Engineering Photocrosslinkable Bicomponent Hydrogel Constructs for Creating 3D Vascularized Bone

Abstract

Engineering bone tissue requires the generation of a highly organized vasculature. Cellular behavior is affected by the respective niche. Directing cellular behavior and differentiation for creating mineralized regions surrounded by vasculature can be achieved by controlling the pattern of osteogenic and angiogenic niches. This manuscript reports on engineering vascularized bone tissues by incorporating osteogenic and angiogenic cell-laden niches in a photocrosslinkable hydrogel construct. Two-step photolithography process is used to control the stiffness of the hydrogel and distribution of cells in the patterned hydrogel. In addittion, osteoinductive nanoparticles are utilized to induce osteogenesis. The size of microfabricated constructs has a pronounced effect on cellular organization and function. It is shown that the simultaneous presence of both osteogenic and angiogenic niches in one construct results in formation of mineralized regions surrounded by organized vasculature. In addition, the presence of angiogenic niche improves bone formation. This approach can be used for engineered constructs that can be used for treatment of bone defects.

Improved vasculogenesis and bone matrix formation through coculture of endothelial cells and stem cells in tissue‐specific methacryloyl gelatin‐based hydrogels

“…In a recent advanced approach, a coculture system was built using biofabrication techniques and bioinks on the basis of GM, similar to the ones used in this study. Combining both an angiogenic and an osteogenic niche made of GM via micropatterning containing ECs/stem cells and preosteoblasts, respectively, led to an increase in osteogenic marker expression (Kazemzadeh‐Narbat et al, ). For this, micropatterned lines of GM hydrogel with 5% (w/v) polymer content containing HUVECs and MSCs were covered with preosteoblast‐laden hydrogel made from 8% (w/v) GM and containing silicate and tricalcium phosphate nanoparticles.…”

“…In a recent advanced approach, a coculture system was built using biofabrication techniques and bioinks on the basis of GM, similar to the ones used in this study. Combining both an angiogenic and an osteogenic niche made of GM via micropatterning containing ECs/stem cells and preosteoblasts, respectively, led to an increase in osteogenic marker expression (Kazemzadeh-Narbat et al, 2017).…”

Injectable Hyaluronic Acid-co-Gelatin Cryogels for Tissue-Engineering Applications

“…Several groups have combined HA and gelatin with other biopolymers to generate hydrogels with tunable biophysical properties [18,20,24,32,35,48,49]. These gels were fabricated using various crosslinking mechanisms, including Michael-type addition reaction [50,51], polycondensation, click reactions [52,53], Schiff’s base formation [54,55], and free-radical polymerization [32,48,56,57,58,59]. These conventional hydrogels typically require invasive implantations for their placement into the body [15].…”

Gelatin methacryloyl (GelMA)-based biomaterials for bone regeneration

“…Ali Khademhosseini and his co-workers simultaneously introduced angiogenic and osteogenic cells into GelMA scaffolds with a predesigned micropattern to enhance the bone regeneration efficiency at defect sites. 46 In their studies, they constructed HUVEC/hMSC-encapsulated parallel angiogenic niches in osteogenic niches, as shown in Fig. 3.…”

“…Khademhosseini and co-workers designed a GelMA-based scaffold entrapped with both osteogenic and angiogenic cells. 46,47 The diligent design successfully led to simultaneous mineralization and angiogenesis. Remarkably, angiogenesis in the scaffold could further promote cell proliferation and spreading that further accelerated bone regeneration.…”