Fibroin Scaffold Repairs Critical-Size Bone Defects In Vivo Supported by Human Amniotic Fluid and Dental Pulp Stem Cells

Abstract

The main aim of this study was the comparative evaluation of fibroin scaffolds combined with human stem cells, such as dental pulp stem cells (hDPSCs) and amniotic fluid stem cells (hAFSCs), used to repair critical-size cranial bone defects in immunocompromised rats. Two symmetric full-thickness cranial defects on each parietal region of rats have been replenished with silk fibroin scaffolds with or without preseeded stem cells addressed toward osteogenic lineage in vitro. Animals were euthanized after 4 weeks postoperatively and cranial tissue samples were taken for histological analysis. The presence of human cells in the new-formed bone was confirmed by confocal analysis with an antibody directed to a human mitochondrial protein. Fibroin scaffolds induced mature bone formation and defect correction, with higher bone amount produced by hAFSC-seeded scaffolds. Our findings demonstrated the strong potential of stem cells/fibroin bioengineered constructs for correcting large cranial defects in animal model and is likely a promising approach for the reconstruction of human large skeletal defects in craniofacial surgery.

CD117+amniotic fluid stem cells

“…Similarly, pre-differentiated AFS cells (human, 2nd trimester and CD117-selected) seeded into silk fibroin scaffolds were able to repair critical-size cranial bone defects in immunocompromised rats via formation mature bone in a four week time. 72 These results demonstrate the potential of AFS cells to produce 3D mineralized bioengineered constructs and suggest that AFS cells may be an effective cell source for the autologous and heterologous repair of large bone defects. Further studies are needed to confirm the long-term functional performance of these grafts into bone injury sites.…”

Can SHED or DPSCs be used to repair/regenerate non-dental tissues? A systematic review of in vivo studies

“…Three groups of researchers used cells from deciduous teeth in their experiments, 3 groups used cells from permanent teeth and the remaining 2 groups compared both types of cells. Notably, both sources of cells (i.e., the pulp of deciduous and permanent teeth) presented bone-formation capacity 13,14,15,16,18 and, in some cases, their osteogenic ability was superior to that of bone marrow-derived SCs. 14,15 In addition, DPSCs were shown to promote the repair of facial nerve gaps in rats 11 and induce neuroplasticity within the recipient nervous system in chicks.…”

“…However, the majority of the studies described in the literature have investigated bone formation. 10,13,14,15,16,17,18,19 Our systematic review aimed to analyse in vivo studies that were performed in humans and animals. The keyword [animals] was not an inclusion criteria, nor was [human] an exclusion one.…”

“…10,13,14,15,16,17,18,19 The use of SHED or DPSCs may avoid the inconvenience and morbidity associated with the removal of autogenous grafts from other sites. 28 Moreover, in contrast to the use of autologous bone grafts, DPSCs or SHED can be expanded in vitro prior to their use in vivo to generate an adequate number of cells for the tissue being repaired.…”

Immune Regulatory Properties of CD117pos Amniotic Fluid Stem Cells Vary According to Gestational Age

“…The therapeutic efficacy of AFS cells has been recently verified in in vivo preclinical studies showing their capabilities to regenerate and improve the functionality of injured tissues and to restore cell niche homeostasis in muscle, bone, lung, and kidney [10,[13][14][15][16]. In addition and similar to MSCs-an already thoroughly characterized immune regulatory cell type [17], AFS cells possess significant immune modulatory properties, as they may both suppress in vitro inflammatory responses, mainly through soluble factors [18], and modulate in vivo cellular immune response and distant organ damage during sublethal endotoxemia in animal models [19].…”