Abstract

Despite excellent self-regeneration capacity of bone tissue, there are some large bone defects that cannot be healed spontaneously. Numerous literature data in the field of cell-based bone tissue engineering showed that adipose-derived stem cells (ADSCs) after isolation could be subsequently applied in a one-step approach for treatment of bone defect, without previous in vitro expansion and osteoinduction. However, standard approaches usually involve in vitro expansion and osteoinduction of ADSCs as an additional preparation step before its final application. Bioreactors are also used for the preparation of ADSC-based graft prior application. The commonly used approaches are reviewed, and their outcomes, advantages, disadvantages, as well as their potential for successful application in the treatment of bone defects are discussed. Difficulty in spontaneous healing of bone defects is very often due to poor vascularization. To overcome this problem, numerous methods in bone tissue engineering (BTE) were developed. We focused on freshly isolated stromal vascular fraction (SVF) cells and ADSCs in vitro induced into endothelial cells (ECs) as cells with vasculogenic capacity for the further application in bone defect treatment. We have reviewed orthotopic and ectopic models in BTE that include the application of SVFs or ADSCs in vitro induced into ECs, with special reference to co-cultivation.

Highlights

  • Structure of the bone tissue is very dynamic due to environmental influence and because of many factors that act inside the body [1]

  • Fernandes and Yang [48] reviewed and summarized some recently published data which implies that adipose-derived stem cells obtained from human, mouse, rat and rabbit in combination with PRP in in vitro and/or in vivo conditions are related with outcomes which are of benefit for bone tissue engineering (BTE) [48]

  • Overall, according to studies published so far [45, 49] that are mostly in accordance with other related studies, it could be concluded that untreated adipose-derived stem cells (ADSCs) contained in freshly isolated stromal vascular fraction (SVF) have different potential from in vitro osteoinduced ADSCs to start and maintain osteogenic process which leads to quite different outcomes, at least in ectopic condition

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Summary

Introduction

Structure of the bone tissue is very dynamic due to environmental influence and because of many factors that act inside the body [1]. The main types of bone grafting materials are autografts, allografts, xenografts, synthetic and biological tissue engineering biomaterials, and combinations of these materials [2–6]. In addition to bone grafts (autograft, allograft, xenograft), newer bone substitutes are the ceramic types (calcium compounds: hydroxyapatite, tricalcium phosphate (TCP), calcium sulfate) and biological factors such as growth factors and others (bone morphogenetic proteins (BMPs), platelet-rich plasma (PRP), demineralized bone matrix (DBM)). Cells (e.g., osteogenic or mesenchymal stem cells and others) are used to create new bone alone or are seeded onto a support matrix or scaffold to form bone tissue in vitro [6, 7, 9, 10, 13] On these principles, engineered vascularized bone grafts can be created with some similarities to autografts [9, 10, 14]. To test the new features and products of BTE, as well as preclinical testing, many in vitro and in vivo methods and models have been developed with various advantages and disadvantages respectively [11, 16]

Sources of cells for tissue-engineered grafts
Adipose-derived stem cells
Bone substitutes and regulatory factors
One-step versus multistep approaches
ADSCs-based grafts prepared in bioreactors
The problem of insufficient vascularization in bone tissue engineering
Orthotopic model
Ectopic model
Co-cultivation
Arteriovenous vascular bundle
Gene therapy
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