No / Significance: Epigenetic regulatory mechanisms are essential for epidermal homeostasis and contribute to the pathogenesis of many skin diseases, including skin cancer and psoriasis. However, while the epigenetic regulation of epidermal homeostasis is now becoming active area of research, the epigenetic mechanisms controlling the wound healing response remain relatively untouched. Recent Advances: Substantial progress achieved within the last two decades in understanding epigenetic mechanisms controlling gene expression allowed defining several levels, including covalent DNA and histone modifications, ATP-dependent and higher-order chromatin chromatin remodeling, as well as noncoding RNA- and microRNA-dependent regulation. Research pertained over the last few years suggests that epigenetic regulatory mechanisms play a pivotal role in the regulation of skin regeneration and control an execution of reparative gene expression programs in both skin epithelium and mesenchyme. Critical Issues: Epigenetic regulators appear to be inherently involved in the processes of skin repair, and are able to dynamically regulate keratinocyte proliferation, differentiation, and migration, together with influencing dermal regeneration and neoangiogenesis. This is achieved through a series of complex regulatory mechanisms that are able to both stimulate and repress gene activation to transiently alter cellular phenotype and behavior, and interact with growth factor activity. Future Directions: Understanding the molecular basis of epigenetic regulation is a priority as it represents potential therapeutic targets for the treatment of both acute and chronic skin conditions. Future research is, therefore, imperative to help distinguish epigenetic modulating drugs that can be used to improve wound healing.

No / Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play roles in embryonic development and postnatal remodelling of the skin. Many indications suggest that BMP signalling regulates keratinocyte proliferation and differentiation. Chronic wounds have been shown to exhibit high levels of BMP ligands; however, the effect of BMP pathway modulation on human skin healing remains undefined. A human ex vivo skin wound healing model was used to analyse the expression of BMP signalling pathway components during healing and to investigate the effects of BMPs and the BMP antagonist Noggin on skin repair. Additionally, the effects of BMP signalling on keratinocyte proliferation, apoptosis and migration were tested using in vitro flow cytometry and ‘scratch’ migration assays, respectively. BMP receptor-1B (BMPR-1B) and downstream signalling protein phosphorylated-Smad-1/5/8 were highly expressed in healing epidermis. Treatment of human skin with exogenous BMPs impaired wound closure by reducing keratinocyte proliferation and increasing apoptosis. The BMP antagonist Noggin negated the inhibitory effects of BMP ligands, and when used alone, Noggin reduced keratinocyte apoptosis in the wound bed. In vitro, BMP ligands suppressed keratinocyte proliferation whilst Noggin stimulated proliferation. Keratinocyte migration was slowed following BMP treatment; in contrast, migration was significantly accelerated due to inhibition of BMP activity by either Noggin or BMPR-1B silencing. BMP signalling is inherently involved in wound healing. BMPs slow skin repair by suppressing keratinocyte proliferation and migration. Thus, modulation of BMP signalling using BMP inhibitors such as Noggin may serve as a new approach to promote cutaneous wound repair. Level of evidence: Not ratable.

Yes / The cutaneous healing response has evolved to occur rapidly, in order to minimize infection and to re‐establish epithelial homeostasis. Rapid healing is achieved through complex coordination of multiple cell types, which importantly includes specific cell populations within the hair follicle (HF). Under physiological conditions, the epithelial compartments of HF and interfollicular epidermis remain discrete, with K15+ve bulge stem cells contributing progeny for HF reconstruction during the hair cycle and as a basis for hair shaft production during anagen. Only upon wounding do HF cells migrate from the follicle to contribute to the neo‐epidermis. However, the identity of the first‐responding cells, and in particular whether this process involves a direct contribution of K15+ve bulge cells to the early stage of epidermal wound repair remains unclear. Here we demonstrate that epidermal injury in murine skin does not induce bulge activation during early epidermal wound repair. Specifically, bulge cells of uninjured HFs neither proliferate nor appear to migrate out of the bulge niche upon epidermal wounding. In support of these observations, Diphtheria toxin‐mediated partial ablation of K15+ve bulge cells fails to delay wound healing. Our data suggest that bulge cells only respond to epidermal wounding during later stages of repair. We discuss that this response may have evolved as a protective safeguarding mechanism against bulge stem cell exhaust and tumorigenesis. / BBSRC.

