New Breakthrough! Milk Transforms into “Living Material” in Seconds, a Novel Biogel is Born
Release time:
2025-08-21
The top - tier international materials journal Matter has published online the groundbreaking research findings of a joint team from Columbia University and the University of Padua. This study is the first to systematically disclose how to utilize bovine - derived extracellular vesicles (EVs) extracted from yogurt whey, a by - product of milk processing, to construct bioactive injectable hydrogels with dynamic cross - linking properties. This innovative technology offers a new paradigm for resolving the dual challenges of “injectability” and “maintenance of biological activity” in the field of tissue engineering.
Matter: Milk Vesicles Unlock New Potential in Biomaterials
Traditional biomaterials often face a difficult choice. Synthetic polymer materials possess good mechanical properties but lack the ability to regulate biological signals. Natural biomaterials contain active ingredients but are difficult to deliver stably. Professor Artemis Margaronis, the leader of the research team, pointed out, “The milk vesicles we discovered are like nanorobots pre - installed with repair programs. The hundreds of bioactive molecules naturally carried on their surfaces can precisely regulate the immune response and the tissue regeneration process.” Data shows that approximately 10¹³ highly active EVs can be extracted from each liter of yogurt whey, with a yield 100 times that of traditional cell culture sources, and the extraction cost is only one - thousandth of the latter.
Microstructure Design: Building an Intelligent Hydrogel Matrix
The research team successfully overcame the problem of stable combination between EVs and biomaterials by precisely controlling the microstructure of the polymer hydroxypropyl methylcellulose (HPMC). Experimental data indicates that with HPMC material modified by a 16 - carbon long chain (C16), only 1/50 of the traditional amount of EVs is required to form a stable hydrogel with a three - fold increase in storage modulus. This “hydrophobic interaction enhancement effect” enables the material to maintain injection flexibility while achieving mechanical strength close to that of natural cartilage.
What is even more remarkable is the universal breakthrough in material design. By systematically optimizing the degree of polymer functionalization (hydrophobic modification ratio from 0.32 to 0.52 mmol/g) and concentration parameters (optimal 3% HPMC), the research team demonstrated that this technical approach can be extended to artificial cell - derived vesicles (ACDVs) from sources such as E. coli and melanoma cells. “We established a synergistic enhancement mechanism between EVs and polymers. EVs not only act as cross - linkers, but their 'macromolecular crowding effect' can also strengthen the network structure,” explained Dr. Caterina Piunti, the first author.
Efficacy Verification: Spontaneous Vascular Network Formation Rewrites Repair Rules
In a subcutaneous implantation experiment in mice, the novel EV hydrogel exhibited astonishing tissue repair capabilities. During the 7 - day observation period, a three - dimensional network containing CD34⁺ nascent blood vessels and CD31⁺ mature blood vessels formed inside the hydrogel, with the blood vessels infiltrating more than 500 microns into the material. Immunohistochemical analysis revealed that the material specifically recruited regulatory T cells expressing FOXP3, which can effectively inhibit excessive inflammation and guide the directional growth of blood vessels.
Compared with traditional liposome hydrogels, the EV hydrogel group showed a 3.2 - fold increase in blood vessel density and a 47% reduction in the level of the inflammatory factor IL - 6. More importantly, the material demonstrated progressive degradation in the body and was completely transformed into new tissue after 28 days without fibrotic encapsulation. “We observed that the hydrogel is like a miniature vascular incubator. It not only provides physical support but also remodels the repair microenvironment through the continuous release of biological signals,” emphasized Professor Margaronis.
This breakthrough technology is opening up new horizons in regenerative medicine. In the treatment of diabetic ulcers, hydrogels with customizable stiffness can meet the repair needs of different tissues. In orthopedic applications, gels loaded with specific EVs can promote the directional differentiation of bone cells. Immunomodulatory formulations are expected to revolutionize the treatment strategies for autoimmune diseases. With the optimization of large - scale production processes, this “living biomaterial” derived from milk may propel tissue engineering into a new era of precise repair.
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