Tonsil-derived mesenchymal stem cells incorporated in reactive oxygen species-releasing hydrogel promote bone formation by increasing the translocation of cell surface GRP78.

Controlling the senescence of mesenchymal stem cells (MSCs) is essential for improving the efficacy of MSC-based therapies. Here, a model of MSC senescence was established by replicative subculture in tonsil-derived MSCs (TMSCs) using senescence-associated ß-galactosidase, telomere-length related genes, stemness, and mitochondrial metabolism. Using transcriptomic and proteomic analyses, we identified glucose-regulated protein 78 (GRP78) as a unique MSC senescence marker. With increasing cell passage number, GRP78 gradually translocated from the cell surface and cytosol to the (peri)nuclear region of TMSCs. A gelatin-based hydrogel releasing a sustained, low level of reactive oxygen species (ROS-hydrogel) was used to improve TMSC quiescence and self-renewal. TMSCs expressing cell surface-specific GRP78 (csGRP78+), collected by magnetic sorting, showed better stem cell function and higher mitochondrial metabolism than unsorted cells. Implantation of csGRP78+ cells embedded in ROS-hydrogel in rats with calvarial defects resulted in increased bone regeneration. Thus, csGRP78 is a promising biomarker of senescent TMSCs, and the combined use of csGRP78+ cells and ROS-hydrogel improved the regenerative capacity of TMSCs by regulating GRP78 translocation.

Multifunctional surfaces through synergistic effects of heparin and nitric oxide release for a highly efficient treatment of blood-contacting devices.

Thrombosis and inflammation after implantation remain unsolved problems associated with various medical devices with blood-contacting applications. In this study, we develop a multifunctional biomaterial with enhanced hemocompatibility and anti-inflammatory effects by combining the anticoagulant activity of heparin with the vasodilatory and anti-inflammatory properties of nitric oxide (NO). The co-immobilization of these two key molecules with distinct therapeutic effects is achieved by simultaneous conjugation of heparin (HT) and copper nanoparticles (Cu NPs), an NO-generating catalyst, via a simple tyrosinase (Tyr)-mediated reaction. The resulting immobilized surface showed long-term, stable and adjustable NO release for 14 days. Importantly, the makeup of the material endows the surface with the ability to promote endothelialization and to inhibit coagulation, platelet activation and smooth muscle cell proliferation. In addition, the HT/Cu NP co-immobilized surface enhanced macrophage polarization towards the M2 phenotype in vitro, which can reduce the inflammatory response and improve the adaptation of implants in vivo. This study demonstrated a simple but efficient method of developing a multifunctional surface for blood-contacting devices.

Bridging the intergenerational gap: the outcomes of a student-initiated, longitudinal, inter-professional, inter-generational home visit program.

BACKGROUND: Older persons consume disproportionately more healthcare resources than younger persons. Tri-Generational HomeCare (TriGen), a service-learning program, aims to reduce hospital admission rates amongst older patients with frequent admissions. The authors evaluated the educational and patient outcomes of TriGen. METHODS: Teams consisting of healthcare undergraduates and secondary school (SS) students - performed fortnightly home visits to patients over 6 months. Self-administered scales were used to evaluate the educational outcomes in knowledge and attitudes towards the older people and nine domains of soft skills pre- and post-intervention. Patients' reported satisfaction and clinical outcomes were also assessed. RESULTS: Two hundred twenty-six healthcare undergraduates and 359 SS students participated in the program from 2015 to 2018. Response rates were 80.1 and 62.4% respectively. One hundred six patients participated in TriGen. There was a significant increase in Kogan's Attitudes towards Old People Scale (KOP) scores for healthcare undergraduates and SS students with a mean increase of 12.8 (95%CI: 9.5-16.2, p <  0.001) and 8.3 (95%CI: 6.2-10.3, p <  0.001) respectively. There was a significant increase in Palmore Facts on Aging Quiz (PFAQ) score for SS students but not for healthcare undergraduates. Most volunteers reported that TriGen was beneficial across all nine domains assessed. There was also a significant decrease in hospital admission rates (p = 0.006) and emergency department visits (p = 0.004) during the 6-month period before and after the program. Fifty-one patients answered the patient feedback survey. Of this, more than 80% reported feeling less lonely and happier. CONCLUSION: TriGen, a student-initiated, longitudinal, inter-generational service-learning program consisting of SS students and healthcare undergraduates can reduce ageism, develop soft skills, inculcate values amongst SS students and healthcare undergraduates. In addition, TriGen potentially reduces hospital admissions and emergency department visits, and loneliness amongst frequently admitted older patients.