Figure 1. The flow diagram of enrolling articles.

Figure 2. Schematic overview of the strategies for constructing biomaterials, inspired by endogenous repair failure that occurs owing to injury or ageing-related pathophysiological changes. Aberrant external impacts cause tissue damage, while ageing often leads to tissue degeneration. After tissue damage or degeneration, the resulting unfavourable microenvironment is characterized by inflammation, oxidative stress, hypoxia, insufficient nutrition, hyperacidity, and abnormal mechanical properties, which impose a great burden on the endogenous cells and non-cellular components. Specifically, mature endogenous cells and stem/progenitor cells typically suffer from cell death and endoplasmic reticulum stress (ERS), and secrete pro-inflammatory factors (interleukin 1β, interleukin 6, tumour necrosis factor α, etc.), while immune cells are also involved in aggravating the inflammation. In addition, the harsh environment also leads to an imbalance in the matrix metabolism and impairs the endothelial cells that are essential for angiogenesis. Cellular and non-cellular alterations in unfavourable environments contribute to endogenous repair failure. However, tissue engineering materials and other bioactive agents are efficient in relieving the pathological changes and their damaging impact on cells and extracellular components, which may help re-establish endogenous repair mechanisms and alleviate tissue damage or degeneration.

Figure 3. Endogenous cellular changes after bone fracture. When a bone is fractured, the MSCs migrate to the bone defect area and differentiate into osteoblasts to form and remodel the bone matrix. In the end, approximately 15% of the osteoblasts become embedded in the bone matrix as osteocytes, 30% of the osteoblasts become quiescent bone lining cells, and the remaining 40–70% of the osteoblasts are likely to undergo death by apoptosis. The apoptotic osteoblasts expressing certain signals are efficiently cleared by macrophages in a process called efferocytosis. This process is initiated by the expression of the apoptotic signals on osteoblasts and is activated by the binding of linking proteins, including MFG-E8 or Gas6, and macrophage proteins, such as αvβ3 or Mer. The efferocytosis-induced production of specific proteins, such as TGF-β, may promote continuous bone modelling by recruiting osteoblasts from progenitor cells.29 Gas6: growth arrest-specific 6; M-CSF: macrophage colony-stimulating factor; MER (tk): receptor tyrosine kinase MerTK; MFG-8: milk fat globule-epidermal growth factor 8; MSCs: mesenchymal stromal cells; OB: osteoblasts; OC: osteoclasts; RANK: receptor activator of nuclear factor-κB; RANKL: receptor activator of nuclear factor-κB ligand; TGF-β: transforming growth factor β; αvβ3: alpha-V beta-3 integrin.

Figure 4. Anatomical structure of an intervertebral disc and identification of the stem cell niche and hypothetical migration paths. (A) The potential stem cell niche is in the perichondrium region adjacent to the epiphyseal plate and outer layers of the annulus fibrosus (AF). In the hypercellular region 1 (HCR 1), the cells are densely distributed, and this is where the stem cell niche is located; while in the hypercellular region 2 (HCR 2), the cells are relatively dispersed and morphologically mature. (B) A magnification of the region of interest shows slow cycling stem/progenitor cells (outlined in orange), the transit amplifying cells (outlined in green), and differentiated cells (outlined in white).153 CEP: cartilage endplate; NP: nucleus pulposus.