340 research outputs found
Regenerative therapies for tympanic membrane
It is estimated that by 2050 one in every ten people will be suffering from disabling hearing loss. Perforated tympanic membranes (TMs) are the most common injury to the human ear, resulting in a partial or complete hearing loss due to inept sound conduction. Commonly known as the eardrum, the TM is a thin, concave tissue of the middle ear that captures sound pressure waves from the environment and transmits them as mechanical vibrations to the inner ear. Microsurgical placement of autologous tissue graft has been the “gold standard” for treating damaged TMs; however, the incongruent structural and mechanical properties of these autografts often impair an optimal hearing restoration following recovery. Moreover, given the lack of available tissues for transplantations, regenerative medicine has emerged as a promising alternative. Several tissue engineered approaches applying bio-instructive scaffolds and stimuli have been reported for the TM regeneration, which can be broadly classified into TM repair and TM reconstruction. This review evaluates the current advantages and challenges of both strategies with a special focus on the use of recent biofabrication technologies for advancing TM tissue engineering
Poly(lactic acid)-Based Electrospun Fibrous Structures for Biomedical Applications
Poly(lactic acid)(PLA) is an aliphatic polyester that can be derived from natural and renewable resources. Owing to favorable features, such as biocompatibility, biodegradability, good thermal and mechanical performance, and processability, PLA has been considered as one of the most promising biopolymers for biomedical applications. Particularly, electrospun PLA nanofibers with distinguishing characteristics, such as similarity to the extracellular matrix, large specific surface area and high porosity with small pore size and tunable mechanical properties for diverse applications, have recently given rise to advanced spillovers in the medical area. A variety of PLA-based nanofibrous structures have been explored for biomedical purposes, such as wound dressing, drug delivery systems, and tissue engineering scaffolds. This review highlights the recent advances in electrospinning of PLA-based structures for biomedical applications. It also gives a comprehensive discussion about the promising approaches suggested for optimizing the electrospun PLA nanofibrous structures towards the design of specific medical devices with appropriate physical, mechanical and biological functions
Mechanics of Mineralized Collagen Fibrils upon Transient Loads
Collagen is a key structural protein in the human body, which undergoes mineralization during the formation of hard tissues. Earlier studies have described the mechanical behavior of bone at different scales, highlighting material features across hierarchical structures. Here we present a study that aims to understand the mechanical properties of mineralized collagen fibrils upon tensile/compressive transient loads, investigating how the kinetic energy propagates and it is dissipated at the molecular scale, thus filling a gap of knowledge in this area. These specific features are the mechanisms that nature has developed to passively dissipate stress and prevent structural failures. In addition to the mechanical properties of the mineralized fibrils, we observe distinct nanomechanical behaviors for the two regions (i.e., overlap and gap) of the D-period to highlight the effect of the mineralization. We notice decreasing trends for both wave speeds and Young's moduli over input velocity with a marked strengthening effect in the gap region due to the accumulation of the hydroxyapatite. In contrast, the dissipative behavior is not affected by either loading conditions or the mineral percentage, showing a stronger damping effect upon faster inputs compatible to the bone behavior at the macroscale. Our results offer insights into the dissipative behavior of mineralized collagen composites to design and characterize bioinspired composites for replacement devices (e.g., prostheses for sound transmission or conduction) or optimized structures able to bear transient loads, for example, impact, fatigue, in structural applications
An Osteosarcoma Model by 3D Printed Polyurethane Scaffold and In Vitro Generated Bone Extracellular Matrix
Osteosarcoma is a primary bone tumor characterized by a dismal prognosis, especially in the case of recurrent disease or metastases. Therefore, tools to understand in-depth osteosarcoma progression and ultimately develop new therapeutics are urgently required. 3D in vitro models can provide an optimal option, as they are highly reproducible, yet sufficiently complex, thus
reliable alternatives to 2D in vitro and in vivo models. Here, we describe 3D in vitro osteosarcoma
models prepared by printing polyurethane (PU) by fused deposition modeling, further enriched with
