Growth factor delivery strategies for rotator cuff repair and regeneration

Anupama Prabhath; Varadraj N Vernekar; Enid Sanchez; Cato T Laurencin

doi:10.1016/j.ijpharm.2018.01.006

Growth factor delivery strategies for rotator cuff repair and regeneration

Int J Pharm. 2018 Jun 15;544(2):358-371. doi: 10.1016/j.ijpharm.2018.01.006. Epub 2018 Jan 6.

Authors

Anupama Prabhath¹, Varadraj N Vernekar², Enid Sanchez², Cato T Laurencin³

Affiliations

¹ Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA.
² Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.
³ Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, 06269, USA; Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, 06269, USA. Electronic address: laurencin@uchc.edu.

Abstract

The high incidence of degenerative tears and prevalence of retears (20-95%) after surgical repair makes rotator cuff injuries a significant health problem. This high retear rate is attributed to the failure of the repaired tissue to regenerate the native tendon-to-bone insertion (enthesis). Biological augmentation of surgical repair such as autografts, allografts, and xenografts are confounded by donor site morbidity, immunogenicity, and disease transmission, respectively. In contrast, these risks may be alleviated via growth factor therapy, which can actively influence the healing environment to promote functional repair. Several challenges have to be overcome before growth factor delivery can translate into clinical practice such as the selection of optimal growth factor(s) or combination, identification of the most efficient stage and duration of delivery, and the design considerations for the delivery device. Emerging insight into the injury-repair microenvironment and our understanding of growth factor mechanisms in healing are informing the design of advanced delivery scaffolds to effectively treat rotator cuff tears. Here, we review potential growth factor candidates, design parameters and material selection for growth factor delivery, innovative and dynamic delivery scaffolds, and novel therapeutic targets from tendon and developmental biology for the structural and functional healing of rotator cuff repair.

Keywords: Delivery; Enthesis; Growth factor; Rotator cuff; Scaffold; Tendon.

Publication types

Review

MeSH terms

Arthroplasty / adverse effects
Arthroplasty / methods
Drug Delivery Systems / methods*
Humans
Incidence
Intercellular Signaling Peptides and Proteins / administration & dosage*
Regeneration / drug effects*
Rotator Cuff / drug effects
Rotator Cuff / physiology*
Rotator Cuff Injuries / epidemiology
Rotator Cuff Injuries / therapy*
Wound Healing / drug effects

Substances

Intercellular Signaling Peptides and Proteins

Grants and funding

DP1 AR068147/AR/NIAMS NIH HHS/United States