Pullulan microbeads/Si-HPMC hydrogel injectable system for the sustained delivery of GDF-5 and TGF-β1: new insight into intervertebral disc regenerative medicine.

Autor: Henry N; a INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team STEP 'Skeletal Physiopathology and Joint Regenerative Medicine' , Nantes , France.; b Institut des Matériaux Jean Rouxel (IMN) , Université de Nantes, CNRS , Nantes , France.; c UFR Odontologie , Université de Nantes , Nantes , France., Clouet J; a INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team STEP 'Skeletal Physiopathology and Joint Regenerative Medicine' , Nantes , France.; c UFR Odontologie , Université de Nantes , Nantes , France.; d CHU Nantes, PHU 11 Pharmacie , Pharmacie Centrale , Nantes , France.; e UFR Sciences Biologiques et Pharmaceutiques , Université de Nantes , Nantes , France., Fragale A; a INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team STEP 'Skeletal Physiopathology and Joint Regenerative Medicine' , Nantes , France.; c UFR Odontologie , Université de Nantes , Nantes , France., Griveau L; a INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team STEP 'Skeletal Physiopathology and Joint Regenerative Medicine' , Nantes , France., Chédeville C; a INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team STEP 'Skeletal Physiopathology and Joint Regenerative Medicine' , Nantes , France., Véziers J; a INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team STEP 'Skeletal Physiopathology and Joint Regenerative Medicine' , Nantes , France.; c UFR Odontologie , Université de Nantes , Nantes , France.; f SC3M platform, UMS INSERM 016/CNRS 3556 , SFR François Bonamy , Nantes , France.; g CHU Nantes , PHU 4 OTONN , Nantes , France., Weiss P; c UFR Odontologie , Université de Nantes , Nantes , France.; h INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team REGOS 'Regenerative Medicine of Bone Tissues' , Nantes , France., Le Bideau J; b Institut des Matériaux Jean Rouxel (IMN) , Université de Nantes, CNRS , Nantes , France., Guicheux J; a INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team STEP 'Skeletal Physiopathology and Joint Regenerative Medicine' , Nantes , France.; c UFR Odontologie , Université de Nantes , Nantes , France.; g CHU Nantes , PHU 4 OTONN , Nantes , France., Le Visage C; a INSERM, UMRS 1229, RMeS 'Regenerative Medicine and Skeleton' , Team STEP 'Skeletal Physiopathology and Joint Regenerative Medicine' , Nantes , France.; c UFR Odontologie , Université de Nantes , Nantes , France.
Jazyk: angličtina
Zdroj: Drug delivery [Drug Deliv] 2017 Nov; Vol. 24 (1), pp. 999-1010.
DOI: 10.1080/10717544.2017.1340362
Abstrakt: Discogenic low back pain is considered a major health concern and no etiological treatments are today available to tackle this disease. To clinically address this issue at early stages, there is a rising interest in the stimulation of local cells by in situ injection of growth factors targeting intervertebral disc (IVD) degenerative process. Despite encouraging safety and tolerability results in clinic, growth factors efficacy may be further improved. To this end, the use of a delivery system allowing a sustained release, while protecting growth factors from degradation appears of particular interest. We propose herein the design of a new injectable biphasic system, based on the association of pullulan microbeads (PMBs) into a cellulose-based hydrogel (Si-HPMC), for the TGF-β1 and GDF-5 growth factors sustained delivery. We present for the first time the design and mechanical characterization of both the PMBs and the called biphasic system (PMBs/Si-HPMC). Their loading and release capacities were also studied and we were able to demonstrate a sustained release of both growth factors, for up to 28 days. Noteworthy, the growth factors biological activity on human cells was maintained. Altogether, these data suggest that this PMBs/Si-HPMC biphasic system may be a promising candidate for the development of an innovative bioactive delivery system for IVD regenerative medicine.
Databáze: MEDLINE
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