3D printing of biomaterials for vascularized and innervated tissue regeneration

Neurovascular networks play significant roles in the metabolism and regeneration of many tissues and organs in the human body. Blood vessels can transport sufficient oxygen, nutrients, and biological factors, while nerve fibers transmit excitation signals to targeted cells. However, traditional scaffolds cannot satisfy the requirement of stimulating angiogenesis and innervation in a timely manner due to the complexity of host neurovascular networks. Three-dimensional (3D) printing, as a versatile and favorable technique, provides an effective approach to fabricating biological scaffolds with biomimetic architectures and multimaterial compositions, which are capable of regulating multiple cell behaviors. This review paper presents a summary of the current progress in 3D-printed biomaterials for vascularized and innervated tissue regeneration by presenting skin, bone, and skeletal muscle tissues as an example. In addition, we highlight the crucial roles of blood vessels and nerve fibers in the process of tissue regeneration and discuss the future perspectives for engineering novel biomaterials. It is expected that 3D-printed biomaterials with angiogenesis and innervation properties can not only recapitulate the physiological microenvironment of damaged tissues but also rapidly integrate with host neurovascular networks, resulting in accelerated functional tissue regeneration.