Growth-factor Enhanced Matrix(ZymoGenetics, Inc.)

Cuttlebone (CB) is a marine waste‐derived biomaterial and a rich source of calcium carbonate for the biosynthesis of the calcium phosphate (CaP) particles. The current study aimed to synthesize CB derived biphasic calcium phosphate (CB‐BCP) and investigate biological activity of the CB‐CaP: hydroxyapatite (CB‐HA), beta‐tricalcium phosphate (CB‐b‐TCP) and biphasic 60:40 (w/w) HA/b‐TCP (CB‐BCP) with the human dental pulp stem cells (hDPSCs). The particles were synthesized using solid state reactions under mild condition and properties of the particles were compared with a commercial BCP as a reference material. Morphology, particle size, physicochemical properties, mineral contents, and the ion released patterns of the particles were examined. Then the particle/cell interaction, cell cytotoxicity and osteogenic property of the particles were investigated in the direct and indirect cell culture models. It was found that an average particles size of the CB‐HA was 304.73 ± 4.19 nm, CB‐b‐TCP, 503.17 ± 23.06 nm and CB‐BCP, 1394.67 ± 168.19 nm. The physicochemical characteristics of the CB‐CaP were consistent with the HA, b‐TCP and BCP. The highest level of calcium (Ca) was found in the mineral contents and the preincubated medium of the CB‐BCP and traces of fluoride, magnesium, strontium, and zinc were identified in the CB‐CaP. The cell cytotoxicity and osteogenic property of the particles were dose dependent. The particles adhered on cell surface and were internalized into the cell cytoplasm. The CB‐BCP and CB‐HA indirectly and directly promote osteoblastic differentiations of the hDPSCs in stronger levels than other groups. The CB‐BCP and CB‐HA were potential bioactive bone substitute materials.

The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in the past 20 years. Most studies reported that such agents, used in different concentrations, doses and combined with various scaffolds, might promote periodontal tissue regeneration, but evidence for the most effective combination of such agents is lacking. The objective of this study 13 was to rank the different combinations of recombinant human-derived growth and differentiation factors with/without scaffold biomaterial in the treatment of periodontal intrabony defects, through network meta-analysis of pre-clinical studies. The systematic review and network meta-analysis protocol was registered on the PROSPERO Systematic Review database with reference number: CRD42021213673. Relevant published articles were obtained after searching five electronic databases. A specific search strategy was followed by using keywords related to intrabony defects, regenerative materials, scaffolds and recombinant factors, and animal studies. All pre-clinical studies used for periodontal regeneration were included. The primary outcomes were: regeneration of junctional epithelium (mm), new cementum, connective tissue attachment, percentage of new bone formation (%), bone area (mm² ), bone volume density (g/cm³ ) and bone height (mm) data was extracted. The analysis was carried out using network meta-analysis methods, that is illustrating network plots, contribution plots, predictive and confidence interval plot, surface under the cumulative ranking (SUCRA), multidimensional scale ranking and net funnel plots using STATA IC statistical software. An SYRCLE's tool for assessing risk of bias was used for reporting risk of bias among individual studies. A total of N = 24 for qualitative and N = 21 studies for quantitative analysis published till 2020 were included. The cumulative total number of animals included in the control and test groups were N = 162 and N = 339, respectively. The duration of the study was between 3 and 102 weeks rhBMP-2 ranked higher in SUCRA as the agent associated with the best performance for bone volume density. rhGDF-5/TCP ranked best in the bone area (mm2), rhPDGF-BB/Equine ranked best in bone height (mm), rhBMP-2 ranked best in the percentage of new bone fill, rhBMP-2/ACS ranked best in new cementum formation, and rhGDF-5/b- TCP/PLGA ranked best in connective tissue attachment and junctional epithelium. There were no adverse effects identified in the literature that could affect the different outcomes for regeneration in intrabony defects. Various recombinant factors are effective in promoting the regeneration of both soft and hard tissue supporting structures of the periodontium. However, when considering different outcomes, different agents, associated or not with biomaterials, ranked best. Keeping into account the limited transferability of results from animal studies to the clinical setting, the choice of the most appropriate formulation of bioactive agents may depend on clinical needs and purpose.