posted on 2024-02-15, 03:29authored byMafalda
S. Santos, Rachel Cordeiro, Carla S. Moura, Joaquim M. S. Cabral, Frederico Castelo Ferreira, João C. Silva, Marta S. Carvalho
Periodontium is a
complex structure that supports the teeth, composed
of gingiva, cementum, periodontal ligament, and alveolar bone. Destruction
of the alveolar bone can occur due to periodontitis, trauma, or following
tumor resection. Current reconstructive treatments are based on the
use of bone grafts with limited efficacy and predictability, lacking
bioactive signals to induce tissue repair and coordinated periodontal
regeneration. Thus, alternative strategies are needed to improve clinical
outcomes. Cell-derived extracellular matrix (ECM) has been combined
with biomaterials to enhance their biofunctionalities for various
tissue engineering (TE) applications. In this work, bioactive cell-derived
ECM-loaded electrospun polycaprolactone/chitosan (PCL/CTS) nanofibrous
scaffolds were developed by combining polymer solutions with lyophilized
decellularized ECM (dECM) derived from human periodontal ligament
stem/stromal cells (PDLSCs). This work aimed to fabricate and characterize
cell-derived ECM electrospun PCL/CTS scaffolds in terms of morphological,
physicochemical, thermal, and mechanical properties and assess their
ability to enhance the osteogenic differentiation of PDLSCs, envisaging
potential applications in periodontal TE, particularly focused on
the regeneration of alveolar bone defects. PDLSCs-derived dECM was
characterized regarding morphology, protein expression, DNA removal
efficiency, glycosaminoglycans and collagen contents. Osteogenic differentiation
of PDLSCs was performed on PCL, PCL/CTS, and PCL/CTS/ECM electrospun
scaffolds for 21 days. The obtained results demonstrate that PCL/CTS/ECM
scaffolds promoted cell proliferation compared to PCL and PCL/CTS
scaffolds while maintaining similar physical and mechanical properties
of PCL/CTS scaffolds. PCL/CTS/ECM scaffolds enhanced the osteogenic
differentiation of PDLSCs, confirmed by increased alkaline phosphatase
activity, calcium deposition, and bone-specific marker gene expression.
Moreover, PCL/CTS scaffolds showed higher levels of cell mineralization
than did PCL scaffolds. Overall, this work describes the first use
of lyophilized cell-derived ECM-loaded electrospun scaffolds for periodontal
TE applications, highlighting the potential of this strategy for innovative
therapeutic strategies, in particular, for alveolar bone regeneration.