In vitro and in vivo studies of a novel bacterial cellulose-based acellular bilayer nanocomposite scaffold for the repair of osteochondral defects

Abstract

Bacterial cellulose (BC) is a naturally occurring nanofibrous biomaterial which exhibits unique physical properties and is amenable to chemical modifications. To explore whether this versatile material can be used in the treatment of osteochondral defects (OCD), we developed and characterized novel BC-based nanocomposite scaffolds, for example, BC-hydroxyapatite (BC-HA) and BC-glycosaminoglycans (BC-GAG) that mimic bone and cartilage, respectively. In vitro biocompatibility of BC-HA and BC-GAG scaffolds was established using osteosarcoma cells, human articular chondrocytes, and human adipose-derived mesenchymal stem cells. On subcutaneous implantation, the scaffolds allowed tissue ingrowth and induced no adverse immunological reactions suggesting excellent in vivo biocompatibility. Implantation of acellular bilayered scaffolds in OCD created in rat knees induced progressive regeneration of cartilage tissue, deposition of extracellular matrix, and regeneration of subchondral bone by the host cells. The results of micro-CT revealed that bone mineral density and ratio of bone volume to tissue volume were significantly higher in animals receiving bilayered scaffold as compared to the control animals. To the best of our knowledge, this study proves for the first time, the functional performance of acellular BC-based bilayered scaffolds. Thus, this strategy has great potential for clinical translation and can be used in repair of OCD.

Applications of bacterial-synthesized cellulose in veterinary medicine – a review

“…Furthermore, full integration of the neo-tissue was noted in the surrounding healthy tissue. The bilayer group showed the presence of a small scaffold portion, yet the scaffold had completely resorbed in the bilayer + GF group (Kumbhar et al 2017).…”

“…In vivo evaluation of BC scaffolds was assessed on Wistar rats, randomly divided into 4 groups: control (no treatment); BC; bilayer scaffold (BC-HA and BC-GAG placed one over the other); and bilayer scaffold supplemented with growth factors (GF) (recombinant human BMP-2) (Kumbhar et al 2017). Osteochondral defects (OCD) were created in the patellar groove of the knee joints and 6 animals from each group were sacrificed at 1 and 3 months.…”

Recent Advances in Modified Cellulose for Tissue Culture Applications

“…Scaffolds with pores in the micrometre and nanometre range have been prepared by blending bacterial cellulose with tri-calcium phosphate and hydroxyapatite and such scaffolds could be used to form implants for bone tissue engineering as mineralisation occurs on the hydroxyapatite [ 82 ]. By forming layers of bacterial cellulose, harvested from the floating pellicles at the air-liquid interface, with hydroxyapatite or glycosaminoglycans, a nanocomposite scaffold could be fabricated that was biocompatible and mimicked the nanoscale fibrous structure of bone and cartilage ECM, respectively, resulting in tissue constructs that could regenerate osteochondral defects when implanted into the body [ 84 ]. Furthermore, hydrogels have been formed by gelation of bacterial cellulose nanofibres, stabilised by procyanidins, and blended with collagen and hydroxyapatite.…”

Cellulose-Based Hydrogels in Tissue Engineering Applications

“…Therefore, BC can be modified to mimic different tissues, desirable progressive regeneration of cartilage tissue and of the subchondral bone being noticed as indicators of functional capability. 121 A different, CMC-HA, hybrid hydrogel scaffold was reported to promote the production of extracellular mineralized matrix, and to enhance osteoblast cell proliferation and metabolic activity. 122 In order to obtain successful bone integration and regeneration, bone-repairing scaffolds require to be functionalized synergistically based on biomimetics.…”