Improved the biocompatibility of cancellous bone with compound physicochemical decellularization process

Due to the unique microstructures and components of extracellular matrix(ECM),decellularized scaffolds had been used widely in clinical.The reaction of the host toward decellularized scaffolds depends on their biocompatibility,which should be satisfied before applied in clinical.The aim of this study is to develop a decellularized xenograft material with good biocompatibility for further bone repair,in an effective and gentle method.The existing chemical and physical decellularization techniques including ethylene diamine tetraacetic acid(EDTA),sodium dodecyl sulfate(SDS)and supercritical carbon dioxide(SC-CO2)were combined and modified to decellularize bovine cancellous bone(CB).After decellularization,almost 100%of A-Gal epitopes were removed,the combination of collagen,calcium and phosphate was reserved.The direct and indirect contact with macrophages was used to evaluate the cytotoxicity and immunological response of the materials.Mesenchymal stem cells(MSCs)were used in the in vitro cells’proliferation assay.The decellularized CB was proved has no cytotoxicity(grade 1)and no immunological response(NO,IL-2,IL-6 and TNF-α secretion inhibited),and could support MSCs proliferated continuedly.These results were similar to that of commercial decellularized human bone.This study suggests the potential of using this kind of combine decellularization process to fabricate heterogeneous ECM scaffolds for clinical application.

Investigating design principles of micropatterned encapsulation systems containing high-density microtissue arrays

Immunoisolation is an important strategy to protect transplanted cells from rejection by the host immune system.Recently,microfabrication techniques have been used to create hydrogel membranes to encapsulate microtissue in an arrayed organization.The method illustrates a new macroencapsulation paradigm that may allow transplantation of a large number of cells with microscale spatial control,while maintaining an encapsulation device that is easily maneuverable and remaining integrated following transplantation.This study aims to investigate the design principles that relate to the translational application of micropatterned encapsulation membranes,namely,the control over the transplantation density/quantity of arrayed microtissues and the fidelity of pre-formed microtissues to micropatterns.Agarose hydrogel membranes with microwell patterns were used as a model encapsulation system to exemplify these principles.Our results show that high-density micropatterns can be generated in hydrogel membranes,which can potentially maximize the percentage volume of cellular content and thereby the transplantation efficiency of the encapsulation device.Direct seeding of microtissues demonstrates that microwell structures can efficiently position and organize pre-formed microtissues,suggesting the capability of micropatterned devices for manipulation of cellular transplants at multicellular or tissue levels.Detailed theoretical analysis was performed to provide insights into the relationship between micropatterns and the transplantation capacity of membrane-based encapsulation.Our study lays the ground for developing new macroencapsulation systems with microscale cellular/tissue patterns for regenerative transplantation.