Current advances in the development of natural meniscus scaffolds: innovative approaches to decellularization and recellularization.

The increasing rate of injuries to the meniscus indicates the urgent need to develop effective repair strategies. Irreparably damaged menisci can be replaced and meniscus allografts represent the treatment of choice; however, they have several limitations, including availability and compatibility. Another approach is the use of artificial implants but their chondroprotective activities are still not proved clinically. In this situation, tissue engineering offers alternative natural decellularized extracellular matrix (ECM) scaffolds, which have shown biomechanical properties comparable to those of native menisci and are characterized by low immunogenicity and promising regenerative potential. In this article, we present an overview of meniscus decellularization methods and discuss their relative merits. In addition, we comparatively evaluate cell types used to repopulate decellularized scaffolds and analyze the biocompatibility of the existing experimental models. At present, acellular ECM hydrogels, as well as slices and powders, have been explored, which seems to be promising for partial meniscus regeneration. However, their inferior biomechanical properties (compressive and tensile stiffness) compared to natural menisci should be improved. Although an optimal decellularized meniscus scaffold still needs to be developed and thoroughly validated for its regenerative potential in vivo, we believe that decellularized ECM scaffolds are the future biomaterials for successful structural and functional replacement of menisci.

Preparation and Evaluation of Tibia- and Calvarium-Derived Decellularized Periosteum Scaffolds.

The periosteum plays a key role in bone regeneration and an artificial bionic material is urgently required. The periostea on the tibia and skull differ with respect to the types of cells, microstructure, and components, leading to different biological functions and biomechanical properties. We aimed to prepare decellularized periosteum scaffolds derived from different origins and evaluate their angiogenic and osteogenic activities. Histological assessment of α-smooth muscle actin, bone morphogenetic protein-2, and alkaline phosphatase in tibial and calvarial periosteum tissues provided preliminary information on their differing angiogenic and osteogenic properties. We developed decellularization protocols to completely remove the periosteum cellular components and for good maintenance of the hierarchical multilayer structures and components of the extracellular matrix (ECM) with no cytotoxicity. Moreover, using a chicken egg chorioallantoic membrane assay and a nude mouse implantation model, we found that tibia-derived periosteum ECM had superior osteogenic activity and calvarium-derived ECM had good angiogenic activity. The preliminary mechanisms of differing activities were then evaluated by osteogenesis- and angiogenesis-related gene expression in human umbilical vein endothelial cell- and MC-3T3 cell-seeded ECM scaffolds. Thus, this study provides periosteum biomaterials that are derived from specific tissues and have different functional properties and structures, for use in bone regeneration.

Decellularized periosteum as a potential biologic scaffold for bone tissue engineering.

Bone grafting or bone substitute is typically used to bridge a bone defect that has been caused by trauma, tumor resection, pathological degeneration, or congenital deformations. However, bone graft healing and remodeling is always a major concern of orthopedic surgeons. Because the periosteum has a remarkable regenerative capacity and is widely recognized to be essential for the initiation of bone graft healing and remodeling, the present study aimed to produce a rabbit decellularized periosteum (D-periosteum) to be used as a biologic scaffold for future bone tissue engineering. We obtained the D-periosteum by employing a combination of commonly used decellularization processes, which include physical methods as well as chemical and enzymatic solutions. The cellular components were effectively removed, and this removal was demonstrated using current decellularization criteria (H&E staining, DAPI staining, DNA quantification and agarose gel electrophoresis); however, there were no significant alterations of the native extracellular matrix (ECM) properties (collagen, glycosaminoglycan (GAG), microarchitecture and mechanical properties). Periosteum-derived cells (PDCs) could adhere, proliferate and infiltrate into the D-periosteum in vitro. The allogenic D-periosteum was implanted subcutaneously into the backs of rabbits over 28 days to study the biocompatibility in vivo. The D-periosteum did not elicit a severe immunogenic response. In summary, a biologic scaffold composed of ECM from periosteum has been successfully developed. The D-periosteum maintains biocompatibility in vitro and in vivo and, therefore, can provide a naturally compatible scaffold for use in future bone tissue engineering.