Application of a Demineralized Cortical Bone Matrix and Bone Marrow-Derived Mesenchymal Stem Cells in a Model of Chronic Rotator Cuff Degeneration

Am J Sports Med. 2018 Jan;46(1):98-108. doi: 10.1177/0363546517727512. Epub 2017 Sep 26.

Abstract

Background: The success of rotator cuff repair is primarily dependent on tendon-bone healing. Failure is common because weak scar tissue replaces the native enthesis, rendering it prone to reruptures. A demineralized bone matrix (DBM) consists of a network of collagen fibers that provide a sustained release of growth factors such as bone morphogenetic proteins. Previous studies have demonstrated that it can regenerate a fibrocartilaginous enthesis.

Hypothesis: The use of a DBM and mesenchymal stem cells (MSCs) at the healing enthesis will result in a higher bone mineral density at the tendon insertion and will enhance the regeneration of a morphologically superior enthesis when compared with an acellular human dermal matrix.

Study design: Controlled laboratory study.

Methods: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Three weeks later, tendon repair was carried out in animals randomized into 3 groups: group 1 received augmentation of the repair with a cortical allogenic DBM (n = 6); group 2 received augmentation with a nonmeshed, ultrathick, acellular human dermal matrix (n = 6); and group 3 underwent tendon-bone repair without a scaffold (n = 6). All animals received 1 × 106 MSCs delivered in fibrin glue to the repair site. Specimens were retrieved at 6 weeks postoperatively for histological analysis and the evaluation of bone mineral density.

Results: All groups demonstrated closure of the tendon-bone gap with a fibrocartilaginous enthesis. Although there were no significant differences in the enthesis maturation and modified Movin scores, repair augmented with a dermal matrix + MSCs exhibited a disorganized enthesis, abnormal collagen fiber arrangement, and greater cellularity compared with other MSC groups. Only repairs augmented with a DBM + MSCs reached a bone mineral density not significantly lower than nonoperated controls.

Conclusion: A DBM enhanced with MSCs can augment rotator cuff healing at 6 weeks and restore bone mineral density at the enthesis to its preinjury levels.

Clinical relevance: Biological augmentation of rotator cuff repair with a DBM and MSCs may reduce the incidence of retears, although further studies are required to determine its effectiveness.

Keywords: demineralized bone matrix; mesenchymal stem cells; rotator cuff; tendon-bone healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acellular Dermis*
  • Animals
  • Biocompatible Materials
  • Bone Density
  • Bone Marrow / pathology
  • Cicatrix
  • Cortical Bone / transplantation*
  • Female
  • Fibrin Tissue Adhesive
  • Fibrocartilage / growth & development
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Rotator Cuff / surgery
  • Rotator Cuff Injuries / pathology
  • Rotator Cuff Injuries / surgery*
  • Tendons / pathology
  • Wound Healing

Substances

  • Biocompatible Materials
  • Fibrin Tissue Adhesive