Spatiotemporal Immunomodulation Using Biomimetic Scaffold Promotes Endochondral Ossification-Mediated Bone Healing.

Advanced Science
Yutong LiuChangsheng Liu

Abstract

Biomaterials play an important role in treating bone defects by promoting direct osteogenic healing through intramembranous ossification (IO). However, majority of the body's bones form via cartilaginous intermediates by endochondral ossification (EO), a process that has not been well mimicked by engineered scaffolds, thus limiting their clinical utility in treating large segmental bone defects. Here, by entrapping corticosteroid dexamethasone within biomimetic recombinant human bone morphogenetic protein (rhBMP)-loaded porous mesoporous bioglass scaffolds and regulating their release kinetics, significant degree of ectopic bone formation through endochondral ossification is achieved. By regulating the recruitment and polarization of immune suppressive macrophage phenotypes, the scaffold promotes rapid chondrogenesis by activating Hif-3α signaling pathway in mesenchymal stem cells, which upregulates the expression of downstream chondrogenic genes. Inhibition of Hif-3α signaling reverses the endochondral ossification phenotype. Together, these results reveal a strategy to facilitate developmental bone growth process using immune modulating biomimetic scaffolds, thus providing new opportunities for developing biomaterials capable...Continue Reading

References

Nov 12, 1965·Science·M R Urist
Oct 1, 1995·Acta Orthopaedica Scandinavica·E GöktürkZ Gülbas
Sep 8, 1997·The Journal of Cell Biology·L CamperE Lundgren-Akerlund
May 16, 2003·Nature·Henry M Kronenberg
Feb 14, 2006·Acta Orthopaedica·Olav ReikeråsStein E Utvåg
Nov 26, 2008·Nature Reviews. Immunology·David M Mosser, Justin P Edwards
Jul 7, 2009·Annual Review of Cell and Developmental Biology·Gerard KarsentyCarmine Settembre
Jan 7, 2011·Journal of Leukocyte Biology·Okan BastianTaco Blokhuis
Feb 10, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kylie A AlexanderAllison R Pettit
May 28, 2011·Tissue Engineering. Part B, Reviews·Paschalia M MountziarisAntonios G Mikos
Jul 27, 2011·Cell and Tissue Research·Katharina Schmidt-BleekGeorg N Duda
Oct 15, 2011·Nature Reviews. Immunology·Peter J Murray, Thomas A Wynn
Feb 2, 2012·Nature Reviews. Rheumatology·Lutz ClaesAnita Ignatius
Jul 10, 2012·Nature Medicine·Thomas A Wynn, Thirumalai R Ramalingam
Apr 27, 2013·Nature·Thomas A WynnJeffrey W Pollard
Mar 29, 2014·F1000prime Reports·Fernando O Martinez, Siamon Gordon
Jun 12, 2014·Journal of Tissue Engineering and Regenerative Medicine·Emmet M ThompsonFergal J O'Brien
Oct 1, 2014·Nature Reviews. Rheumatology·Thomas A Einhorn, Louis C Gerstenfeld
Mar 27, 2015·Nature Communications·Michiko YoshidaToshiyuki Yoneda
Jul 16, 2015·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Brandon D MarkwayBrian Johnstone
Nov 4, 2015·Bone·Claudia SchlundtKatharina Schmidt-Bleek
Dec 5, 2018·Npj Regenerative Medicine·A LongoniD Gawlitta
Feb 28, 2020·Nature·Nick van GastelGeert Carmeliet
May 21, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Bing DuanChangsheng Liu

❮ Previous
Next ❯

Software Mentioned

FlowJo

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.