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Abstract
Bone defects in human, caused by fractures/nonunions or trauma, gain increasing impact and have become a medical challenge in the present-day aging population. Frequently, those fractures require surgical intervention which ideally relies on autografts or suboptimally on allografts. Therefore, it is pressing and likewise challenging to develop bone substitution materials to heal bone defects. During the differentiation of osteoblasts from their mesenchymal progenitor/stem cells and of osteoclasts from their hemopoietic precursor cells, a lineage-specific release of growth factors and a trans-lineage homeostatic cross-talk via signaling molecules take place. Hence, the major hurdle is to fabricate a template that is functioning in a way mimicking the morphogenetic, inductive role(s) of the native extracellular matrix. In the last few years, two naturally occurring polymers that are produced by deep-sea sponges, the biogenic polyphosphate (bio-polyP) and biogenic silica (bio-silica) have also been identified as promoting morphogenetic on both osteoblasts and osteoclasts. These polymers elicit cytokines that affect bone mineralization (hydroxyapatite formation). In this manner, bio-silica and bio-polyP cause an increased release of BMP-2, the key mediator activating the anabolic arm of the hydroxyapatite forming cells, and of RANKL. In addition, bio-polyP inhibits the progression of the pre-osteoclasts to functionally active osteoclasts. Based on these findings, new bioinspired strategies for the fabrication of bone biomimetic templates have been developed applying 3D-printing techniques. Finally, a strategy is outlined by which these two morphogenetically active polymers might be used to develop a novel functionally active polymer.
Highlights
The inorganic, extracellularly located and assembled bone structures play crucial roles in human physiology, e.g., protection and support of soft tissue and organs, movement of the individual, mineral storage and in turn blood pH regulation
The red staining reflects the extent of hydroxyapatite mineralization. (E) In parallel, plastic coverslips were likewise stained with alizarin red S and documented/photographed as well. Taken these data together we show that bio-polyP affects the tuned balance between the osteoblasts and osteoclasts in the anabolic direction, implying that hydroxyapatite synthesis is favored at the expense of hydroxyapatite degradation/dissolution
The cell layers that were grown on hydroxyapatite did not form hydroxyapatite crystals on their surfaces (Figure 3B), while the cells that had been cultivated for 5 days on bio-silica well formed hydroxyapatite crystals that are often fusing to clusters (Figure 3C–E; [38])
Summary
The inorganic, extracellularly located and assembled bone structures play crucial roles in human physiology, e.g., protection and support of soft tissue and organs, movement of the individual, mineral storage and in turn blood pH regulation (see [1]). As summarized [1], non-union processes in joint arthroplasties, primary tumor resection or massive traumatic bone loss, do not heal with mechanical fixation only In those clinical signs, a stabile substitution material must be used to fill in the bone defect. The prime characteristics of such a biomimetic bone substitution material should be at least osteoconductive (able to guide cells, involved in the reparative growth of the natural bone, to the lesion) or better osteoinductive (stimulation of osteoprogenitor stem cells to differentiate into osteoblasts and triggering them to start with the formation of new bone), as described in [7] In both cases, the healing process should result in osseointegration, a tight structural and functional connection and interaction between the existing living bone and the artificial implant
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