Encapsulation of Cells in Hyaluronic Encapsulation of Cells in Hyaluronic Acid as a Means of Cell DeliveryAcid as a Means of Cell Delivery

Daniel Wilson, 11/15/2006Daniel Wilson, 11/15/2006

What is a cell delivery system?What is a cell delivery system? A cell delivery system is a A cell delivery system is a

vector by which cells can vector by which cells can be implanted into the body.be implanted into the body.

The delivery system should The delivery system should support (limited) cell support (limited) cell proliferation, maturation, proliferation, maturation, and function.and function.

Many different variations Many different variations including ceramic and including ceramic and polymer scaffolds as well polymer scaffolds as well as injectable hydrogels.as injectable hydrogels.

Polyester scaffold

http://www.cbmm.lodz.pl/res/sppb_big2.jpg

Why Use Injectable Hydrogels as a Why Use Injectable Hydrogels as a Delivery Mechanism?Delivery Mechanism?

Minimally invasive Minimally invasive procedureprocedure

Shape-formingShape-forming

Conducive to cell support – Conducive to cell support – highly permeable to oxygen highly permeable to oxygen and nutrients.and nutrients.

BiodegradibilityBiodegradibility

Easy incorporation of Easy incorporation of therapeutics such as growth therapeutics such as growth factorsfactors

http://www.wwu.edu/depts/healthyliving/PE511info/arthritis/oatreatment.htm

Pure HA?Pure HA? Pure HA has met significant success

as a dermal implant for cosmetics and hormone release1.

“Hyaluronan hydrogels resist attachment and spreading of fibroblasts”2. Hydrophilic and poly-anionic surfaces restrict attachment.

Decreased viscocity with increased temperature leads to difficulty in controlling placement as well as stasis of implant.

1 Anna Gutowska, Gyeongmoon Jeong, Marek Jasionowski. “Injectable Gels for TissueEngineering.” The Anatomical Record 263 (2001):342–3492 Xiao Zheng Shu, Kaustabh Ghosh, Yanchun Liu, Fabio S. Palumbo3 Yi Luo, Richard A. Clark,Glenn D. Prestwich. “Attachment and spreading of fibroblasts on an RGDpeptide–modified injectable hyaluronan hydrogel.” Journal of Biomedical Materials Research. Part A. 63(2) (2004): 365-75.

Alternative HA-derived Cell Alternative HA-derived Cell Delivery SystemsDelivery Systems

Hydrogel beads.

Conventional or electrospun HA scaffolds.

“RGD” peptide-modified injectable HA hydrogels.

“Fabrication of Hyaluronic Acid Hydrogel Beads for Cell Encapsulation.” Biotechnol. Prog. 2006, 22, 297-302

“Electrospun three-dimensional hyaluronic acid nanofibrous scaffolds.” Biomaterials 27 (2006): 3782–3792

RGD peptide-modified injectable HA hydrogels

Arg-Gly-Asp (RGD) promotes cellular attachment and proliferation by binding through integrin receptors.

RGD can be added to polyethylene glycol diacrylate (PEGDA) via a conjugate addition reaction.

The RGD/PEGDA complex can then be added to thiol-modified HA (HA-DTPH) to form a cytocompatible hydrogel.

“Attachment and spreading of fibroblasts on an RGD peptide–modified injectable hyaluronan hydrogel.” Journal of Biomedical Materials Research. Part A. 63(2) (2004): 365-75.

Yea, fancy pants, but does it work?

In vitro: 31 years old Caucasian female fibroblasts reached concentrations of 80% of the density of a polystyrene scaffold control after 4 days. However, hydrogel surfaces exhibited much greater proliferation of fibroblasts than the interior of the gels.

In vivo: murine fibroblasts were injected into nude mice. “RGD peptides accelerated the formation of fibrous tissue in vivo, with increased production of procollagen by the fibroblasts in the newly formed fibrous tissue at 4 weeks post-injection.”

Fibroblast-seeded HA-DTPH–PEGDA hydrogel. “Attachment and spreading of fibroblasts on an RGD peptide–modified injectable hyaluronan hydrogel.” Journal of Biomedical Materials Research. Part A. 63(2) (2004): 365-75.

The Wrap Use of pure HA as a cell

delivery system, especially for fibroblasts, is non-condusive to cell proliferation.

In order to encourage proliferation of fibroblasts in HA, some form of cell-anchoring must be used.

Watch Out For:

Glenn D. Prestwich from the University of Utah. It seems that if it has to do with HA, he has done it.

http://www.pharmacy.utah.edu/medchem/prestwich/aboutus.html