Native extracellular matrix/fibroin hydrogels for adipose tissue engineering with enhanced vascularization

Abstract

Adipose tissue engineering is a promising field for regeneration of soft tissue defects. However, vascularization is needed since nutrients and oxygen cannot reach cells in thick implants by diffusion. Obtaining a biocompatible scaffold with good mechanical properties is another problem. In this study, we aimed to develop thick and vascularized adipose tissue constructs supporting cell viability and adipose tissue regeneration. Hydrogels were prepared by mixing rat decellularized adipose tissue (DAT) and silk fibroin (Fib) at different v/v ratios (3:1, 1:1 and 1:3) and vortexing. Gelation times decreased with increasing fibroin ratio Among hydrogel groups 1:3-DAT:Fib ratio group showed similar mechanical properties with adipose tissue. Both pre-adipocytes and pre-endothelial cells, pre-differentiated from adipose derived stem cells (ASCs), were encapsulated in hydrogels at a 1: 3 ratio. In vitro analyses showed that hydrogels with 1:3 (v/v) DAT:Fib ratio supported better cell viability. Pre-adipocytes had lipid vesicles, and pre-endothelial cells formed tubular structures inside hydrogels only after 3 days in vitro. When endothelial and adipogenic pre-differentiated ASCs (for 7 days before encapsulation) were encapsulated together into 1:3-DAT:Fib hydrogels both cell types continued to differentiate into the committed cell lineage. Vascularization process in the hydrogels implanted with adipogenic and endothelial pre-differentiated ASCs took place between the first and second week after implantation which was faster than observed in the empty hydrogels. ASCs pre-differentiated towards adipogenic lineage inside hydrogels had begun to accumulate lipid vesicles after 1 week of subcutaneous implantation Based on these results, we suggest that 1:3-DAT:Fib hydrogels with enhanced vascularization hold promise for adipose tissue engineering.

Adipose tissue-derived ECM hydrogels and their use as 3D culture scaffold

“…We surmise that these ECM hydrogels may act to retains growth factors with the benefit that these are released with distinct kinetics over time. The released growth factors are able to induce angiogenesis by stimulation of endothelial cells to form new blood vessels which, in turn, stimulates tissue regeneration resulting in wound healing [24]. Wound healing is especially impaired in diabetic patients because of decreased peripheral blood flow leading to diabetic ulcers formation.…”

Hydrogels in adipose tissue engineering—Potential application in post‐mastectomy breast regeneration

“…For example, soft matrices direct differentiation towards a neurogenic phenotype, matrices that mimic muscle encourage myogenic differentiation, and rigid matrices resembling bone result in osteogenesis (Engler, Sen, Sweeney, & Discher, ; Kim et al, ; Shoham & Gefen, ). ADSC tend to differentiate towards an adipogenic cell type when seeded onto a softer scaffold (Kayabolen et al, ). Other cellular behaviours such as spreading, migration, and attachment within a scaffold micro‐environment are also influenced by physical properties of the scaffold, such as stiffness/softness, elastic modulus, degradation, and adhesion (Hassan, Dong, & Wang, ).…”

“…Several factors within the tissue micro‐environment also influence the growth and development of engineered tissues (Figure ). An appropriate scaffold for tissue engineering should accurately mimic the natural tissue three‐dimensional (3D) architecture (Kayabolen et al, ). The choice of scaffold biomaterial is paramount to the success of tissue regeneration and varies depending on the tissue to be replaced.…”

An optimized procedure to develop a 3‐dimensional microfluidic hydrogel with parallel transport networks

“…It is well known that an ideal hydrogel should provide a rich environment of nutrients and improve cell proliferation and reduce cell death . By embedding microfluidic channels within the hydrogels, instant perfusion of culture media can be created and cell viability will be improved .…”

“…3 It is well known that an ideal hydrogel should provide a rich environment of nutrients and improve cell proliferation and reduce cell death. 4 By embedding microfluidic channels within the hydrogels, instant perfusion of culture media can be created and cell viability will be improved. 5,6 Indeed, microfabrication techniques are great tools to facilitate nutrient transfer in the hydrogel constructs and ultimately generate a functional tissue.…”