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Traditional Anterior Cruciate Ligament (ACL) reconstruction is commonly performed using an allograft or autograft and possesses limitations such as donor site morbidity, decreased range of motion, and potential infection. However, a biodegradable synthetic graft could greatly assist in the prevention of such restrictions after ACL reconstruction. In this study, artificial grafts were generated using "wet" and "dry" electrospinning processes with a biodegradable elastomer, poly (ester urethane) urea (PEUU), and were evaluated in vitro and in vivo in a rat model. Four groups were established: (1) Wet PEUU artificial ligament, (2) Dry PEUU artificial ligament, (3) Dry polycaprolactone artificial ligament (PCL), and (4) autologous flexor digitorum longus tendon graft. Eight weeks after surgery, the in vivo tensile strength of wet PEUU ligaments had significantly increased compared to the other synthetic ligaments. These results aligned with increased infiltration of host cells and decreased inflammation within the wet PEUU grafts. In contrast, very little cellular infiltration was observed in PCL and dry PEUU grafts. Micro-computed tomography analysis performed at 4 and 8 weeks postoperatively revealed significantly smaller bone tunnels in the tendon autograft and wet PEUU groups. The Wet PEUU grafts served as an adequate functioning material and allowed for the creation of tissues that closely resembled the ACL.

In small intestinal submucosa scaffolds for functional tissue engineering, the impact of scaffold fabrication parameters on success rate may be related to the mechanotransductory properties of the final microstructural organization of collagen fibers. We hypothesized that two fabrication parameters, 1) preservation (P) or removal (R) of a dense collagen layer present in SIS and 2) SIS in a final dehydrated (D) or hydrated (H) state, have an effect on scaffold void area, microstructural anisotropy (fiber alignment) and mechanical anisotropy (global mechanical compliance). We further integrated our experimental measurements in a constitutive model to explore final effects on the micromechanical environment inside the scaffold volume. Our results indicated that PH scaffolds might exhibit recurrent and large force fluctuations between layers (up to 195 pN), while fluctuations in RH scaffolds might be larger (up to 256 pN) but not as recurrent. In contrast, both PD and RD groups were estimated to produce scarcer and smaller fluctuations (not larger than 50 pN). We concluded that the hydration parameter strongly affects the micromechanics of SIS and that an adequate choice of fabrication parameters, assisted by the herein developed method, might leverage the use of SIS for functional tissue engineering applications, where forces at the cellular level are of concern in the guidance of new tissue formation.