A Multi‐Functional Implant Induces Bone Formation in a Diabetic Model

Behnoush Khorsand; Timothy M Acri; Anh‐Vu Do; John E Femino; Emily Petersen; Douglas C Fredericks; Aliasger K Salem

doi:10.1002/adhm.202000770

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Journal article

A Multi‐Functional Implant Induces Bone Formation in a Diabetic Model

Behnoush Khorsand, Timothy M Acri, Anh‐Vu Do, John E Femino, Emily Petersen, Douglas C Fredericks and Aliasger K Salem

Advanced healthcare materials, Vol.9(18), 2000770

08/19/2020

DOI: 10.1002/adhm.202000770

PMID: 32815306

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https://www.ncbi.nlm.nih.gov/pmc/articles/12236994View

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Abstract

Patients with diabetes mellitus (DM) have defective healing of bone fractures. It was previously shown that nonviral gene delivery of plasmid DNA (pDNA) that independently encodes bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2), acts synergistically to promote bone regeneration in a DM animal model. Additionally, both insulin (INS) and the hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) (VD3) have independently been shown to play key roles in regulating bone fracture healing in DM patients. However, these individual therapies fail to adequately stimulate bone regeneration, illustrating a need for novel treatment of bone fractures in diabetic patients. Here, the ability of local delivery of INS and VD3 along with BMP-2 and FGF-2 genes is investigated to promote bone formation ectopically in Type-2 diabetic rats. A composite consisting of VD3 and INS is developed that contains poly(lactic-co-glycolic acid) microparticles (MPs) embedded in a fibrin gel surrounded by a collagen matrix that is permeated with polyethylenimine (PEI)-(pBMP-2+pFGF-2) nanoplexes. Using a submuscular osteoinduction model, it is demonstrated that local delivery of INS, VD3, and PEI-(pBMP-2+pFGF-2) significantly improves bone generation compared to other treatments, thusimplicating this approach as a method to promote bone regeneration in DM patients with bone fractures.

Details

Title: Subtitle: A Multi‐Functional Implant Induces Bone Formation in a Diabetic Model
Creators: Behnoush Khorsand - Department of Pharmaceutical Sciences and Experimental TherapeuticsUniversity of Iowa College of Pharmacy Iowa City IA 52242 USA
Timothy M Acri - Department of Pharmaceutical Sciences and Experimental TherapeuticsUniversity of Iowa College of Pharmacy Iowa City IA 52242 USA
Anh‐Vu Do - Department of Pharmaceutical Sciences and Experimental TherapeuticsUniversity of Iowa College of Pharmacy Iowa City IA 52242 USA
John E Femino - Department of Orthopedics and RehabilitationUniversity of Iowa Iowa City IA 52242 USA
Emily Petersen - Department of Orthopedics and RehabilitationUniversity of Iowa Iowa City IA 52242 USA
Douglas C Fredericks - Department of Orthopedics and RehabilitationUniversity of Iowa Iowa City IA 52242 USA
Aliasger K Salem - Department of Pharmaceutical Sciences and Experimental TherapeuticsUniversity of Iowa College of Pharmacy Iowa City IA 52242 USA
Resource Type: Journal article
Publication Details: Advanced healthcare materials, Vol.9(18), 2000770
DOI: 10.1002/adhm.202000770
PMID: 32815306
NLM abbreviation: Adv Healthc Mater
ISSN: 2192-2640
eISSN: 2192-2659
Grant note: DOI: 10.13039/100011343, name: Holden Comprehensive Cancer Center, University of Iowa, award: P30CA086862
Language: English
Date published: 08/19/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9984216709802771

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