Vitamin D might reduce suture infection when time-released from nano-structure suture – Nov 2017

Nanofiber sutures promote production of infection-thwarting peptide OSU Press Release

CORVALLIS, Ore. – Loading nanofiber sutures with vitamin D induces the production of an infection-fighting peptide, new research shows.

The discovery could represent an important advance in the prevention of surgical site infections, a multibillion-dollar challenge each year in the United States alone.

A collaboration that included Adrian Gombart of the Linus Pauling Institute at Oregon State University used coaxial electrospinning deposition and rolling to fabricate sutures that contained 25-hydroxyvitamin D3 and the pam3CSK4 peptide.

A peptide is a compound consisting of two or more amino acids linked in a chain; pam3CSK4’s function is to activate a cell’s toll-like receptor, which in turn triggers immune responses, in which vitamin D plays a key role.

The research showed the sutures released 25D3 – the same form of the vitamin that’s measured in the blood when a patient’s vitamin D levels are tested – on a sustained basis over four weeks. The sutures released pam3CSK4 via an initial burst followed by a four-week prolonged release.

“When the toll-like receptor is activated, you induce a particular enzyme to convert 25D3 to its bioactive form, known as 1,25-dihydroxy vitamin D3, that activates the vitamin D receptor,” Gombart said. “When activity increases, that increases expression of vitamin D receptor target genes, one of which produces the LL-37 peptide, which kills microbes by disrupting their membranes.

“The idea is, if you were to have an infection, the sutures would activate the toll-like receptors and start increasing production of 1,25D3 from the 25D3 that’s being released from sutures – so you get both local induction and an increase in the production of the antimicrobial peptide.”

The study’s corresponding author, Jingwei Xie of the University of Nebraska Medical Center, notes that the anti-infective sutures currently in use contain triclosan, an antibacterial and antifungal agent also found in a variety of consumer products.

“However, the frequent use has resulted in bacterial resistance,” Xie said. “Triclosan also shows a wide range of health risks including endocrine disruption, impaired muscle function, liver damage and the development of cancerous tumors. Compared to the currently available products and treatment options, the anti-infective sutures we develop could circumvent the selection for multidrug resistance and other health-associated shortcomings. The new sutures are also highly configurable and can deliver a variety of bioactive compounds to minimize infection risk, optimize healing and minimize scarring. None of the currently available sutures has this level of function.”

Gombart adds that the vitamin D delivered by the sutures could also affect additional genes involved in the immune response as well as LL-37.

“So a compound like vitamin D not only targets bacteria via the antimicrobial peptide, but other immune responses can also be modulated to help combat infection,” he said. “Targeting on multiple fronts helps minimize the chance of resistance.”

The University of Nebraska Medical Center, the National Institutes of Health, and the Otis Glebe Medical Research Foundation supported this research.

Also involved in the collaboration were researchers from the Joan C. Edwards School of Medicine at Marshall University in Huntington, West Virginia, and the Chongqing Academy of Animal Sciences & Key Laboratory of Pig Industry Sciences in Chongqing, China.

Findings were recently published in Nanomedicine.

UNMC researcher receives $1.3 million grant to study use of nanofiber sutures to reduce infections

A biomedical engineer at the University of Nebraska Medical Center has been awarded a four-year, $1.3 million grant by the National Institutes of Health to study using nanofiber sutures to deliver immune-modulating compounds at surgical sites in order to prevent costly infections.

The nanofiber sutures that researchers are testing contain vitamin D, which is thought to be able to induce production of an infection-fighting peptide at the surgical site.

Jingwei Xie, the principal investigator on the grant, said infections at surgical sites are a common problem, affecting as many as 300,000 patients a year in the United States. “If we could reduce these infections, it would be a major breakthrough,” he said in a statement.

The infections include those in the area of the skin where incisions are made, those below the incision in muscles and their surrounding tissues and in other parts of the body involved in the surgery. They’re the most common and costly of all hospital-acquired infections, accounting for 20 percent of all such infections and occurring in up to an estimated 5 percent of patients undergoing inpatient surgery. The estimated annual cost ranges from $3.5 billion to $10 billion, according to UNMC.

The research, published recently in the journal Nanomedicine, indicated that the sutures released vitamin D on a sustained basis over four weeks. They released an accompanying peptide involved in the response in an initial burst followed by sustained release over four weeks.

Xie said the anti-infective sutures currently in use contain triclosan, which also is found in hand soaps and other consumer products. When used frequently, however, triclosan sutures have resulted in bacterial resistance.

Xie is an assistant professor in UNMC’s transplant surgery department and the Holland Regenerative Medicine Program. He is collaborating with Adrian Gombart, an associate professor of biochemistry and biophysics at Oregon State University’s Linus Pauling Institute. OSU is conducting the testing on the transgenic mice.

Nanofiber-based sutures induce endogenous antimicrobial peptide - Journal article

Nanomedicine (Lond). 2017 Nov;12(21):2597-2609. doi: 10.2217/nnm-2017-0161. Epub 2017 Sep 29.
Chen S1, Ge L2, Gombart AF3, Shuler FD4, Carlson MA5, Reilly DA6, Xie J1.

1 Dept. of Surgery-Transplant & Mary & Dick Holland Regenerative Medicine Program, U. of Nebraska Medical Center, Omaha, NE 68198, USA.
2 Chongqing Academy of Animal Sciences & Key Laboratory of Pig Industry Sciences, Ministry of Agriculture, Chongqing, China.
3 Department of Biochemistry & Biophysics & Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
4 Department of Orthopedic Surgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
5 Department of Surgery-General Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA.
6 Department of Surgery-Plastic Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA.

AIM: The aim of this study was to develop nanofiber-based sutures capable of inducing endogenous antimicrobial peptide production.

METHODS: We used co-axial electrospinning deposition and rolling to fabricate sutures containing pam3CSK4 peptide and 25-hydroxyvitamin D3 (25D3).

RESULTS:
The diameters and mechanical properties of the sutures were adjustable to meet the criteria of United States Pharmacopeia designation. 25D3 exhibited a sustained release from nanofiber sutures over 4 weeks. Pam3CSK4 peptide also showed an initial burst followed by a sustained release over 4 weeks. The co-delivery of 25D3 and pam3CSK4 peptide enhanced cathelicidin antimicrobial peptide production from U937 cells and keratinocytes compared with 25D3 delivery alone. In addition, the 25D3/pam3CSK4 peptide co-loaded nanofiber sutures did not significantly influence proliferation of keratinocytes, fibroblasts, or the monocytic cell lines U937 and HL-60.

CONCLUSION: The use of 25D3/pam3CSK4 peptide co-loaded nanofiber sutures could potentially induce endogenous antimicrobial peptide production and reduce surgical site infections.

PMID: 28960168 PMCID: PMC5674207 Available on 2018-11-01 DOI: 10.2217/nnm-2017-0161

Publisher wants $67 for PDF – but will be $0 after Nov 2018