Abstract

Defects in craniofacial bones occur congenitally, after high-energy impacts, and during the course of treatment for stroke and cancer. These injuries are difficult to heal due to the overwhelming size of the injury area and the inflammatory environment surrounding the injury. Significant inflammatory response after injury may greatly inhibit regenerative healing. We have developed mineralized collagen scaffolds that can induce osteogenic differentiation and matrix biosynthesis in the absence of osteogenic media or supplemental proteins. The amniotic membrane is derived from placentas and has been recently investigated as an extracellular matrix to prevent chronic inflammation. Herein, we hypothesized that a mineralized collagen–amnion composite scaffold could increase osteogenic activity in the presence of inflammatory cytokines. We report mechanical properties of a mineralized collagen–amnion scaffold and investigated osteogenic differentiation and mineral deposition of porcine adipose-derived stem cells within these scaffolds as a function of inflammatory challenge. Incorporation of amniotic membrane matrix promotes osteogenesis similarly to un-modified mineralized collagen scaffolds, and increases in mineralized collagen–amnion scaffolds under inflammatory challenge. Together, these findings suggest that a mineralized collagen–amnion scaffold may provide a beneficial environment to aid craniomaxillofacial bone repair, especially in the course of defects presenting significant inflammatory complications.

Highlights

  • The immune system plays a vital role in the outcome of tissue regeneration in bone defects, contributing to successful healing of the injury or inhibiting bone formation

  • Overall number of porcine adipose-derived stem cells (pASC) increased in the mineralized collagen scaffolds over the course of 28 days, but the overall number of pASC within the mineralized collagen–amnion scaffolds remained constant over the course of the experiment (Fig. 5A)

  • We subsequently examined whether inclusion of amniotic membrane matrix within the mineralized collagen scaffold reduced the deleterious effect of 1 ng/ml soluble IL-1b upon pASC bioactivity, monitoring pASC metabolic activity and cell number over the course of 28 days

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Summary

Introduction

The immune system plays a vital role in the outcome of tissue regeneration in bone defects, contributing to successful healing of the injury or inhibiting bone formation. Many strategies to promote bone regeneration exist, most commonly through the use of autografts and allografts. These strategies involve extensive processing of the bone substitute and residual material can be difficult to completely remove, causing an immune response [1, 2].

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