Abstract
Research in bone tissue engineering is focused on the development of alternatives to autologous bone grafts for bone reconstruction. Although multiple stem cell-based products and biomaterials are currently being investigated, comparative studies are rarely achieved to evaluate the most appropriate approach in this context. Here, we aimed to compare different clinically relevant bone tissue engineering methods and evaluated the kinetic repair and the bone healing efficiency supported by mesenchymal stem cells and two different biomaterials, a new hydrogel scaffold and a commercial hydroxyapatite/tricalcium phosphate ceramic, alone or in combination.Syngeneic mesenchymal stem cells (5 × 105) and macroporous biphasic calcium phosphate ceramic granules (Calciresorb C35®, Ceraver) or porous pullulan/dextran-based hydrogel scaffold were implanted alone or combined in a drilled-hole bone defect in rats. Using quantitative microtomography measurements and qualitative histological examinations, their osteogenic properties were evaluated 7, 30, and 90 days after implantation. Three months after surgery, only minimal repair was evidenced in control rats while newly mineralized bone was massively observed in animals treated with either hydrogels (bone volume/tissue volume = 20%) or ceramics (bone volume/tissue volume = 26%). Repair mechanism and resorption kinetics were strikingly different: rapidly-resorbed hydrogels induced a dense bone mineralization from the edges of the defect while ceramics triggered newly woven bone formation in close contact with the ceramic surface that remained unresorbed. Delivery of mesenchymal stem cells in combination with these biomaterials enhanced both bone healing (>20%) and neovascularization after 1 month, mainly in hydrogel.Osteogenic and angiogenic properties combined with rapid resorption make hydrogels a promising alternative to ceramics for bone repair by cell therapy.
Highlights
Bone reconstruction after tumors, traumas or pathologies is a common challenge encountered in regenerative medicine
We demonstrated that calcium carbonate porogen agent caused the formation of large pores of about 200 μm, favorable for Mesenchymal stem cells (MSCs) infiltration [22, 23] while sodium chloride would create smaller pores (40 μm) that would allow seeding of smaller cells such as endothelial cells [24]
Clear and transparent hydrated hydrogels (Fig. 1e) allowed for a direct observation of large MSCs clusters spotted inside the hydrogel pores (50–200 μm diameters, Fig. 1f), in the entire thickness of the scaffold validating the instantaneous cellularization of hydrogels with MSCs
Summary
Traumas or pathologies is a common challenge encountered in regenerative medicine. Scaffolds must be selected for their ability to optimize bone healing, promote cell survival, proliferation and differentiation and must be nonimmunogeneic, while exhibiting appropriate degradation, mechanical strength and 35 Page 2 of 13. Most commonly approved biomaterials are hydroxyapatite (HA) and tricalcium phosphate (TCP)-mixed scaffolds according to their natural bone mineral similarities and their biocompatibility and bioreactivity. HA/TCP ceramics exhibit extensive in situ resorption latencies preventing the gradual replacement with newly formed bone [2]. Biomaterial design is expanding with new material syntheses, including synthetic polymers, fibrous scaffold, bioactive ceramics, metals, composite scaffolds, and processing techniques to enhance the complexity of 3D environments [3,4,5]. A growing interest for polymer hydrogels to enhance bone healing is arising on the basis of their easy shaping capacity, radiotransparency and high resorption ability
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