{"doi":"10.3389/fbioe.2024.1308161","title":"Novel bisphosphonate-based cathepsin K-triggered compound targets the enthesis without impairing soft tissue-to-bone healing","abstract":"Background: Osteoadsorptive fluorogenic sentinel 3 (OFS-3) is a recently described compound that contains a bone-targeting bisphosphonate (BP) and cathepsin K (Ctsk)-triggered fluorescence signal. A prior study in a murine Achilles repair model demonstrated its effectiveness at targeting the site of tendon-to-bone repair, but the intrinsic effect of this novel bisphosphonate chaperone on tendon-to-bone healing has not been previously explored. We hypothesized that application of this bisphosphonate-fluorophore cargo conjugate would not affect the biomechanical properties or histologic appearance of tendon-bone repairs. Materials and Methods: Right hindlimb Achilles tendon-to-bone repair was performed on 12-week old male mice. Animals were divided into 2 groups of 18 each: 1) Achilles repair with OFS-3 applied directly to the repair site prior to closure, and 2) Achilles repair with saline applied prior to closure. Repaired hindlimbs from 12 animals per group were harvested at 6 weeks for biomechanical analysis with a custom 3D-printed jig. At 4 and 6 weeks, repaired hindlimbs from the remaining animals were assessed histologically using H&E, immunohistochemistry (IHC) staining for the presence of Ctsk, and second harmonic generation (SHG) imaging to evaluate collagen fibers. Results: At 6 weeks, there was no significant difference in failure load, stiffness, toughness, or displacement to failure between repaired hindlimbs that received OFS-3 versus saline. There was no difference in tissue healing on H&E or Ctsk staining on immunohistochemistry between animals that received OFS-3 versus saline. Finally, second harmonic generation imaging demonstrated no difference in collagen fiber parameters between the two groups. Conclusion: OFS-3 did not significantly affect the biomechanical properties or histologic appearance of murine Achilles tendon-to-bone repairs. This study demonstrates that OFS-3 can target the site of tendon-to-bone repair without causing intrinsic negative effects on healing. Further development of this drug delivery platform to target growth factors to the site of tendon-bone repair is warranted.","journal":"Frontiers in Bioengineering and Biotechnology","year":2024,"id":470525,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1304955,"name":"Varun Sriram","orcid":"0009-0005-8464-0498","position":1,"is_corresponding":false},{"id":1305298,"name":"Shannon Y. Wu","orcid":null,"position":2,"is_corresponding":false},{"id":1082484,"name":"Dave Huang","orcid":"0000-0003-0332-5823","position":3,"is_corresponding":false},{"id":1305299,"name":"Alexis Cheney","orcid":null,"position":4,"is_corresponding":false},{"id":418400,"name":"Melodie F. Metzger","orcid":"0000-0001-8892-7035","position":5,"is_corresponding":false},{"id":899773,"name":"Oskar Sundberg","orcid":"0009-0004-0869-9191","position":6,"is_corresponding":false},{"id":402790,"name":"Karen M. Lyons","orcid":"0000-0001-9420-5813","position":7,"is_corresponding":false},{"id":452556,"name":"Charles E. McKenna","orcid":"0000-0002-3540-6663","position":8,"is_corresponding":false},{"id":631846,"name":"Ichiro Nishimura","orcid":"0000-0002-3749-9445","position":9,"is_corresponding":false},{"id":1304956,"name":"Thomas J. Kremen","orcid":"0000-0003-1643-4869","position":10,"is_corresponding":false},{"id":1304954,"name":"Brendan Y. Shi","orcid":"0000-0002-6949-7401","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:05:40.740958Z","pmid":"38433822","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}