Assembled Cell-Decorated Collagen (AC-DC) bioprinted implants mimic musculoskeletal tissue properties and promote functional recovery

Musculoskeletal tissue injuries, including the damage and rupture of ligaments and tendons, and volumetric muscle loss (VML), are exceptionally commonplace and often lead to permanent disability and deformation. We developed an advanced biomanufacturing platform producing cellularized collagen microfiber implants to facilitate functional repair and regeneration of musculoskeletal soft tissues. This Assembled Cell-Decorated Collagen (AC-DC) bioprinting process rapidly and reproducibly forms 3D implants using clinically relevant cells and strong, microfluidic extruded collagen fibers. Quantitative analysis showed that the directionality and distribution of cells throughout AC-DC implants mimic the cellular properties of native musculoskeletal tissue. AC-DC bioprinted implants further approximate or exceed the strength and stiffness of human tendons and ligaments and exceeded the properties of commonplace collagen hydrogels by orders of magnitude. The regenerative potential of AC-DC implants was also assessed in vivo in a rodent VML model. A critically sized muscle injury in the hindlimb was created and repaired, and limb torque generation potential was measured over 12 weeks. Both acellular and cellular implants were found to promote functional recovery compared to the unrepaired group, with AC-DC implants containing therapeutic muscle progenitor cells promoting the highest degree of recovery. Histological analysis and automated image processing of explanted muscle cross-sections revealed increased total muscle fiber count, median muscle fiber size, and increased cellularization for injuries repaired with cellularized implants. These studies introduce the tremendous potential of an advanced bioprinting method for generating tissue analogs with near-native biological and biomechanical properties with the potential to repair numerous challenging musculoskeletal injuries. One Sentence SummaryBioprinted collagen microfiber-based implants mimic musculoskeletal tissue properties in vitro and promote functional recovery in vivo.