Beyond Encapsulation: Exploring Macrophage-Fibroblast Cross Talk in Implant-Induced Fibrosis.

The foreign body response (FBR) and organ fibrosis are complex biological processes involving the interaction between macrophages and fibroblasts. Understanding the molecular mechanisms underlying macrophage-fibroblast cross talk is crucial for developing strategies to mitigate implant encapsulation, a major cause of implant failure. This article reviews the current knowledge on the role of macrophages and fibroblasts in the FBR and organ fibrosis, highlighting the similarities between these processes.

A Review of the Role of Bioreactors for iPSCs-Based Tissue-Engineered Articular Cartilage.

Background: Osteoarthritis (OA) is the most common degenerative joint disease without an ultimate treatment. In a search for novel approaches, tissue engineering (TE) has shown great potential to be an effective way for hyaline cartilage regeneration and repair in advanced stages of OA. Recently, induced pluripotent stem cells (iPSCs) have been appointed to be essential stem cells for degenerative disease treatment because they allow a personalized medicine approach.

Viscoelastic properties of plasma-agarose hydrogels dictate favorable fibroblast responses for skin tissue engineering applications.

Dermal wound healing relies on the properties of the extracellular matrix (ECM). Thus, hydrogels that replicate skin ECM have reached clinical application. After a dermal injury, a transient, biodegradable fibrin clot is instrumental in wound healing.

Micrococcal Nuclease stimulates Biofilm Formation in a Murine Implant Infection Model.

Advancements in contemporary medicine have led to an increasing life expectancy which has broadened the application of biomaterial implants. As each implant procedure has an innate risk of infection, the number of biomaterial-associated infections keeps rising. causes 34% of such infections and is known as a potent biofilm producer.

Nonviral Expression of LL-37 in a Human Skin Equivalent to Prevent Infection in Skin Wounds.

Inefficient autologous tissue recovery in skin wounds increases the susceptibility of patients to infections caused by multidrug resistant microorganisms, resulting in a high mortality rate. Genetic modification of skin cells has become an important field of study because it could lead to the construction of more functional skin grafts, through the overexpression of antimicrobial peptides that would prevent early contamination and infection with bacteria. In this study, we produce and evaluate human skin equivalents (HSEs) containing transfected human primary fibroblasts and keratinocytes by polyplexes to express the antimicrobial peptide LL-37.

Accepting higher morbidity in exchange for sacrificing fewer animals in studies developing novel infection-control strategies.

Preventing bacterial infections from becoming the leading cause of death by the year 2050 requires the development of novel, infection-control strategies, building heavily on biomaterials science, including nanotechnology. Pre-clinical (animal) studies are indispensable for this development. Often, animal infection outcomes bear little relation to human clinical outcome.

Long-term prevention of capsular opacification after lens-refilling surgery in a rabbit model.

Purpose: To reduce capsular opacification by a peri-surgical treatment of the lens capsule with drugs in an in vivo rabbit model. Lens-refilling surgery is a potential therapeutic intervention to treat patients with a cataract lens. The lens material is replaced with an injectable (bio)polymer that retains the natural mechanical and optical lens properties, therewith allowing accommodation.

Nanocarriers with conjugated antimicrobials to eradicate pathogenic biofilms evaluated in murine in vivo and human ex vivo infection models.

Conventional antimicrobials are becoming increasingly ineffective for treating bacterial infection due to the emergence of multi-drug resistant (MDR) pathogens. In addition, the biofilm-mode-of-growth of infecting bacteria impedes antimicrobial penetration in biofilms. Here, we report on poly(ethylene)glycol-poly(β-amino esters) (PEG-PAE) micelles with conjugated antimicrobials, that can uniquely penetrate biofilms, target themselves to bacterial cell surfaces once inside the low-pH environment of a biofilm and release conjugated antimicrobials through degradation of their ester-linkage with PAE by bacterial lipases.

