Multifunctional Three-Dimensional Bioprinted Scaffolds Reduce Epidural Fibrosis and Promote Bone Regeneration in a...

Epidural fibrosis and insufficient bone regeneration following laminectomy remain an unresolved clinical problem. Artificial laminate has been proposed to address post-surgical complications by establishing a barrier between soft and mineralized tissues while providing spinal mechanical support. Herein, we developed and evaluated three-dimensional (3D) bioprinted polycaprolactone (PCL)/gelatin methacryloyl (GelMA) biocomplexes functionalized with either human dental pulp stem cells (hDPSCs) or thermostable fibroblast growth factor-2 (FGF-2) to address post-laminectomy tissue regeneration and fibrosis. In vitro characterization identified an optimal GelMA formulation (10%) exhibiting pseudoplastic behavior, sustained cell viability, and enhanced mineralized matrix deposition. Four in vivo experimental groups (n = 5/group) were analyzed: laminectomy without treatment (LWT), biocomplex alone (BC), BC+FGF-2, and BC+hDPSC. All implanted biocomplexes were well-tolerated, with preserved motor function and no evidence of radiological changes. Histological and immunohistochemical analyses revealed that all biocomplex groups significantly reduced the expression of fibrotic markers (MMP-2, MMP-9, vimentin) when compared to the LWT group (p < 0.05). Functionalized groups showed superior outcomes: BC+FGF-2 enhanced tissue organization and vascularization, while BC+hDPSC produced lamellar bone trabeculae with hematopoietic tissue. These results demonstrate that bioactive functionalization establishes pro-regenerative microenvironments that actively modulate post-surgical healing beyond a passive barrier function. Ultimately, these bioactive biomaterials hold strong translational potential for the functional restoration of spinal surgical defects.