human mesenchymal stromal cell (hMSC)-secreted biomolecules. We printed scaffolds with different
morphologies by changing their design (i.e., the distance between printed filaments and printed
patterns) to obtain different pore geometry, size, and distribution. The printed PU scaffolds were
stable during in vitro cultures, showed adequate porosity (55–67%) and tunable mechanical properties
(Young’s modulus ranging in 0.5–4.0 MPa), and resulted in cytocompatible. We developed the in vitro
model by seeding SAOS-2 cells on the optimal PU scaffold (i.e., 0.7 mm inter-filament distance, 60
pattern), by testing different pre-conditioning factors: none, undifferentiated hMSC-secreted, and
osteo-differentiated hMSC-secreted extracellular matrix (ECM), which were obtained by cell lysis
before SAOS-2 seeding. Scaffolds pre-cultured with osteo-differentiated hMSCs, subsequently lysed,
and seeded with SAOS-2 cells showed optimal colonization, thus disclosing a suitable biomimetic
microenvironment for osteosarcoma cells, which can be useful both in tumor biology study and,
possibly, treatment
Growing bone tissue-engineered niches with graded osteogenicity: an in vitro method for biomimetic construct assembly
The traditional bone tissue-engineering approach exploits mesenchymal stem cells ( MSCs) to be seeded once only on three-dimensional (3D) scaffolds, hence, differentiated for a certain period of time and resulting in a homogeneous osteoblast population at the endpoint. However, after achieving terminal osteodifferentiation, cell viability is usually markedly compromised. On the other hand, naturally occurring osteogenesis results from the coexistence of MSC progenies at distinct differentiative stages in the same microenvironment. This diversification also enables long-term viability of the mature tissue. We report an easy and tunable in vitro method to engineer simple osteogenic cell niches in a biomimetic fashion. The niches were grown via periodic reseeding of undifferentiated MSCs on MSC/scaffold constructs, the latter undergoing osteogenic commitment. Timefractioning of the seeded cell number during differentiation time of the constructs allowed graded osteogenic cell populations to be grown together on the same scaffolds (i.e., not only terminally differentiated osteoblasts). In such cell-dynamic systems, the overall differentiative stage of the constructs could also be tuned by varying the cell density seeded at each inoculation. In this way, we generated two different biomimetic niche models able to host good reservoirs of preosteoblasts and other osteoprogenitors after 21 culture days. At that time, the niche type resulting in 40.8% of immature osteogenic progenies and only 59.2% of mature osteoblasts showed a calcium content comparable to the constructs obtained with the traditional culture method (i.e., 100.03 – 29.30 vs. 78.51 – 28.50 pg/cell, respectively; p = not significant), the latter colonized only by fully differentiated osteoblasts showing exhausted viability. This assembly method for tissue-engineered constructs enabled a set of important parameters, such as viability, colonization, and osteogenic yield of the MSCs to be balanced on 3D scaffolds, thus achieving biomimetic in vitro models with graded osteogenicity, which are more complex and reliable than those currently used by tissue engineers
Pullulan for advanced sustainable body- And skin-contact applications
The present review had the aim of describing the methodologies of synthesis and properties of biobased pullulan, a microbial polysaccharide investigated in the last decade because of its interesting potentialities in several applications. After describing the implications of pullulan in nano-technology, biodegradation, compatibility with body and skin, and sustainability, the current applications of pullulan are described, with the aim of assessing the potentialities of this biopolymer in the biomedical, personal care, and cosmetic sector, especially in applications in contact with skin
Neuron Compatibility and Antioxidant Activity of Barium Titanate and Lithium Niobate Nanoparticles
The biocompatibility and the antioxidant activity of barium titanate (BaTiO3) and lithium niobate (LiNbO3) were investigated on a neuronal cell line, the PC12, to explore the possibility of using piezoelectric nanoparticles in the treatment of inner ear diseases, avoiding damage to neurons, the most delicate and sensitive human cells. The cytocompatibility of the compounds was verified by analysing cell viability, cell morphology, apoptotic markers, oxidative stress and neurite outgrowth. The results showed that BaTiO3 and LiNbO3 nanoparticles do not affect the viability, morphological features, cytochrome c distribution and production of reactive oxygen species (ROS) by PC12 cells, and stimulate neurite branching. These data suggest the biocompatibility of BaTiO3 and LiNbO3 nanoparticles, and that they could be suitable candidates to improve the efficiency of new implantable hearing devices without damaging the neuronal cells
