Simple signaling molecules for inductive bone regenerative engineering.

Emily K Cushnie,Yusuf M Khan,Cato T Laurencin,Swaminathan Sethuraman,Meng Deng,Kevin W H Lo,Bret D Ulery,Stephen B Doty,Stephen J Nelson,Wei-Chun Chin

doi:10.1371/journal.pone.0101627

Abstract

With greater than 500,000 orthopaedic procedures performed in the United States each year requiring a bone graft, the development of novel graft materials is necessary. We report that some porous polymer/ceramic composite scaffolds possess intrinsic osteoinductivity as shown through their capacity to induce in vivo host osteoid mineralization and in vitro stem cell osteogenesis making them attractive synthetic bone graft substitutes. It was discovered that certain low crystallinity ceramics partially dissociate into simple signaling molecules (i.e., calcium and phosphate ions) that induce stem cells to endogenously produce their own osteoinductive proteins. Review of the literature has uncovered a variety of simple signaling molecules (i.e., gases, ions, and redox reagents) capable of inducing other desirable stem cell differentiation through endogenous growth factor production. Inductive simple signaling molecules, which we have termed inducerons, represent a paradigm shift in the field of regenerative engineering where they can be utilized in place of recombinant protein growth factors.

Highlights

IntroductionIt is estimated that 50% of Americans will suffer from a traumatic bone fracture that requires orthopaedic services before the age of 65 [1], many of which will require the use of bone grafts such as autografts (the patient’s own tissue) or allografts (another person’s tissue)
It is estimated that 50% of Americans will suffer from a traumatic bone fracture that requires orthopaedic services before the age of 65 [1], many of which will require the use of bone grafts such as autografts or allografts
Mononuclear cells were found in a band along von Kossa stained calcium phosphate (CaP) analogous to osteoblasts lining up along mineralizing fronts of remodeled bone tissue

Summary

Introduction

It is estimated that 50% of Americans will suffer from a traumatic bone fracture that requires orthopaedic services before the age of 65 [1], many of which will require the use of bone grafts such as autografts (the patient’s own tissue) or allografts (another person’s tissue). Autografts are of limited supply and can cause significant pain at the graft donor site [2,3], and allografts have the potential to transmit disease and induce an undesirable immune response [4,5]. To overcome these issues, bone graft substitutes have been heavily researched and are utilized in approximately 18–20% of all grafting procedures [6]. Some of the most clinically successful bone graft substitutes utilize scaffold-based systems for the spatio-temporally controlled delivery of recombinant human bone morphogenetic proteins (rhBMPs) [7,8]. By engineering novel materials-based systems capable of adjuvanting the effects of rhBMPs or replacing them all together, clinical outcomes can be significantly improved while greatly decreasing costs

Methods

Results

Conclusion