Self-Healing Hydrogel Delivers Growth Factor to Keep Transplanted Fat Alive

Soft tissue defects caused by trauma, tumor removal, or congenital deformity remain one of the most stubborn challenges in reconstructive medicine, and a team of researchers in China now reports a material that could change how surgeons rebuild lost fat. Writing in the journal Materials Today Bio, the group describes an injectable, self-healing hydrogel built from two natural body constituents, gelatin and hyaluronic acid, that carries the growth factor b-FGF and a patient’s own fat tissue directly into the defect site. In experiments with rats, the composite dramatically improved the survival of transplanted fat, raising volume retention from under 2 percent with fat grafting alone to more than 58 percent when the growth factor was added. The result addresses a problem that has plagued plastic and reconstructive surgeons for decades: grafted fat often dies.

The scale of that problem is striking. Autologous fat grafting, in which fat is harvested from one part of the body and reinjected into another, is attractive because the material is biocompatible, easy to obtain, inexpensive, and causes minimal donor-site damage. Yet studies cited by the team indicate that simple fat grafting loses between 20 and 70 percent of its volume, largely because the transplanted tissue is starved of blood supply and suffers mechanical trauma during injection. Without rapid revascularization, adipocytes in the center of the graft suffocate and die, triggering necrosis, resorption, and the need for repeated procedures. Improving graft survival therefore requires not just keeping fat cells alive but encouraging new capillaries to grow into the tissue and prompting resident stem cells to become mature fat cells.

The researchers’ solution hinges on a well-known but powerful chemical reaction. They first oxidized hyaluronic acid with sodium periodate, converting some of its sugar units into aldehyde-bearing molecules, and separately grafted carbohydrazide onto gelatin. When the two modified polymers are mixed in water, the aldehyde groups on the oxidized hyaluronic acid react with the hydrazide groups on the gelatin to form hydrazone bonds, a dynamic covalent linkage produced through a Schiff base reaction. Because these bonds form and break reversibly under mild, body-friendly conditions, the resulting hydrogel is not a brittle solid but a resilient, self-repairing network. Spectroscopic analysis confirmed the chemistry: the aldehyde peak at 1735 wavenumbers vanished from the hydrogel spectrum while a new C=N stretching signal appeared, and nuclear magnetic resonance showed hydrazone proton signatures, verifying successful crosslinking.

After screening formulations at three concentrations and several mixing ratios, the team identified an optimal composition, labeled B1, containing 5 percent Gel-CDH and 2 percent OHA mixed one to one. This formulation gelled in just under 13 seconds, a speed the authors note is close to the roughly 10-second window considered ideal for clinical injectability, since material that sets too slowly can leak away from the target site. Scanning electron microscopy revealed an irregular, porous interior with pores averaging 116 micrometers and porosity near 84 percent, dimensions well suited to oxygen and nutrient exchange and to the survival of fat cells. The hydrogel’s compressive modulus measured 2.18 kilopascals, sitting comfortably within the 0.5 to 25 kilopascal range reported for native human adipose tissue, an important match because cells respond to the stiffness of their surroundings and differentiate best on matrices that mimic the target tissue.

The self-healing behavior is perhaps the most visually compelling property. When the team cut hydrogel samples in half and pressed the pieces back together, the material fused seamlessly within five minutes at room temperature, forming a single cohesive blob that could be lifted with tweezers without breaking. Rheological tests explained why: when the gel was strained beyond a critical threshold of 480 percent, its storage modulus dropped below its loss modulus and the network collapsed into a fluid, but once the strain was released the dynamic hydrazone bonds reformed and the gel recovered its original stiffness. The material also showed classic shear-thinning, meaning it flows easily under the pressure of a syringe and then rapidly regains its solid character once injected. Injected through a standard needle into heart-shaped, triangular, and square molds, the gel set into complete, well-defined shapes, demonstrating that it can conform precisely to the irregular cavities left by tumors or trauma.

Controlling the release of b-FGF was central to the design. Free growth factor is dangerous in excess, with the authors noting that too much b-FGF can cause tissue overgrowth or even tumorigenesis, while a burst release wastes the payload before new vessels can form. Encapsulated in the hydrogel, the growth factor was retained by dynamic crosslinking between its amino groups and the aldehyde groups of the oxidized hyaluronic acid. Release experiments showed a gentle profile: a modest initial phase over three days followed by a plateau, with cumulative release reaching 80 to 90 percent by day seven. The B1 formulation released about 40 percent on the first day and roughly 90 percent by the end of the week, a sustained supply the authors attribute to its larger pores and lower aldehyde content, which eased adsorption of the protein. Hydrogels of this kind, the team notes, can extend the half-life of growth factors and avoid the burst release and rapid proteolysis that plague free injections.

