Bone regeneration: current concepts and future directions

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis

Scaffolds for cartilage regeneration: to use or not to use?

Joint cartilage has been a significant focus on the field of tissue engineering and regenerative medicine (TERM) since its inception in the 1980s. Represented by only one cell type, cartilage has been a simple tissue that is thought to be straightforward to deal with. After three decades, engineering cartilage has proven to be anything but easy. With the demographic shift in the distribution of world population towards ageing, it is expected that there is a growing need for more effective options for joint restoration and repair. Despite the increasing understanding of the factors governing cartilage development, there is still a lot to do to bridge the gap from bench to bedside. Dedicated methods to regenerate reliable articular cartilage that would be equivalent to the original tissue are still lacking. The use of cells, scaffolds and signalling factors has always been central to the TERM. However, without denying the importance of cells and signalling factors, the question posed in this chapter is whether the answer would come from the methods to use or not to use scaffold for cartilage TERM. This paper presents some efforts in TERM area and proposes a solution that will transpire from the ongoing attempts to understand certain aspects of cartilage development, degeneration and regeneration. While an ideal formulation for cartilage regeneration has yet to be resolved, it is felt that scaffold is still needed for cartilage TERM for years to come

Correction: MicroRNA-200c Represses IL-6, IL-8, and CCL-5 Expression and Enhances Osteogenic Differentiation.

[This corrects the article DOI: 10.1371/journal.pone.0160915.]

<i>miR-200c</i> delivered using PEI nanoparticles inhibits IL-6, IL-8, and CCL-5 in primary human periodontal ligament fibroblasts.

<p><b>A-C</b>: The transcripts of IL-6 (<b>A</b>), IL-8 (<b>B</b>), and CCL-5 (<b>C</b>) in the cells with <i>miR-200c</i> or empty vector cultured in DMEM supplemented with LPS after 24 hours; <b>D</b> and <b>E</b>: the amounts of IL-6 (<b>D</b>), IL-8 (<b>E</b>), and CCL-5 (<b>F</b>) secreted by the cells with miR-200c or empty vector cultured in DMEM supplemented with LPS after 12 and 32 hrs, respectively. *: p<0.05 vs empty vector with the same amount.</p

<i>miR-200c</i> modulates proinflammatory mediators in human preosteoblasts.

<p><b>A</b> and <b>B:</b> the transcripts of IL-6 <b>(A)</b> and IL-8 (<b>B</b>) in non-treated HEPM cells and the cells with <i>miR-200c</i> or scrambled <i>miRs</i> cultured in DMEM supplemented with LPS at 0, 1, 5 and 10 μg/mL after 24 hours; *:p<0.05 vs non-treated; <b>C:</b> the amounts of IL-8 secreted by HEPM cells with <i>miR-200c</i> or scrambled <i>miRs</i> cultured in DMEM supplemented with or without LPS at different time points; *: p<0.05 vs cells with scrambled miRs; <b>D</b> and <b>E:</b> the amounts of IL-6 (<b>D</b>) and CCL-5 (<b>E</b>) secreted by HEPM cells with <i>miR-200c</i> or <i>scrambled miRs</i> cultured in DMEM supplemented with or without LPS after 24 hrs; <b>F:</b> the amounts of OPG secreted by HEPM cells with different <i>miRs</i> cultured in DMEM supplemented with or without LPS after 32 hours. *: p<0.05.</p

<i>miR-200c</i> increases osteogenic biomarkers in human preosteoblasts.

<p><b>A</b> and <b>B</b>: the amounts of the transcript of OCN (<b>A</b>) and calcium content (<b>B</b>) in non-treated HEPM cells and the cells with <i>miR-200c</i> or scrambled <i>miRs</i> cultured in DMEM supplemented <i>β</i>-glycerophosphate and ascorbic acid after 1 and 2 weeks, respectively. *: p<0.05.</p