The complexity of mammary tissue and the variety of cells involved make tissue regeneration an ambitious goal. This review, supported by both detailed macro and micro anatomy, illustrates the potential of regenerative medicine in terms of mammary gland reconstruction to restore breast physiology and morphology, damaged by mastectomy. Despite the widespread use of conventional therapies, many critical issues have been solved using the potential of stem cells resident in adipose tissue, leading to commercial products. in vitro research has reported that adipose stem cells are the principal cellular source for reconstructing adipose tissue, ductal epithelium, and nipple structures. In addition to simple cell injection, construct made by cells seeded on a suitable biodegradable scaffold is a viable alternative from a long‐term perspective. Preclinical studies on mice and clinical studies, most of which have reached Phase II, are essential in the commercialization of cellular therapy products. Recent studies have revealed that the enrichment of fat grafting with stromal vascular fraction cells is a viable alternative to breast reconstruction. Although in the future, organ‐on‐a‐chip can be envisioned, for the moment researchers are still focusing on therapies that are a long way from regenerating the whole organ, but which nevertheless prevent complications, such as relapse and loss in terms of morphology.

The investigation of bone damage processes is a crucial point to understand the mechanisms of age-related bone fractures. In order to reduce their impact, early diagnosis is key. The intricate architecture of bone and the complexity of multiscale damage processes make fracture prediction an ambitious goal. This review, supported by a detailed analysis of bone damage physical principles, aims at presenting a critical overview of how multiscale imaging techniques could be used to implement reliable and validated numerical tools for the study and prediction of bone fractures. While macro- and meso-scale imaging find applications in clinical practice, micro- and nano-scale imaging are commonly used only for research purposes, with the objective to extract fragility indexes. Those images are used as a source for multiscale computational damage models. As an example, micro-computed tomography (micro-CT) images in combination with micro-finite element models could shed some light on the comprehension of the interaction between micro-cracks and micro-scale bone features. As future insights, the actual state of technology suggests that these models could be a potential substitute for invasive clinical practice for the prediction of age-related bone fractures. However, the translation to clinical practice requires experimental validation, which is still in progress.

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Ultra-high-resolution imaging of the osteocyte lacuno-canalicular network (LCN) three-dimensionally (3D) in a high-throughput fashion has greatly improved the morphological knowledge about the constituent structures – positioning them as potential biomarkers. Technologies such as serial focused ion beam/scanning electron microscopy (FIB/SEM) and confocal scanning laser microscopy (CLSM) can image in extremely high resolution, yet only capture a small number of lacunae. Synchrotron radiation computed tomography (SR-CT) can image with both high resolution and high throughput but has a limited availability. Desktop micro-computed tomography (micro-CT) provides an attractive balance: high-throughput imaging on the micron level without the restrictions of SR-CT availability. Over the past decade, desktop micro-CT has been used to image osteocyte lacunae in a variety of animals, yet few studies have employed it to image human lacunae using clinical biopsies.In this study, accuracy, precision, and sensitivity of large-scale quantification of human osteocyte lacunar morphometries were assessed by ultra-high-resolution desktop micro-computed tomography. For this purpose, thirty-one transiliac human bone biopsies containing trabecular and cortical regions were imaged using ultra-high-resolution desktop micro-CT at a nominal isotropic voxel resolution of 1.2µm. The resulting 3D images were segmented, component labeled, and the following morphometric parameters of 7.71 million lacunae were measured: Lacunar number (Lc.N), density (Lc.N/BV), porosity (Lc.TV/BV), volume (Lc.V), surface area (Lc.S), surface area to volume ratio (Lc.S/Lc.V), stretch (Lc.St), oblateness (Lc.Ob), sphericity (Lc.Sr), equancy (Lc.Eq), and angle (Lc.θ).Accuracy was quantified by comparing automated lacunar segmentation to manual segmentation. Mean true positive rate (TPR), false positive rate (FPR), and false negative rate (FNR) were 89.0%, 3.4%, and 11.0%, respectively. Regarding the reproducibility of lacunar morphometry from repeated measurements, precision errors were low (0.2 – 3.0%) and intraclass correlation coefficients were high (0.960 – 0.999). Significant differences between cortical and trabecular regions (p<0.001) existed for Lc.N/BV, Lc.TV/BV, local lacunar surface area (<Lc.S>), and local lacunar volume (<Lc.V>), all of which demonstrate the sensitivity of the method and are possible biomarker candidates. This study provides the rigorous foundation required for future large-scale morphometric studies using ultra-high-resolution desktop micro-CT and high-throughput analysis of millions of osteocyte lacunae in human bone samples. Furthermore, the validation of this technology for imaging of human lacunar properties establishes the quality and reliability required for the accurate, precise, and sensitive assessment of osteocyte morphometry in clinical bone biopsies.