LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration.
Ye. Peng P; Yang. Yusheng Y; Qu. Ying Y; Yang. Wenxin W; Tan. Jiulin J; Zhang. Chengmin C; Sun. Dong D; Zhang. Jie J; Zhao. Weikang W; Guo. Shuquan S; Song. Lei L; Hou. Tianyong T; Zhang. Zehua Z; Tang. Yong Y; Limjunyawong. Nathachit N; Xu. Jianzhong J; Dong. Shiwu S; Dou. Ce C; Luo. Fei F
Key Findings
- A freeze‑dried scaffold containing LL‑37 and pamidronate can be made with a porous structure suitable for bone cells.
- The scaffold showed strong antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa in vitro.
- In a mouse model of infected bone defects, the scaffold reduced bacterial load and inflammation while promoting bone regeneration.
- RNA sequencing revealed gene expression changes linked to bone healing and immune modulation.
Practical Outcomes
- For DIY biohackers, the main takeaway is that LL‑37 is a potent antimicrobial that can work locally when embedded in a material, but there’s no simple way to apply this now. Pamidronate’s anti‑resorptive effect is confirmed in this context. More research is needed before any at‑home protocols can be devised.
Summary
Researchers built a 3‑D bone‑repair scaffold that mixes silk, chitosan, tiny bone‑like particles, the antimicrobial peptide LL‑37, and the drug pamidronate. In lab tests and mouse experiments the scaffold killed common bone‑infection bacteria, cut inflammation, and helped new bone grow. The study shows the combo works together, but it’s still early‑stage and not ready for personal use.
Abstract
This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.
Study Information
pubmed
2024
2024-07-25T00:00:00.000Z
10.1016/j.ijbiomac.2024.134091
9
70