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Upon injury, inflammation and repair processes are orchestrated to maintain tissue homeostasis. The Wnt ligands play essential roles in cell differentiation and proliferation for tissue repair and regeneration. It is increasingly clear that Wnt ligands play crucial immune-modulatory roles in inflammatory diseases. It is predicted that comprehensive research regarding the cross-talk between nonimmune and immune cells in tissue injury and repair will flourish. The Wnt system and immune system interaction will be critical to understanding tissue injury, inflammation, and repair. In this study, we will first introduce the Wnt system and review the role of the Wnt system in tissue regeneration and repair. We will review the previous literature regarding how the Wnt ligands regulate the immune system. Next, we will discuss the current and future perspectives of Wnt ligands to target cancer and other immunological diseases. Finally, we will discuss the quintessential Wnt antagonist Dickkopf1 as an immunomodulatory ligand.

Microglia are the immune guardians of the central nervous system (CNS), with critical functions in development, maintenance of homeostatic tissue balance, injury and repair. For a long time considered a forgotten ‘third element’ with basic phagocytic functions, a recent surge in interest, accompanied by technological progress, has demonstrated that these distinct myeloid cells have a wide-ranging importance for brain function. This review reports microglial origins, development, and function in the healthy brain. Moreover, it also targets microglia dysfunction and how it contributes to the progression of several neurological disorders, focusing on particular molecular mechanisms and whether these may present themselves as opportunities for novel, microglia-targeted therapeutic approaches, an ever-enticing prospect. Finally, as it has been recently celebrated 100 years of microglia research, the review highlights key landmarks from the past century and looked into the future. Many challenging problems have arisen, thus it points out some of the most pressing questions and experimental challenges for the ensuing century.

To summarize and critically review recent literature on spontaneous recovery from unilateral vocal fold paralysis (UVFP), with emphasis on the time to vocal recovery and its implications for the physiology of recurrent laryngeal nerve (RLN) injury and repair. Analyses of the time to spontaneous vocal recovery in UVFP have generated probabilities of recovery that can be used to counsel patients within the first 12 months of the onset of UVFP, replacing the traditional recommendation of waiting 12 months prior to pursuing permanent intervention. In addition, mathematical modeling of the recovery times has yielded insights into the physiology of RLN reinnervation following injury. Most patients with UVFP who experience vocal recovery do so within 6–9 months. The recovery pattern differs between idiopathic UVFP and iatrogenic UVFP. For iatrogenic UVFP, the severity of RLN injury dictates the time to recovery and the eventual probability of recovery, not the distance between the injury site and the larynx.

The conventional hand tendon zones and subzones do not reflect the actual lengths covered by the involved locus of the tendon during full digital and wrist motion, which warrant reappraisal of the tendon zone concept. Because of the tendon excursions many lacerations should be regarded as multiple zone injuries. Furthermore, the length-spans of glide of the distal tendon stump and of the tendon junction (i.e. the glide zones of tendon injury and repair, respectively) are mostly not of the same length because, due to pulley release and bulkiness of the tenorrhaphy, the glide zone of tendon repair is shorter than that of tendon injury. Therefore, it would be practical to notate the glide zones of the lacerated tendon by indicating the anatomic position of the distal tendon stump and tendon junction in full extension and flexion. This data can be provided separately or along with the conventional tendon zones, e.g. II (A4–C2) or II–III (A2–PA), where A, C, and PA stand for the annular, cruciform, and palmar aponeurosis pulleys, respectively. The conventional tendon zone classification could be improved with a tendon glide zone concept. Documentation of the actual excursions of the distal tendon stump and of the tenorrhaphy interface would prevent misinterpretation of the actual level of tendon injury and repair.

