Failed Experimental Samples? Don’t Throw Them Away!

In the journey of scientific exploration, every minute moment can spark the illumination of the unknown world. Today, we want to share a story about an “unexpected delight” – this is the second article from our EFL team to be published in the Nature series, and its inspiration came from a nearly forgotten “failure”.

It was an ordinary day in the lab, busy and orderly. We were freeze-drying a batch of 3D-printed hydrogel scaffolds and preparing to observe their internal morphology using a scanning electron microscope. Unexpectedly, due to a schedule change, the reserved equipment could only be used the next morning. To preserve the samples, we decided to temporarily store these lyophilized hydrogel scaffolds in a cell culture incubator, neglecting the high humidity inside. This small oversight unexpectedly became the key to unlocking a new discovery.
The next day, when we opened the incubator, the scene that greeted us was surprising: the freeze-dried hydrogel scaffolds, expected to be intact, had miraculously shrunk into a clump. At that moment, we were stunned and disappointed because the prepared experimental samples could not be used for scanning electron microscope observation, which would delay the progress of the experiment. Just as we were about to discard these samples, confusion and puzzlement flooded our minds. What caused these scaffolds to undergo such unprecedented shrinkage?
After dinner, we walked along the West Lake to alleviate the frustration of the failure of the experiment. We saw street vendors selling cotton candy, so we bought two and played with them while eating, even pretending to be old men with big mustaches by biting into them. Unexpectedly, it started to drizzle, and we went into a store to avoid the rain. At this moment, a miraculous scene occurred – the cotton candy, exposed to the light rain, clumped together and lost its fluffiness. That instant, I recalled the sensation of “melting in the mouth” when eating certain foods: crispy potato chips and shrimp crackers, fluffy cakes, and freshly popped popcorn… So that’s it! Like puffed food, freeze-dried hydrogel scaffolds have thousands of pores inside. Once exposed to a humid environment, their inherent hydrophilic properties rapidly bind water molecules, causing the pore walls to adhere to each other, leading to shrinkage!

As mentioned in the main text of the paper, we proposed the “lyophilization + dampening” hydrogel scaffold treatment method and applied it to the scenario combining hydrogel scaffolds with minimally invasive surgeries. Compared to hydrogel fluids or solid bulk without special topological structures, the macroscopic grid structure of 3D-printed hydrogel scaffolds provides a more extensive nutrition exchange network and growth space for cells in the body, accelerating tissue defect repair. However, traditional hydrogel scaffold implantation often requires larger skin incisions, leaving scars and causing significant bleeding. By first reducing the volume of the hydrogel scaffold through the “lyophilization + dampening” method and then injecting it subcutaneously through minimally invasive means using specially designed “BioBullet” and “BioGun”, these issues can be perfectly resolved. This strategy holds significant potential for clinical applications in the future.

Failure in scientific research is not the end but a bridge to the unknown. Every experimental sample that seems destined for discard and every seemingly useless experimental datum may hide clues leading to the next significant discovery. Therefore, when faced with seemingly failed experiments that cause confusion or even anger, please remember to pause, take a deep breath, and examine everything with an explorer’s heart. Maybe it is this inadvertent failure that is quietly writing the most exciting opening chapter of your scientific story. In the world of science, every minute detail is filled with infinite possibilities, waiting for us to discover and create.

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