Abstract
BackgroundDelayed bone regeneration of fractures in osteoporosis patients or of critical-size bone defects after tumor resection are a major medical and socio-economic challenge. Therefore, the development of more effective and osteoinductive biomaterials is crucial.MethodsWe examined the osteogenic potential of macroporous scaffolds with varying pore sizes after biofunctionalization with a collagen/high-sulfated hyaluronan (sHA3) coating in vitro. The three-dimensional scaffolds were made up from a biodegradable three-armed lactic acid-based macromer (TriLA) by cross-polymerization. Templating with solid lipid particles that melt during fabrication generates a continuous pore network. Human mesenchymal stem cells (hMSC) cultivated on the functionalized scaffolds in vitro were investigated for cell viability, production of alkaline phosphatase (ALP) and bone matrix formation. Statistical analysis was performed using studentās t-test or two-way ANOVA.ResultsWe succeeded in generating scaffolds that feature a significantly higher average pore size and a broader distribution of individual pore sizes (HiPo) by modifying composition and relative amount of lipid particles, macromer concentration and temperature for cross-polymerization during scaffold fabrication. Overall porosity was retained, while the scaffolds showed a 25% decrease in compressive modulus compared to the initial TriLA scaffolds with a lower pore size (LoPo). These HiPo scaffolds were more readily coated as shown by higher amounts of immobilized collagen (+ 44%) and sHA3 (+ 25%) compared to LoPo scaffolds. In vitro, culture of hMSCs on collagen and/or sHA3-coated HiPo scaffolds demonstrated unaltered cell viability. Furthermore, the production of ALP, an early marker of osteogenesis (+ 3-fold), and formation of new bone matrix (+ 2.5-fold) was enhanced by the functionalization with sHA3 of both scaffold types. Nevertheless, effects were more pronounced on HiPo scaffolds about 112%.ConclusionIn summary, we showed that the improvement of scaffold pore sizes enhanced the coating efficiency with collagen and sHA3, which had a significant positive effect on bone formation markers, underlining the promise of using this material approach for in vivo studies.
Highlights
Primary and secondary osteoporosis caused by e.g. long term glucocorticoid application or diabetes mellitus are highly prevalent diseases in the ageing society
In summary, we showed that the improvement of scaffold pore sizes enhanced the coating efficiency with collagen and sHA3, which had a significant positive effect on bone formation markers, underlining the promise of using this material approach for in vivo studies
Porosity adjustment As reference material, porous TriLA scaffolds made from the Tri134LA6 macromer were fabricated employing the parameter set and porogen fraction (300ā500 Ī¼m) established during the development of the TriLA material platform (Fig. 1a, lower pore size (LoPo))
Summary
Primary and secondary osteoporosis caused by e.g. long term glucocorticoid application or diabetes mellitus are highly prevalent diseases in the ageing society. Worldwide almost 390 million people aged over 50 suffer from low bone mass and strength, resulting in increased fracture risk [1, 2]. These patients often display delayed fracture healing which leads to a persistent immobility and the need for special care [1]. Often patients are only diagnosed after a fragility fracture At this stage detrimental bone changes are far more advanced and pose a challenge. Whereas the underlying disease can be managed long term with e.g. anti-resorptive or osteoanabolic drugs, bone healing and/or osseo-integration at a fracture site have different needs. The development of more effective and osteoinductive biomaterials is crucial
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