Abstract
Aligned topography and biomolecular gradients exist in various native tissues and play pivotal roles in a set of biological processes. Scaffolds that recapitulate the complex structure and microenvironment show great potential in promoting tissue regeneration and repair. We begin with a discussion on the fabrication of aligned scaffolds, followed by how biomolecular gradients can be immobilized on aligned scaffolds. In particular, we emphasize how electrospinning, freeze drying, and 3D printing technology can accomplish aligned topography and biomolecular gradients flexibly and robustly. We then highlight several applications of aligned scaffolds and biomolecular gradients in regenerative medicine including nerve, tendon/ligament, and tendon/ligament-to-bone insertion regeneration. Finally, we finish with conclusions and future perspectives on the use of aligned scaffolds with biomolecular gradients in regenerative medicine.
Highlights
In recent decades, tissue-engineered scaffolds have shown great therapeutic potential in regenerative medicine for improving clinical outcomes
The 3D printing technique opens up a new avenue for producing gradual scaffolds, and enable incorporation of physical, chemical, biological, and cellular gradients into scaffolds to recapitulate the heterogeneous environment of native tissues/organs [44]
In the past ten years, the NeuroRegen scaffold has been functionalized with biomolecules including neurotropin factors, antibodies, and stem cells including NSCs [64] and mesenchymal stem cell (MSC) [65,66], and it was found that axon outgrowth, neural differentiation of transplanted [64] and endogenous stem cells [67,68], electrophysiological and motor functional recovery could be achieved in both rat [63,64] and canine [65,66,69,70] Spinal cord injury (SCI) models
Summary
Tissue-engineered scaffolds have shown great therapeutic potential in regenerative medicine for improving clinical outcomes. A linear retinoic acid gradient is present in embryo and is essential for normal embryonic development [3]. Biomimetic scaffolds capable of imitating aligned structures and biomolecular gradients may be essential for tissue regeneration. Structural mimicry of the fibrous network of native ECM and ease of control of fiber organization make electrospun fibrous scaffolds potential candidates for a variety of applications in tissue regeneration. The objective of this article is to present recent progress in the fabrication of aligned scaffolds with biomolecular gradients as well as their applications and future directions in regenerative medicine. We first introduced the preparation of aligned scaffolds, and focus on the fabrication of aligned scaffolds with biomolecular gradients We highlighted their applications in regenerative medicine including nerve, tendon/ligament, and tendon/ligament-bone insertion regeneration. The challenges and future directions in the field will be discussed
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