Frontiers in Bioengineering and Biotechnology最新文献

Introduction: Diabetes mellitus often leads to bone metabolism disorders, hindering bone regeneration and delaying the healing of bone defects. β-Ecdysone, a plant-derived hormone known for its wide range of physiological activities, possesses hypoglycemic effects and promotes osteogenic differentiation. This study developed a composite PLGA slow-release scaffold loaded with β-ecdysone to enhance its bioavailability through topical administration and to investigate its potential to heal diabetic bone defects.

Methods: The composite scaffolds were fabricated using solution casting/particle leaching and freeze-drying techniques. Then a series of characterizations were subjected to test the performance of composite scaffolds, and in vitro safety of the composite scaffolds was tested by CCK8 assay and live/dead cell staining. Further, micro-CT and histology to evaluate the effect of β-E/PLGA composite scaffolds on healing of skull defects in diabetic rats at 4 and 8 weeks after implantation. Simultaneously, the safety of the scaffolds in vivo was also evaluated.

Results: The material characterization results indicated that, in comparison to the single-pore size scaffold, the composite scaffold exhibited superior porosity, swelling ratio, drug loading capacity, and mechanical properties. Additionally, the composite scaffolds showed appropriate degradation performance and sustained drug release profiles. The CCK8 cytotoxicity assay and live/dead cell staining demonstrated that BMSCs survived and proliferated on the composite scaffold under both low-glucose and high-glucose conditions. Micro-CT and histological investigation demonstrated that β-E/PLGA composite scaffolds promoted new bone growth in the skull defect region of diabetic rats.

Conclusion: Overall, these findings suggest that the β-E/PLGA composite scaffolds promote the healing of bone defects in diabetic rats. The combination of β-ecdysone and tissue-engineered scaffolds presents a promising approach for treating diabetes-related bone defects.

Introduction: Aging-related deficits in the physiological properties of skeletal muscles limit the control of dynamic stability during walking. However, the specific causal relationships between these factors remain unclear. This study evaluated the effects of aging-related deficits in muscle properties on dynamic stability during walking.

Methods: Walking movements were simulated using two-dimensional musculoskeletal models consisting of 18 Hill-type muscles. To assess the effects of aging-related deficits in muscle function on dynamic stability during walking, five models with different muscle properties were created, namely young adult (YA) and older adult (OA) models, models with reduced maximum isometric muscle force, reduced maximum muscle contraction velocity, and prolonged muscle deactivation time (∆F, ∆V, and ∆T models, respectively). The margin of stability (MoS) was used as a measure of dynamic stability during walking.

Results and discussion: The MoS value of the OA model was greater than that of the YA model, and the ∆F model yielded a larger MoS value than those of the ∆V and ∆T models. Therefore, the OA model achieved a more dynamically stable state than the YA model and the ∆F model required a more stable state to sustain continuous walking compared to the ∆V and ∆T models. These findings indicate that aging-related deficits in muscle function limit the control of dynamic stability during walking with the degeneration of maximum isometric muscle force being the most influential factor. These findings could aid in the development of an intervention program to reduce the risk of falls in older adults effectively.

Medical implants are designed to replace missing parts or improve body functions and must be capable of providing structural support or therapeutic intervention for a medical condition. Advances in materials science have enabled the development of devices made from metals, polymers, bioceramics, and composites, each with its specific advantages and limitations. This review analyzes the incorporation of biopolymers, proteins, and other biomacromolecules into implants, focusing on their role in biological integration and therapeutic functions. It synthesizes advancements in surface modification, discusses biomacromolecules as carriers for controlled drug release, and explores the application of nanoceramics and composites to improve osseointegration and tissue regeneration. Biomacromolecule systems are capable of interacting with device components and therapeutic agents - such as growth factors (GFs), antibiotics, and nanoceramics - allowing control over substance release. Incorporating therapeutic agents into these systems enables localized treatments for tissue regeneration, osseointegration, post-surgery infection control, and disease and pre-existing conditions. The review highlights these materials' therapeutic advantages and customization opportunities, by covering mechanical and biological perspectives. Developing composites and hybrid drug delivery systems align with recent efforts in interdisciplinary personalized medicine and implant innovations. For instance, a trend was observed for integrating inorganic (especially nanoceramics, e.g., hydroxyapatite) and organic phases in composites for better implant interaction with biological tissues and faster recovery. This article supports understanding how integrating these materials can create more personalized, functional, durable, and biocompatible implant devices.

