Definition and Concept
The term “mechanobiomaterials” was proposed to describe biomaterials designed to engage with living tissues through mechanical interactions rather than passive biochemical compatibility (Lin et al., 2024, Sui et al., 2024), a new class of biomaterials designed to actively engage mechanobiological principles to enhance tissue regeneration.
The authors discussed how materials can be engineered to deliver mechanical cues—such as stiffness, viscoelasticity, and dynamic stress—to modulate cellular behaviors including adhesion, proliferation, and differentiation. They highlighted that these materials interact with cells through mechanotransduction pathways involving integrins, focal adhesions, and the cytoskeleton, thereby directing regenerative outcomes in a controlled manner.
These materials are engineered to modulate cellular behavior via mechanotransduction, translating physical cues—such as stiffness, strain, or topography—into biological responses that promote tissue regeneration and homeostasis, definitely it is a smart, adaptive biomaterials capable of mimicking native tissue mechanics, responding to biological feedback, and promoting functional regeneration in bone, muscle, and soft tissues.
According to Lin et al. (2024), mechanobiomaterials are “biomaterials with precisely programmed mechanical properties capable of regulating the biomechanical environment of living tissues to restore or regenerate structure and function.” Their effectiveness relies on their ability to respond dynamically to mechanical stimuli in vivo, adapting to local loading and promoting regeneration through controlled mechanosensitive signaling.
In this paradigm, the mechanical behavior of the biomaterial—elasticity, viscoelasticity, or dynamic stiffness—is as crucial as its chemical composition (Özkale et al., 2020). Mechanobiomaterials thus merge materials science and cellular mechanobiology into a unified regenerative strategy.
Mechanobiological Background
Mechanotransduction is the process by which cells sense and respond to mechanical forces through molecular complexes that connect the extracellular matrix (ECM) to the cytoskeleton (Özkale et al., 2020). Key players are integrins, focal adhesion kinases (FAK), YAP/TAZ, and the Rho/ROCK pathway, which together convert physical forces into transcriptional programs controlling proliferation, differentiation, and apoptosis (Rajendran et al., 2023).
When a mechanobiomaterial is implanted, its mechanical parameters (stiffness, strain distribution, viscoelasticity) modulate these pathways, guiding the fate of resident or stem cells. For example, high substrate stiffness promotes osteogenic differentiation, whereas lower stiffness supports myogenic or neurogenic lineages (Velasco et al., 2015).
In regenerative medicine, this concept underlies the need for biomaterials that can replicate or restore the mechanical microenvironment of healthy tissue (Donati et al., 2024).
Material Design and Functional Principles
Mechanobiomaterials are designed according to several mechanical and structural principles:
- Tunable Elastic Modulus:
The scaffold stiffness must match or modulate that of the target tissue to elicit optimal cell responses. Soft materials (<10 kPa) mimic neural or adipose tissue, while stiffer scaffolds (100 kPa–1 GPa) promote osteogenesis (Velasco et al., 2015). - Dynamic and Stimuli-Responsive Mechanics:
Mechanobiomaterials may change stiffness under load or time, allowing dynamic adaptation to tissue regeneration phases (Özkale et al., 2020). For instance, hydrogels with reversible crosslinking or piezoelectric polymers can stiffen during load and relax afterward, mimicking physiological mechanoadaptation. - Architectural Guidance:
Micro- and nano-patterns (porosity, fiber alignment) orient cell growth and cytoskeletal tension (Rajendran et al., 2023).
Scaffold architecture also determines how mechanical forces are transmitted to the cells (Donati et al., 2024). - Surface Chemistry and Bioactivity:
Integrin-binding ligands (RGD, fibronectin-mimetic peptides) and bioactive coatings complement mechanical stimulation by enhancing adhesion and cytoskeletal coupling (Donati et al., 2024).
Materials Used as Mechanobiomaterials
Natural and Synthetic Polymers
Natural polymers (collagen, gelatin, chitosan) exhibit high bioactivity but limited mechanical tunability. Synthetic polymers—such as polylactic acid (PLA), polycaprolactone (PCL), polyethylene glycol (PEG), and polyamides (PA)—enable precise control of mechanical stiffness and degradation kinetics (Donati et al., 2024).
Hydrogels
Hydrogels such as GelMA, alginate, and polyacrylamide can mimic the viscoelasticity of soft tissues while transmitting mechanical signals. Mechanically activated hydrogels may also release growth factors upon deformation, creating a feedback loop between force and biochemical signaling (Özkale et al., 2020).
Nanocomposites and Hybrid Systems
Hybrid composites combining polymers with bioactive ceramics (e.g., hydroxyapatite, bioactive glass) or nanocarbon components (graphene, CNTs) enhance stiffness and mechanical signaling through stress distribution at the nano-scale (Velasco et al., 2015).
Smart and Active Materials
Mechanically active polymers—such as shape-memory, magnetoactive, or piezoelectric materials—generate or transform mechanical and electrical stimuli in situ. They can transmit controlled physical forces to tissues, thus promoting mechanically guided regeneration (Rajendran et al., 2023).
Polyamides as Mechanobiomaterials
Polyamides (PAs) are synthetic polymers characterized by amide linkages (-CONH-) that confer high mechanical strength, chemical stability, and tunable elasticity.
They have been used in medical devices for decades (sutures, membranes, meshes) and more recently explored as structural scaffolds for bone and soft tissue engineering due to their balance between toughness, processability, and biocompatibility (Worch et al., 2020).
