Vascularization remains the principle obstacle that impedes the translation of most bone tissue engineered constructs to clinical practice. Pre-vascularization of large constructs has great potential to improve functional vasculature throughout the scaffold to rapidly facilitate integration with the surrounding tissue and circumvent necrosis in the core of the scaffold. In our previous studies, we have developed microengineered gels to co- culture human endothelial progenitor cells (hEPCs) and human mesenchymal stem cells (hMSCs) to engineer microvasculature, but observed limited anastomotic potential. We have also developed a number of approaches in which engineered hydrogels can be assembled into graded tissue scaffolds to generate vascularized constructs, and determined the need to protect structural integrity of microvasculature using mechanically-robust scaffolds. A major remaining challenge in our work is that despite the initial remodeling of the cells into functioning microvessels, efficient integration to major vessels has not been observed. The main premise of this renewal proposal is that by incorporating a perfusable vessel graft that connects the microvasculature of the engineered construct to large host vessels, we will be able to address this challenging issue. In this renewal project, we propose to engineer a bone scaffold that integrates microvasculature with a surgically-anastomizable large vessel graft to heal critical size segmental bone defects. This construct will be developed in vitr such that the microvascular capillaries in gels connect with the large vessel graft and subsequently to the host vessel in vivo. Our hypothesis is this construct can substantially improve on the integration to the host tissue by restoring blood supply immediately after transplantation. To test our hypothesis, our team comprised of experts in tissue engineering, biomaterials, microengineering, and orthopedics proposes the following aims:
Aim 1. Develop components for fabrication of surgically-anastomizable pre- vascularized bone construct.
Aim 2. Engineer and characterize surgically-anastomizable pre-vascularized bone construct in vitro.
Aim 3. Evaluate the efficiency of surgically-anastomizable pre-vascularized bone construct in repair of critical size segmental bone defects. The completion of this work will be a paradigm shift and a landmark achievement in efforts to clinical treatments for bone critical size defects.
Vascularization remains a strategic challenge that prevents the translation of most bone tissue engineered constructs to clinical practice such as treatment of large bone defects. The success of the novel bone grafts that integrates microvasculature with large vessel graft will aid to translate pre-vascularized large constructs into clinical environments and significantly improve the existing methods for integrating pre-vascularized, engineered grafts, a long standing problem in regenerative medicine and bone tissue engineering. The completion of this work will be a paradigm shift and a landmark achievement in efforts to clinical treatments for bone critical size defects.
|Maruyama, Masahiro; Nabeshima, Akira; Pan, Chi-Chun et al. (2018) The effects of a functionally-graded scaffold and bone marrow-derived mononuclear cells on steroid-induced femoral head osteonecrosis. Biomaterials 187:39-46|
|Miri, Amir K; Nieto, Daniel; Iglesias, Luis et al. (2018) Microfluidics-Enabled Multimaterial Maskless Stereolithographic Bioprinting. Adv Mater 30:e1800242|
|Cheng, Hao; Chabok, Rosa; Guan, Xiaofei et al. (2018) Synergistic interplay between the two major bone minerals, hydroxyapatite and whitlockite nanoparticles, for osteogenic differentiation of mesenchymal stem cells. Acta Biomater 69:342-351|
|Liu, Wanjun; Zhong, Zhe; Hu, Ning et al. (2018) Coaxial extrusion bioprinting of 3D microfibrous constructs with cell-favorable gelatin methacryloyl microenvironments. Biofabrication 10:024102|
|Seo, Jungmok; Shin, Jung-Youn; Leijten, Jeroen et al. (2018) High-throughput approaches for screening and analysis of cell behaviors. Biomaterials 153:85-101|
|Kawai, Toshiyuki; Shanjani, Yaser; Fazeli, Saba et al. (2018) Customized, degradable, functionally graded scaffold for potential treatment of early stage osteonecrosis of the femoral head. J Orthop Res 36:1002-1011|
|Yue, Kan; Liu, Yanhui; Byambaa, Batzaya et al. (2018) Visible light crosslinkable human hair keratin hydrogels. Bioeng Transl Med 3:37-48|
|Ker, Dai Fei Elmer; Wang, Dan; Behn, Anthony William et al. (2018) Functionally Graded, Bone- and Tendon-Like Polyurethane for Rotator Cuff Repair. Adv Funct Mater 28:|
|Alarçin, Emine; Lee, Tae Yong; Karuthedom, Sobha et al. (2018) Injectable shear-thinning hydrogels for delivering osteogenic and angiogenic cells and growth factors. Biomater Sci 6:1604-1615|
|Stahl, Alexander M; Yang, Yunzhi Peter (2018) Tunable Elastomers with an Antithrombotic Component for Cardiovascular Applications. Adv Healthc Mater 7:e1800222|
Showing the most recent 10 out of 194 publications