A Moldable Putty Containing Silk Fibroin Yolk Shell Particles for Improved Hemostasis and Bone Repair

Abstract

During minimally invasive orthopedic surgeries, surgical intervention is required at two stages; to attain hemostasis and subsequently to implant the bone graft or its substitute. There is an apparent need for a material which can simultaneously control bone bleeding and provide support for bone repair. In this work, a moldable putty, which can be applied to bone defects (usually irregular in shape), was developed to address this need. It comprises of a hemostatic factor thrombin, osteoinductive "yolk-shell" particles containing bone growth factor (BMP-2), and an osteoconductive component hydroxyapatite. The yolk shell particles allowed controlled release of BMP-2 and showed significantly enhanced osteogenic differentiation of C2C12 (mouse myoblast) cells as demonstrated by increased alkaline phosphatase (ALP) activity and relative gene expressions of osteogenic differentiation markers. These particles were assembled into a moldable putty by mixing them with hydroxyapatite and silk fibroin solution (binding agent) supplemented with thrombin. The putty showed non-cytotoxicity, hemostatic ability, sustained release of BMP-2 and induced increased mineralization in C2C12 cells. This putty, if applied to bone defects during surgeries, may help attain hemostasis and may enhance bone repair by providing sustained release of bone growth factors.

Silk fibroin based carrier system for delivery of fibrinogen and thrombin as coagulant supplements

“…The delivery of a coagulation substrate, catalyst, and main platelet agonist might represent a promising approach to rapidly counter severe bleeding where factor depletion is involved, in cases of fibrinolytic activation and during platelet dysfunction. The previous study of the delivery of thrombin via a silk carrier described a putty consisting of hydroxyapatite and silk for the repair of small bone defects during surgeries in which silk was present as microparticles for dual delivery of osteoinductive BMP2 and hemostatic thrombin. Similar to this study we were also able to preserve the bioactivity of thrombin during scaffold fabrication in which silk proteins were conformationally changed from water‐soluble random coils to insoluble beta‐sheet structures.…”

Systematic Review of Silk Scaffolds in Musculoskeletal Tissue Engineering Applications in the Recent Decade

“…BMP-2 appears to be one of the most potent growth factors in the field of bone tissue regeneration so far. Saran et al 104 fabricated osteoinductive "yolk−shell" particles including a "yolk" consisting of BMP-2 loaded SF nanoparticles encapsulated by a SF shell, and the particles enabled the controlled release of BMP-2 and induced significantly enhanced osteogenic differentiation of seeded cells. On the other hand, VEGF, as a major regulator of angiogenesis, was incorporated into the scaffold with the intention of increasing proliferation, migration, differentiation of osteoblasts, and angiogenesis of endothelial cells.…”

A three-dimensional hydroxyapatite/polyacrylonitrile composite scaffold designed for bone tissue engineering

“…5 Therefore, a variety of biomaterials have been fabricated for bone repairing and regeneration in the past decades, [6][7][8][9][10][11][12] such as three dimensional (3D) scaffolds, [13][14][15][16] functional membranes [17][18][19][20] and particles. [21][22][23] In particular, 3D bone scaffolds made from polymeric materials, carrying cells or growth factors to induce the regeneration of new bone, have received increasing attention. 24,25 Several researches have claimed that these 3D biomaterials not only possess porous structure, but also mimic the biological functions of the extracellular matrix (ECM) contributing to bone repair and regeneration.…”