Table 1 New Developments related to AMP research against Bone and Joint Infections

Engineered chimeric bifunctional peptides (TiBP1-GGG-AMP, and TiBP2-GGG-AMP)

• Two bi-functional chimeric peptides synthesized with an aim to strongly bind to titanium substrate (high affinity) while retaining antimicrobial motif free.

• Significant reduction in bacterial adhesion and colonization of S. aureus, S. mutans and E. coli as tested.

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OP-145 incorporated into Polymer-Lipid Encapsulation Matrix (PLEX)-coating

• Breij and co-workers incorporated a synthetic peptide OP-145 into PLEX coating to obtain high peptide levels for prolonged periods at the implant-tissue interphase.

• PLEX coated nails inserted into rabbits inoculated with S. aureus.

• Result showed sustained release of OP-145 from plex coatings into the joint space and around the nails.

• Effective resolution of induced infection in 67% of test animals within 28 days as shown by culture tests.

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Five Artificial Peptides synthesized from optimized peptide library

• Bormann and co-researchers synthesized short artificial AMPs using solid phase peptide library.

• Later, studied their anti- biofilm potency and their effect on human osteoblast cells.

• Peptides showed marked reduction in biofilm formation by S. aureus, E.coli, P. aeruginosa, MRSA and MSSA strains as tested by microcalorimetry and FISH.

• Peptides able to significantly reduce internalization of bacteria within osteoblast cells with no effect of viability of human osteoblast cells.

[115]

Novel in house designed potent ultrashort AMP i.e RBRBR

• Research team developed novel in house designed potent ultrashort AMP i.e RBRBR and encapsulated it in chitosan based nanoparticles using ionotrophic gelation method (RBRBR-CS-NP).

• Encapsulated peptide showed progressive sustained release till 14 days.

• Signficant decrease in S. aureus counts by three log counts with 98% inhibition of biofilm formation.

• No toxicity against mammalian cells and human erythrocytes.

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LL-37

• Kang and co-researchers developed 24 hour S. aureus biofilm on cobalt chromium discs followed by treatment with LL-37, AgNP’s and conventional antibiotics combinations.

• LL-37 effective in decreasing counts of S. aureus by as high as four log reduction in CFU and this was even more than combination groups i.e AgNP’s and rifampin and even combination of gentamycin and rifampin.

• Potential application of LL-37 against bone and joint related biofilm mediated infections strongly advocated.

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HHC36 peptides

• Chen and co-workers developed a Pandora box approach i.e a novel system promoting on demand release of AMP in and around the affected joint area and implant when bacterial infection occurs and lowers the surrounding pH.

• This Pandora box was loaded with HHC36 peptide inside the specially designed titania nanotubes (Ti-NTs) nanotubes and “closed” (surface-modified) with a pH-responsive molecular gate.

• The poly (methacrylic acid) (PMAA) swelled under normal conditions (pH 7.4) and collapsed under bacterial infection when pH drops below 6.0 allowing release of AMPs to kill bacteria immediately.

• This approach exhibited excellent activity against MRSA, E. coli, P. aeruginosa thus representing a novel smart drug delivery technology worth exploring.

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Romo1-Derived Antimicrobial Peptide (AMPR-11)

• Lee and team developed AMPR-11, the antimicrobial peptide (AMP) derived from mitochondrial nonselective channel Romo1.

• Peptide represents a novel class of fast acting AMP exhibiting broad spectrum antibacterial activity against range of clinical pathogens and multi-drug resistance (MDR) strains.

• Exhibits unique mechanism of killing which includes bacterial membranes by interacting with cardiolipin and lipid A.

• Exhibited significant activity against intracellular invading bacteria and superior in vivo efficacy in murine model of sepsis.

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