Biologically-coupled bisphosphonate chaperones effectively deliver molecules to the site of soft tissue-bone healing.
J Orthop Res
; 41(10): 2250-2260, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37087676
ABSTRACT
Tendon injuries are common and often treated surgically, however, current tendon repair healing results in poorly organized fibrotic tissue. While certain growth factors have been reported to improve both the strength and organization of the repaired enthesis, their clinical applicability is severely limited due to a lack of appropriate delivery strategies. In this study, we evaluated a recently developed fluorescent probe, Osteoadsorptive Fluorogenic Sentinel-3 that is composed of a bone-targeting bisphosphonate (BP) moiety linked to fluorochrome and quencher molecules joined via a cathepsin K-sensitive peptide sequence. Using a murine Achilles tendon-to-bone repair model, BP-based and/or Ctsk-coupled imaging probes were applied either locally or systemically. Fluorescence imaging was used to quantify the resultant signal in vivo. After tendon-bone repair, animals that received either local or systemic administration of imaging probes demonstrated significantly higher fluorescence signal at the repair site compared to the sham surgery group at all time points (p < 0.001), with signal peaking at 7-10 days after surgery. Our findings demonstrate the feasibility of using a novel BP-based targeting and Ctsk-activated delivery of molecules to the site of tendon-to-bone repair and creates a foundation for further development of this platform as an effective strategy to deliver bioactive molecules to sites of musculoskeletal injury.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismos dos Tendões
/
Procedimentos de Cirurgia Plástica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Orthop Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos