Self-assembled Collagen-Fibrin Hydrogel Reinforces Tissue Engineered Adventitia Vessels Seeded with Human Fibroblasts

Abstract

Efforts for tissue engineering vascular grafts focuses on the tunica media and intima, although the tunica adventitia serves as the primary structural support for blood vessels. In surgery, during endarterectomies, surgeons can strip the vessel, leaving the adventitia as the main strength layer to close the vessel. Here, we adapted our recently developed technique of forming vascular tissue rings then stacking the rings into a tubular structure, to accommodate human fibroblasts to create adventitia vessels in 8 days. Collagen production and fibril cross-linking was augmented with TGF-β and ascorbic acid, significantly increasing tensile strength to 57.8 ± 3.07 kPa (p = 0.008). Collagen type I gel was added to the base fibrin hydrogel to further increase strength. Groups were: Fibrin only; 0.7 mg/ml COL; 1.7 mg/ml COL; and 2.2 mg/ml COL. The 0.7 mg/ml collagen rings resulted in the highest tensile strength at 77.0 ± 18.1 kPa (p = 0.015). Culture periods of 1–2 weeks resulted in an increase in extracellular matrix deposition and significantly higher failure strength but not ultimate tensile strength. Histological analysis showed the 0.7 mg/ml COL group had significantly more, mature collagen. Thus, a hydrogel of 0.7 mg/ml collagen in fibrin was ideal for creating and strengthening engineered adventitia vessels.

Engineering of Human Skeletal Muscle With an Autologous Deposited Extracellular Matrix

“…Ascorbic acid has already been known for a long time to stimulate collagen deposition ( Schwarz et al, 1981 ). It has been used to stimulate collagen deposition from human tenocytes for tendon tissue engineering ( Hakimi et al, 2014 ), from vascular interstitial cells for heart valve tissue engineering ( Wu et al, 2017 ) and from fibroblasts for vascular graft tissue engineering ( Patel et al, 2018 ). The use of ascorbic acid-releasing scaffolds has also been suggested for use in pelvic floor repair ( Mangır et al, 2016 ).…”

Decellularized Skin Extracellular Matrix (dsECM) Improves the Physical and Biological Properties of Fibrinogen Hydrogel for Skin Bioprinting Applications

“…This lack of ECM maturity may result from the relatively insufficient ECM components in the fibrinogen hydrogel used for bioprinting. It is also known that fibrinogen post-printing mechanical strength is limited [15], and the addition of collagen is known to increase fibrinogen hydrogel's mechanical strength significantly [16]. The objective of this study is to determine if the addition of a decellularized skin ECM (dsECM) improves the biological and physical properties of fibrinogen hydrogel for skin bioprinting applications.…”

MOFs-Based Nitric Oxide Therapy for Tendon Regeneration

“…The area proportion of collagen type I increased continuously in the NMPGA group (Fig. S13), which indicated the increasing maturity of the collagen fibers [53][54][55][56]. Furthermore, as exhibited in Fig.…”