Yes / The paper presents a new healing system that uses pre-tensioned hybrid tendons to close cracks in cementitious structural elements. The tendons comprise an inner core, formed from aramid fibre ropes, and an outer sleeve made from a shape memory PET. During the manufacturing process, the inner core of a tendon is put into tension and the outer sleeve into compression, such that the tendon is in equilibrium. A set of tendons are then cast in a cementitious structural element and heat activated once cracking occurs. This triggers the shrinkage potential of the PET sleeve, which in turn releases the stored strain energy in the inner core. The tensile force thereby released applies a compressive force to the cementitious element, in which the tendons are embedded, that acts to close any cracks that have formed perpendicular to the axis of the tendons. Details of the component materials used to form the tendon are given along with the tendon manufacturing process. A set of experiments are then reported that explore the performance of three different tendon configurations in prismatic mortar beams. The results from these experiments show that the tendons can completely close 0.3 mm cracks in the mortar beams and act as effective reinforcement both before and after activation. A nonlinear hinge-based numerical model is also described, which is shown to be able to reproduce the experimental behaviour with reasonable accuracy. The model is used to help interpret the results of the experiments and, in particular, to explore the effects of slip at the tendon anchorages and the amount of prestress force that remains after activation. It is shown that, with two of the tendon configurations tested, over 75% of the prestress potential of the tendon remains after crack closure. / UK-EPSRC (Grant No. EP/P02081X/1, Resilient Materials 4 Life, RM4L).

No / The increasing prevalence of chronic wounds has significant financial implications for nations with advanced healthcare provision. Although the diseases that predispose to hard-to-heal wounds are recognized, their etiology is less well understood, partly because practitioners in wound management lack specialized diagnostic support. Prognostic indicators for healing may be inherent to wound biochemistry but remain invisible under routine clinical investigation; lactate is an example of this. In this study, lactate concentration in exudate obtained from 20 patients undergoing wound management in hospital was variable but in some cases approached or exceeded 20 mM. In vitro viability studies indicated that fibroblasts and endothelial cells tolerated low levels of lactate (1-10 mM), but cell viability was severely compromised by high lactate concentrations (=20 mM). Scratched monolayer experiments revealed that cell migration was affected earlier than viability in response to increasing lactate dose, and this was shown by immunocytochemistry to be associated with cytoskeletal disruption. A prototype enzyme-based colorimetric assay for lactate generating a color change that was rapid in the context of clinical practise, and capable of functioning within a gel vehicle, was developed with point-of-care dipstick applications in mind. A randomized single-blinded trial involving 30 volunteers and using a color chart to calibrate the assay demonstrated that lactate concentration could be reliably estimated with 5 mM precision; this suggesting that "physiological" and "pathological" lactate concentration could be distinguished. The present data suggest that a dipstick-type colorimetric assay could comprise a viable diagnostic tool for identifying patients at-risk from high-wound lactate.

No / Wound pain, odour and exudate have a major impact on patient quality of life. Understanding the management of these core components of wound healing is essential if patient outcomes are to be optimised. This paper discusses the role and types of exudate, the impact of high viscosity exudate on management and what to consider when selecting an appropriate dressing with the aim of restoring a satisfactory moist wound environment for healing.

Many scholars have argued that existing conceptualizations of trauma such as the Diagnostic and Statistical Manual of Mental Disorders (5th Ed.; DSM-5) conceptualization are inapplicable for individuals of marginalized communities. Individuals of marginalized communities may experience historical trauma, racial trauma, identity-related trauma, or collective trauma. Moreover, the effects of these forms of trauma may persist throughout different generations via biological transmission (e.g., epigenetics) or via interpersonal transmission (e.g., emotion socialization, cultural socialization, attachment, communication styles, behavioral socialization). The generational effects of these forms of trauma are referred to as intergenerational trauma. There has been a paucity of empirical explorations of intergenerational trauma, especially among those with multiple marginalized identities (e.g., LGBTQ+ BIPOC individuals). This study explored experiences of intergenerational trauma and healing among 10 LGBTQ+ BIPOC individuals through semi-structured interviews. Their responses were analyzed using constructivist grounded theory methodology and the Intergenerational Trauma Experiences and Healing (ITEH) model was generated to describe the social processes involved in the participants’ experiences of intergenerational trauma. The ITEH model involves several social processes including: (a) experiencing multifaceted forms of intergenerational trauma, (b) carrying intergenerational trauma’s impacts on the self, (c) seeing intergenerational trauma’s impact on others/generations, and (d) healing from intergenerational trauma. Research, clinical, and advocacy implications of the ITEH model are discussed. Keywords: trauma, intergenerational, resilience, healing, QTBIPOC

