(247h) Promoting Regenerative Tendon Healing through Hydrogel-Based Engineered Extracellular Matrix Biomechanical Cues

Tendon injuries impact over 300 million people per year in the United States, resulting in the need for costly medical treatment. For example, flexor tendon lacerations alone surpass $400 million in costs yearly. When a tendon is repaired after injury, the natural healing process typically results in fibrotic scarring and limited restoration of function after injury. Therefore, intervention in the healing process by materials that promote regenerative healing is a promising route to restoring function and limiting re-injury after repair. Specifically, the design of hydrogels as an engineered extracellular matrix (eECM) provides a platform to provide cellular cues that promote regenerative healing.

Given that the primary function of the tendon is transmission of force from muscle to bone, recapitulation of the native anisotropy is critical to the load-bearing capacity of healing tendon after injury. In this work, we design hydrogel eECM using a two-stage polymerization approach to fabricate anisotropic hydrogel networks that mimic the anisotropic mechanical properties of native tendon. In the first stage of eECM fabrication, an aza-Michael reaction is used to create a lightly crosslinked network using poly(ethylene glycol) (PEG) diacrylates in combination with multifunctional amines as crosslinkers and adhesive peptides integrated as pendant groups on the polymer backbone. Anisotropy is introduced by mechanical stretching of the initial network and subsequent photopolymerization of unreacted acrylate end-groups. Characterization of directional elastic modulus is used to compare the mechanical anisotropy of the hydrogels to the properties of native tendon. We also characterize the impact of hydrolysis of the b-amino ester linkages on mechanical anisotropy over time. Using the eECM as a scaffold for 3T3 fibroblasts, we demonstrate preferential alignment of cells relative to the anisotropy and degradability of the eECM and analyze collagen deposition as a metric for regenerative healing.