Trabecular meshwork cell differentiation in response to collagen and TGFβ-2 spatial interactions.

Primary open-angle glaucoma (POAG) is currently the most prevalent cause of irreversible blindness globally. To date, few in vitro models that can faithfully recapitulate the complex architecture of the trabecular meshwork (TM) and the specialised trabecular meshwork cell (TMC) characteristics that are local to the structurally opposing regions. This study aimed to investigate the parameters that govern TMC phenotype by adapting the extracellular matrix structure to mimic the juxtacanalicular tissue (JCT) region of the TM.

Erratum: Publisher's Note: "A suspended layer additive manufacturing approach to the bioprinting of tri-layered skin equivalents" [APL Bioeng. , 046103 (2021)].

[This corrects the article DOI: 10.1063/5.0061361.

Cobalt containing glass fibres and their synergistic effect on the HIF-1 pathway for wound healing applications.

Chronic wounds are a major healthcare problem, but their healing may be improved by developing biomaterials which can stimulate angiogenesis, e.g. by activating the Hypoxia Inducible Factor (HIF) pathway.

A suspended layer additive manufacturing approach to the bioprinting of tri-layered skin equivalents.

Skin exhibits a complex structure consisting of three predominant layers (epidermis, dermis, and hypodermis). Extensive trauma may result in the loss of these structures and poor repair, in the longer term, forming scarred tissue and associated reduction in function. Although a number of skin replacements exist, there have been no solutions that recapitulate the chemical, mechanical, and biological roles that exist within native skin.

Trabecular bone organoids: a micron-scale 'humanised' prototype designed to study the effects of microgravity and degeneration.

Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface.

In vitro modelling of disease-induced changes in the diabetic wound fibroblast.

Objective: Fibroblasts have been shown to play an increasingly important role within diabetic wounds. While several in vitro models of diabetic wound fibroblasts have been reported, none replicate the natural progression of the disease over time, recapitulating the acquisition of the diseased phenotype. Therefore, this study aimed to establish an in vitro model of the diabetic wound fibroblast through sustained exposure of healthy dermal fibroblasts to hyperglycaemia.

Bioactive glasses and electrospun composites that release cobalt to stimulate the HIF pathway for wound healing applications.

Background: Bioactive glasses are traditionally associated with bonding to bone through a hydroxycarbonate apatite (HCA) surface layer but the release of active ions is more important for bone regeneration. They are now being used to deliver ions for soft tissue applications, particularly wound healing. Cobalt is known to simulate hypoxia and provoke angiogenesis.

Ex vivo culture of keratinocytes on papillary and reticular dermal layers remodels skin explants differently: towards improved wound care.

In this study, we characterised the effect that seeding keratinocytes on the papillary and reticular dermis had on the extracellular matrix and tissue integrity ex vivo. Human skin explants from consented patients (n = 6) undergoing routine surgery were cultured at a liquid-air interface, dermal-side up, and autologous keratinocytes seeded on the exposed papillary or reticular layer. After 7-21 days, histological and immunohistochemical evaluation of the morphology and extracellular matrix was performed.

Development of a High-Throughput Burn Wound Model Using Porcine Skin, and Its Application to Evaluate New Approaches to Control Wound Infection.

Biofilm formation in wounds is considered a major barrier to successful treatment, and has been associated with the transition of wounds to a chronic non-healing state. Here, we present a novel laboratory model of wound biofilm formation using porcine skin and a custom burn wound array device. The model supports high-throughput studies of biofilm formation and is compatible with a range of established methods for monitoring bacterial growth, biofilm formation, and gene expression.

Bacteriophage Can Prevent Encrustation and Blockage of Urinary Catheters by Proteus mirabilis.

Proteus mirabilis forms dense crystalline biofilms on catheter surfaces that occlude urine flow, leading to serious clinical complications in long-term catheterized patients, but there are presently no truly effective approaches to control catheter blockage by this organism. This study evaluated the potential for bacteriophage therapy to control P. mirabilis infection and prevent catheter blockage.

Reduction of tendon adhesions following administration of Adaprev, a hypertonic solution of mannose-6-phosphate: mechanism of action studies.

Repaired tendons may be complicated by progressive fibrosis, causing adhesion formation or tendon softening leading to tendon rupture and subsequent reduced range of motion. There are few therapies available which improve the gliding of damaged tendons in the hand. We investigate the role of Mannose 6-phosphate (M6P) in a 600 mM hypertonic solution (Adaprev) on tendon adhesion formation in vivo using a mouse model of severed tendon in conjunction with analysis of collagen synthesis, cellular proliferation and receptors involved in TGF beta signalling.

The effect of isolation and culture methods on epithelial stem cell populations and their progeny-toward an improved cell expansion protocol for clinical application.

Background Aims: The use of cultured epithelial keratinocytes in the treatment of burns and skin graft donor sites is well established in clinical practice. The most widely used culture method for clinical use was originally developed by Rheinwald and Green 40 years ago. This system uses irradiated mouse dermal fibroblasts as a feeder cell layer to promote keratinocyte growth, a process that is costly and labor-intensive for health care providers.

Effects of interleukin-10 on cutaneous wounds and scars in humans of African continental ancestral origin.

