Immunomodulatory Biomaterials in Tissue Engineering

Immunomodulatory biomaterials represent a paradigm shift in tissue engineering by moving beyond inert scaffolds to active regulators of host immunity. These materials are engineered to present biochemical and biophysical cues that steer the innate and adaptive immune systems towards outcomes that favour tissue repair rather than chronic inflammation or fibrosis. Central to this approach is the control of macrophage phenotype, typically by promoting a transition from a pro-inflammatory (M1) state to a pro-healing (M2) state. Strategies include tailoring surface chemistry, topography, porosity and mechanical stiffness to influence cellular adhesion, cytokine release and extracellular matrix deposition. Emerging classes of materials—ranging from hydrogels and nanoparticle assemblies to hybrid protein–polymer constructs—are being leveraged to deliver immunomodulatory ligands, growth factors and even living cells in a spatially and temporally defined manner. By harnessing mechanobiological principles, such scaffolds can mimic native tissue mechanics and dynamically adapt to evolving wound environments. The global significance of this work is underscored by applications spanning skin, cardiac and musculoskeletal repair, as well as by the development of advanced in vitro models that better predict clinical outcomes. Taken together, immunomodulatory biomaterials offer a versatile platform for orchestrating the complex interplay between implanted constructs and host defence mechanisms.

Research from Nature Portfolio

Recent studies have revealed how precise physical control of scaffold architecture can direct immune cell behaviour. One investigation used cryoprotectant-mediated ice crystal growth to decouple pore size and stiffness in gelatin scaffolds, demonstrating that larger, stiffer pores bias macrophages towards an anti-inflammatory phenotype both in vitro and in vivo. Another report describes a reversible nanoassembly built on gold nanoparticles coated with bisphosphonate ligands and magnesium ions; this system enables on-demand attachment and detachment of macrophages and promotes their polarisation to a regenerative M2 state through dynamic presentation of adhesive moieties. Together, these works highlight the power of combining material design with mechanistic insight to create implants that actively engage and resolve host immunity.

Immunomodulatory Biomaterials in Tissue Engineering publication trend

The graph below shows the total number of articles in immunomodulatory biomaterials in tissue engineering across all publications each year (not limited to Nature Index journals).

Technical terms

Immunomodulatory biomaterials: Engineered materials that actively direct immune cell responses to enhance tissue repair.

Macrophage polarization: The process by which macrophages adopt distinct functional states (for example M1 or M2) in response to environmental cues.

Foreign body reaction: The host’s coordinated immune response, including inflammation and fibrous encapsulation, to implanted materials.

Porosity: The presence, size and interconnectivity of pores within a scaffold, influencing cell infiltration and nutrient transport.

Topography: The micro- and nanoscale surface features of a material that affect cell adhesion, morphology and function.

Mechanobiology: The study of how mechanical properties and forces influence cellular behaviour and fate.

References

1. Cryoprotectant enables structural control of porous scaffolds for exploration of cellular mechano-responsiveness in 3D. Nature Communications (2019).
2. Immunoregulation of macrophages by dynamic ligand presentation via ligand–cation coordination. Nature Communications (2019).
3. Therapeutic synthetic and natural materials for immunoengineering. Chemical Society Reviews (2024).
4. Precisely defined fiber scaffolds with 40 m porosity induce elongation driven M2-like polarization of human macrophages. Biofabrication (2020).
5. Immune Modulation by Design: Using Topography to Control Human Monocyte Attachment and Macrophage Differentiation. Advanced Science (2020).