A novel calcium aluminate‐melatonin scaffold enhances bone regeneration within a calvarial defect

Abstract

Over 500,000 bone graft or bio-implant procedures are performed annually in the United States. It has been reported that osseous autograft procurement may result in donor site complications and bio-implant allografts have been associated with disease transmission. Ceramic scaffolds are only osteoconductive, limiting their clinical use. The objective of this study was to create a bone filler substitute with regenerating properties similar to natural bone. Therefore, melatonin and platelet-rich plasma (PRP) were utilized for their known osteoinductive properties. It was hypothesized that melatonin and/or PRP would enhance the osteoinductive and osteoconductive properties of calcium aluminate (CA) scaffolds to promote bone regeneration in a model of calvarial defects. The biocompatibility of CA and CA-Mel scaffolds was tested in vitro and in vivo. Data show that CA-Mel scaffolds, in comparison with CA scaffolds, enhanced the adhesion, viability, and proliferation of normal human osteoblasts cells but not that of NIH3T3 fibroblasts. Data also showed that human adult mesenchymal stem cells grown on CA or CA-Mel scaffolds showed a time-dependent induction into osteoblasts over 14days revealed through scanning electron microscopy and by alkaline phosphatase analyses. Implantation of CA-Mel scaffolds into critical size calvarial defects in female, ovariectomized rats showed that the CA-Mel scaffolds were biocompatible, allowed for tissue infiltration, and showed evidence of scaffold biodegradation by 3 and 6months. Bone regeneration, assessed using fluorochrome labeling at 3 and 6months, was greatest in animals implanted with the CA-Mel scaffold. Overall, results from this study show that CA-Mel scaffolds were osteoconductive and osteoinductive.

Clinical and Radiographic Evaluation of Immediate Loaded Dental Implants With Local Application of Melatonin: A Preliminary Randomized Controlled Clinical Trial

“…21. 32 The enhanced ossointergration and minimal bone changes at the first follow up assessment in our study was in the same line with Clafshenkel et al 33 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 reduces the matrix metalloproteinase-1/tissue inhibitor of metalloproteinases-1(MMP1/TIMP1) ratio and promotes wound healing without scars, in addition to its antioxidant properties. This was in agreement with the findings of Guardia et al 2009 31 .…”

Scaffold Design for Bone Regeneration

“…However, the combination of calcium aluminate with osteoinductive materials such as melatonin and platelet-rich plasma was used by Clafshenkel et al 164 to form a bone filler substitute with regenerating properties similar to that of natural bone. In vitro results showed adhesion, viability, and proliferation of normal human osteoblasts cells but not that of NIH3T3 fibroblasts.…”

Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion

“…Emerging evidences showed that melatonin regulates several characteristics of MSCs in vitro 37-40. Melatonin treatment has been reported to promote osteogenic differentiation, vitality, and mobility of MSCs, resulting in improved MSCs therapy of skeletal defect 41, sepsis-induced kidney injury 42, acute lung ischemia-reperfusion injury 43 and skin wound healing 44. Recently, Zhou and colleagues showed that melatonin treatment prevents H 2 O 2 -induced premature senescence of MSCs 45, suggesting melatonin is a promising candidate to optimize in vitro MSCs expansion.…”