Enhanced regeneration of osteochondral defects by using an aggrecanase-1 responsively degradable and N-cadherin mimetic peptide-conjugated hydrogel loaded with BMSCs
BIOMATERIALS SCIENCE
Authors: Feng, Xue; Zhou, Tong; Xu, Peifang; Ye, Juan; Gou, Zhongru; Gao, Changyou
Abstract
Due to the poor self-repair capabilities of articular cartilage, chondral or osteochondral injuries are difficult to be recovered. In this study, an N-cadherin mimetic peptide sequence HAVDIGGGC (HAV) was conjugated to direct cell-cell interactions, and an aggrecanase-1 cleavable peptide sequence CRDTEGE-ARGSVIDRC (ACpep) was used to crosslink hyperbranched PEG-based multi-acrylate polymer (HBPEG) with cysteamine-modified chondroitin sulfate (Cys-CS), obtaining an aggrecanase-1 responsively degradable and HAV-conjugated hydrogel ((HAV-HBPEG)-CS-ACpep). A HBPEG-CS-ACpep hydrogel without the HAV motif was also prepared. The two hydrogels exhibited similar equilibrium swelling ratios, elastic moduli and pore sizes after lyophilization, indicating the negligible influence of conjugated HAV on the crosslinking networks and mechanical properties of the hydrogels. After being degraded in PBS, aggrecanase-1 (ADAMTS4) and trypsin, the HBPEG-CS-ACpep hydrogel exhibited significantly decreased elastic moduli with a much lower value when incubated in enzyme solutions. The two hydrogels could maintain the viability of encapsulated bone marrow-derived mesenchymal stem cells (BMSCs), and the (HAV-HBPEG)-CS-ACpep hydrogel better promoted the cell-cell interactions. After being implanted into osteochondral defects in rabbits for 18 weeks, the two cell-laden hydrogel groups achieved better repair effects than the blank control group. Moreover, hyaline cartilage was formed in the (HAV-HBPEG)-CS-ACpep/BMSCs hydrogel group, while a hybrid of hyaline cartilage and fibrocartilage was found in the HBPEG-CS-ACpep/BMSCs hydrogel group.
Is there a higher risk of a complicated course of hepatitis A in kidney transplant patients?
JOURNAL OF CLINICAL VIROLOGY
Authors: Hanssen, D. A. T.; Dackus, J.; Posthouwer, D.; Vennema, H.; van Loo, I. H. M.
Abstract
Background: We describe a patient who was planned to receive a kidney transplant from his wife. Both were infected with Hepatitis A virus (HAV) two weeks prior to the planned transplantation. Due to prolonged shedding of HAV (up until 126 days) we decided to postpone the kidney transplant in order to prevent long term complications. Objectives: The main question in this case was is there a higher risk of a complicated course of HAV-infection after kidney transplantation? We discuss the need for upscale of preventative measures of HAV infections in solid organ transplant candidates. Study design: We performed a literature study on risks of a complicated course of HAV in solid organ transplant recipients and performed a seroprevalence study on anti-HAV in a cohort of 106 hemodialysis patients. Results: Little is known whether HAV infection in solid organ transplant patients causes a more aggressive course of diseases. However, HAV infections in these populations are associated with increased risk of liver failure. Conclusions: This case highlights the need of scaling up preventative measures against HAV infections in solid organ transplant candidates.