Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells

Abstract

Therapies using mesenchymal stem cell (MSC) seeded scaffolds may be applicable to various fields of regenerative medicine, including craniomaxillofacial surgery. Plastic compression of collagen scaffolds seeded with MSC has been shown to enhance the osteogenic differentiation of MSC as it increases the collagen fibrillary density. The aim of the present study was to evaluate the osteogenic effects of dense collagen gel scaffolds seeded with mesenchymal dental pulp stem cells (DPSC) on bone regeneration in a rat critical-size calvarial defect model. Two symmetrical full-thickness defects were created (5 mm diameter) and filled with either a rat DPSC-containing dense collagen gel scaffold (n = 15), or an acellular scaffold (n = 15). Animals were imaged in vivo by microcomputer tomography (Micro-CT) once a week during 5 weeks, whereas some animals were sacrificed each week for histology and histomorphometry analysis. Bone mineral density and bone micro-architectural parameters were significantly increased when DPSC-seeded scaffolds were used. Histological and histomorphometrical data also revealed significant increases in fibrous connective and mineralized tissue volume when DPSC-seeded scaffolds were used, associated with expression of type I collagen, osteoblast-associated alkaline phosphatase and osteoclastic-related tartrate-resistant acid phosphatase. Results demonstrate the potential of DPSC-loaded-dense collagen gel scaffolds to benefit of bone healing process.

Application of Stem Cells in Oral Disease Therapy: Progresses and Perspectives

“…And plastic compression of collagen scaffolds seeded with DPSCs was shown to enhance the osteogenic differentiation of DPSCs as it increased the collagen fibrillary density in a rat critical-size calvarial defect model (Chamieh et al, 2016). In a clinical trial (NCT00001391) to examine the potential of cultured human bone marrow stromal cells which will ultimately be used to graft into craniofacial osseous defects, prolonged bone formation by transplanted bone marrow stromal cells was observed in mouse models and consistent bone formation by human marrow stromal fibroblasts was achieved within vehicles containing hydroxyapatite/tricalcium phosphate ceramics (HA/TCP) in the form of blocks, powder, and HA/TCP powder-type I bovine fibrillar collagen strips (Krebsbach et al, 1997).…”

Nanomedicine for safe healing of bone trauma: Opportunities and challenges

“…Besides approaches presented in a recent review by Bobbert and Zadpoor [111], another strategy is to use plastic compression (PC) of hydrogels [112–115]. For example, cellular collagen hydrogels had previously been used as 3D structures for model creation, but their culture-dependent growth is slow, and they cannot provide sufficient mechanical strength [116].…”

“…In another study, Chamieh et al investigated the osteogenic effects of collagen scaffolds produced by PC and seeded with mesenchymal dental pulp stem cells on bone regeneration in a calvarial defect model. The dense collagen-based scaffolds supported the long-term metabolic activity of the stem cells, eliciting an increase in fibrous connective and mineralized tissue volume [115]. …”

Bioinspired Collagen Scaffolds in Cranial Bone Regeneration: From Bedside to Bench

“…[107] Similarly, Chamieh et al utilized compressed collagen gel scaffolds in a rat cranial defect model with primary DPSCs. [108] They demonstrated 8–9% of bone volume/total volume (BV/TV) based on micro-computed tomographic data (micro-CT). Using a more differentiated set of progenitor cells, Bartold and colleagues expanded and implanted primary human alveolar osteoblasts cultured on collagen scaffolds into 3.5 mm cranial defects in SCID mice.…”