Cell loaded hydrogel containing Ag‐doped bioactive glass–ceramic nanoparticles as skin substitute: Antibacterial properties, immune response, and scarless cutaneous wound regeneration

Abstract

An ideal tissue-engineered dermal substitute should possess angiogenesis potential to promote wound healing, antibacterial activity to relieve the bacterial burden on skin, as well as sufficient porosity for air and moisture exchange. In light of this, a glass-ceramic (GC) has been incorporated into chitosan and gelatin electrospun nanofibers (240-360 nm), which MEFs were loaded on it for healing acceleration. The GC was doped with silver to improve the antibacterial activity. The bioactive nanofibrous scaffolds demonstrated antibacterial and superior antibiofilm activities against Gramnegative and Gram-positive bacteria. The nanofibrous scaffolds were biocompatible, hemocompatible, and promoted cell attachment and proliferation. Nanofibrous skin substitutes with or without Ag-doped GC nanoparticles did not induce an inflammatory response and attenuated LPS-induced interleukin-6 release by dendritic cells. The rate of biodegradation of the nanocomposite was similar to the rate of skin regeneration under in vivo conditions. Histopathological evaluation of full-thickness excisional wounds in BALB/c mice treated with mouse embryonic fibroblasts-loaded nanofibrous scaffolds showed enhanced angiogenesis, and collagen synthesis as well as regeneration of the sebaceous glands and hair follicles in vivo.

Bioceramic materials with ion‐mediated multifunctionality for wound healing

“…can be integrated into their flexible glass network to improve the biological properties of BG such as angiogenesis, osteogenesis, and antibacterial effects. 25,27,30,33,[51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] The biological responses to ionic dissolution products of BGs are schemed in Figure 2. 26 Generally, the metallic ions are important components of many enzymes and function as cofactors that stimulate metabolic reactions associated with cell signaling pathways during tissue regeneration.…”

Gelatin and Bioactive Glass Composites for Tissue Engineering: A Review

“…Sharifi et al [ 23 ] reported the use of silver, obtained the bioactive glass 45S5-Ag and incorporated it into scaffolds based on gelatin, chitosan and polyethylene oxide. Biological tests showed antibacterial activity against gram-positive and gram-negative species for samples containing BG-Ag (~36 nm particles), in addition to an improved regenerative response.…”

“… Images obtained by scanning electron microscopy (SEM) of the scaffolds used for 24 h culture of fibroblasts: chitosan, gelatin and PEO matrix ( a ), polymeric matrix modified by BG ( b ) and polymeric matrix combined with BG-Ag ( c ). Adapted from Sharifi et al [ 23 ]. …”

“…Regarding soft tissue applications, the gelatin/BG combination has accelerated wound closure, stimulating increased angiogenesis and granulation [ 23 ]. This is due to the presence of bioactive ions capable of reducing the inflammatory response and stimulating the secretion of proteins and growth factors [ 24 ].…”

“…For example, the presence of Si promotes an upregulation in the expression of vascular endothelial growth factor (VEGF), and the difference between the results achieved only with the polymeric matrix after the addition of BG is evident [ 25 ]. In this scenario, there are many possibilities for the application of products based on gelatin and BG including: treatment of subcutaneous and cutaneous lesions [ 23 , 26 ], chronic wounds [ 27 ], nerve regeneration [ 28 ], muscles [ 29 ], cartilage [ 30 ] and others.…”