Table 2 Overview of HDPs with respect to their expression patterns, biological functions, advantages and limitations

LL-37

· Macrophages

· Neutrophils

· NK cells

· Mast cells

· Monocytes

· lymphocytes

· Epithelial cells

· Disrupt bacterial walls/membranes (The models of membrane disruption proposed include aggregate, toroidal, barrel-stave, and carpet models)

· Inhibit internal targets (such as protein synthesis, DNA/RNA synthesis, translation, and protein folding)

· Recruit immunocytes (such as neutrophils, eosinophils, monocytes, and T cells)

· Induce apoptosis in some cell types (such as epithelial cells and regulatory T cells) and inhibit neutrophil apoptosis

· Induce Mast cell degranulation to enhance diapedesis

· Inhibit proinflammatory responses selectively

· Induce M1 macrophage switch and upregulate phagocytosis

· Facilitate angiogenesis and wound healing

· Induce cytokine and chemokine production (such as CXCL8, and CCL7)

· Adjuvant effects

· Powerful and broad-range immunomodulator functions

· Inflammation suppressive effects

· Prohealing effects

· Synergistic interaction with antibacterial agents

· Pro-osteogenic effects described

· Anti-biofilm/Antifungal/Antiviral activity

· Weak direct antibacterial effects

· Limited preclinical evidence for IAI prevention

· High cost of production

· Limited stability in vivo

· Limited tissue penetration

[165,166,167] [175,176,177]

Defensins

· Macrophages

· Neutrophils

· NK cells

· Mast cells

· Monocytes

· DCs

· Disrupt bacterial walls/membranes (The models of membrane disruption proposed include aggregate, toroidal, barrel-stave, and carpet models)

· Inhibit internal targets (such as protein synthesis, DNA/RNA synthesis, translation, and protein folding)

· Recruit immunocytes (such as neutrophils, eosinophils, monocytes, and T cells)

· Induce cytokine and chemokine production (such as CXCL8, IL-6, CCL2, and GM-CSF)

· Induce apoptosis in some cell types and inhibit neutrophil apoptosis

· Promote or inhibit inflammatory

· Promote or inhibit angiogenesis; promote wound healing

· Maintain gut homeostasis

· Form nanonets

· Adjuvant effects

· Powerful and broad-range immunomodulator functions

· Prohealing/angiogenic effects

· Synergistic interaction with antibacterial agents

· Antifungal/Antiviral activity

· Each type of defensins has a unique role in innate immunity

· Weak direct antibacterial effects

· Induce undesirable proinflammatory processes around the biomaterial.

· Unpredictable off-target effects

· Limited preclinical evidence for IAI prevention

· High cost of production

· Limited stability in vivo

· Limited tissue penetration

[165,166,167,168]