Abstract
Patients with a skull defect are at risk of developing cerebrospinal fluid leakage and ascending bacterial meningitis at >10% per year. However, treatment with stem cells has brought great hope to large-area cranial defects. Having found that transforming growth factor (TGF)-β3 can promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), we designed a hybrid TGF-β3/recombinant human-like collagen recombinant human collagen/chitosan (CS) freeze-dried sponge (TRFS) loading hPDLSCs (TRFS-h) to repair skull defects in rats. CFS with 2% CS was selected based on the swelling degree, water absorption, and moisture retention. The CS freeze-dried sponge (CFS) formed a porous three-dimensional structure, as observed by scanning electron microscopy. In addition, cytotoxicity experiments and calcein-AM/PI staining showed that TRFS had a good cellular compatibility and could be degraded completely at 90 days in the implantation site. Furthermore, bone healing was evaluated using micro-computed tomography in rat skull defect models. The bone volume and bone volume fraction were higher in TRFS loaded with hPDLSCs (TRFS-h) group than in the controls (p < 0.01, vs. CFS or TRFS alone). The immunohistochemical results indicated that the expression of Runx2, BMP-2, and collagen-1 (COL Ⅰ) in cells surrounding bone defects in the experimental group was higher than those in the other groups (p < 0.01, vs. CFS or TRFS alone). Taken together, hPDLSCs could proliferate and undergo osteogenic differentiation in TRFS (p < 0.05), and TRFS-h accelerated bone repair in calvarial defect rats. Our research revealed that hPDLSCs could function as seeded cells for skull injury, and their osteogenic differentiation could be accelerated by TGF-β3. This represents an effective therapeutic strategy for restoring traumatic defects of the skull.
Highlights
Craniocerebral injury is a global public health concern
Our research revealed that human periodontal ligament stem cells (hPDLSCs) could function as seeded cells for skull injury, and their osteogenic differentiation could be accelerated by transforming growth factor (TGF)-β3
CS was supplied by Zhengzhou Corey Fine Chemical (MW 30–36 kDa), transforming growth factor-β3 (TGF-β3) and recombinant human-like collagen (RHC) were provided by Jinan University Biopharmaceutical R and D Center (Guangzhou, China), and α-modified minimum essential medium (α-MEM), fetal bovine serum (FBS), and trypsinEDTA were purchased from Gibco BRL
Summary
Craniocerebral injury is a global public health concern. In Australia, there are approximately 338,700 people with disabilities related to craniocerebral injuries (1.9% of the population). Large-scale skull defects are very difficult to repair and are associated with the risk of cerebrospinal fluid leakage and ascending bacterial meningitis, causing approximately 30% of deaths each year in the United States (Gardner and Zafonte, 2016). Autologous bone transplantation is a widely recognized clinical treatment method. Sources of autologous bone are limited, and the required bone needs to be removed from other parts of the patient’s body, increasing the risk of infection during surgery. Stem cell therapy has rapidly developed in bone defect repair. Bioactive materials loaded with mesenchymal stem cells (MSCs) are the most promising materials for the treatment of bone injuries
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