Photoswitchable Micelles for the Control of Singlet-Oxygen Generation in Photodynamic Therapies.

Inadvertent photosensitizer-activation and singlet-oxygen generation hampers clinical application of photodynamic therapies of superficial tumors or subcutaneous infections. Therefore, a reversible photoswitchable system was designed in micellar nanocarriers using ZnTPP as a photosensitizer and BDTE as a photoswitch. Singlet-oxygen generation upon irradiation didnot occur in closed-switch micelles with ZnTPP/BDTE feeding ratios >1:10.

Screening Platform for Cell Contact Guidance Based on Inorganic Biomaterial Micro/nanotopographical Gradients.

High-throughput screening (HTS) methods based on topography gradients or arrays have been extensively used to investigate cell-material interactions. However, it is a huge technological challenge to cost efficiently prepare topographical gradients of inorganic biomaterials due to their inherent material properties. Here, we developed a novel strategy translating PDMS-based wrinkled topography gradients with amplitudes from 49 to 2561 nm and wavelengths between 464 and 7121 nm to inorganic biomaterials (SiO, Ti/TiO, Cr/CrO, and AlO) which are frequently used clinical materials.

Self-assembled nanofiber coatings for controlling cell responses.

Nanofibers are thought to enhance cell adhesion, growth, and function. We demonstrate that the choice of building blocks in self-assembling nanofiber systems can be used to control cell behavior. The use of 2 D-coated, self-assembled nanofibers in controlling lens epithelial cells, fibroblasts, and mesenchymal stem cells was investigated, focusing on gene and protein expression related to the fibrotic response.

Effects of peptide ratios in nanofibre-based hydrogels for the prevention of capsular opacification.

Purpose: To moderate the capsular opacification (CO) response after lens surgery, an experimental study was performed in which nanofibre-based hydrogels (nanogels) with different ratios of attached peptides were applied to provide extracellular matrix-related cues for lens epithelial cells (LECs) in a porcine eye model.

Methods: The lens content was removed, and the capsules were refilled with nanogel. Lenses were divided into two groups, the first group (n = 34) was refilled with nanogels containing different ratios of two laminin-derived peptides (IKVAV + YIGSR), and the latter group (n = 26) was refilled with nanogel combinations of a fibronectin-derived and a type IV collagen-derived peptide (RGDS + DGEA).

Non-Covalently Stabilized Alginate Hydrogels as Functional Cell Scaffold Material.

Biopolymers are an attractive class of compounds for being used in biomedical applications as they are widely available from biomass. Their drawback is the lack of mechanical stability and the ability to tune this properly. Covalent chemical cross-linking is an often used approach but it limits usability due to legislation as well as the need of advanced and specialized knowledge by end users such as clinicians.

Directional nanotopographic gradients: a high-throughput screening platform for cell contact guidance.

A novel approach was developed using PDMS-substrates with surface-aligned nanotopography gradients, varying unidirectional in amplitude and wavelength, for studying cell behavior with regard to adhesion and alignment. The gradients target more surface feature parameters simultaneously and provide more information with fewer experiments and are therefore vastly superior with respect to individual topography substrates. Cellular adhesion experiments on non-gradient aligned nanowrinkled surfaces displayed a linear relationship of osteoblast cell adhesion with respect to topography aspect ratio.

Nanofiber-based hydrogels with extracellular matrix-based synthetic peptides for the prevention of capsular opacification.

Nanofiber-based hydrogels (nanogels) with different, covalently bound peptides were used as an extracellular environment for lens epithelial cells (LECs) in order to modulate the capsular opacification (CO) response after lens surgery in a porcine eye model. Lenses were divided into 15 groups (n = 4 per group), the lens content was removed and the empty capsules were refilled with nanogel without peptides and nanogels with 13 combinations of 5 different peptides: two laminin-derived, two fibronectin-derived, and one collagen IV-derived peptide representing cell adhesion motifs. A control group of 4 lenses was refilled with hyaluronan.

