Objective. Poor clinical outcomes following peripheral nerve injury (PNI) are partly attributable to the limited rate of neuronal regeneration. Despite numerous potential drug candidates demonstrating positive effects on nerve regeneration rate in preclinical models, no drugs are routinely used to improve restoration of function in clinical practice. A key challenge associated with clinical adoption of drug treatments in nerve injured patients is the requirement for sustained administration of doses associated with undesirable systemic sideeffects. Local controlled-release drug delivery systems could potentially address this challenge, particularly through the use of biomaterials that can be implanted at the repair site during the microsurgical repair procedure. Approach. In order to test this concept, this study used various biomaterials to deliver ibuprofen sodium or sulindac sulfide locally in a controlled manner in a rat sciatic nerve injury model. Following characterisation of release parameters in vitro, ethylene vinyl acetate tubes or polylactic-co-glycolic acid wraps, loaded with ibuprofen sodium or sulindac sulfide, were placed around directly-repaired nerve transection or nerve crush injuries in rats. Main results. Ibuprofen sodium, but not sulindac sulfide caused an increase in neurites in distal nerve segments and improvements in functional recovery in comparison to controls with no drug treatment. Significance. This study showed for the first time that local delivery of ibuprofen sodium using biomaterials improves neurite growth and functional recovery following PNI and provides the basis for future development of drug-loaded biomaterials suitable for clinical translation.

With over two decades of evidence available including from randomised clinical trials, we explore whether the use of low-cost mosquito net mesh for inguinal hernia repair, common practice only in low-income and middle-income countries, represents a double standard in surgical care. We explore the clinical evidence, biomechanical properties and sterilisation requirements for mosquito net mesh for hernia repair and discuss the rationale for its use routinely in all settings, including in high-income settings. Considering that mosquito net mesh is as effective and safe as commercial mesh, and also with features that more closely resemble normal abdominal wall tissue, there is a strong case for its use in all settings, not just low-income and middle-income countries. In the healthcare sector specifically, either innovations should be acceptable for all contexts, or none at all. If such a double standard exists and worse, persists, it raises serious questions about the ethics of promoting healthcare innovations in some but not all contexts in terms of risks to health outcomes, equitable access, and barriers to learning.

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There is an up-surge of interest in antioxidants because of their potential use in mitigating a wide array of oxidative stress mediated diseases. In the course of our literature search for diverse functional groups, with utility in the design of potential drugs for preventing oxidative stress related cell injury, we have collected a small literature library of core structures or moieties possessing antioxidant activities. These functional groups can be re-configured into robust antioxidants drug molecules, in their own right, or incorporated into drug structures where the antioxidant capability is required. The lack of single papers presenting a collection of diverse small molecule antioxidant moieties as potential design leads prompted us to write this short review of twenty five such functionalities.

Purpose Low-cost meshes (LCM) were repurposed for the repair of hernias in the developing world. In vivo studies have shown LCM to have comparable results to commercial meshes (CM) at a fraction of the cost. However, little has been done to characterise the mechanical and biocompatible properties of LCM, preventing its clinical use in the UK. The objectives of the research are to assess mechanical and ultrastructural properties of two UK-sourced low-cost meshes (LCM) and the characterisation of the LCMs in vitro biocompatibility. Methods Mechanical properties of the two LCM were measured through uniaxial tensile test and ultrastructure was evaluated with Scanning Electron Microscopy. LIVE/DEAD® Viability/Cytotoxicity Assay kit and alamarBlue were used to assess cellular viability and proliferation, respectively. Images were acquired with a fluorescence microscope and analysed using ImageJ (NIH, USA). Results LCM1 and LCM2 were both multifilament meshes, with the first having smaller pores than the latter. LCM1 exhibited significantly higher tensile strength (p < 0.05) than LCM2 but significantly lower extensibility (p < 0.0001), while Young’s Modulus of the two samples was not significantly different. No significant difference was found in the cellular viability and morphology cultured in LCM1 and LCM2 conditioned media. Metabolic assay and fluorescence imaging showed cellular attachment and proliferation on both LCMs over 14 days. Conclusion The characterisation of the two UK-sourced LCMs showed in vitro biocompatibility and mechanical and ultrastructural properties comparable to the equivalent CM. This in vitro data represents a step forward for the feasibility of adopting LCM for surgical repair of hernias in the UK.

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Aim To isolate human rectus sheath fibroblasts (hRSFs) from tissue samples, and characterise those cells - establishing their capacity to contract collagen matrix. Methods Samples of posterior rectus sheath were taken from 3 patients undergoing stoma formation. Samples underwent collagenase digestion, and isolated cells grown in culture media. Cultures were grown to confluence at 2nd passage, then cryopreserved. Cells were successfully thawed and re-animated at 3rd passage. 3 Cell lines of hRSFs and one of human dermal fibroblasts (HDFs) were all studied. Cell lines were assessed for their morphology and underwent immunofluorescent staining for Vimentin and α-smooth muscle actin. Cell lines were also seeded into collagen matrices to assess stromal contraction. Results Our protocol produced confluent clusters of fibroblasts within 2 weeks, and healthy cultures of cells into their 3rd passage within 6 weeks. Cells were successfully cryopreserved in liquid nitrogen after 3rd passage and were thawed and reanimated thereafter. Notable differences in morphology were observed between different cell lines – all of which stained positively for vimentin and α-smooth muscle actin. All cell lines induced a different speed of contraction within a collagen matrix from the HDFs achieving 82% contraction after 5 days, to 54% in the slowest RSF group. Conclusion Our work is the first to describe the isolation and characterisation of human rectus sheath fibroblasts and prove the concept of their introduction into 3D tissue models. This work opens exciting future prospects of both forming 3D models of rectus sheath tissue and in vitro mesh testing.

The vast majority of pelvic and intra‐abdominal surgery is undertaken through at least one incision, through either the linea alba or the rectus sheath. These connective tissue layers are formed from the aponeuroses of the rectus muscles (anterior and posterior rectus sheath) and are vital for the structural integrity of the abdominal wall. Poor healing of these connective tissues after surgery can lead to significant morbidity for patients, who can develop unsightly and painful incisional hernias. Fibroblasts within the rectus sheath are responsible for laying down and remodeling collagen during the healing process after surgery. Despite their importance for this healing process, such cells have not been studied in vitro. In order to carry out such work, researchers must first be able to isolate these cells from human tissue and culture them successfully so they may be used for experimentation. This article provides an extensive and detailed protocol for the isolation, culture, cryopreservation, and thawing of human rectus sheath fibroblasts (RSFs). In our hands, this protocol develops confluent cultures of primary fibroblasts within 2 weeks, and sufficient cultures ready for freezing and storage after a further 2 to 4 weeks. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Collagenase digestion of human rectus sheath and isolation of RSFs Alternate Protocol: Collagenase digestion of human rectus sheath and isolation of RSFs, digestion in flask Support Protocol: Cryopreservation and thawing of human RSFs