Side-effects associated to the use of bone morphogenetic proteins into scaffold-based devices for bone repair highlight the necessity for identifying new therapeutic targets that potentially improve bone healing in adults. In this sense, we recently demonstrated the age-associated decrease in the mechanosensitivity of bone marrow mesenchymal stromal/stem cells (MSCs) and identified c-Jun N-terminal kinase 3 (JNK3) as a mechanically-activated modulator of the superior osteogenic potential of MSCs derived from children (C-MSCs) in comparison to adults (A-MSCs). Building on this work, the aim of this study was to design a JNK3-activated collagen-nanohydroxyapatite (coll-nHA) scaffold that restore the child bone healing capacity in adults. Results revealed that JNK3 activator (JNK3*) enhanced A-MSC’ alkaline phosphatase (ALP) activity to the same extent of C-MSCs by facilitating the activation of JNK3. Moreover, A-MSCs cultured on the coll-JNK3* scaffold (collagen-scaffold containing JNK3*) showed positive uptake of the JNK3*, upregulation of early osteogenic markers as well as increased ALP activity and mineralization. More importantly, rat critical calvarial defects treated with coll-JNK3* for 28 days showed a significantly higher 18.07 % bone volume fraction in comparison to rats treated with Coll-nHA −6.04%- and empty defects −2.58%. Which correlated with the presence of a larger amount of blood vessels and mineralized tissue in samples treated with coll-JNK3* when compared with coll-nHA and empty defects. In conclusion, the coll-JNK3* capacity to enhance osteogenesis and bone healing by activating JNK3 highlights how by understanding the stem cell mechanobiology we can improve the development of next generation therapeutics for tissue repair.
Smoking has been associated with poor tissue oxygenation and vascularisation, predisposing smokers to a higher risk for postsurgical infections. The aim of this study was to estimate and compare the incidence of prosthetic joint infection (PJI) following primary total joint arthroplasty (TJA) according to smoking status. A prospective hospital-registry based cohort was used including all primary total knee and hip arthroplasties performed between 03/1996 and 12/2013 and following them until 06/2014. Smoking status at time of surgery was classified in never, former and current smoker. Incidence rates and incidence rate ratios (IRR) for PJI according to smoking status were assessed within the first year and over the whole study period. Adjusted IRRs were obtained using cox regression model. Adjustment was performed for the following baseline characteristics: age, sex, BMI, ASA score, diabetes, arthroplasty site (knee or hip) and surgery duration.Background
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