Increased pore size of scaffolds improves coating efficiency with sulfated hyaluronan and mineralization capacity of osteoblasts

Background: Delayed 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. Methods: We 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 student's t-test or two-way ANOVA. Results: We 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%. Conclusion: 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. © 2019 The Author(s)

The Phagocyte, Metchnikoff, and the Foundation of Immunology

ABSTRACTSince the ability of some cells to engulf particulate material was observed before Metchnikoff, he did not "discover" phagocytosis, as is sometimes mentioned in textbooks. Rather, he assigned to particle internalization the role of defending the host against noxious stimuli, which represented a new function relative to the previously recognized task of intracellular digestion. With this proposal, Metchnikoff built the conceptual framework within which immunity could finally be seen as an active host function triggered by noxious stimuli. In this sense, Metchnikoff can be rightly regarded as the father of all immunological sciences and not only of innate immunity or myeloid cell biology. Moreover, the recognition properties of his phagocyte fit surprisingly well with recent discoveries and modern models of immune sensing. For example, rather than assigning to immune recognition exclusively the function of eliminating nonself components (as others did after him), Metchnikoff viewed phagocytes as homeostatic agents capable of monitoring the internal environment and promoting tissue remodeling, thereby continuously defining the identity of the organism. No doubt, Metchnikoff's life and creativity can provide, still today, a rich source of inspiration