Tissue engineering: TGF-[beta] superfamily members and delivery systems in bone regeneration

Abstract

The induction of bone formation requires three parameters that interact in a highly regulated process: soluble osteoinductive signals, capable responding cells, and a supporting matrix substratum or insoluble signal. The use of recombinant and naturally derived bone morphogenetic proteins and transforming growth factor βs (TGF-βs) has increased our understanding of the functions of these morphogens during the induction of endochondral bone formation. In addition, growing understanding of the cellular interactions of living tissues with synthetic biomaterials has led to the in vivo induction of bone formation using porous biomimetic matrices as an alternative to the use of autografts for bone regeneration. This review outlines the basis of bone tissue engineering by members of the TGF-β superfamily, focusing on their delivery systems and the intrinsic induction of bone formation by specific biomimetic matrices with a defined geometry.

Bone Regeneration Mediated by BMP4-Expressing Muscle-Derived Stem Cells Is Affected by Delivery System

“…From these scans, we generated three-dimensional renderings by thresholding to segment each 16-bit gray-scale image. We also calculated the regenerated bone volume (mm 3 ) and regenerated bone mineral density (mg hydroxyapatite (HA)=cm 3 ) within the original defect for each treatment group using Scanco evaluation software, Scanco Medical, Switzerland. We also determined the density of the normal calvarial bone outside the zone of the initial defect to compare the bone mineral densities of the regenerated and native bone for each group of mice that received different scaffolds.…”

“…1,3 Skeletal muscle contains stem cells with the ability to differentiate into osteoblasts under the influence of proper inductive factors that have driven other progenitor cells toward the osteogenic lineage. Muscle-derived stem cells (MDSCs) stimulated or genetically engineered to express bone morphogenetic protein (BMP)2 or BMP4 have been shown to undergo osteogenic differentiation in vitro, form ectopic bone in vivo, and heal bone defects of the skull and long bones.…”

Treatment With a Growth Factor–Protein Mixture Inhibits Formation of Mineralized Nodules in Osteogenic Cell Cultures Grown on Titanium

“…(J Histochem Cytochem 57:265-276, 2009) K E Y W O R D S cell culture osteoblasts growth factors cell proliferation cell differentiation mineralization titanium THE ABILITY to induce new bone formation around endosseous implants is of critical importance for improving healing, increasing stability, and accelerating functional loading. Various regenerative therapies with growth factors (GFs) have been applied to promote and, in some cases, to induce new bone formation in bone defects, at sites of fracture healing, and around metal implant devices (Bessho et al 1999;Ramoshebi et al 2002;Schliephake 2002;Kloen et al 2003). Recombinant human bone morphogenetic proteins (rhBMPs) and transforming growth factor b (rhTGF-b) have been shown in various experimental models to improve key parameters associated with successful osseointegration (Bessho et al 1999;Clokie and Bell 2003;De Ranieri et al 2005;Jones et al 2006;Hall et al 2007;Liu et al 2007).…”

Effects of a Mixture of Growth Factors and Proteins on the Development of the Osteogenic Phenotype in Human Alveolar Bone Cell Cultures

“…In bone tissue, therapies with GFs have been applied to promote, and in some cases to induce, desirable amounts of new bone formation in bone defects, in sites of fracture healing, and adjacent to metal implant devices (Bessho et al 1999;Ramoshebi et al 2002;Schliephake 2002;Kloen et al 2003). Considering that in the body, cells are exposed to diverse GFs simultaneously, ideally any therapy should involve a mixture of GFs with similarities to those implicated in bone tissue healing (Cheifetz et al 1996;Roethy et al 2001;Raiche and Puleo 2004;Arosarena and Puleo 2007).…”