Abstract
Tissue engineering‐based bone graft is an emerging viable treatment modality to repair and regenerate tissues damaged as a result of diseases or injuries. The structure and composition of scaffolds should modulate the classical osteogenic pathways in human stem cells. The osteoinductivity properties of the hydroxylapatite‐collagen hybrid scaffold named Coll/Pro Osteon 200 were investigated in an in vitro model of human adipose mesenchymal stem cells (hASCs), whereas the clinical evaluation was carried out in maxillofacial patients. Differentially expressed genes (DEGs) induced by the scaffold were analyzed using the Osteogenesis RT2 PCR Array. The osteoinductivity potential of the scaffold was also investigated by studying the alkaline phosphatase (ALP) activity, matrix mineralization, osteocalcin (OCN), and CLEC3B expression protein. Fifty patients who underwent zygomatic augmentation and bimaxillary osteotomy were evaluated clinically, radiologically, and histologically during a 3‐year follow‐up. Among DEGs, osteogenesis‐related genes, including BMP1/2, ALP, BGLAP, SP7, RUNX2, SPP1, and EGFR, which play important roles in osteogenesis, were found to be upregulated. The genes to cartilage condensation SOX9, BMPR1B, and osteoclast cells TNFSF11 were detected upregulated at every time point of the investigation. This scaffold has a high osteoinductivity revealed by the matrix mineralization, ALP activity, OCN, and CLEC3B expression proteins. Clinical evaluation evidences that the biomaterial promotes bone regrowth. Histological results of biopsy specimens from patients showed prominent ossification. Experimental data using the Coll/Pro Osteon 200 indicate that clinical evaluation of bone regrowth in patients, after scaffold implantation, was supported by DEGs implicated in skeletal development as shown in “in vitro” experiments with hASCs.
Highlights
Bone fractures/injuries can have a highly deleterious impact on patients' quality of life
PCR technology demonstrated that biomaterial induces in human adipose mesenchymal stem cells (hASCs) upregulation of specific genes, such as Secreted Phosphoprotein 1 (SPP1) and CLEC3B, which are involved in bone mineralization and ossification processes, at days 3 and 9 post-cell seeding
Biocompatibility, osteoinductivity, and osteoconductivity properties of the innovative scaffold composed by Avitene Microfibrillar Collagen Hemostat and Granular Pro Osteon 200 coralline HA (Coll/Pro Osteon 200) were analyzed in hASC grown on the scaffold up to day 40
Summary
Bone fractures/injuries can have a highly deleterious impact on patients' quality of life. Tissue-engineered approaches to regenerate bone in the craniomaxillofacial region utilize scaffolds to provide structural and biological cues to stem cells to stimulate osteogenic differentiation. The biomaterial known as Pro Osteon 200 is a coral derived porous HA, which is available in granule and block forms This scaffold has been shown to be highly biocompatible in cellular[3,4,5] and animal models,[6,7,8] and in some clinical applications.[9] Scaffolds used for the bone regrowth can be assayed for specific features, such as osteoinductivity, osteoconductivity, and biocompatibility proprieties. The osteogenesis potential of cells was investigated to verify the matrix
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