The non-enzymatic reaction of proteins with glucose (glycation) is a topic of rapidly growing importance in human health and medicine. There is increasing evidence that this reaction plays a central role in ageing and disease of connective tissues. Of particular interest are changes in type-I collagens, long-lived proteins that form the mechanical backbone of connective tissues in nearly every human organ. Despite considerable correlative evidence relating extracellular matrix (ECM) glycation to disease, little is known of how ECM modification by glucose impacts matrix mechanics and damage, cell-matrix interactions, and matrix turnover during aging. More daunting is to understand how these factors interact to cumulatively affect local repair of matrix damage, progression of tissue disease, or systemic health and longevity. This focused review will summarize what is currently known regarding collagen glycation as a potential driver of connective tissue disease. We concentrate attention on tendon as an affected connective tissue with large clinical relevance, and as a tissue that can serve as a useful model tissue for investigation into glycation as a potentially critical player in tissue fibrosis related to ageing and diabetes.

Augmented reality (AR)-based surgical navigation may offer new possibilities for safe and accurate surgical execution of complex osteotomies. In this study we investigated the feasibility of navigating the periacetabular osteotomy of Ganz (PAO), known as one of the most complex orthopedic interventions, on two cadaveric pelves under realistic operating room conditions. Preoperative planning was conducted on computed tomography (CT)-reconstructed 3D models using an in-house developed software, which allowed creating cutting plane objects for planning of the osteotomies and reorientation of the acetabular fragment. An AR application was developed comprising point-based registration, motion compensation and guidance for osteotomies as well as fragment reorientation. Navigation accuracy was evaluated on CT-reconstructed 3D models, resulting in an error of 10.8 mm for osteotomy starting points and 5.4° for osteotomy directions. The reorientation errors were 6.7°, 7.0° and 0.9° for the x-, y- and z-axis, respectively. Average postoperative error of LCE angle was 4.5°. Our study demonstrated that the AR-based execution of complex osteotomies is feasible. Fragment realignment navigation needs further improvement, although it is more accurate than the state of the art in PAO surgery.

Tendon extracellular matrix (ECM) mechanical unloading results in tissue degradation and breakdown, with niche-dependent cellular stress directing proteolytic degradation of tendon. Here, we show that the extracellular-signal regulated kinase (ERK) pathway is central in tendon degradation of load-deprived tissue explants. We show that ERK 1/2 are highly phosphorylated in mechanically unloaded tendon fascicles in a vascular niche-dependent manner. Pharmacological inhibition of ERK 1/2 abolishes the induction of ECM catabolic gene expression (MMPs) and fully prevents loss of mechanical properties. Moreover, ERK 1/2 inhibition in unloaded tendon fascicles suppresses features of pathological tissue remodeling such as collagen type 3 matrix switch and the induction of the pro-fibrotic cytokine interleukin 11. This work demonstrates ERK signaling as a central checkpoint to trigger tendon matrix degradation and remodeling using load-deprived tissue explants.