Abstract
Regeneration of alveolar bone for dental implant remains a major issue, partifcularly for patients suffering from severe bone adsorption and irregular socket trauma. Recapitulating embryological development is becoming an attractive approach for engineer organ or three-dimensional tissues from stem cells. In this study, we aimed to develop an injectable “cartilaginous” graft with adequate mechanical resistance and ideal bone remodelling potential. The cartilaginous graft was composed of a particulate decellularised cartilage matrix (PDCM), chondrogenically primed bone mesenchymal stem cell (BMSC) bricks (CB), and enriched platelet-rich plasma (P) gel. In immunodeficient mice, we found that angiogenesis occurred quickly inside PDCM-CB-P constructs after implantation, thereby improving tissue survival and bone formation. In rabbit tibia bone defects around implants, we confirmed that CBs not only transformed into bone tissue rapidly, but also significantly promoted bone remodelling and replacement of PDCM, thus realising osseointegration of dental implants within 3 months. In conclusion, CBs exhibited the potential for endochondral ossification in vivo, and application of a cartilaginous template composed of PDCM, CB, and P provided a minimally-invasive, “free material residual” approach to regenerate alveolar bone tissues in vivo. This method could have applications in peri-implant bone regeneration.
Highlights
The development of injectable cell macroaggregates may offer a micro-invasive and shapeable approach to alveolar bone regeneration, even for loading dental implants
For histological analysis of cell sheets, safranin-O staining showed that a large amount of glycosaminoglycan (GAG) occupied the extracellular space, which confirmed the formation of cartilaginous extracellular matrix (ECM) (Fig. 1D)
We demonstrated that injectable particulate decellularised cartilage matrices (PDCMs) retained the most collagen and sulphated glycosaminoglycans (sGAGs) and possessed adequate mechanical strength; these materials could stabilise the BMSCs and platelet-rich plasma (PRP) gel efficiently once injected in vivo
Summary
The development of injectable cell macroaggregates may offer a micro-invasive and shapeable approach to alveolar bone regeneration, even for loading dental implants. For alveolar bone regeneration via injectable grafts, adequate mechanical resistance and rapid osteogenic remodelling remain challenges for peri-implant filling[7,8]. BMSC-platelet-rich plasma (PRP) compounds exhibit significant bone forming potential in humans; contraction and intrinsic mechanical weakness still limit the applications of these materials. Attempts to reconstitute BMSC-PRP mixtures with solid bioceramics, show reduced remodelling potential owing to the toughness and slow biodegradation of the materials. As alternatives to cell-plasma-bioceramic mixtures, “cartilaginous” grafts showing adequate mechanical resistance may show more potential for remodelling and clinical translation. In this study, instead of seeding BMSCs onto the decellularised cartilage extracellular matrix (ECM), we fabricated particulate decellularised cartilage, and incorporated the materials into PRP to increase the mechanical resistance. Our results provide important insights into the applications of decellularised cartilage matrices, CBs and PRP in clinical treatments
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