review showed that the current total number of studies covering the entire topic of vascularized composite tissue engineering is only 25, with a majority published within the past 5 years. This promising area of research should be investigated in the future.

Assessment of Native Human Articular Cartilage: A Biomechanical Protocol.

Recapitulating the mechanical properties of articular cartilage (AC) is vital to facilitate the clinical translation of cartilage tissue engineering. Prior to evaluation of tissue-engineered constructs, it is fundamental to investigate the biomechanical properties of native AC under sudden, prolonged, and cyclic loads in a practical manner. However, previous studies have typically reported only the response of native AC to one or other of these loading regimes. We therefore developed a streamlined testing protocol to characterize the elastic and viscoelastic properties of human knee AC, generating values for several important parameters from the same sample. Human AC was harvested from macroscopically normal regions of distal femoral condyles of patients (n = 3) undergoing total knee arthroplasty. Indentation and unconfined compression tests were conducted under physiological conditions (temperature 37 °C and pH 7.4) and testing parameters (strain rates and loading frequency) to assess elastic and viscoelastic parameters. The biomechanical properties obtained were as follows: Poisson ratio (0.4 ± 0.1), instantaneous modulus (52.14 ± 9.47 MPa) at a loading rate of 1 mm/s, Young's modulus (1.03 ± 0.48 MPa), equilibrium modulus (7.48 ± 4.42 MPa), compressive modulus (10.60 ± 3.62 MPa), dynamic modulus (7.71 ± 4.62 MPa) at 1 Hz and loss factor (0.11 ± 0.02). The measurements fell within the range of reported values for human knee AC biomechanics. To the authors' knowledge this study is the first to report such a range of biomechanical properties for human distal femoral AC. This protocol may facilitate the assessment of tissue-engineered composites for their functionality and biomechanical similarity to native AC prior to clinical trials.

Recent Progress in Carbon Nanotube Polymer Composites in Tissue Engineering and Regeneration.

Scaffolds are important to tissue regeneration and engineering because they can sustain the continuous release of various cell types and provide a location where new bone-forming cells can attach and propagate. Scaffolds produced from diverse processes have been studied and analyzed in recent decades. They are structurally efficient for improving cell affinity and synthetic and mechanical strength. Carbon nanotubes are spongy nanoparticles with high strength and thermal inertness, and they have been used as filler particles in the manufacturing industry to increase the performance of scaffold particles. The regeneration of tissue and organs requires a significant level of spatial and temporal control over physiological processes, as well as experiments in actual environments. This has led to an upsurge in the use of nanoparticle-based tissue scaffolds with numerous cell types for contrast imaging and managing scaffold characteristics. In this review, we emphasize the usage of carbon nanotubes (CNTs) and CNT–polymer composites in tissue engineering and regenerative medicine and also summarize challenges and prospects for their potential applications in different areas.

Carbon-based nanostructured composites for tissue engineering and drug delivery

Nanomaterials comprise extraordinary physicochemical and biological properties for therapeutic applications including three-dimensional porous structures as scaffolds for tissue engineering and as controlled release drug/gen delivery vehicles due to their small size, large surface area, and ability to interact with cells/tissues. Carbon-based nanostructures such as graphene, carbon nanotube, and nanodiamond have attracted both academic and industrial interest because they improve the chemical, mechanical, and biological properties to cellular adhesion tendency of different natural and synthetic polymers in bioapplication. This review covers the fabrication technique of carbon nanostructures and the development of carbon-based nanostructured polymer composites for application in drug/gen delivery and tissue engineering.

Morphological and biomechanical effects of annulus fibrosus injury and repair in an ovine cervical model.

Tissue engineering repair of annulus fibrosus (AF) defects has the potential to prevent disability and pain from intervertebral disc (IVD) herniation and its progression to degeneration. Clinical translation of AF repair methods requires assessment in long‐term large animal models. An ovine AF injury model was developed using cervical spinal levels and a biopsy‐type AF defect to assess composite tissue engineering repair in 1‐month and 12‐month studies. The repair used a fibrin hydrogel crosslinked with genipin (FibGen) to seal defects, poly(trimethylene carbonate) (PTMC) scaffolds to replace lost AF tissue, and polyurethane membranes to prevent herniation. In the 1‐month study, PTMC scaffolds sealed with FibGen herniated with polyurethane membranes. When applied alone, FibGen integrated with the surrounding AF tissue without herniation, showing promise for long‐term studies. The 12‐month long‐term study used only FibGen which showed fibrous healing, biomaterial resorption and no obvious hydrogel‐related complications. However, the 2 mm biopsy punch injury condition also exhibited fibrotic healing at 12 months. Both untreated and FibGen treated groups showed equivalency with no detectable differences in histological grades of proteoglycans, cellular morphology, IVD structure and blood vessel formation, biomechanical properties including torque range and axial range of motion, Pfirrmann grade, IVD height, and quantitative scores of vertebral body changes from clinical computed tomography. The biopsy‐type injury caused endplate defects with a high prevalence of osteophytes in all groups and no nucleus herniation, indicating that the biopsy‐type injury requires further refinement, such as reduction to a slit‐type defect that could penetrate the full depth of the AF without damaging the endplate. Results demonstrate translational feasibility of FibGen for AF repair to seal AF defects, although future study with a more refined injury model is required to validate the efficacy of FibGen before translation.