Safety testing produced consistently reassuring results. Rat adipose-derived stem cells cultured with the hydrogel and its precursors maintained viability above 90 percent throughout a week of observation, and by day seven the cells exposed to the full hydrogel actually proliferated slightly faster than untreated controls. Live-dead staining confirmed abundant healthy, spindle-shaped cells, and hemolysis assays showed that none of the materials damaged red blood cells, with hemolysis rates below 1 percent. When the hydrogel was injected under the skin of rats and monitored for three months, ultrasound tracking showed gradual degradation, from about 42 percent at ten days to more than 95 percent by day thirty for the B1 formulation, while histology of the implant site and of the heart, liver, spleen, lungs, and kidneys revealed no inflammation, necrosis, or organ abnormalities. Immunostaining for the inflammatory markers TNF-alpha and CD206 showed no significant differences from saline controls.

The decisive test combined the hydrogel, the growth factor, and autologous fat in living animals. Four groups of rats received subcutaneous injections: hydrogel alone, fat alone, fat in hydrogel, and fat in hydrogel with b-FGF. Four weeks later, the plain fat grafts had shriveled to a retention rate of just 1.92 percent of the original 4-milliliter volume, with histology showing enlarged, hypoxic adipocytes and extensive liquefactive necrosis. Fat embedded in the hydrogel fared far better, retaining 36.67 percent, while the addition of b-FGF pushed retention to 58.33 percent, with the grafts appearing soft, glossy, and threaded with visible surface vessels. Adipocyte diameters in the growth-factor group measured about 70 micrometers, squarely within the 60 to 110 micrometer range of normal mature fat cells, and the adipose tissue area reached nearly 77 percent of the graft, versus 38 percent for fat alone. Fibrosis also fell, dropping to about 15 percent of tissue area by four weeks.

Molecular evidence reinforced the picture. Immunofluorescence for the endothelial markers CD31 and CD34 showed steadily rising vascular density, peaking at roughly 3.8 to 3.9 percent in the growth-factor group at four weeks, significantly above all controls, indicating that new capillaries had grown both around and into the implant. Staining for PPAR-gamma, a master transcription factor that initiates fat-cell differentiation, and for Perilipin-1, the gold-standard marker of mature lipid-filled adipocytes, both climbed over time and were highest in the composite group. Reverse transcription PCR likewise showed marked upregulation of the angiogenic gene CD31 and the adipogenic genes AP-2, C/EBP-beta, and PPAR-gamma. Together these data trace a coherent sequence in which sustained b-FGF delivery first drives vessel formation and then supports the maturation of functional fat tissue, exactly the coupling the designers intended.

The authors are candid that longer follow-up is needed, noting that observation periods of eight to twelve weeks would establish whether the early gains translate into durable adipose regeneration, and the work so far rests on rat models rather than human trials. Even so, the study offers a compelling template: a hydrogel assembled in seconds from FDA-familiar building blocks, matched mechanically to native fat, capable of healing itself and conforming to any defect shape, and able to meter out a potent growth factor over a week. If the approach survives longer-term and larger-animal testing, it could shift fat grafting from a procedure plagued by unpredictable resorption toward a controlled regenerative therapy for breast reconstruction, facial restoration, and the many patients whose soft tissue defects currently outpace what surgery alone can rebuild.

Subject of Research: An injectable self-healing gelatin-hyaluronic acid hydrogel with slow-release b-FGF for adipose tissue regeneration

Article Title: Injectable self-healing polysaccharide hydrogel with slow-release b-FGF for adipose tissue regeneration

Article References: Wu, S., Shu, W., Zhu, X., Chen, Y. M., Liu, Z., Wang, Y., Song, H., Xiao, D., Zhai, C., Jiang, N., & Li, J. (2026). Injectable self-healing polysaccharide hydrogel with slow-release b-FGF for adipose tissue regeneration. Materials Today Bio, 41, Article 103739. https://doi.org/10.1016/j.mtbio.2026.103739

Image Credits: AI Generated

DOI: Not provided

Keywords: hydrogel, adipose tissue regeneration, b-FGF, fat grafting, tissue engineering, hyaluronic acid, gelatin, self-healing materials, drug delivery, angiogenesis, adipogenesis, soft tissue repair