Chinese Medical Journal Review unveils the potential of collagen-based micro/nanogels

Collagen-based microgels and nanogels are extremely small in size and consist of cross-linked polymer networks made of the protein collagen or its derivatives. They can function as a ‘delivery system’ that releases substances such as drugs at specifically targeted sites in the body. Now, researchers have published an in-depth review on the manufacturing processes, drug release mechanisms, and biomedical applications of these hydrogel systems, including wound repair and cancer treatment.

The term ‘hydrogel’ refers to three-dimensional cross-linked networks of polymers that are capable of absorbing and retaining large amounts of fluid. While hydrogels can be classified into different types based on their size, microgels (with a size of 1–1000 µm) and nanogels (< 1000 nm) are particularly relevant when it comes to biomedical applications like drug delivery. In addition, while there are numerous polymers available for manufacturing micro- and nanogels, collagen and its derivatives are considered especially important to this process.

Collagen is a structural protein that makes up the bulk of the extracellular matrix (a network that provides structural and biochemical support to other cells) in vertebrates. Collagen-based micro/nanogels are particularly valued for many reasons, such as their increased surface area, tunable degradation rates, and most importantly, their ability to specifically deliver drugs to sites of interest.

Now, a group of researchers from China have published a review article that takes an in-depth, detailed look at collagen-based microgels and nanogels – including the manufacturing technologies involved, their drug release mechanisms, and a wide variety of biomedical applications. This research led by Professor Yaqin Huang, Professor Shiqi Wang, and Professor Tengfei Yu, was made available online on April 22, 2025, and published in Volume 138 Issue 12 of the Chinese Medical Journal on May 20, 2025. “Although extensive reviews on micro/nanogels exist, they tend to cover a wide range of biomaterials and lack a specific focus on collagen-based materials”, says Professor Huang, explaining the team’s rationale for putting this review together.

First, the study tackles the various techniques (both physical and chemical) that can be used to create cross-links in these collagen-based materials, as well as manufacturing processes that are currently used to synthesize microgels and nanogels. These processes allow the size, shape, and mechanical strength of these micro/nanogels to be very precisely controlled, as these properties can affect their use in different biomedical applications.

A very interesting property of these micro/nanogels is their responsiveness to the environment – their sensitivity to enzymes, pH levels, and even temperature makes them ideal vehicles for controlled drug release under different conditions in the body. This review highlights different systems used for this controlled release, particularly micro/nanogels that can release their ‘cargo’ in response to specific enzymes or changes in pH levels. An example of how such a system can be used is in the case of antimicrobial treatment, since tissues affected by bacteria tend to have lower pH levels, this characteristic can be used for targeted drug release from hydrogels.

The review then focusses on some of the most promising applications of these micro/nanogels in the biomedical field. “The structural versatility of collagen-based micro/nanogels, combined with environmentally responsive drug release profiles, results in a wide range of therapeutic applications, from tissue regeneration to cancer treatment and diagnosis,” Professor Wang remarks, emphasizing the sheer versatility of these tiny delivery systems.

The authors highlight how collagen-based micro/nanogel delivery systems can be used to promote the regeneration of bone tissue by delivering drugs or even stem cells to the injured site. Wound repair is another such area which can immensely benefit from these micro/nanogels, as substances such as small-molecule drugs and even zinc ions can be delivered to accelerate the process of wound healing. Collagen-based micro/nanogels can even deliver materials such as fluorescent probes or contrast dyes, which are substances which allow for better detection of diseased tissues, and even visualization of processes such as tissue repair and regeneration. Another fascinating application of these delivery systems is in anticancer treatment. Collagen-based nanogels can be loaded with different anticancer drugs, such as doxorubicin and can be formulated in a manner that allows them to specifically target cancer cells.

Finally, the study concludes with a discussion of current limitations and the future of the field. Some challenges include the potential immune response to collagen (especially collagen derived from animals) and the large-scale production of these micro/nanogels. The authors conclude by emphasizing the need for translating this research into clinical practice, as these delivery systems will play an increasingly important role in health care.

“This comprehensive review serves as a valuable resource for researchers, clinicians, and scientists alike, providing insights into the current state and future directions of collagen-based micro/nanogel research and development,” Professor Yu concludes. We hope this study will serve as an invaluable resource for anyone who is interested in the biomedical applications of collagen-based microgels and nanogels!

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Reference

DOI: 10.1097/CM9.0000000000003611