Mineralization of Hydrogels for Bone Regeneration

Abstract

Hydrogels are an important class of highly hydrated polymers that are widely investigated for potential use in soft tissue engineering. Generally, however, hydrogels lack the ability to mineralize, preventing the formation of chemical bonds with hard tissues such as bone. A recent trend in tissue engineering involves the development of hydrogels that possess the capacity to mineralize. The strategy that has attracted most interest has been the incorporation of inorganic phases such as calcium phosphate ceramics and bioglasses into hydrogel matrices. These inorganic particles act as nucleation sites that enable further mineralization, thus improving the mechanical properties of the composite material. A second route to create nucleation sites for calcification of hydrogels involves the use of features from the physiological mineralization process. Examples of these biomimetic mineralization strategies include (1) soaking of hydrogels in solutions that are saturated with respect to calcium phosphate, (2) incorporation of enzymes that catalyze deposition of bone mineral, and (3) incorporation of synthetic analogues to matrix vesicles that are the initial sites of biomineralization. Functionalization of the polymeric hydrogel backbone with negatively charged groups is a third mechanism to promote mineralization in otherwise inert hydrogels. This review summarizes the main strategies that have been developed in the past decade to calcify hydrogel matrices and render these hydrogels suitable for applications in bone regeneration.

Recapitulating cranial osteogenesis with neural crest cells in 3-D microenvironments

“…During the second and third week of 3-D osteo-differentiatiation CNCCs demonstrate the expression of i) OSX, a bone-specific transcription factor that is specifically expressed in osteoblasts of all skeletal elements [41], ii) OCN, an osteoblastderived hormone expressed only in fully differentiated osteoblasts and osteocytes, iii) OPN, a late osteogenic protein that regulates the biomineralization and boneremodelling [42,43] and iv) BSP, a non-collagenous protein that is a key component of the bone extracellular matrix [44,45] (Figure 3E, F, Figure 4B, C, E, F, G and Supplementary Figure 2). The formation of mature bone tissue is further characterized by the mineralization in terms of hydroxyapatite deposition in the newly formed extracellular matrix [46]. We demonstrate the ability of newly differentiated osteogenic cells to mineralize the hydrogels with hydroxyapatite from second week.…”

Hydroxyapatite nanoparticle injectable hydrogel scaffold to support osteogenic differentiation of human mesenchymal stem cells

“…Traditionally, the use of bone autografts has been regarded as the gold standard clinical intervention for bone repair; however, this therapeutic strategy is limited by the amount of bone that can be used and poses clinical risk in terms of increased operative blood loss and donor-site morbidity (Goulet et al, 1997;Sen and Miclau, 2007). Consequently, a considerable amount of research has been undertaken which aims to develop effective regenerative strategies leading to bone augmentation (Kraus and Kirker-Head, 2006;Mistry and Mikos, 2005).…”

Mineralization and bone regeneration using a bioactive elastin-like recombinamer membrane

“…An ideal periosteal graft would not only provide a physical structure that facilitates osteoconduction, but also osteoinductive signals that stimulate osteogenesis and ultimately promote biomineralization [8]. Membranes made of amniotic tissue [9], chitosan-silica [10] or silk fibroin nanofibers [11] have been reported to induce osteoblastic differentiation in vitro.…”