Efficacy and outcomes of osteosynthesis depend on various factors including types of injury and repair, host factors, characteristics of implant materials and type of implantation. One of the most important host factors appears to be the extent of bone damage due to the mechanical force and thermal injury which are produced at cutting site during bone drilling. The temperature above the critical temperature (47 °C) produces thermal osteonecrosis in the bones. In the present work, experimental investigations were performed to determine the effect of drilling parameters (rotational speed, feed rate and drill diameter) and techniques (conventional surgical bone drilling and rotary ultrasonic bone drilling) on cutting force and temperature generated during bone drilling. The drilling experiments were performed by a newly developed bone drilling machine on different types of human bones (femur, tibia and fibula) having different biological structure and mechanical behaviour. The bone samples were procured from male cadavers with the age of second to fourth decades. The results revealed that there was a significant difference ( p

Recent adjustments to the histological diagnosis and the introduction of molecular classification are providing renewed support for the paradigm that antibody-mediated rejection (ABMR) is an important clinical problem for which there is an urgent need for better therapies. Acute ABMR is observed when the graft is exposed to rapid increases high-titer donor-specific antibodies (DSA) that are most often generated as anamnestic responses in sensitized recipients or de novo responses in non-sensitized patients that are non-adherent. Chronic ABMR is associated with slower increases in DSA, which may be high or low titer and transient or persistent. These DSA elicit cycles of injury and repair that manifest as multilamination of the peritubular capillary basement membrane or arteriopathy manifesting as intimal fibrosis. Mitigating the problem of AMBR requires the anamnestic and de novo DSA responses to be prevented, and established DSA responses to be reversed. To this end, a better understanding the immunobiology of DSA production is necessary, and also the development of assays capable of detecting early humoral immune responses. How recent advances in understanding the immunobiology of B cells, and areas requiring further investigation that might lead to new therapies or better diagnosis are discussed in this review.

Volumetric muscle loss (VML) injuries, by definition, exceed the endogenous repair capacity of skeletal muscle resulting in permanent structural and functional deficits. VML injuries present a significant burden for both civilian and military medicine. Despite progress, there is still considerable room for therapeutic improvement. In this regard, tissue-engineered constructs show promise for VML repair, as they provide an opportunity to introduce both scaffolding and cellular components. We have pioneered the development of a tissue-engineered muscle repair (TEMR) technology created by seeding muscle progenitor cells onto a porcine-derived bladder acellular matrix followed by cyclic stretch preconditioning before implantation. Our work to date has demonstrated significant functional repair (60–90% functional recovery) in progressively larger rodent models of VML injury following TEMR implantation. Notwithstanding this success, TEMR implantation in cylindrically shaped VML injuries in the tibialis anterior (TA) muscle was associated with more variable functional outcomes than has been observed in sheet-like muscles such as the latissimus dorsi. In fact, previous observations documented a dichotomy of responses following TEMR implantation in a rodent TA VML injury model; with an ≈61% functional improvement observed in fewer than half (46%) of TEMR-implanted animals at 12 weeks postinjury. This current study builds directly from those observations as we modified the geometry of both the VML injury and the TEMR construct to determine if improved matching of the implanted TEMR construct to the surgically created VML injury resulted in increased functional recovery posttreatment. Following these modifications, we observed a comparable degree of functional improvement in a larger proportion of animals (≈67%) that was durable up to 24 weeks post-TEMR implantation. Moreover, in ≈25% of all TEMR-implanted animals, functional recovery was virtually complete (TEMR max responders), and furthermore, the functional recovery in all 67% of responding animals was accompanied by the presence of native-like muscle properties within the repaired TA muscle, including fiber cross-sectional area, fiber type, vascularization, and innervation. This study emphasizes the importance of tuning the application of tissue engineering technology platforms to the specific requirements of diverse VML injuries to improve functional outcomes. IMPACT STATEMENT: This report confirms and extends previous observations with our implantable tissue-engineered technology platform for repair of volumetric muscle loss (VML) injuries. Based on our prior work, we addressed factors hypothesized to be responsible for significant outcome variability following treatment of VML injuries in a rat tibialis anterior model. Through customization of the muscle repair technology to a specific VML injury, we were able to significantly increase the frequency at which functional recovery occurred, and furthermore, demonstrate durability out to 6 months. In addition, the enhanced biomimetic qualities of repaired muscle tissue were associated with the most robust functional outcomes.

