Table 1.

Summary of the research studies on NP–hydrogel composites for tissue engineering applications.

Tissue Regeneration	Nanoparticles	Scaffolds	Synthesis Method	Cell Line/Animal Tested	Effect of NPs Addition on the Physical Property of Material	Effect of NPs Addition on the Biological Property of Material	Reference
Soft Tissues	Collagen-coated Ag NPs	Collagen	Crosslinking of the hydrogel in NPs/polymer mixture	Primary human epidermal keratinocytes; Dermal fibroblasts; Mice	Hydrogel containing 0.2 µM Ag NPs has similar Young’s modulus as human skin	Biocompatibility, anti-inflammatory, and anti-bacterial activities	[71]
	Ag NPs	Poly(hydroxyethyl methacrylate)	In situ synthesis of NPs during hydrogel formation	Mouse embryo fibroblasts (NIH-3T3); BALB/c female mice	Increased amounts of Ag NPs loading slightly enhanced the compressive modulus of hydrogel	Biocompatibility, anti-bacterial, and in vivo resistance to foreign-body reactions	[68]
	Ag NPs	Hydroxyethyl cellulose	Crosslinking of the hydrogel in NPs/polymer mixture	Human fibroblasts	Glass transition temperature of scaffold increases as concentration of AgNO3 increases	Biocompatibility	[70]
	Ag NPs & Ag-Palladium NPs	Chitosan/Hydroxyapatite & Chitosan/Beta-tricalcium phosphate	Crosslinking of hydrogel in NPs/polymer mixture	Normal skin fibroblasts (BJ1); Hepatocellular carcinoma cells (HEPG2); Breast cancer cells (MCF7);	N/A	Biocompatibility and anti-bacterial activity	[69]
	Chitosan-coated Ag NPs	Agarose	Crosslinking of the hydrogel in NPs/polymer mixture	Human cervical carcinoma cells (HeLa); Human pancreatic epithelial carcinoma cells (MiaPaCa2); Human embryonic kidney cells (HEK);	Mechanical strength (five to eight Mpa) falls within range for soft tissue engineering	Biocompatibility, anti-bacterial activity, and hemocompatibility	[72]
	Au NPs	Alginate	Crosslinking of the hydrogel in NPs/polymer mixture	Human umbilical vein endothelial cells (HUVECs)	N/A	Enhanced HUVECs adhesion rate and cell spreading	[74]
	Au NPs	Collagen	Conjugation of Au NPs to collagen fibrils	Swine	Enhanced longevity of the material	Biocompatibility and low irritation	[73]
Bone Tissues	Ag NPs	α-chitin and β-chitin/Bioactive glass ceramic NPs	Crosslinking of hydrogel in NPs/polymer mixture	Human periodontal ligament cells (hPDL); Human primary osteoblasts (POB)	Composite scaffold has decreased porosity and enhanced compressive strength.	Anti-bacterial activity, differentiation, and mineralization of POB in the absence of osteogenic supplements	[78]
	Ag NPs	Poly (ethylene glycol)	In situ synthesis of NPs within the hydrogel matrix	Osteoblast cells (MC3T3-E1); Sprague–Dawley rats	N/A	Anti-bacterial activity, promoted osteogenesis in vitro and in vivo	[75]
	Ag NPs	Methacrylate	Crosslinking of hydrogel in NPs/polymer mixture; diffusion reaction; adsorption of NPs	Osteoblast cells (MC-3T3)	No effect on mechanical properties (absorption method)	Biocompatibility and anti-bacterial activity (absorption method)	[76]
	Au NPs	Chitosan/Pectin	Crosslinking of the hydrogel in NPs/polymer mixture; diffusion reaction; adsorption of NPs	Normal kidney epithelial cells (VERO); Epithelial colorectal adenocarcinoma cells (HT-29); HPV-16 positive human cervical tumor cells (SiHa); Kidney epithelial cells (LLCMK2); Murine macrophage cells (J774A1 cells); Mouse preosteoblastic cells (MC3T3-E1)	Gelation temperature decreases with decrease in pectin concentration and increase in Au NPs levels	Biocompatibility and promoted growth of MC3T3-E1 cells	[77]
	Au NPs	Gelatin	Crosslinking of the hydrogel in NPs/polymer mixture	Human adipose-derived stem cells (ADSCs); New Zealand Rabbit	N/A	Biocompatibility, promoted differentiation toward osteoblast cells, and improved bone regeneration in vivo	[80]
	N-acetyl cysteine-Au NPs	Gelatin-tyramine	Crosslinking of hydrogel in NPs/polymer mixture	Human adipose derived-stem cells (hASCs)	N/A	Biocompatibility and promoted osteodifferentiation	[81]
	Ag and Au NPs	Silk fibroin/Nanohydroxyapatite	In situ synthesis of NPs within the hydrogel matrix	Osteoblast-like cells (MG63)	Hydrogels containing Ag and Au NPs have enhanced mechanical stiffness	Biocompatibility and anti-bacterial activity	[16]
Cardiac Tissues	Peptide-modified Ag and Au NPs	Collagen	Crosslinking of the hydrogel in NPs/polymer mixture	Neonatal rat ventricular cardiomyocytes and cardiac fibroblasts	Enhanced mechanical and electrical properties of the material	Promoted reparative macrophage migration	[87]
	Au NPs	Decellularized omental matrices	Evaporation of Au for deposition	Neonatal rat ventricular cardiomyocytes, Cardiac fibroblasts	Au NPs patches have enhanced conductivity and similar longitudinal elastic modulus as pristine patches	Aligned cardiac cells with organized connexin 43 and attenuation of fibroblast proliferation	[84]
	Au NPs	Thiol 2-hydroxyethyl methacrylate (HEMA)/HEMA	In situ synthesis of NPs within the hydrogel matrix	Neonatal rat ventricular cardiomyocytes	Conductive hydrogel has tunable conductive and mechanical property, with Young’s modulus similar to myocardium	Increased expression of connexin 43	[86]
	Chitosan-modified Au NPs	Chitosan	Crosslinking of the hydrogel in NPs/polymer mixture	Mesenchymal stem cells	Tunable electrical conductivity of the hydrogel by different concentration of Au NPs	Biocompatibility, enhanced differentiation into cardiac lineages	[91]
	Au nanorods	Gelatin methacrylate	Crosslinking of the hydrogel in NPs/polymer mixture	Neonatal rat ventricular cardiomyocytes	Enhanced mechanical and electrical properties of the material	Enhanced formation of cardiac tissues	[88,89]
	Au nanorods	Gelatin methacryloyl	Crosslinking of the hydrogel in NPs/polymer mixture (3D bioprinting)	Neonatal rat ventricular cardiomyocytes and cardiac fibroblasts	Nanocomposite bioink has increased shear-thinning effect and enhanced printability	Enhanced cell adhesion and organization, electrical propagation, and synchronized contraction	[90]