Purpose: Pelvic and hip motion are pivotal in maintaining postural control and energy efficient gait. An insight into influence of age and gender on the coupled motion of hip and pelvis in gait-cycle will guide clinical rehabilitation strategies and pertinent technology-design for specific age-groups. Therefore, present study evaluated pelvic and hip-joint gait kinematics in healthy females and males across adult-hood.

Methods: Following signed-informed consent, pelvic and hip kinematics in 3-planes during stance-phase of gait were measured using 12-camera motion system and 2 force-plates, in 200 healthy Indian female and male volunteers (19-60years) stratified into 4-groups (19-30 years; 31-40 years; 41-50years; 51-60 years).

Results: With advancing age, males and females demonstrated a gradual rise in hip adduction (p < 0.01) in coronal plane. Sagittal plane pelvic and hip kinematics did not change with advancing age among males whereas females above 30 years Demonstrated greater pelvic drop (49%), pelvic tilt (35%) and hip adduction (69%) compared to females below 30 years (p < 0.01). In comparison to males, females demonstrated greater peak anterior pelvic tilt (32%), greater pelvic hike (28%) and protraction (28%) in 50-60 years age-group (p < 0.05). Females across all age-groups demonstrated greater hip adduction compared to males (p < 0.05).

Conclusion: Present findings add age and gender characterized gait-kinematics data of healthy adults from the most populous country to the existing 3-D data of gait from different populations. Clinicians and engineers, can leverage this knowledge of changing gait kinematics of healthy adults to design specific therapeutic strategies for aging men and women to optimize gait kinematics and advance design and development of locomotor technology suitable for people with rehabilitation needs across the globe.

Polysorbates, in particular polysorbate (PS) 20 and 80, are the most commonly used surfactants for stabilising biotherapeutics produced by biotechnological processes. PSs are derived from ethoxylated sorbitan (a derivative of sorbitol) esterified with fatty acids of varying chain length and degree of saturation. In the past, these surfactants have been reported to have specific liabilities. Chemical (oxidations and hydrolyses) and enzymatic degradations have been reported to affect the stability of PS in drug products. Specifically, the presence of trace amounts (sub-ppm) of certain host cell proteins (HCPs) can induce enzymatic PS degradation, which can lead to the release of free fatty acids during storage over time. Enzymatic polysorbate degradation may impair the functionality of the surfactant in stabilising therapeutic proteins, leading to the formation of visible and/or sub-visible particles in biopharmaceutical drug products. This review summarises the enzymes currently known to be involved in the degradation of polysorbate in mammalian biotechnological processes for therapeutic proteins. In recent years, advanced analytical methods have been developed to qualify and quantify the PS-degrading enzymes. Most of these assays are based on mass spectrometry with a preceding HCP enrichment approach. Efforts were made to measure the enzyme activity and correlate it with observed PS degradation. The impact on drug product quality attributes, including fatty acid solubility and phase separation, up to the formation of visible particles, and the potential induction of protein and protein/fatty acid mixed particles as well as the sensitivity of specific PS quality towards enzymatic degradation, was considered. Various drug substance (DS) mitigation strategies related to the occurrence of PS degrading enzymes are discussed as amongst them the generation of stable HCP knockout cell lines, which are also carefully analysed. The underlying opinion article reflects the undergoing discussions related to PS degrading enzymes and focusses on (i) impact on drug product, (ii) analytics for identification/quantification (characterisation) of the PS degrading enzymes, (iii) enzyme activity (iv) currently identified enzymes, and (v) potential mitigation strategies to avoid enzymatic PS degradation during DS manufacturing.

Introduction: Bacterial infection, a complex wound microenvironment, and a persistent inflammatory response in acute wounds can result in delayed healing and abnormal scar formation, thereby compromising the normal function and aesthetic appearance of skin tissue. This issue represents one of the most challenging problems in clinical practice. This study aims to develop a hydrogel dressing specifically designed for the treatment of acute wounds, providing immediate and effective protection for the affected areas. This innovation seeks to offer a novel and advanced solution for the management of acute wounds.