This chapter explores the role that sex hormones play in the development and progression of renal disease. Possible pathogenic mechanisms are described including the effects of sex hormones on cell biology and on the synthesis and release of vasoactive factors and inflammatory and profibrotic cytokines. Next, the role of sex hormones in influencing repair and regeneration following renal injury is discussed and possible pathogenic mechanisms explored. In light of the paucity of data that examine interactions between sex hormones and regeneration in the kidney, this chapter also draws on data which examine the role of sex hormones in the regeneration of nonrenal tissue to suggest avenues for future translational research involving the kidney.

Immune responses contribute to tissue injury and repair during and after ischemic stroke. However, the spatiotemporal and initiating molecular events remain incompletely understood. Here, we show that mice deficient in the phosphatidylserine receptor CD300a, which is highly expressed on brain myeloid cells including Ly6C

Introduction/Background* Vessel injury is a common event in retroperitoneal procedures and technique of vessel injury repair should be a part of gynecological oncology education. Methodology Video presentation of a) a point injury to external iliac vein and technique of suture as an example of common surgical complication and way of solution b) large damage to vena cave and repair with vascular prosthesis as an example of rare and potentially catastropic complication Result(s)* Two surgical complication – vessel injuries – were managed step-by-step with intention to reduce the blood loss and repair vessel to prevent long-term complications as a vein thrombosis. Conclusion* Knowledge of appropriate surgical vessel repair techniques protects against long-term postoperative complications. Even dramatic vessel injury can be repaired with a sequence of steps preventing massive hemorhage and using vesseel prosthesis.

As new applications for human pluripotent stem cell-derived organoids in drug screenings and tissue replacement therapies emerge, there is a need to examine the mechanisms of tissue injury and repair recently reported for various organoid models. In most cases, organoids contain the main cell types and tissues present in human organs, spatially arranged in a manner that largely resembles the architecture of the organ. Depending on the differentiation protocol used, variations may exist in cell type ratios relative to the organ of reference, and certain tissues, including some parenchymal components and the endothelium, might be poorly represented, or lacking altogether. Despite those caveats, recent studies have shown that organoid tissue injury recapitulates major events and histopathological features of damaged human tissues. In particular, major mechanisms of parenchyma cell damage and interstitial fibrosis can be reproduced with remarkable faithfulness. Although further validation remains to be done in order to establish the relevance of using organoid for either mechanistic studies or drug assays, this technology is becoming a promising tool for the study of human tissue homeostasis, injury, and repair.

Chronic intestinal injury after pelvic radiotherapy affects countless cancer survivors worldwide. A comprehensive understanding of the long-term injury dynamics is prevented in available animal models. With linear accelerators that are used to treat cancer in patients, we irradiated a small volume encompassing the colorectum in mice with four fractions of 8 Gy per fraction. We then determined the long-term dynamics of mucosal injury, repair, and the duration of inflammation. We show that crypt fission, not cell proliferation, is the main long-term mechanism for rescuing crypt density after irradiation, and provides a potentially wide window for clinical interventions. Persisting macrophage aggregations indicate a chronic mucosal inflammation. A better understanding as to how crypt fission is triggered and why it fails to repair fully the mucosa may help restore bowel health after pelvic radiotherapy. Moreover, anti-inflammatory interventions, even if implemented long after completed radiotherapy, could promote bowel health in pelvic cancer survivors.