Mimicking the Human Tympanic Membrane: The Significance of Scaffold Geometry
The human tympanic membrane (TM) captures sound waves from the environment and transforms them into mechanical motion. The successful transmission of these acoustic vibrations is attributed to the unique architecture of the TM. However, a limited knowledge is available on the contribution of its discrete anatomical features, which is important for fabricating functional TM replacements. This work synergizes theoretical and experimental approaches toward understanding the significance of geometry in tissue-engineered TM scaffolds. Three test designs along with a plain control are chosen to decouple some of the dominant structural elements, such as the radial and circumferential alignment of the collagen fibrils. In silico models suggest a geometrical dependency of their mechanical and acoustical responses, where the presence of radially aligned fibers is observed to have a more prominent effect compared to their circumferential counterparts. Following which, a hybrid fabrication strategy combining electrospinning and additive manufacturing has been optimized to manufacture biomimetic scaffolds within the dimensions of the native TM. The experimental characterizations conducted using macroindentation and laser Doppler vibrometry corroborate the computational findings. Finally, biological studies with human dermal fibroblasts and human mesenchymal stromal cells reveal a favorable influence of scaffold hierarchy on cellular alignment and subsequent collagen deposition
Experimental Assessment of Cuff Pressures on the Walls of a Trachea-Like Model Using Force Sensing Resistors: Insights for Patient Management in Intensive Care Unit Settings
The COVID-19 outbreak has increased the incidence of tracheal lesions in patients who underwent invasive mechanical ventilation. We measured the pressure exerted by the cuff on the walls of a test bench mimicking the laryngotracheal tract. The test bench was designed to acquire the pressure exerted by endotracheal tube cuffs inflated inside an artificial model of a human trachea. The experimental protocol consisted of measuring pressure values before and after applying a maneuver on two types of endotracheal tubes placed in two mock-ups resembling two different sized tracheal tracts. Increasing pressure values were used to inflate the cuff and the pressures were recorded in two different body positions. The recorded pressure increased proportionally to the input pressure. Moreover, the pressure values measured when using the non-armored (NA) tube were usually higher than those recorded when using the armored (A) tube. A periodic check of the cuff pressure upon changing the body position and/or when performing maneuvers on the tube appears to be necessary to prevent a pressure increase on the tracheal wall. In addition, in our model, the cuff of the A tube gave a more stable output pressure on the tracheal wall than that of the NA tube
Bio-based electrospun fibers for wound healing
Being designated to protect other tissues, skin is the first and largest human body organ to be injured and for this reason, it is accredited with a high capacity for self-repairing. However, in the case of profound lesions or large surface loss, the natural wound healing process may be ineffective or insufficient, leading to detrimental and painful conditions that require repair adjuvants and tissue substitutes. In addition to the conventional wound care options, biodegradable polymers, both synthetic and biologic origin, are gaining increased importance for their high biocompatibility, biodegradation, and bioactive properties, such as antimicrobial, immunomodulatory, cell proliferative, and angiogenic. To create a microenvironment suitable for the healing process, a key property is the ability of a polymer to be spun into submicrometric fibers (e.g., via electrospinning), since they mimic the fibrous extracellular matrix and can support neo- tissue growth. A number of biodegradable polymers used in the biomedical sector comply with the definition of bio-based polymers (known also as biopolymers), which are recently being used in other industrial sectors for reducing the material and energy impact on the environment, as they are derived from renewable biological resources. In this review, after a description of the fundamental concepts of wound healing, with emphasis on advanced wound dressings, the recent developments of bio-based natural and synthetic electrospun structures for efficient wound healing applications are highlighted and discussed. This review aims to improve awareness on the use of bio-based polymers in medical devices
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