Journal article
High Molecular Weight Poly(glutamic acid) to Improve BMP2-Induced Osteogenic Differentiation
Molecular pharmaceutics, Vol.19(12), pp.4565-4575
12/05/2022
DOI: 10.1021/acs.molpharmaceut.2c00141
PMCID: PMC9729371
PMID: 35675584
Abstract
FDA-approved bone morphogenetic protein 2 (BMP2) has serious side effects due to the super high dose requirement. Heparin is one of the most well-studied sulfated polymers to stabilize BMP2 and improve its functionality. However, the clinical use of heparin is questionable because of its undesired anticoagulant activity. Recent studies suggest that poly(glutamic acid) (pGlu) has the potential to improve BMP2 bioactivity with less safety concerns; however, the knowledge on pGlu’s contribution remains largely unknown. Therefore, we aimed to study the role of pGlu in BMP2-induced osteogenesis and its potential application in bone tissue engineering. Our data, for the first time, indicated that both low (L-pGlu) and high molecular weight pGlu (H-pGlu) were able to significantly improve the BMP2-induced early osteoblastic differentiation marker (ALP) in MC3T3-E1 preosteoblasts. Importantly, the matrix mineralization was more rapidly enhanced by H-pGlu compared to L-pGlu. Additionally, our data indicated that only α-H-pGlu could significantly improve BMP2’s activity, whereas γ-H-pGlu failed to do so. Moreover, both gene expression and mineralization data demonstrated that α-H-pGlu enabled a single dose of BMP2 to induce a high level of osteoblastic differentiation without multiple doses of BMP2. To study the potential application of pGlu in tissue engineering, we incorporated the H-pGlu+BMP2 nanocomplexes into the collagen hydrogel with significantly elevated osteoblastic differentiation. Furthermore, H-pGlu-coated 3D porous gelatin and chitosan scaffolds significantly enhanced osteogenic differentiation through enabling sustained release of BMP2. Thus, our findings suggest that H-pGlu is a promising new alternative with great potential for bone tissue engineering applications.
Details
- Title: Subtitle
- High Molecular Weight Poly(glutamic acid) to Improve BMP2-Induced Osteogenic Differentiation
- Creators
- Jue Hu - University of IowaZhuozhi Wang - Iowa Institute for Oral Health ResearchJacob M. Miszuk - University of IowaErliang Zeng - University of IowaHongli Sun - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.19(12), pp.4565-4575
- DOI
- 10.1021/acs.molpharmaceut.2c00141
- PMID
- 35675584
- PMCID
- PMC9729371
- NLM abbreviation
- Mol Pharm
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Publisher
- American Chemical Society
- Grant note
- DOI: 10.13039/100008893, name: University of Iowa; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01DE029159, R03DE027491, T90DE023520
- Language
- English
- Date published
- 12/05/2022
- Academic Unit
- Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Biostatistics; Craniofacial Anomalies Research Center; Oral and Maxillofacial Surgery; Dental Research
- Record Identifier
- 9984367731602771
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