Introduction: Animal models have provided significant insights into the mechanisms responsible for the development of glomerular lesions and proteinuria; they have also helped to identify molecules that control the podocyte function as suitable target-specific therapeutics. Areas covered: We discuss putative therapeutic targets for proteinuric glomerular diseases. An exhaustive search for eligible studies was performed in PubMed/MEDLINE. Most of the selected reports were published in the last decade, but we did not exclude older relevant milestone publications. We consider the molecules that regulate podocyte cytoskeletal dynamics and the transcription factors that regulate the expression of slit-diaphragm proteins. There is a focus on SGLT2 and sirtuins which have recently emerged as mediators of podocyte injury and repair. We also examine paracrine signallings involved in the cross-talk of injured podocytes with the neighbouring glomerular endothelial cells and parietal epithelial cells. Expert opinion: There is a need to discover novel therapeutic moleecules with renoprotective effects for those patients with glomerular diseases who do not respond completely to standard therapy. Emerging strategies targeting components of the podocyte cytoskeleton or signallings that regulate cellular communication within the glomerulus are promising avenues for treating glomerular diseases.

It is estimated that 780 million people do not have access to improved drinking water sources and approximately 2 billion people use fecally contaminated drinking water. Effective point-of-use water treatment systems (POU) can provide water with sufficiently reduced concentrations of pathogenic enteric microorganisms to not pose significant health risks to consumers. Household water treatment (HWT) systems utilize various technologies that physically remove and/or inactivate pathogens. A limited number of governmental and other institutional entities have developed testing protocols to evaluate the performance of POU water treatment systems. Such testing protocols are essential to documenting effective performance because inferior and ineffective POU treatment technologies are thought to be in widespread use. This critical review examines specific practices, procedures and specification of widely available POU system evaluation protocols. Testing protocols should provide standardized and detailed instructions yet be sufficiently flexible to deal with different treatment technologies, test microbe priorities and choices, testing facility capabilities and public health needs. Appropriate infectivity or culture assays should be used to quantify test enteric bacteria, viruses and protozoan parasites, or other appropriate surrogates or substitutes for them, although processes based on physical removal can be tested by methods that detect microbes as particles. Recommendations include further research of stock microbe production and handling methods to consistently yield test microbes in a realistic state of aggregation and, in the case of bacteria, appropriately physiologically stressed. Bacterial quantification methods should address the phenomenon of bacterial injury and repair in order to maximally recover those that are culturable and potentially infectious. It is only with harmonized national and international testing protocols and performance targets that independent and unbiased testing can be done to assure consumers that POU treatment technologies are able to produce water of high microbial quality and low health risk.

Background Many surgical procedures are proposed to manage shoulder instability with recurrent dislocation but there is still a high rate of failure or complications. Repairs are often limited to anterior part of inferior glenohumeral ligament but some authors are reporting better clinical results if its posterior band is also repaired. This biomechanical study aimed to investigate the impact of a supplementary posterior injury compared with an isolated anterior injury and to analyze the contribution of a posterior repair of the inferior glenohumeral ligament compared with an isolated anterior repair. Methods Six fresh-frozen cadaveric shoulders were tested intact and after both anterior and posterior injuries and repairs of the inferior glenohumeral ligament. Shoulders were placed at 90° of humerothoracic elevation in scapular plane and 60° of external rotation. Joint stability was analyzed by successively applying anterior, posterior, inferior and superior glenohumeral displacements and measuring the resulting forces or by applying an anteroinferior loading and measuring three-dimensional head displacements. Maximal range of external rotation was also measured. Findings Combined anterior and posterior injuries of the inferior glenohumeral ligament were necessary to obtain significant instabilities in anterior and inferior directions. A complementary repair of the posterior band improved the biomechanical stability of the glenohumeral joint compared to an isolated anterior repair when anterior and posterior bands are injured. No reduction of external rotation was observed after repairs compared to intact condition. Interpretation These results show the biomechanical interest of this surgical procedure and contribute to document its relevance in clinical practice.