<p dir="ltr">Connective Tissue Matrix (CTM) allografts are structural implants intended to supplement or replace damaged or inadequate tissues. Generated from human amnion, chorion, and umbilical elements, these allografts contain structural proteins as well as tissue-specific and –agnostic growth factors. In these studies, we examined the efficacy of CTM allografts to improve bone healing and whether CTM alters injury-associated pain behaviors in a pre-clinical animal model.</p><p dir="ltr">The study involved two surgery models: a surgically induced femoral fracture model and a segmental bone defect (SBD) model. In the femoral fracture model, 12-week-old male C57BL/6J mice were divided into four groups: Saline Control, CTM Membrane, CTM Paste, and CTM Membrane + Paste. For the SBD model, the same age strain of male mice was divided into five groups: Saline Control, BMP-2, CTM Paste, CTM Membrane, and CTM Membrane + Paste.</p><p dir="ltr">Complete blood count analysis demonstrated no significant alterations in blood cell numbers due to CTM treatments in the femoral fracture model. Despite the presence of various pro-inflammatory cytokines and growth factors in CTM, treated mice showed no significant increase in pain-associated behaviors post-fracture. Bioluminescence imaging demonstrated a significant reduction in inflammation for the CTM Membrane + Paste group on day 14 post-surgery. µCT analysis indicated significant improvement in the mineralized callus area for the CTM Membrane + Paste group when compared to all the other groups in the surgically induced femoral fracture model. Histomorphometric analysis further supported these findings, revealing an increased bone percentage in the callus area for CTM Membrane + Paste group compared to Saline controls in the surgical fracture model. However, biomechanical testing indicated no significant differences between Saline Control and the CTM treated groups. Interestingly, an increasing trend was observed in stiffness and toughness for the CTM Membrane group.</p><p dir="ltr">Surgical fracture, being a simpler model of fracture, and heal without intervention with time. Hence, that led us to test our hypothesis that CTM products can promote bone healing in a more difficult model, of SBD mice. Long-term evaluations at 13 weeks for the SBD model showed that the BMP-2 group significantly increased the callus area compared to saline controls, with increasing trends observed in CTM-treated groups. Biomechanical testing demonstrated an increasing trend in the ultimate torque in all the groups when compared to Saline Control.</p><p dir="ltr">Overall, the CTM Membrane + Paste group demonstrated promising potential in enhancing bone healing and reducing inflammation in the surgical fracture model, without triggering additional pain behaviors. The findings from the SBD model revealed that CTM Membrane + Paste has similar impact on bone healing, as observed in the surgical fracture model. Specifically, having a larger callus area as compared to Saline Control group and a significantly higher bone volume / tissue volume (BV/TV) percentage compared to all the other groups. These preclinical findings suggest that CTM allografts may promote fracture repair, providing rationale for further investigations, including a randomized controlled trial for human fractures in weightbearing bones.</p>

Thousands of years ago in Ancient Mesopotamia there was an abundant Pantheon of gods and goddesses. Circa 3000–2300 B.C.E, separate cults started to form relating to two of these goddesses: Ninisina and Gula. They were quite similar, both associated with healing, as were several other goddesses in the area. Over time they all fused, and their names disappeared one by one, until one remained; Gula. Scholars of today often tend to see them all as one type of goddess, their names interchangeable. This essay researches Ninisina and Gula, and the intention is to see if they truly are the “same”. A number of hymns and healing spells are analysed and used to compare the goddesses. This comparison is based on three themes; “Healing”, “Praise” and “Prayer &amp; Intention”, and finds that indeed the manner of their healing and their characters differ. The essay also discusses how central their roles as healers are. It is shown that even though healing is always mentioned in every chosen text, other traits are often emphasised more.

M.A. / Prisons in the South African context are considered to be places of correction for deviant individuals. The perception of the functioning of a correctional space is the correction of a particular type of functioning and the construction of another. One of the underlying assumptions of a penal system is the notion of a subject who is able to undergo a process of normalisation. This dissertation is directed towards the exploration of a different type of space that has been created within the correctional system at the Diepkloof Prison. It will be suggested herein that creative workshops, run within the prison by an outside facilitator, have succeeded in subverting the normalising discourse of the penal system, and have helped to facilitate a different type of healing experience within the confines of the institutional space. In order to place the discussion of the workshopping process within a sound theoretical framework, various theoretical questions regarding the shift from modernist to postmodern psychology are explored in some depth. It will be argued that the ideas emerging from social constructionist and narrative psychology, deconstructionist notions of language and subjectivity, as well as post-structuralist ideas on disciplinary power, offer a theoretical framework from within which to understand the healing process that occurs in the workshops themselves.