Small Molecules Enhance Scaffold-Based Bone Grafts via Purinergic Receptor Signaling in Stem Cells

Abstract

The need for bone grafts is high, due to age-related diseases, such as tumor resections, but also accidents, risky sports, and military conflicts. The gold standard for bone grafting is the use of autografts from the iliac crest, but the limited amount of accessible material demands new sources of bone replacement. The use of mesenchymal stem cells or their descendant cells, namely osteoblast, the bone-building cells and endothelial cells for angiogenesis, combined with artificial scaffolds, is a new approach. Mesenchymal stem cells (MSCs) can be obtained from the patient themselves, or from donors, as they barely cause an immune response in the recipient. However, MSCs never fully differentiate in vitro which might lead to unwanted effects in vivo. Interestingly, purinergic receptors can positively influence the differentiation of both osteoblasts and endothelial cells, using specific artificial ligands. An overview is given on purinergic receptor signaling in the most-needed cell types involved in bone metabolism—namely osteoblasts, osteoclasts, and endothelial cells. Furthermore, different types of scaffolds and their production methods will be elucidated. Finally, recent patents on scaffold materials, as wells as purinergic receptor-influencing molecules which might impact bone grafting, are discussed.

Chitlac-Coated Thermosets Enhance Osteogenesis and Angiogenesis in a Co-culture of Dental Pulp Stem Cells and Endothelial Cells

“…First, the evaluation of the metabolic activity in different experimental conditions confirms the mutual beneficial effects exerted by the two cell types on each other. These findings are in line with already published papers which highlighted communal signaling pathways between angiogenesis and osteogenesis [24] and confirmed a lively cross-talk between bone and endothelial progenitors [25,26].…”

Polysaccharide-Based Systems for Targeted Stem Cell Differentiation and Bone Regeneration

“…Large defects would take more than a lifespan of a patient to heal naturally, thus bone grafts are currently the most used method to treat such defects [42]. Bone autografts are considered the gold standard treatment, mainly because of their immune and histological compatibility, but the need for an operation to acquire the graft and limited quantity of attainable material limits its use [43][44][45]. Allografts and xenografts possess high risks of immune rejection and disease transmission [43,46].…”

“…Bone autografts are considered the gold standard treatment, mainly because of their immune and histological compatibility, but the need for an operation to acquire the graft and limited quantity of attainable material limits its use [43][44][45]. Allografts and xenografts possess high risks of immune rejection and disease transmission [43,46]. Scaffolds combined with appropriate cells are the other option to produce a compatible bone graft.…”

“…For creating scaffold-based bone grafts, cells with good proliferative and osteogenic capacity are needed. Mesenchymal stem cells present in various niches in the adult body, such as bone marrow, adipose tissue, dental pulp, and umbilical tissues, show promising results in preclinical models and thus are considered as a potential cellular source for bone tissue regeneration and repair of large bone defects [43,47,48], but their lifespan is limited and differentiation efficacy is decreasing with patients age [42,49]. A promising approach to counter this issue is to preselect the MSCs according to their osteogenic potential or modulate their properties via activating certain cell signaling pathways.…”

“…A promising approach to counter this issue is to preselect the MSCs according to their osteogenic potential or modulate their properties via activating certain cell signaling pathways. For example, modulating purinergic receptors with specific ligands can enhance the integration and vascularization of the graft [43,50]. Scaffolds can also be combined with growth factors to enhance their osteoinductivity, osteoconductivity, and induce angiogenesis.…”