Supplemental Digital Content is available in the text., Background: The purpose of this study was to determine the feasibility of using mouse models for translational study of flexor tendon repair and reconstruction. Methods: Quantitative data detailing the gross anatomy, biomechanical characteristics, and microscopic structure of the deep digit flexor tendon (DDF) of the mouse hindpaw were obtained. Histological characterization of the DDF and the anatomy of the digit in the mouse hindpaw are detailed. Biomechanical testing determined the load-to-failure, stress, elastic modulus, and the site of tendon failure. Results: In gross anatomy, the origins and insertions of the mouse deep digit flexor tendon are similar to those of the human digit, surrounded by a synovial sheath that is only 1- to 2-cells thick. A neurovascular network runs on each side of the digit outside the synovial sheath, but does not clearly penetrate it. The thickness of the DDF is 0.14 ± 0.03 mm and the width is 0.3 ± 0.03 mm. The thickness of the DDF is less than that of 9-0 nylon needle. The mean failure force of the deep flexor tendon was 2.79 ± 0.53N. Conclusions: The gross anatomy of the mouse hindpaw digit is similar to that of the human digit except for key differences seen in the synovial sheath and vascular supply. The dimensions of the mouse DDF make it challenging to create a clinically translatable repair model using currently available surgical techniques. Despite the similarities between the human and mouse anatomy, and the powerful basic science tools available in murine models, mice are an unreliable model for assessing flexor tendon injury and repair.

The kinematics and biomechanics of the acromioclavicular (AC) joint in relation to its investing ligamentous structures and dynamic stabilizers to allow physiologic motion of the upper extremity with respect to the torso have been widely investigated. The acromioclavicular ligamentous complex (ACLC) including the deltotrapezial fascia and the individual coracoclavicular (CC) ligaments have been identified as important stabilizers against horizontal, vertical, and rotational forces. Investigations into these anatomic structures and their role in providing stability have prompted biomechanical investigations of various repair techniques, in attempts to identify surgical constructs that best replicate the native anatomy, motion, and stability. Over the years, acromioclavicular joint injuries have been repaired with a significant variety of techniques and devices, with more recent techniques favoring anatomic reconstructions of the individual CC ligaments and ACLC using natural and/or synthetic materials. This chapter serves to discuss the biomechanical implications of AC joint anatomy and injury and how the various treatment options and their respective biomechanical investigations have advanced our understanding of this pathology to better our patients.

Background: The balance of tissue injury and repair ultimately determines outcomes of chronic neurological disorders, such as progressive multiple sclerosis (MS). However, the extent of pathology can be difficult to detect, particularly when it is insidious and/or offset by tissue regeneration. Objectives: The objective of this research is to evaluate whether tissue autofluorescence—typically a source of contamination—provides a surrogate marker of white matter injury. Methods: Tissue autofluorescence in autopsied specimens both experimental and clinical was characterized by spectral confocal microscopy and correlated to severity and chronicity as determined by standard histopathology. Results: Months after cuprizone (CPZ)-induced demyelination, despite robust remyelination, autofluorescent deposits progressively accumulated in regions of prior pathology. Autofluorescent deposits (likely reflecting myelin debris remnants) were conspicuously localized to white matter, proportional to lesion severity, and displayed differential fluorescence over time. Strikingly, similar features were apparent also in autopsied MS tissue. Conclusion: Autofluorescence spectroscopy illuminates prior and ongoing white matter injury. The accumulation of autofluorescence in proportion to the extent of progressive atrophy, despite robust remyelination in the CPZ brain, provides important proof-of-concept of a phenomenon (insidious ongoing damage masked by mechanisms of tissue repair) that we hypothesize is highly relevant to the progressive phase of MS.

