Engineered Vascularized Flaps, Composed of Polymeric Soft Tissue and Live Bone, Repair Complex Tibial Defects

Abstract

Functional regeneration of complex large-scaled defects requires both softand hard-tissue grafts. Moreover, bone constructs within these grafts require an extensive vascular supply for survival and metabolism during the engraftment. Soft-tissue pedicles are often used to vascularize bony constructs. However, extensive autologous tissue-harvest required for the fabrication of these grafts remains a major procedural drawback. In the current work, a composite flap is fabricated using synthetic soft-tissue matrices and decellularized bone, combined in vivo to form de novo composite tissue with its own vascular supply. Pre-vascularization of the soft-tissue matrix using dental pulp stem cells (DPSCs) and human adipose microvascular endothelial cells (HAMECs) enhances vascular development within decellularized bones. In addition, osteogenic induction of bone constructs engineered using adipose derived mesenchymal stromal cells positively affects micro-capillary organization within the mineralized component of the neo-tissue. Eventually, these neo-tissues used as axial reconstructive flaps support long-term bone defect repair, as well as muscle defect bridging. The composite flaps described here may help eliminate invasive autologous tissue-harvest for patients in need of viable grafts for transplantation.

Advances in hydrogel-based vascularized tissues for tissue repair and drug screening

“…In this vein, the combination of alternative cell types, controllable shaping of architectures, and tunable biochemical cues offer the merits in engineering designed tissue or organs [ 69 , 82 ]. Thus, increasing the versatility of the designed scaffold materials is extremely demanding, which faces some critical challenges, such as (1) compromising vasculatures with a microenvironment that is highly similar to native ECM, (2) integrating biochemical cues inside scaffold materials to regulate cell growth, as well as tissue morphogenesis, and (3) carrying the automated process for reliable and precise fabrication of scaffolds with designed geometry and features [ 12 , 13 , 46 ].…”

“…However, this angiogenesis process sometimes is too slow to form sufficient newly-born capillaries upon severe damage, leading to the final tissue necrosis [ 173 , 174 ]. More recently, the implantation of pre-vascularized constructs showed great potentials in facilitating the anastomosis of the host vessels and the in vitro formed vascular networks [ 11 , 12 , 30 , 95 , 165 ] ( Fig. 5 A).…”

“…The capillary endothelial cells (ECs) were cultured in a two-dimensional (2D) tumor-conditioned medium, demonstrating the development of capillary tubes. Since then, research interests in engineering the vascularized tissue constructs have been increasing [ [10] , [11] , [12] ].…”

“…In addition, multiple bioactive components, such as GFs and peptides, can be incorporated into the 3D artificial ECM, achieving the diffusion and immobilization of molecules at temporal and spatial gradients whenever necessary [ 19 , 33 ]. Moreover, adjustable mechanical properties and specific simulations of the tissues or organs based on artificial ECM can be achieved by varying scaffold materials [ 12 , 13 , 21 ]. However, it should be noted that the selection of biomaterials, cells, and biomolecules to reproducing the physiological conditions of the native tissue in vitro is critical towards the fabrication of vascularized tissue constructs, maintenance of tissue morphogenesis, as well as final achievement of organ homeostasis.…”

Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

“…PLGA can be combined with poly-L-lactic acid (PLLA) to form the PLLA/PLGA scaffolds, which serve as biocompatible and biodegradable matrices for cell attachment, proliferation, differentiation and organization in muscle, bone and spinal cord tissue engineering [34,64,[94][95][96]. Using the salt-leaching technique, highly porous PLLA/PLGA scaffolds can be fabricated with pore sizes of 212-600 µm and 93% porosity [34,64,[94][95][96].…”