Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

Abstract

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

Evaluation of double network hydrogel of poloxamer-heparin/gellan gum for bone marrow stem cells delivery carrier

“…Engineered hydrogels are considered as a promising material to provide an optimal environment to maintain long lasting cell viability of stem cells in situ [19,51,52]. These materials allow the cells to be delivered appropriately into the defect sites for the treatment purpose [5,[52][53][54]. However, various limits in cell function and growth have been exhibited when stem cells are encapsulated into biomaterials [2,5,6,57].…”

Preparation and biological characterization of the mixture of poly(lactic-co-glycolic acid)/chitosan/Ag nanoparticles for periodontal tissue engineering

“…Bone tissue regeneration is important in periodontal therapy. Tissue regeneration can be induced by growth factors, 19 scaffolds, 20 and stem cell transplantation. 21 It was found in our previous study that calcium alginate, PLGA, and CS have an excellent biocompatibility and are able to improve cell mineralization.…”

Natural and Synthetic Polymers for Bone Scaffolds Optimization

“…Moreover, their usage reduces the surgical operation time, minimizes the post-operative pain and scar size, achieves rapid recovery and reduces the clinical costs. In addition, the hydrogels can be filled with bioactive molecules and/or cells, that can directly take part as building blocks in tissue regeneration or just stimulate host response [46,47]. Despite several advantages, hydrogels are characterized by low mechanical properties that favours their application in lesion filling rather than in load-bearing lesions.…”