Background: The muscle quality of the rotator cuff (RC), measured by atrophy and fatty infiltration (FI), is a key determinant of outcomes in RC injury and repair. The ability to regenerate muscle after repair has been shown to be limited. Purpose: To determine if there is a source of resident endogenous stem cells, fibroadipogenic progenitor cells (FAPs), within RC injury patients, and if these cells are capable of adipogenic, fibrogenic, and pro-myogenic differentiation. Study Design: Controlled laboratory study. Methods: A total of 20 patients between the ages of 40 and 75 years with partial- or full-thickness RC tears of the supraspinatus and evidence of atrophy and FI Goutallier grade 1, 2, or 3 were selected from 2 surgeons at an orthopaedic center. During the surgical repair procedure, supraspinatus muscle biopsy specimens were obtained for analysis as were deltoid muscle biopsy specimens to serve as the control. FAPs and satellite cells were quantified using fluorescence-activated cell sorting. Muscle FI and fibrosis was quantified using Oil Red O and Masson trichrome staining. FAP differentiation and gene expression profiles were compared across tear sizes after culture in adipogenic, fibrogenic, and beta-3 agonist (amibegron) conditions. Analysis of variance was used for statistical comparisons between groups, with P < .05 as statistically significant. Results: Histologic analysis confirmed the presence of fat in biopsy specimens from patients with full-thickness tears. There were more FAPs in the full-thickness tear group compared with the partial-thickness tear group (9.43% ± 4.25% vs 3.84% ± 2.54%; P < .01). Full-thickness tears were divided by tear size, with patients with larger tears having significantly more FAPs than those with smaller tears. FAPs from muscles with full-thickness tendon tears had more adipogenic and fibrogenic potential than those with partial tears. Induction of a beige adipose tissue (BAT) phenotype in FAPs was possible, as demonstrated by increased expression of BAT markers and pro-myogenic genes including insulin-like growth factor 1 and follistatin. Conclusion: Endogenous FAPs are present within the RC and likely are the source of FI. These FAPs were increased in muscles with in larger tears but are capable of adopting a pro-myogenic BAT phenotype that could be utilized to improve muscle quality and patient function after RC repair.

Background/ObjectivesProlonged hospital care is described as deployed medical care, applied beyond doctrinal planning timelines and military medical planning envisages that in future conflicts, patients will have to be managed for up to five days without evacuation to their home country. We aimed to investigate the effect of prolonged hospital care on visual outcomes in the management of open and closed globe injures.MethodsWe conducted a retrospective cohort study in the setting of British military operations in Afghanistan. We included consecutive UK military patients with ocular trauma evacuated from Afghanistan between December 2005 and April 2013. We assessed outcome using best corrected visual acuity (VA) 6-12 months after injury.ResultsAll patients were male, with a mean age of 25. Outcomes adjusted for ocular trauma score (OTS) at presentation were similar to previous reports of military ocular trauma. The mean time to arrival at a centre with an ophthalmologist was 1.74 days. Both patients with penetrating open globe injuries and patients with hyphaema and an OTS of 3 or less displayed an association between worsening 6-12 month VA and time between injury and repair or assessment by an ophthalmologist.ConclusionTime to specialist ophthalmic care contributes to outcome after military open and closed globe injuries, supporting deployment of ophthalmologists on military operations.

Clinical sepsis is a highly dynamic state that progresses at variable rates and has life-threatening consequences. Staging patients along the sepsis timeline requires a thorough knowledge of the evolution of cellular and molecular events at the tissue level. Here, we investigated the kidney, an organ central to the pathophysiology of sepsis. Single cell RNA sequencing revealed the involvement of various cell populations in injury and repair to be temporally organized and highly orchestrated. We identified key changes in gene expression that altered cellular functions and can explain features of clinical sepsis. These changes converged towards a remarkable global cell-cell communication failure and organ shutdown at a well-defined point in the sepsis timeline. Importantly, this time point was also a transition towards the emergence of recovery pathways. This rigorous spatial and temporal definition of murine sepsis will uncover precise biomarkers and targets that can help stage and treat human sepsis.

BACKGROUND/OBJECTIVES: Prolonged hospital care is described as deployed medical care, applied beyond doctrinal planning timelines and military medical planning envisages that in future conflicts, patients will have to be managed for up to 5 days without evacuation to their home country. We aimed to investigate the effect of prolonged hospital care on visual outcomes in the management of open and closed globe injures. METHODS: We conducted a retrospective cohort study in the setting of British military operations in Afghanistan. We included consecutive UK military patients with ocular trauma evacuated from Afghanistan between December 2005 and April 2013. We assessed outcome using best-corrected visual acuity (VA) 6–12 months after injury. RESULTS: All patients were male, with a mean age of 25. Outcomes adjusted for ocular trauma score (OTS) at presentation were similar to previous reports of military ocular trauma. The mean time to arrival at a centre with an ophthalmologist was 1.74 days. Both patients with penetrating open globe injuries and patients with hyphaema and an OTS of 3 or less displayed an association between worsening 6–12 month VA and time between injury and repair or assessment by an ophthalmologist. CONCLUSION: Time to specialist ophthalmic care contributes to outcome after military open and closed globe injuries, supporting deployment of ophthalmologists on military operations.

