Table 3.
Summary of the biomaterial‐based regulation strategies and the regulated metabolic pathways
| Regulation strategy | Biomaterials examples | Metabolic pathways | Cell function | Ref. |
|---|---|---|---|---|
| 1) Release of inherent metabolic regulator | ||||
| Ions | ||||
| Co2+‐doped bioactive glass | Enhanced HIF‐1α activity (oxygen homeostasis) | Improved hMSCs survival and elevated VEGF production | 76 | |
| Regulatory metabolite | ||||
| Citrate‐based biomaterials | Facilitated the metabolic switch from glycolysis to OXPHOS leading to elevated ATP level (energy and biosynthetic homeostasis) | Promoted the phenotype progression of osteo‐differentiation with high energy demand | 80 | |
| Calcium phosphate‐bearing matrix | Elevated ATP level by providing inorganic phosphate (energy homeostasis) | Induced osteogenic differentiation | 19 | |
| Poly (Ethylene Glycol) Hydrogel containing lactate | Reducing intracellular ROS after lactate entered cells (redox homeostasis) | Improved the cell survival and function of neural pro cells | 91 | |
| Oxygen | Sodium percarbonate (SPO), and PDMS–CaO2 | Attenuated HIF‐1α accumulation under hypoxia (oxygen homeostasis) | Maintained contractility of resting skeletal muscle and under hypoxic environment | 97, 100 |
| 2) Biochemical cues | ||||
| Antioxidant properties | ||||
| poly (octamethylene citrate ascorbate) (POCA) enabling radical scavenging and iron chelation | Reduced intracellular oxidative stress (redox homeostasis) | Prolonged the viability of endothelial cells in expose to H2O2 and during rapid intracellular ROS generation | 93 | |
| Alginate/cerium oxide nanoparticles composite | Reduced intracellular oxidative stress (redox homeostasis) | protected the islet cells from oxidative damages | 107 | |
| Cell adhesivity | ||||
| Thin films of alternately layered polyelectrolytes that are biocompatible but provides poor adhesivity | Increased metabolic stress displayed as accelerated mitochondria activity (energy homeostasis) | Diffuesd organization of the actin cytoskeleton and stunted fibroblast proliferation | 102 | |
| Chemical composition | ||||
| Graphene and graphene oxide nanosheets | Disrupting mitochondria ETC and downregulating TCA cycle enzymes (energy homeostasis) | Disrupting cytoskeletal assembly and inhibitng cancner cell migration | 103 | |
| 3) Biophysical cues | ||||
| Surface topography | ||||
| PDMS surface containing grooves (spacing of 1 µm, depth of 250 or 500 nm) | Enhanced ATP‐producing mitochondrial activity (energy homeostasis) | Enhanced astrocytes excitability via ATP signaling | 114 | |
| Titanium surface with micropillars (5 µm × 5 µm × 5 µm, spacing of 5 µm) | Reduced ATP and increased ROS level due to the attempted phagocytosis (energy and redox homeostasis) | Impaired osteoblast function | 115 | |
| Surface stiffness | ||||
| Collagen matrix with increasing stiffness by altering matrix density | Promoted the shift toward a more glycolytic phenotype (energy and biosynthetic homeostasis) | Increased cancer cell invasiveness | 116, 117 | |
| Self‐assembly nanofibrillar hydrogel with rigid substrate (32 KPa) | Facilitated the consumption of exogenous cholesterol sulfate for steroid biosynthesis (biosynthetic homeostasis) | Stimulated the osteogenic differentiation | 113 | |
| Self‐assembly nanofibrillar hydrogel with rigid substrate (13 KPa) | Facilitated the consumption of exogenous lysophosphatidic acid for glycerolipid biosynthesis (biosynthetic homeostasis) | Stimulated the chrondrogenic differentiaion | 113 | |