Investigation of Friction-induced Damage to the Pig Cornea.

Mechanical friction causes damage to the cornea. A friction measurement device with minimal intervention with the pig cornea tear film revealed a low friction coefficient of 0.011 in glycerine solution.

Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress.

Aims: Neointimal hyperplasia is a common feature of fibro-proliferative vascular disease and characterizes initial stages of atherosclerosis. Neointimal lesions mainly comprise smooth muscle-like cells. The presence of these lesions is related to local differences in shear stress.

Prevention of posterior capsular opacification.

Posterior capsular opacification (PCO) is a common complication of cataract surgery. The development of PCO is due to a combination of the processes of proliferation, migration, and transdifferentiation of residual lens epithelial cells (LECs) on the lens capsule. In the past decades, various forms of PCO prevention have been examined, including adjustments of techniques and intraocular lens materials, pharmacological treatments, and prevention by interfering with biological processes in LECs.

Macrophage phagocytic activity toward adhering staphylococci on cationic and patterned hydrogel coatings versus common biomaterials.

Biomaterial-associated-infection causes failure of biomaterial implants. Many new biomaterials have been evaluated for their ability to inhibit bacterial colonization and stimulate tissue-cell-integration, but neglect the role of immune cells. This paper compares macrophage phagocytosis of adhering Staphylococcus aureus on cationic-coatings and patterned poly(ethylene)glycol-hydrogels versus common biomaterials and stainless steel in order to identify surface conditions that promote clearance of adhering bacteria.

Lipid droplets hypertrophy: a crucial determining factor in insulin regulation by adipocytes.

Lipid droplets (LDs) hypertrophy in adipocytes is the main cause of energy metabolic system dysfunction, obesity and its afflictions such as T2D. However, the role of adipocytes in linking energy metabolic disorders with insulin regulation is unknown in humans. Human adipocytes constitutively synthesize and secrete insulin, which is biologically functional.

Changes in lens stiffness due to capsular opacification in accommodative lens refilling.

Accommodation may be restored to presbyopic lenses by refilling the lens capsular bag with a soft polymer. After this accommodative lens refilling prevention of capsular opacification is a requirement, since capsular opacification leads to a decreased clarity of the refilled lens. It has been hypothesized that capsular fibrosis causing the capsular opacification results in increased stiffness of the lens capsular bag, therewith contributing to a decrease in accommodative amplitude of the lens.

Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants.

Purpose: Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage.

Methods: Explants of porcine cartilage and human osteoarthritic cartilage were cultured for four weeks and subjected to daily LIPUS or PEMF treatments.

Prevention of capsule opacification after accommodating lens refilling: pilot study of strategies evaluated in a monkey model.

Purpose: To test 2 strategies to prevent capsule opacification after accommodating lens refilling in a rhesus monkey model.

Setting: Animal laboratory and laboratory of European university medical centers.

Design: Experimental study.

An annulus fibrosus closure device based on a biodegradable shape-memory polymer network.

Injuries to the intervertebral disc caused by degeneration or trauma often lead to tearing of the annulus fibrosus (AF) and extrusion of the nucleus pulposus (NP). This can compress nerves and cause lower back pain. In this study, the characteristics of poly(D,L-lactide-co-trimethylene carbonate) networks with shape-memory properties have been evaluated in order to prepare biodegradable AF closure devices that can be implanted minimally invasively.

Phagocytosis of bacteria adhering to a biomaterial surface in a surface thermodynamic perspective.

Bacterial biofilms can increase the pathogenicity of infection and constitute a major problem in modern health-care, especially on biomaterial implants and devices. Biofilms are difficult to eradicate by the host immune system, even with antibiotics, and have been the number one cause of biomaterial implant and device failure for decades. Therefore, it is important to understand how immune cells interact with adhering pathogens.