Decellularized tissue and cell-derived extracellular matrices as scaffolds for orthopaedic tissue engineering

Abstract

The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic.

Decellularized Bovine Bone Graft for Zygomatic Bone Reconstruction

“…Many authors report on the successful clinical use of decellularized bovine bone to reconstruct bone defects [25][26][27][28]. However, the number of articles dealing with the use of declerulated bovine bone grafts of large sizes is very limited.…”

Growth plate extracellular matrix-derived scaffolds for large bone defect healing

“…These small pieces were then minced in distilled H 2 0 using a homogeniser (IKAT10, IKA ® Works Inc., NC, USA) to create an ECM slurry. The effect of decellularisation was evaluated, comparing native GP (no additional treatment prior to freeze-drying), to a detergent-based technique using 0.1 % sodium dodecyl sulphate (SDS; Sigma-Aldrich); following comparisons with other detergents commonly used for decellularisation (Cheng et al, 2014;Gilbert et al, 2006;Luo et al, 2016;Luo et al, 2015), results not shown. Decellularised GP slurry underwent two freeze-thaw cycles in a hypotonic buffer (10 mM Trizma hydrochloride and 5 mM ethylenediaminetetraacetic acid (EDTA) at pH 7.4), washed in saline (PBS), and treated for 1 h at room temperature in 0.1 % SDS.…”

In VivoCellular Infiltration and Remodeling in a Decellularized Ovine Osteochondral Allograft

“…Continuous feedback mechanisms between the local cell population and ECM serve to maintain the structural and biochemical composition of the native tissue. 1,2 Alterations in the ECM structure, beyond a critical size, incurred by either traumatic injury or biochemical changes can introduce a cascade effect leading to the development of a disease state in the tissue. 2,3 This is especially prevalent in tissue such as articular cartilage, which is populated with a low density of semiquiescent chondrocytes known for poor regeneration of damaged tissue.…”

“…1,2 Alterations in the ECM structure, beyond a critical size, incurred by either traumatic injury or biochemical changes can introduce a cascade effect leading to the development of a disease state in the tissue. 2,3 This is especially prevalent in tissue such as articular cartilage, which is populated with a low density of semiquiescent chondrocytes known for poor regeneration of damaged tissue. 3 Weakening of the cartilage tissue structure can result in the formation of a local defect, which can act as the genesis point for progressive inflammation and wear, eventually leading to total degradation of the tissue and clinical osteoarthritis (OA), which currently affects over 27 million Americans.…”