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

Abstract

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.