Mechanobiological Properties
- Tunable stiffness: Polyamide 6 (PA6) and Polyamide 66 (PA66) can achieve Young’s moduli from 1 to 4 GPa, providing a mechanically favorable environment for osteogenesis (Xu et al., 2010).
- Fatigue resistance: Unlike brittle ceramics, polyamides tolerate cyclic loading, allowing the transmission of physiological micro-strain to bone cells, enhancing mechanotransduction (Zeng et al., 2024).
- Surface modification: PA scaffolds can be functionalized with calcium phosphates or collagen to improve cell adhesion while preserving mechanical function (Paari-Molnar et al., 2025).
Experimental Studies
- Xu et al. (2010) developed porous nanohydroxyapatite/polyamide 66 (n-HA/PA66) scaffolds, showing new bone ingrowth and early osteointegration in rabbit models.
- Zeng et al. (2024) used 3D-printed n-HA/PA66 scaffolds to achieve optimized pore geometry and stiffness gradients, promoting osteogenic differentiation and vascularization in bone defects.
- Worch et al. (2020) synthesized stereochemically tunable polyamides with shape-memory behavior, enabling implantable biomaterials capable of dynamic stiffness modulation. These materials can store mechanical energy and release it gradually, reproducing physiological mechanical adaptation.
- Paari-Molnar et al. (2025) described 3D-printed medical-grade polyamides as a new class of customizable mechanobiomaterials for craniofacial and orthopedic applications, emphasizing the integration of biomechanical performance with geometric precision.
Mechanisms of Action in Mechanobiology
Polyamide-based scaffolds influence tissue regeneration through force transmission and cell mechanosensing.
Mechanical loads applied to the scaffold are transmitted through the ECM–integrin–cytoskeleton axis, activating intracellular pathways (FAK, YAP/TAZ, RhoA/ROCK) that regulate osteogenic and fibrogenic gene expression (Velasco et al., 2015; Rajendran et al., 2023).
The pore architecture and mechanical heterogeneity of PA66 scaffolds generate local strain gradients, promoting cell alignment and matrix mineralization (Zeng et al., 2024).
In soft-tissue applications, elastic polyamide derivatives (Worch et al., 2020) provide cyclical micromechanical stimulation that enhances angiogenesis and fibroblast proliferation.
Applications
Mechanobiomaterials—including polyamide-based ones—have been investigated in several regenerative contexts:
- Bone regeneration: n-HA/PA66 scaffolds demonstrated effective osteointegration and bone remodeling in animal models (Xu et al., 2010; Zeng et al., 2024).
- Craniofacial and orthopedic implants: 3D-printed PA66 scaffolds provide load-bearing capacity and mechanical adaptability for mandibular or calvarial defects (Paari-Molnar et al., 2025).
- Musculoskeletal tissue: shape-memory polyamides provide dynamic elastic cues for tendon and ligament regeneration (Worch et al., 2020).
- Future prospects: integration of smart polyamides with embedded sensors could enable self-adaptive mechanobiomaterials that modulate stiffness in real time.
Conclusion
Mechanobiomaterials embody a new regenerative strategy that leverages mechanical signaling to guide biological repair.
Within this paradigm, polyamides—particularly PA66 and its modern stereochemically tunable variants—represent a promising material class because they combine mechanical robustness, adaptability, and biocompatibility.
Future research should focus on:
- developing dynamic polyamide composites that can alter stiffness with time or strain,
- integrating piezoelectric or magnetic coupling for active mechanostimulation, and
- advancing in vivo mechanistic studies correlating scaffold mechanics, mechanotransduction, and functional tissue outcomes.
References
- Shi, H., & Lv, J. (2024). Mechanobiomaterials: Harnessing mechanobiology principles for regenerative medicine. Materials Today, 57: 32–43. –
- Lin X., et al. (2024). Mechanobiomaterials: Harnessing mechanobiology to drive material–tissue mechanical interactions. Bioactive Materials, in press. ScienceDirect
- Özkale B., et al. (2020). Active biomaterials for mechanobiology. Acta Biomaterialia, 113: 23–45. PMC7719094
- Donati L., et al. (2024). Mechanically Tunable Polymers for Regenerative Medicine. International Journal of Molecular Sciences, 25(19): 10386. DOI: 10.3390/ijms251910386
- Rajendran A.K., et al. (2023). Trends in mechanobiology-guided tissue engineering and regenerative medicine. Biomaterials Research, 27: 37. DOI: 10.1186/s40824-023-00393-8
- Velasco M.A., Narváez-Tovar C.A., Garzón-Alvarado D.A. (2015). Design, Materials, and Mechanobiology of Biodegradable Scaffolds for Bone Tissue Engineering. BioMed Research International, 2015: 729076. PMC4391163
- Worch J.C., Weems A.C., Yu J., et al. (2020). Elastomeric polyamide biomaterials with stereochemically tunable mechanical properties and shape memory. Nature Communications, 11: 3250. DOI: 10.1038/s41467-020-16945-8
- Xu Q., et al. (2010). Tissue engineering scaffold material of porous nanohydroxyapatite/polyamide 66 (n-HA/PA66). Journal of Biomedical Materials Research Part A, 94(3): 658–666. PMC2875726
- Zeng Z., et al. (2024). 3D printed nanohydroxyapatite/polyamide 66 scaffolds with mechanical gradient for bone regeneration. Composites Part B: Engineering, 285: 110213. ScienceDirect
- Paari-Molnar E., et al. (2025). Biomedical Applications of 3D-Printed Polyamide. Macromolecular Materials and Engineering, 350(2): 240019. DOI: 10.1002/mame.202500156