Complete Human Penile Scaffold for Composite Tissue Engineering: Organ Decellularization and Characterization

Reconstruction for total penile defects presents unique challenges due to its anatomical and functional complexity. Standard methods suffer from high complication rates and poor functional outcomes. In this work we have developed the first protocol for decellularizing whole-organ human penile specimens for total penile tissue engineering. The use of a hybrid decellularization scheme combining micro-arterial perfusion, urethral catheter perfusion and external diffusion enabled the creation of a full-size scaffold with removal of immunogenic components. Decellularization was complete as assessed by H&E and immunohistochemistry, while quantification of residual DNA showed acceptably low levels (<50 ng/mg). An intact ECM was maintained with histologic architecture preservation on H&E and SEM as well as preservation of key proteins such as collagen-1, laminin and fibronectin and retention of growth factors VEGF (45%), EGF (57%) and TGF-beta1 (42%) on ELISA. Post-decellularization patency of the cavernosal arteries for future use in reseeding was demonstrated. Scaffold biocompatibility was evaluated using human adipose-derived stromal vascular cells. Live/Dead stains showed the scaffold successfully supported cell survival and expansion. Influence on cellular behavior was seen with significantly higher expression of VWF, COL1, SM22 and Desmin as compared to cell monolayer. Preliminary evidence for regional tropism was also seen, with formation of microtubules and increased endothelial marker expression in the cavernosa. This report of successful decellularization of the complete human phallus is an initial step towards developing a tissue engineered human penile scaffold with potential for more successfully restoring cosmetic, urinary and sexual function after complete penile loss.

Influence of low-temperature reaction time on morphology and phase composition of short calcium phosphate whiskers

The present work shows the results of the synthesis of multiphasic calcium phosphate whiskers from a mixture of biphasic calcium phosphate (?-tricalcium phosphate (?-TCP) and calcium pyrophosphate (CPP)) in the hydrogen peroxide solution-mediated process carried out in different time ranges. The process was performed at considerably lower temperature than typical hydrothermal methods used for obtaining of whiskers. Test results show that using the above-mentioned procedure triphasic calcium phosphate consisting of hydroxyapatite (HA),(?-TCP) and CPP can be obtained, where the whiskers are formed mainly from hydroxyapatite. It was found that morphology, phase composition and specific surface area of the reaction product can be controlled by changing the reaction time. The obtained triphasic HA/?-TCP/CPP short whiskers may be considered as a promising biocompatible and resorbable reinforcement in composites for bone tissue engineering with a faster resorption rate than that of HA.

Progress in electrospun composite nanofibers: composition, performance and applications for tissue engineering.

The discovery of novel methods to fabricate optimal scaffolds that mimic both mechanical and functional properties of the extracellular matrix (ECM) has always been the "holy grail" in tissue engineering. In recent years, electrospinning has emerged as an attractive material fabrication method and has been widely applied in tissue engineering due to its capability of producing non-woven and nanoscale fibers. However, from the perspective of biomimicry, it is difficult for single-component electrospun fiber membranes to achieve the biomimetic purposes of the multi-component extracellular matrix. Based on electrospinning, various functional components can be efficiently and expediently introduced into the membranes, and through the complementation and correlation of the properties of each component, composite materials with comprehensive and superior properties are obtained while maintaining the primitive merits of each component. In this review, we will provide an overview of the attempts made to fabricate electrospinning-based composite tissue engineering materials in the past few decades, which have been divided into organic additives, inorganic additives and organic-inorganic additives.

Preparation of gelatin/genipin nanofibrous membrane for tympanic member repair

The wound healing for tympanic membrane (TM) perforations is one of the most common clinical treatment in otomicrosurgery. Recently, tissue-engineered composites and grafts, also new designs of biomaterials are applied to the management of TM perforation. In this work, a series of gelatin/genipin nanofibrous films were prepared as a patch for repairing TM perforation. Gelatin, a type of biomaterial with excellent electrospinning performance, has been used for preparing the nanofibers. The genipin, as a crosslinking agent, has been blended into the gelatin nanofibers. The reaction between gelatin and genipin engender suitable tensile strength and water-resistance for TM patch. The survival rate of human umbilical vein endothelial cells and fibroblasts demonstrated that the gelatin/genipin nanofiber scaffolds had good biocompatibility, which indicated the genipin was a kind of effective and nontoxic crosslinking agent for improving the mechanical property and water-resistance of gelatin films. In short, our work provides a novel macromolecular material with good mechanical properties, water-tolerance and excellent biocompatibility which could be used as a potential patch for TM repair.

Preparation of CS/PVA Nanofibrous Membrane with Tunable Mechanical Properties for Tympanic Member Repair

The wound healing for tympanic membrane (TM) perforations is one of the most common clinic treatment. New designs of biomaterials, and lately tissue-engineered composites and grafts, have been applied for the management of TM perforation. In this work, a series of chitosan (CS)/polyvinyl alcohol (PVA) nanofibrous films have been fabricated as a kind of patch for repairing TM perforation. The scaffolds were crosslinked by glutaraldehyde solution to prevent them from being dissolved in the culture medium. The morphology of nanofibers from different precursors has been observed by using scanning electron microscopy (SEM). And the crosslinked films have been characterized by SEM and Fourier transform infrared spectroscopy for confirming its morphology and chemical structure. We found the films with crosslinking showed stronger tensile strength and modulus compared to the uncrosslinked one. And the mechanical properties could be tuned by the crosslinking time. In addition, after crosslinked, the films showed good thermostability and water-resistance, characterized by thermo gravimetric analyzer and contact angle meter. The cell viability studies with human umbilical vein endothelial cells, fibroblasts and mesenchymal stem cells demonstrated that the nanofibrous scaffolds formed by electrospinning process had no side effects for cell proliferation. However, a better way of crosslinking CS/PVA films needs to be further studied.