Methods: In this study, a composite hydrogel scaffold was synthesized through the reaction between oxidized glycyrrhizic acid and carboxymethyl chitosan Schiff base. The material properties of the hydrogel were systematically characterized, and its biocompatibility and antibacterial efficacy were rigorously evaluated. A rat wound model was established to compare multiple groups, thereby assessing the impact of the hydrogel on the wound microenvironment and wound repair.

Results: The results demonstrated that the OGA-CMCS hydrogel exhibited excellent injectability, biocompatibility, and antibacterial properties. It was capable of enhancing the wound microenvironment, which in turn influenced the polarization of macrophages from the M1 to the M2 phenotype, thereby mitigating the inflammatory response, promoting angiogenesis and granulation tissue regeneration, and accelerating wound healing.

Discussion: This study successfully developed a novel glycyrrhizin-based hydrogel dressing, which not only introduces innovative approaches for the emergency management of acute surface wound defects but also provides an experimental foundation. It is anticipated to contribute significantly to addressing relevant clinical challenges.

Background: Bacteria in physiological environments can generate mineralizing biofilms, which are associated with diseases like periodontitis or kidney stones. Modelling complex environments presents a challenge for the study of mineralization in biofilms. Here, we developed an experimental setup which could be applied to study the fundamental principles behind biofilm mineralization on rigid substrates, using a model organism and in a tailored bioreactor that mimics a humid environment. We developed a simple yet effective method to produce rigid specimens with the desired shape.

Materials and methods: To simulate humid growth conditions, rigid specimens were conditioned with human saliva, inoculated with the chosen model bacterial strain and placed in a chamber with continuous drop-wise supply of nutritious media. The preconditioning stage did not affect significantly the bacteria proliferation, but considering this option was instrumental to future evolutions of the model, where saliva could be substituted with other substances (e.g., urine, plasma or antimicrobial solutions). Two different growth media were used: a control medium with nutritious substances and a mineralizing medium consisting in control medium supplemented with mineral precursors. Both the specimen shape and the bioreactor designs resulted from an optimization process thoroughly documented in this work. As a proof of concept, we showed that it is possible to locate the bacteria and minerals using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM).

Results: We achieved an in vitro model representative of the conditions of growth and mineralization of biofilms in humid environments on a rigid substrate: something between the traditional solid-air and solid-liquid interface models.

Conclusion: Such model will be useful to understand fundamental mechanisms happening in complex environments.

The posterior mandible is the primary area for occlusal function. However, long-term tooth loss in the posterior mandible often leads to rapid absorption of both buccal and lingual trabecular bone plates and subsequent atrophy of the alveolar ridge. This ultimately results in horizontal bone deficiencies that complicate achieving an optimal three-dimensional placement for dental implants. Conventional techniques employed clinically for horizontal bone augmentation have limited efficacy, cause significant surgical trauma, and require extended treatment duration. Consequently, the selection of an effective and minimally invasive bone augmentation technique for restoring bone width is an essential prerequisite for successful implant restoration in the posterior mandible. This clinical case study presented a treatment approach involving guided bone regeneration (GBR) and in situ Onlay grafting for bone level augmentation in the blade-shaped alveolar ridge of the posterior mandible, followed by implant restoration. By rotating the in situ sourced bone block, the denser bone volume at the base of the blade-shaped alveolar ridge was transferred to the crest of the alveolar ridge, obviating the necessity for a secondary operative site and mitigating complications such as pain, edema, sensory abnormalities, and nerve injury. Incorporation of trabecular bone within the recipient area enhanced fixation while augmenting vascular supply. A significant increase in bone volume by 1,628.21 mm³ was achieved within 7 months postoperatively. Overall, this novel approach offers valuable insights into minimally invasive and stable techniques for alveolar bone augmentation.

Humerus greater tuberosity (HGT) avulsion fracture is one of the most common types of proximal humerus fractures. The presence of motion and gap lead to the failure of implants, due to the force pulling from the supraspinatus. In this work, electrospinning technology was applied to fabricate PCL-PEG/CS/AST nanofiber with superior biocompatibility and mechanical property. Furthermore, PCL-PEG/CS/AST nanofiber could promote proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) in vitro. We believe that this work indicates a promising way to promote the union of HGT avulsion fractures by using PCL-PEG/CS/AST nanofiber.