UNASSIGNED: Our long-term goal is to develop smart biomaterials that can facilitate regeneration of critical-size craniofacial lesions. In this study, we tested the hypothesis that biomimetic scaffolds electrospun from chitosan (CTS) will promote tissue repair and regeneration in a critical size @entity9332 . To test this hypothesis, we first compared in vitro ability of electrospun CTS scaffolds crosslinked with @entity21644 (CTS-GP) to those of mineralized CTS-GP scaffolds containing @entity692 (CTS-HA-GP), by assessing proliferation/metabolic activity and alkaline phosphatase (ALP) levels of @entity19 mesenchymal stem cells (mMSCs). The cells' metabolic activity exhibited a biphasic behavior, indicative of initial proliferation followed by subsequent differentiation for all scaffolds. ALP activity of mMSCs, a surrogate measure of osteogenic differentiation, increased over time in culture. After 3 weeks in maintenance medium, ALP activity of mMSCs seeded onto CTS-HA-GP scaffolds was approximately two times higher than that of cells cultured on CTS-GP scaffolds. The mineralized CTS-HA-GP scaffolds were also osseointegrative in vivo, as inferred from the enhanced bone regeneration in a @entity19 model of critical size @entity9332 . Tissue regeneration was evaluated over a 3 month period by microCT and histology ( @entity1710 and Eosin and Masson's Trichrome). Treatment of the lesions with CTS-HA-GP scaffolds induced a 38% increase in the area of de novo generated mineralized tissue area after 3 months, whereas CTS-GP scaffolds only led to a 10% increase. Preseeding with mMSCs significantly enhanced the regenerative capacity of CTS-GP scaffolds (by    3-fold), to 35% increase in mineralized tissue area after 3 months. CTS-HA-GP scaffolds preseeded with mMSCs yielded 45% new mineralized tissue formation in the defects. We conclude that the presence of HA in the CTS-GP scaffolds significantly enhances their osseointegrative capacity and that mineralized chitosan-based scaffolds crosslinked with @entity21644 may represent a unique biomaterial with possible clinical relevance for the repair of critical @entity79 .

Osseointegrative Properties of Electrospun XXXX -Containing Nanofibrous Chitosan Scaffolds.

@entity21644 :: ('MESH:C007834', 'Chemical') :: ['genipin'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity9332 :: ('MESH:C537963', 'Disease') :: ['calvarial defect', 'calvarial defects'] @entity692 :: ('MESH:D017886', 'Chemical') :: ['hydroxyapatite'] @entity79 :: ('MESH:D001847', 'Disease') :: ['calvarial bone defects'] @entity1710 :: ('MESH:D006416', 'Chemical') :: ['Hematoxylin']
@entity692 :: (MESH:D017886,Chemical) :: ['Hydroxyapatite']
