Abstract
Tissue–biomaterial interactions in different microenvironments influence significantly the repair and regeneration outcomes when a scaffold or construct is implanted. In order to elucidate this issue, a fibrin gel filled macroporous fibrin scaffold (fibrin-based scaffold) was fabricated by loading fibrinogen via a negative pressure method, following with thrombin crosslinking. The macroporous fibrin scaffold exhibited a porous structure with porosity of (88.1 ± 1.3)%, and achieved a modulus of 19.8 ± 0.4 kPa at a wet state after fibrin gel filling, providing a suitable microenvironment for bone marrow-derived mesenchymal stem cells (BMSCs). The in vitro cellular culture revealed that the fibrin-based scaffold could support the adhesion, spreading, and proliferation of BMSCs in appropriate cell encapsulation concentrations. The fibrin-based scaffolds were then combined with BMSCs and lipofectamine/plasmid deoxyribonucleic acid (DNA) encoding mouse-transforming growth factor β1 (pDNA-TGF-β1) complexes to obtain the fibrin-based constructs, which were implanted into osteochondral and tibial defects at young adult rabbits (3 months old) and aged adult rabbits (12 months old) to evaluate their respective repair effects. Partial repair of osteochondral defects and perfect restoration of tibial defects were realized at 18 weeks post-surgery for the young adult rabbits, whereas only partial repair of subchondral bone and tibial bone defects were found at the same time for the aged adult rabbits, confirming the adaptability of the fibrin-based constructs to the different tissue microenvironments by tissue-biomaterial interplays.
Highlights
The damaged tissues need to be treated properly and timely to avoid further degeneration and even tissue dysfunction, especially for those with limited self-regenerative capability such as cartilage (Goldring and Goldring, 2016)
The macroporous fibrin scaffold was prepared, into which fibrin gel, bone marrowderived mesenchymal stem cells (BMSCs), and lipofectamine/pDNA-transforming growth factor (TGF)-β1 complexes were loaded to obtain the fibrin-based construct for the regeneration of osteochondral and tibial defects of both young and aged adult rabbits in vivo
A macroporous fibrin scaffold was fabricated by using PCL microspheres as porogen, into which fibrin gel was filled by a negative pressure method and thrombin crosslinking to obtain a fibrin-based scaffold
Summary
The damaged tissues need to be treated properly and timely to avoid further degeneration and even tissue dysfunction, especially for those with limited self-regenerative capability such as cartilage (Goldring and Goldring, 2016). Microfracture, mosaicplasty or autograft, allograft, autologous chondrocyte transplantation (ACI), and matrix-assisted ACI (MACI) have been applied to treat cartilage and osteochondral defects of different degrees (Panseri et al, 2012; Nukavarapu and Dorcemus, 2013). Owing to its spontaneous self-regeneration, the bone with a defect smaller than a critical size (two times of bone diameter of long bones; Bigham-Sadegh and Oryan, 2015) could be self-repaired or regenerated with traditional therapies such as Ilizarov method, despite that large bone defects still need to be treated with autologous/allogenic transplantation and synthetic bone substitutes, usually consisting of metal or calcium phosphate and bioactive glasses (Puppi et al, 2010; Huey et al, 2012). Tissue engineering applies “biological, chemical, and engineering principles toward the repair, restoration, or regeneration of living tissue by using biomaterials, cells, and factors alone or in combination” (Swieszkowski et al, 2007), which provides promising alternatives for dealing with chondral or bone defects
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