Sustained Release of Melatonin from GelMA Liposomes Reduced Osteoblast Apoptosis and Improved Implant Osseointegration in Osteoporosis

Abstract

A reduction in bone mass around an implant is the main cause of implant loosening, especially in postmenopausal osteoporosis patients. In osteoporosis, excessive oxidative stress, resulting in osteoblast apoptosis, largely contributes to abnormal bone remodeling. Melatonin (MT) synthesized by the pineal gland promotes osteoblast differentiation and bone formation and has been effectively used to combat oxidative stress. Therefore, we hypothesized that MT attenuates osteoblast apoptosis induced by oxidative stress, promotes osteogenesis in osteoporosis, and improves bone mass around prostheses. Moreover, considering the distribution and metabolism of MT, its systemic administration would require a large amount of MT, increasing the probability of drug side effects, so the local administration of MT is more effective than its systemic administration. In this study, we constructed a composite adhesive hydrogel system (GelMA-DOPA@MT) to bring about sustained MT release in a local area. Additionally, MT-reduced apoptosis caused by hydrogen peroxide- (H2O2-) induced oxidative stress and restored the osteogenic potential of MC3T3-E1 cells. Furthermore, apoptosis in osteoblasts around the implant was significantly attenuated, and increased bone mass around the implant was observed in ovariectomized (OVX) rats treated with this composite system. In conclusion, our results show that GelMA-DOPA@MT can inhibit osteoblast apoptosis caused by oxidative stress, thereby promoting osteogenesis and improving bone quality around a prosthesis. Therefore, this system of local, sustained MT release is a suitable candidate to address implant loosening in patients with osteoporosis.

Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries

“…RGD and MMPs) because of its crosslinking is less than 5% [ 30 ]. GelMA hydrogel has been proven as an optimal biomaterial for tissue engineering and drug delivery due to its unique features such as polymerization under normal conditions, temporal and spatial control of reaction, tunable mechanical property and good biocompatibility [ 31 , 32 ]. Therefore, GelMA hydrogel is an ideal scaffold that can play dual roles in substituting ECM for cell attachment and controlling the release of growth factors for tissue engineering [ 25 , 27 , 33 ].…”

Integration of Network Pharmacology and Experimental Validation to Explore the Pharmacological Mechanisms of Zhuanggu Busui Formula Against Osteoporosis

“…Previous studies have shown that the excessive apoptosis of osteoblasts may exacerbate the progression of osteoporosis (53). Inhibiting the apoptosis of osteoblasts significantly enhanced osteogenic differentiation, thereby exerting anti-OP effects (54).…”

Engineering Smart Targeting Nanovesicles and Their Combination with Hydrogels for Controlled Drug Delivery

“…In a more recent study, Xiao et al, generated a sustained Melatonin (MT) release system composed of MT liposomes embedded in a GelMA-Dopamine (DOPA) hydrogel, and studied its release behavior and ability to induce implant osseointegration in an osteoporotic state ( Figure 3 B) [ 102 ]. As for the release behavior, the samples exhibited various release characteristics depending on the density of the hydrogel network, with 5% GelMA constructs having only 5 days of sustained release and 20% GelMA constructs exhibiting up to 25 days of sustained release.…”

“…( B ) The bone regeneration mechanism promoted by Melatonin-loaded liposomes embedded in a GelMA-Dopamine hydrogel. Reproduced from [ 102 ], Hindawi, 2020. ( C ) The mechanism of UV induced crosslinking and ( D ) the appearance of UV crosslinked GelMA and Gemcitabine-loaded liposomes embedded in GelMA (GEM30-Lip@Gel).…”