Delivery of cellular factors to regulate bone healing

Alexander Haumer; Paul Emile Bourgine; Paola Occhetta; Gordian Born; Roberta Tasso; Ivan Martin

doi:10.1016/j.addr.2018.01.010

Delivery of cellular factors to regulate bone healing

Adv Drug Deliv Rev. 2018 Apr:129:285-294. doi: 10.1016/j.addr.2018.01.010. Epub 2018 Jan 31.

Authors

Alexander Haumer¹, Paul Emile Bourgine², Paola Occhetta³, Gordian Born⁴, Roberta Tasso⁵, Ivan Martin⁶

Affiliations

¹ Department of Biomedicine, University Hospital Basel, University of Basel, Switzerland; Department of Biomedical Engineering, University of Basel, Switzerland. Electronic address: alexander.haumer@usb.ch.
² Department of Biomedicine, University Hospital Basel, University of Basel, Switzerland; Department of Biomedical Engineering, University of Basel, Switzerland. Electronic address: paul.bourgine@usb.ch.
³ Department of Biomedicine, University Hospital Basel, University of Basel, Switzerland; Department of Biomedical Engineering, University of Basel, Switzerland. Electronic address: paola.occhetta@usb.ch.
⁴ Department of Biomedicine, University Hospital Basel, University of Basel, Switzerland; Department of Biomedical Engineering, University of Basel, Switzerland. Electronic address: gordian.born@unibas.ch.
⁵ Ospedale Policlinico San Martino-IST, IRCCS per l'Oncologia, Genova, Italy.
⁶ Department of Biomedicine, University Hospital Basel, University of Basel, Switzerland; Department of Biomedical Engineering, University of Basel, Switzerland. Electronic address: ivan.martin@usb.ch.

PMID: 29357301
DOI: 10.1016/j.addr.2018.01.010

Abstract

Bone tissue has a strong intrinsic regenerative capacity, thanks to a delicate and complex interplay of cellular and molecular processes, which tightly involve the immune system. Pathological settings of anatomical, biomechanical or inflammatory nature may lead to impaired bone healing. Innovative strategies to enhance bone repair, including the delivery of osteoprogenitor cells or of potent cytokines/morphogens, indicate the potential of 'orthobiologics', but are not fully satisfactory. Here, we review different approaches based on the delivery of regenerative cues produced by cells but in cell-free, possibly off-the-shelf configurations. Such strategies exploit the paracrine effect of the secretome of mesenchymal stem/stromal cells, presented in soluble form, shuttled through extracellular vesicles, or embedded within the network of extracellular matrix molecules. In addition to osteoinductive molecules, attention is given to factors targeting the resident immune cells, to reshape inflammatory and immunity processes from scarring to regenerative patterns.

Keywords: Bone repair; Extracellular matrix; Extracellular vesicles; Immunomodulation; Inflammation; Mesenchymal stem cells; Paracrine factors; Regenerative medicine; Tissue engineering.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Bone and Bones / immunology*
Extracellular Matrix / immunology*
Extracellular Vesicles / immunology*
Humans
Mesenchymal Stem Cells / immunology*
Wound Healing / immunology*