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

AbstractDiscogenic 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 ...