Bone defects due to traumas, fractures, diseases and tumors lead to dramatic changes in the quality of life of patients including frequent social and psychological problems (Doherty and Gaughran, 2014). The autografts, allografts and xenografts have been used for tissue engineering and regenerative medicine applications. However, autografts have the drawbacks of donor site morbidity and limited availability while allografts and xenografts have the drawbacks of immune rejection and disease transmission (Delloye et al., 2007).

Natural polymeric biomaterials used in regenerative medicine are classified into two major categories: i) polysaccharides, as chitosan, hyaluronan and alginate; ii) proteins, as collagen, fibrin, elastin and silk (Pina et al., 2022). Scaffolds made of synthetic or natural biomaterials promote the migration, proliferation, and differentiation of bone cells (Chatterjea et al., 2010). Numerous organic and inorganic biomaterials and hybrids of them have been widely tested with varying success. However, the low mechanical properties, composite biomaterials, lack of biocompatibility, chronic inflammation or immunological reactions and toxicity represent problems with the current scaffolds. Also, some synthetic scaffolds create a local acidity due to rapid degradation leading to adverse tissue responses (Abedin et al., 2018).

Acellular biological scaffolds, composed of extracellular matrix (ECM) components maintained in their natural state that can aid cellular repopulation, differentiation, and proliferation have been utilized in tissue repair (Jeuken et al., 2016). Demineralized bone matrix consists of type I collagen and matrix proteins of bone, and has been widely used in bone repair due to its similar physical and chemical structure to native bone. Decellularization of demineralized bone matrix creates a natural scaffold material for cell growth, cell differentiation, and tissue regeneration while also eliminating the adverse immune reaction through repopulating the matrix with a patient’s own cells. However, few studies have dealt with the decellularization of demineralized bone matrix (Yang et al., 2018; Li et al., 2018).

Acellular dermal matrix (ADM) formed mainly of collagen, serves as a framework to support cellular repopulation, revascularization at the surgical site, and soft tissue regeneration by the recipient’s own cells. It has been used in abdominal wall reconstruction, alloplastic breast reconstruction, vaginal repair, osteochondral repair and skull bone repair. These reports illustrate the ability of the ADM to remodel to tissue at the site of implantation (Ye et al., 2018; Elkhateb et al., 2018). ADMs are derived from full-thickness skin that has been physically or chemically treated to remove cells and cellular components and retain the native structure of the dermal fiber meshwork (Callcut et al., 2006).

Scaffolds can be loaded with osteogenic cells in order to generate a living bone graft in vitro, and thus improve clinical outcome (Chatterjea et al., 2010). They have angiogenic, anti-apoptotic, anti-inflammatory and immunomodulatory effects (Cao et al., 2015). Comparing adipose stem cells (ASCs) with bone marrow stem cells (BMSCs), ASCs secrete more trophic factors, have higher proliferative capacity, are less tumorigenic with less telomerase activity and have better immunomodulatory effects (Ock et al., 2016). The survival of seeded cells in conventional bone scaffold is a challenge due to the lack of blood supply. The microcarrier form of bone scaffold enables better vascularization of the neo-tissue and the engineered bone graft. It is much potent for osteogenesis and can greatly enlarge the surface area for cell proliferation (Li et al., 2018).

In this study, we investigated and compared the effect of demineralized decellularized microcarrier form of bone matrix and ADM, both loaded with ASCs on the repair of compact bone defect in-vivo.