Materials exhibit a dichotomy between flexibility and stiffness. It sparks curiosity: How can a material be soft yet robust enough to withstand pressure or load? This question is particularly important in soft tissue engineering, where the goal is to replicate the load-bearing properties of soft tissues using biomaterials. Tissues like the human breast or cardiac tissue are incredibly soft and pliable yet possess remarkable strength and resilience, displaying exceptional toughness. These tissues effortlessly revert to their original shape upon compression release, showcasing their intriguing mechanical properties.

In the laboratory of Dr. Jingwei Xie in the Department of Surgery at the University of Nebraska Medical Center, we are engaged in developing various fibrous aerogels for tissue engineering and regenerative applications. However, we encounter a persistent challenge: the inherent conflict between the strength and flexibility of aerogel materials. With their distinctive structure and adaptable design, aerogels have great soft tissue engineering potential. However, their inherent fragility and limited elasticity present formidable obstacles.

Conventional approaches to enhance mechanical properties, often involving increased crosslinking density, tend to worsen brittleness, thereby restricting their suitability for dynamic soft tissues (Figure 1a).

To tackle these challenges, we propose an innovative solution—a hybrid aerogel constructed from self-reinforcing networks of micro- and nanofibers. This groundbreaking technique entails physically entangling nanofiber segments with microfiber pillars, establishing a robust stress distribution system within interconnected fiber networks (Figure 1b).

The optimized hybrid aerogels showcase remarkable specific tensile moduli and fracture energies. Additionally, they exhibit super-elastic characteristics with swift shape recovery. These aerogels exceed established mechanical benchmarks, facilitate rapid tissue ingrowth, encourage extracellular matrix deposition, and incite neovascularization upon subcutaneous implantation. Beyond their mechanical prowess, these hybrid aerogels provide adaptability in engineering soft tissues through minimally invasive procedures. Their potential is further amplified by the capability to integrate magnetically responsive or electrically conductive features, opening avenues for pressure sensing and actuation applications.

Despite aerogels exhibiting promise in various biomedical applications, their mechanical limitations have impeded broader utilization. Previous efforts to enhance mechanical properties often sacrificed crucial aspects such as porosity and flexibility. Our innovative hybrid aerogel tackles this challenge by employing polymeric nanofibers and microfibers, establishing a dual-scale fibrillar network that harmonizes high strength, flexibility, and efficient shape recovery. This groundbreaking aerogel design holds substantial potential to revolutionize regenerative medicine, tissue engineering, and beyond. The entangled fibrillar network serves as both a mechanical support and a facilitator of cellular infiltration, paving the way for applications in load-bearing tissues. As we push the boundaries of aerogel capabilities, the implications for soft tissue engineering become increasingly profound.

In conclusion, our study introduces a paradigm shift in aerogel technology, laying the groundwork for further advancements in regenerative medicine. The hybrid aerogel's capacity to balance strength, flexibility, and cellular response demonstrates a significant advancement in overcoming limitations and unlocking unprecedented possibilities in the field.