Cited by 15Hydrogels: synthesis, properties, applicationsCollagen: Extraction and CharacterizationSilk-based biomaterials and applications

Effects of Tunable Keratin Hydrogel Erosion on Recombinant Human Bone Morphogenetic Protein 2 Release, Bioactivity, and Bone Induction

Open access
Cohen, David Joshua, Hyzy, Sharon L., Haque, Salma, Olson, Lucas C., Boyan, Barbara D., Saul, Justin M., Schwartz, Zvi·2018·Tissue Engineering Part A

Abstract

Keratin proteins derived from human hair are known to contain a large number of cysteine residues. In hydrogels composed of oxidatively extracted keratin (keratose, KOS), sulfonic acid on the cysteine residues prevents disulfide cross-linking. Reductively extracted keratin (kerateine, KTN) has thiol groups on cysteine residues that can form disulfide cross-links. The rates of keratin hydrogel erosion and, in some cases, drug release can be tuned by manipulating disulfide cross-linking levels via the KOS:KTN ratio. To investigate the use of these hydrogel mixtures as carriers for growth factors in tissue engineering applications, we fabricated 15% (w/v) hydrogels with KOS:KTN ratios of 100:0, 70:30, 50:50, 30:70, and 0:100 with and without recombinant human bone morphogenetic protein 2 (rhBMP-2). We compared the keratin rhBMP-2 carriers with the clinical system of resorbable collagen sponges, which are known to elicit problems such as edema, inflammation, and ectopic bone growth. In vitro , hydrogels with increasing levels of KOS eroded more rapidly. However, there was little difference among the various keratin formulations in amounts of rhBMP-2 released after 12 h. Collagen had similar total rhBMP-2 release, although with significantly greater release over the first 12 h compared with all keratin formulations, except for 0:100 KOS:KTN. However, increasing levels of KTN led to increasing release of bioactive rhBMP-2 based on the stimulation of alkaline phosphatase activity in MC3T3-E1 cells by the hydrogel releasate. Micro-CT analysis of heterotopic bone growth in a mouse model indicated that with rhBMP-2, the 30:70 formulation led to significant increases in bone volume compared with KOS and collagen, whereas the 50:50 formulation led to significant bone volume increases compared with all of the formulations except for 30:70 KOS:KTN. Histological analysis of images from the heterotopic mouse model indicated differences in the quality and type of bone among the various carriers of rhBMP-2. KOS:KTN in the ratio of 70:30 with rhBMP-2 elicited greater amounts of cortical bone, whereas the ratio 30:70 resulted in greater amounts of marrow, total bone, and residual material. The results indicate that in addition to the rate of rhBMP-2 release, the carrier itself can have important effects on bone volume, type, distribution, and quality. Impact Statement: Recombinant human bone morphogenetic protein 2 (rhBMP-2) delivery from collagen sponges for bone formation is an important clinical example of growth factors in tissue engineering. Side effects from rhBMP-2 burst release and rapid collagen resorption have led to investigation of alternative carriers. Here, keratin carriers with tunable erosion rates were formulated by varying disulfide crosslinking via ratios of oxidatively (keratose) to reductively (kerateine) extracted keratin. In vitro rhBMP-2 bioactivity increased with kerateine content, reaching levels greater than with collagen. Heterotopic bone formation in a mouse model depended on the keratin formulation, highlighting the importance of the growth factor carrier.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1089/ten.tea.2017.0471

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. [10]Van Dyke M. Keratin. In: Neves N.M., and Reis R.L., eds. Biomaterials from Nature for Advanced Devices and Therapies. Hoboken, NJ: John Wiley & Sons, Inc., 2016, p. 93 [Google Scholar]
  2. [14]Roy D., Kowalczewski C., Hall R., et al. Antibiotic-loaded keratin hydrogels prevent infection in a full-thickness porcine excision wound. Tissue Eng Part A 20, S64, 2014 [Google Scholar]
  3. [29]ASTM International. Standard Guide for In Vivo Evaluation of Osteoinductive Potential for Materials Containing Demineralized Bone (DBM). West; Conshohocken, PA: ASTM International, 2013 [Google Scholar]
  4. [45]Boyan B.D., Lohmann C.H., Somers A., et al. Potential of porous poly-D,L-lactide-co-glycolide particles as a carrier for recombinant human bone morphogenetic protein-2 during osteoinduction in vivo. J Biomed Mater Res 46, 51, 1999 [DOI] [PubMed] [Google Scholar]

Cited by

Sorted by citations

Authors
Cohen, D. J., Hyzy, S. L., Haque, S., Olson, L. C., Boyan, B. D., Saul, J. M., & Schwartz, Z.
Affiliations
  • Virginia Commonwealth University (US)
  • Miami University (US)
  • Georgia Institute of Technology (US)
  • The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Saul, Justin M.
Venue
Tissue Engineering Part A
Published
2018-09-06
Volume
24
Issue
21-22
Pages
1616-1630
ISSN
  • 1937-3341 (ISSN-L)
  • 1937-335X
OpenAlex
W2889974115
Cited by
15
References
46
Citations by year
2025: 3 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 3
FWCI
0.38
Type
journal article
Language
en
Open access
Locations
  • Tissue Engineering Part A (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR061391)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
  • Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
Keywords
keratin hydrogels, rhBMP-2, disulfide cross-linking, keratosis, growth factor delivery, bone induction, ectopic bone formation, collagen sponge, alkaline phosphatase activity, MC3T3-E1 cells
MeSH terms
Animals, Cell Line, Delayed-Action Preparations, Humans, Keratins, Osteogenesis, Recombinant Proteins, Hydrogels, Mice, Bone Morphogenetic Protein 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review