Magnetic Alignment of Collagen: Principles, Methods, Applications, and Fiber Alignment Analyses

Anisotropically aligned collagen scaffolds mimic the microarchitectural properties of native tissue, possess superior mechanical properties, and provide the essential physicochemical cues to guide cell response. Biofabrication methodologies to align collagen fibers include mechanical, electrical, magnetic, and microfluidic approaches. Magnetic alignment of collagen was first published in 1983 but widespread use of this technique was hindered mainly due to the low diamagnetism of collagen molecules and the need for very strong tesla-order magnetic fields. Over the last decade, there is a renewed interest in the use of magnetic approaches that employ magnetic particles and low-level magnetic fields to align collagen fibers. In this review, the working principle, advantages, and limitations of different collagen alignment techniques with special emphasis on the magnetic alignment approach are detailed. Key findings from studies that employ high-strength magnetic fields and the magnetic particle-based approach to align collagen fibers are highlighted. In addition, the most common qualitative and quantitative image analyses methods to assess collagen alignment are discussed. Finally, current challenges and future directions are presented for further development and clinical translation of magnetically aligned collagen scaffolds. Aligning collagen fibers using the magnetic approach entails two different modalities: (1) use of high-strength tesla-order magnetic fields (4T–12T) to trigger collagen fiber alignment, and (2) magnetic particle-based approach to guide collagen fiber alignment in the presence of a low-level magnetic field (<0.25T). This review elaborates on the principles of collagen alignment, methods employed to optimize the process parameters, and tissue-specific applications of magnetically aligned collagen scaffolds. Biomedical imaging methods employed for the assessment of collagen fiber alignment are also detailed.