Scars in humans of African continental ancestry heal with an exaggerated inflammatory response and a generally wider scar. Interleukin-10 is an anti-inflammatory and antifibrotic cytokine. A randomized controlled trial in Caucasians found that exogenous interleukin-10 resulted in improved macroscopic scar appearance and reduced scar redness.

Interleukin-10 reduces scar formation in both animal and human cutaneous wounds: results of two preclinical and phase II randomized control studies.

Cutaneous scarring affects up to 100 million people per annum. There is no effective scar reducing/preventing therapeutic developed to date. Interleukin (IL)-10 is an anti-inflammatory and antifibrotic cytokine.

Denervation affects regenerative responses in MRL/MpJ and repair in C57BL/6 ear wounds.

The MRL/MpJ mouse displays the rare ability amongst mammals to heal injured ear tissue without scarring. Numerous studies have shown that the formation of a blastema-like structure leads to subsequent tissue regeneration in this model, indicating many parallels with amphibian limb regeneration and mammalian embryogenesis. We have recently shown that the MRL/MpJ mouse also possesses an enhanced capacity for peripheral nerve regeneration within the ear wound.

Histomorphometric changes in repaired mouse sciatic nerves are unaffected by the application of a scar-reducing agent.

Microsurgical repair of transected peripheral nerves is compromised by the formation of scar tissue and the development of a neuroma, thereby limiting the success of regeneration. The aim of this study was to quantify histomorphometrically the structural changes in neural tissue that result from repair, and determine the effect of mannose-6-phosphate (M6P), a scar-reducing agent previously shown to enhance regeneration. In anaesthetised C57-black-6 mice, the left sciatic nerve was sectioned and repaired using four epineurial sutures.

Avotermin for scar improvement following scar revision surgery: a randomized, double-blind, within-patient, placebo-controlled, phase II clinical trial.

Background: Skin scarring is associated with psychosocial distress and has a negative effect on quality of life. The transforming growth factor (TGF)-β family of cytokines plays a key role in scarring. TGF-β3 improves scar appearance in a range of mammalian species.

The effect of Mannose-6-Phosphate on recovery after sciatic nerve repair.

We have determined the effect of applying Mannose-6-Phosphate (M6P), a scar reducing agent, to a site of sciatic nerve repair. In anaesthetised C57-Black-6 mice, the left sciatic nerve was sectioned and repaired using 4 epineurial sutures. Either 100 μl of 600 mM Mannose-6-Phosphate (29 animals), or 100 μl of phosphate buffered saline as a placebo control (29 animals), was injected into and around the nerve repair site.

Peripheral nerve regeneration in the MRL/MpJ ear wound model.

The MRL/MpJ mouse displays an accelerated ability to heal ear punch wounds without scar formation (whereas wounds on the dorsal surface of the trunk heal with scar formation), offering a rare opportunity for studying tissue regeneration in adult mammals. A blastema-like structure develops and subsequently the structure of the wounded ear is restored, including cartilage, skin, hair follicles and adipose tissue. We sought to assess if the MRL/MpJ strain also possessed an enhanced capacity for peripheral nerve regeneration.

Therapeutic improvement of scarring: mechanisms of scarless and scar-forming healing and approaches to the discovery of new treatments.

Scarring in the skin after trauma, surgery, burn or sports injury is a major medical problem, often resulting in loss of function, restriction of tissue movement and adverse psychological effects. Whilst various studies have utilised a range of model systems that have increased our understanding of the pathways and processes underlying scar formation, they have typically not translated to the development of effective therapeutic approaches for scar management. Existing treatments are unreliable and unpredictable and there are no prescription drugs for the prevention or treatment of dermal scarring.

Bioengineering skin using mechanisms of regeneration and repair.

The development and use of artificial skin in treating acute and chronic wounds has, over the last 30 years, advanced from a scientific concept to a series of commercially viable products. Many important clinical milestones have been reached and the number of artificial skin substitutes licensed for clinical use is growing, but they have yet to replace the current "gold standard" of an autologous skin graft. Currently available skin substitutes often suffer from a range of problems that include poor integration (which in many cases is a direct result of inadequate vascularisation), scarring at the graft margins and a complete lack of differentiated structures.

Bounds on the distribution of the number of gaps when circles and lines are covered by fragments: theory and practical application to genomic and metagenomic projects.

Background: The question of how a circle or line segment becomes covered when random arcs are marked off has arisen repeatedly in bioinformatics. The number of uncovered gaps is of particular interest. Approximate distributions for the number of gaps have been given in the literature, one motivation being ease of computation.

Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration.

Advanced therapies combating acute and chronic skin wounds are likely to be brought about using our knowledge of regenerative medicine coupled with appropriately tissue-engineered skin substitutes. At the present time, there are no models of an artificial skin that completely replicate normal uninjured skin. Natural biopolymers such as collagen and fibronectin have been investigated as potential sources of biomaterial to which cells can attach.

Characterizing regeneration in the vertebrate ear.

We have previously shown that MRL/MpJ mice have a capacity for regeneration instead of scar formation following an ear punch wound. Understanding the differences that occur between scar-free regeneration or repair with scarring will have great impact upon advances in skin tissue engineering. A key question that remains unanswered in the MRL/MpJ mouse model is whether regeneration was restricted to the ear or whether it extended to the skin.