Abstract
Critical-sized bone defects fail to heal and often cause non-union. Standard treatments employ autologous bone grafting, which can cause donor tissue loss/pain. Although several scaffold types can enhance bone regeneration, multiple factors limit their level of success. To address this issue, this study evaluated a novel decellularized human adipose tissue (DAT) hydrogel as an alternative. In this study, DAT hydrogel alone, or in combination with adipose-derived stromal/stem cells (ASC), osteo-induced ASCs (OIASC), and hydroxyapatite were tested for their ability to mediate repair of a critical-sized (3 mm) femoral defect created in C57BL/6 mice. Micro-computed tomography results showed that all DAT hydrogel treated groups significantly enhanced bone regeneration, with OIASC + hydroxyapatite treated group displaying the most robust bone regeneration. Histological analyses revealed that all treatments resulted in significantly higher tissue areas with the relative mineralized tissue area significantly increased at 12 weeks; however, cartilaginous content was lowest among treatment groups with OIASC. Immunohistochemical analyses showed that DAT hydrogel enhanced collagen I and osteopontin expression, while the addition of OIASCs to the hydrogel reduced collagen II levels. Thus, DAT hydrogel promotes bone regeneration in a critical-sized femoral defect model that is further enhanced in the presence of OIASCs and hydroxyapatite.
Highlights
Bones possess robust regenerative capacity allowing animals to repair fractures rapidly and effectively
A distinct callus was visible around the region of the defect, while the callus was more prominent in the hydrogel + adipose-derived stromal/stem cells (ASC) + HA, hydrogel + osteo-induced ASCs (OIASC) and hydrogel + OIASC + HA treated groups (Figure 2A)
Our findings show that the addition of OIASCs was able to enhance the regenerative potential of decellularized adipose tissue (DAT) hydrogel
Summary
Bones possess robust regenerative capacity allowing animals to repair fractures rapidly and effectively. Ceramic scaffolds including hydroxyapatite (HA) and tricalcium phosphate (TCP) are biocompatible and osteo-inductive, though they are brittle and poorly resorbed (Ghassemi et al, 2018; Roddy et al, 2018; Schmidt et al, 2019; Zhang et al, 2019) Synthetic polymers, such as polylactic acid (PLA) are bioresorbable with limited osteoinductive capability (Roddy et al, 2018). Despite accumulating evidence supporting the potential of DAT scaffold for tissue regeneration, its use remains unexplored for the treatment of critical-sized bone defects. The present study evaluates a novel application of decellularized adipose tissue (DAT) as a bio-scaffold for the regeneration of critical-sized long bone defects. To test these hypotheses; a 3 mm femoral defect was created in immunocompetent mice and subsequently treated with different combinations of hydrogel with un-induced or osteoinduced ASCs (OIASCs) and HA
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