Bacterial cellulose membrane functionalized with hydroxiapatite and anti-bone morphogenetic protein 2: A promising material for bone regeneration

Abstract

Bone tissue engineering seeks to adequately restore functions related to physical and biological properties, aiming at a repair process similar to natural bone. The use of compatible biopolymers, such as bacterial cellulose (BC), as well as having interesting mechanical characteristics, presents a slow in vivo degradation rate, and the ability to be chemically modified. To promote better bioactivity towards BC, we synthesized an innovative BC membrane associated to hydroxyapatite (HA) and anti-bone morphogenetic protein antibody (anti-BMP-2) (BC-HA-anti-BMP-2). We present the physical-chemical, biological and toxicological characterization of BC-HA-anti-BMP-2. Presence of BC and HA components in the membranes was confirmed by SEM-EDS and FTIR assays. No toxic potential was found in MC3T3-E1 cells by cytotoxicity assays (XTT Assay and Clonogenic Survival), genotoxicity (Comet Assay) and mutagenicity (Cytokinesis-blocked micronucleus Test). The in vitro release kinetics of anti-BMP-2 antibodies detected gradually reducing antibody levels, reducing approximately 70% in 7 days and 90% in 14 days. BC-HA-anti-BMP-2 increased SPP1 , BGLAP , VEGF , ALPL , RUNX2 and TNFRSF11B expression, genes involved in bone repair and also increased mineralization nodules and phosphatase alcalin (ALP) activity levels. In conclusion, we developed BC-HA-anti-BMP-2 as an innovative and promising biomaterial with interesting physical-chemical and biological properties which may be a good alternative to treatment with commercial BMP-2 protein.

Comprehensive In Vitro Testing of Calcium Phosphate-Based Bioceramics with Orthopedic and Dentistry Applications

“…There were several studies that demonstrated that HA and its related dissolution products could be quite harmless for use in devices, such as, for instance, bone implants [41,42,43]. However, some other studies still considered the potential risks of such materials, mainly due to the addition of other “doping” elements, such as Sr, Zn, etc.…”

“…Coelho et al [41] investigated both cytotoxic and genotoxic effects of a bacterial cellulose membrane functionalized with HA and bone morphogenetic protein (BMP). Genotoxicity was evaluated by applying the in vitro Comet and micronucleus (cytokinesis-blocked micronucleus) assays on C3T3-E1 cells.…”

Advances in Growth Factor Delivery for Bone Tissue Engineering

“…Nonetheless, cellulose hydrogels show restricted mechanical attributes that hold back their utilization in hard tissue applications. To surpass this limitation of cellulose-based scaffolds and to build on the functional properties for hard tissue application, mineralization of cellulose hydrogels with HAp and other materials has been actively investigated in recent years [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. Bacterial cellulose was successfully combined with HAp to deliver BMP-2 [ 94 ].…”

Bacterial Nanocellulose in Dentistry: Perspectives and Challenges

“…Coelho et al [ 110 ] synthesized an innovative BC membrane associated with HA and an antibody of a bone morphogenetic protein (anti-BMP-2) (BC-HA-anti-BMP-2). The SEM-EDS and FTIR assays confirmed the presence of BC and HA.…”