TY - JOUR
T1 - Multi-channel silk sponge mimicking bone marrow vascular niche for platelet production
AU - Tozzi, Lorenzo
AU - Laurent, Pierre Alexandre
AU - Di Buduo, Christian A.
AU - Mu, Xuan
AU - Massaro, Angelo
AU - Bretherton, Ross
AU - Stoppel, Whitney
AU - Kaplan, David L.
AU - Balduini, Alessandra
PY - 2018/9/1
Y1 - 2018/9/1
N2 - In the bone marrow, the interaction of progenitor cells with the vasculature is fundamental for the release of blood cells into circulation. Silk fibroin, derived from Bombyx mori silkworm cocoons, is a promising protein biomaterial for bone marrow tissue engineering, because of its tunable architecture and mechanical properties, the capacity to incorporate labile compounds without loss of bioactivity and the demonstrated ability to support blood cell formation without premature activation. In this study, we fabricated a custom perfusion chamber to contain a multi-channel lyophilized silk sponge mimicking the vascular network in the bone marrow niche. The perfusion system consisted in an inlet and an outlet and 2 splitters that allowed funneling flow in each single channel of the silk sponge. Computational Fluid Dynamic analysis demonstrated that this design permitted confined flow inside the vascular channels. The silk channeled sponge supported efficient platelet release from megakaryocytes (Mks). After seeding, the Mks localized along SDF-1α functionalized vascular channels in the sponge. Perfusion of the channels allowed the recovery of functional platelets as demonstrated by increased PAC-1 binding upon thrombin stimulation. Further, increasing the number of channels in the silk sponge resulted in a proportional increase in the numbers of platelets recovered, suggesting applicability to scale-up for platelet production. In conclusion, we have developed a scalable system consisting of a multi-channeled silk sponge incorporated in a perfusion chamber that can provide useful technology for functional platelet production ex vivo.
AB - In the bone marrow, the interaction of progenitor cells with the vasculature is fundamental for the release of blood cells into circulation. Silk fibroin, derived from Bombyx mori silkworm cocoons, is a promising protein biomaterial for bone marrow tissue engineering, because of its tunable architecture and mechanical properties, the capacity to incorporate labile compounds without loss of bioactivity and the demonstrated ability to support blood cell formation without premature activation. In this study, we fabricated a custom perfusion chamber to contain a multi-channel lyophilized silk sponge mimicking the vascular network in the bone marrow niche. The perfusion system consisted in an inlet and an outlet and 2 splitters that allowed funneling flow in each single channel of the silk sponge. Computational Fluid Dynamic analysis demonstrated that this design permitted confined flow inside the vascular channels. The silk channeled sponge supported efficient platelet release from megakaryocytes (Mks). After seeding, the Mks localized along SDF-1α functionalized vascular channels in the sponge. Perfusion of the channels allowed the recovery of functional platelets as demonstrated by increased PAC-1 binding upon thrombin stimulation. Further, increasing the number of channels in the silk sponge resulted in a proportional increase in the numbers of platelets recovered, suggesting applicability to scale-up for platelet production. In conclusion, we have developed a scalable system consisting of a multi-channeled silk sponge incorporated in a perfusion chamber that can provide useful technology for functional platelet production ex vivo.
KW - Bone marrow
KW - Computational Fluid Dynamic
KW - Haematopoiesis
KW - Megakaryocyte
KW - Platelet
KW - Silk
UR - http://www.scopus.com/inward/record.url?scp=85049304696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049304696&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2018.06.018
DO - 10.1016/j.biomaterials.2018.06.018
M3 - Article
AN - SCOPUS:85049304696
VL - 178
SP - 122
EP - 133
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
ER -