Inflammatory response after traumatic brain injury plays an essential role in secondary brain injury. Cytokines, as critical inflammatory mediators in vivo, are involved in a variety of pathophysiological processes and play a significant role in the inflammatory cascade after brain injury. There are two kinds of cytokines involved in secondary brain injury and repair after brain trauma: pro-inflammatory cytokines and anti-inflammatory cytokines. Among them, nuclear factor kB(NF-kB), tumor necrosis factor α(TNF-α), soluble intercellular adhesion molecule 1(sICAM-1), vascular endothelial adhesion molecule 1(VCAM-1), and interleukin 1β(IL-1β), IL-6, IL-8, IL-16 are the major pro-inflammatory cytokines; IL-2, IL-4, IL-10 and IL-13are anti-inflammatory cytokines. This paper mainly summarizes the current research status of inflammatory cytokines, reaction mechanism and its relationship with TBI secondary brain injury.

Introduction: Liver organ slices are a multicellular three-dimensional tissue model, relevant for defining the dose–response profile of drug-induced injury, and for demonstrating which is ...

Tendons and ligaments share many similar features in structure and function. They are load-bearing structures, with tendons transmitting forces from muscle to bone and ligaments transmitting forces from bone to bone. They have specialized zones (at the myotendinous junction for tendons and at the insertion to bone for both), which manage stress loading at these specific areas. They both have a hierarchical physical structure, mainly composed of type I collagen, and both elongate with a typical stress–strain pattern. Injury to both tendons and ligaments is followed by the same pattern of healing phases and can take up to two years to remodel back to a normal structure. The major cell type is the tenocyte (specialised fibroblast) in both tendons and ligaments. They are found within an extracellular matrix. Tendinopathy causes pain and swelling within tendons. Inflammatory cells and myxoid degeneration are characteristic features, with angiogenesis and small fibre nerve growth also seen. The causes are multifactorial and brought together by several hypotheses.

A need exists for pre-clinical large animal models of the spine to translate biomaterials capable of repairing intervertebral disc defects. This study characterized the effects of cervical spinal level, loading rate as well as injury and repair with genipin-crosslinked fibrin (FibGen) on axial and torsional mechanics in an ovine cervical spine model. Cervical intervertebral discs C2-C7) from 9 animals were tested with cyclic tension-compression (−240 – 100 N) and cyclic torsion (±2° & ±4°) tests at three rates (0.1, 1 & 2 Hz) in intact, injured and repaired conditions. Intact IVDs from upper cervical levels (C2-C4) had significantly higher torque range and torsional stiffness and significantly lower axial range of motion and tensile compliance than IVDs from lower cervical levels (C5-C7). A 10× increase in loading rate significantly increased torque range and torsional stiffness 4–8% (depending on amplitude) (p < 0.001). When normalized to intact, FibGen significantly restored torque range (FibGen: 0.96±0.14, Injury: 0.88±0.14, p = 0.03) and axial range of motion (FibGen: 1.00±0.05, Injury: 1.04±0.15, p = 0.02) compared to Injury, with a values of 1 indicating full repair. Cervical spinal level must be considered for controlling biomechanical evaluations, and FibGen restored some torsional and axial biomechanical properties to intact levels.

Macrophages in the heart have dual roles in injury and repair after myocardial infarction, and understanding the two sides of this coin using traditional 'bulk cell' technologies has been challenging. By combining genetic fate-mapping and single-cell transcriptomics, a new study (Nat. Immunol. 2019;20:29-39) reveals how distinct macrophage populations expand and diverge across the healthy heart and after infarction.