Gelatinized Copper–Capillary Alginate Gel Functions as an Injectable Tissue Scaffolding System for Stem Cell Transplants

Abstract

In severe hypoxic–ischemic brain injury, cellular components such as neurons and astrocytes are injured or destroyed along with the supporting extracellular matrix. This presents a challenge to the field of regenerative medicine since the lack of extracellular matrix and supporting structures makes the transplant milieu inhospitable to the transplanted cells. A potential solution to this problem is the use of a biomaterial to provide the extracellular components needed to keep cells localized in cystic brain regions, allowing the cells to form connections and repair lost brain tissue. Ideally, this biomaterial would be combined with stem cells, which have been proven to have therapeutic potentials, and could be delivered via an injection. To study this approach, we derived a hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper–capillary alginate gel (GCCAG). We then demonstrated that our multipotent astrocytic stem cells (MASCs) could be maintained in GCCAG scaffolds for up to 2 weeks in vitro and that the cells retained their multipotency. We next performed a pilot transplant study in which GCCAG was mixed with MASCs and injected into the brain of a neonatal rat pup. After a week in vivo, our results showed that: the GCCAG biomaterial did not cause a significant reactive gliosis; viable cells were retained within the injected scaffolds; and some delivered cells migrated into the surrounding brain tissue. Therefore, GCCAG tissue scaffolds are a promising, novel injectable system for transplantation of stem cells to the brain.

An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats

“…Gelatin incorporated into the formulation enables cell adhesion, and this new formulation cross-linked using EDC chemistry was implemented as an injectable stem cell delivery/retention system [23,24]. Capgel was previously utilized by our group for neuroregenerative tissue scaffolding and was also shown to support growth of mouse embryonic stem cells [8]. Capgel could be useful to deliver stem cells for cardiac repair or molecules that limit cell death, promote vessel formation, or recruit stem cells for repair [23].…”

“…All other chemicals used were purchased from Fisher Scientific (Pittsburgh, PA) and Sigma-Aldrich (St. Louis, MO). Capgel was synthesized as previously described [8]. Briefly, a solution of 2% (w/v) alginate and 2.6% (w/v) oligo-gelatin was poured into an alginate-coated glass petri dish; a primary membrane was formed on the top of the gel using a Kimwipe ® soaked in 0.5M CuSO 4 .…”

A degradable, bioactive, gelatinized alginate hydrogel to improve stem cell/growth factor delivery and facilitate healing after myocardial infarction

“…We therefore propose for use post-MI an innovative biomaterial hydrogel (Capgel) that is both structured and bioactive [9]. This self-assembled material is composed of low M w gelatin (hydrolyzed collagen I) and alginate [a negatively charged, linear polysaccharide composed of β-1,4-linked D-mannuronic acid (M) and α-1,4-linked L-guluronic acid (G) monosaccharides].…”

“…A potential breakthrough post-MI therapy is intramyocardial injection of a novel, degradable, bioactive material that has a unique capillary-like microstructure of uniform channels (termed Capgel, Fig. 1) [8,9]. We hypothesize that intramyocardial injection of Capgel will modulate scar tissue formation and stimulate repair of ischemia-injured/infarcted myocardial tissue to help preserve cardiac contractile function.…”

Intranasal delivery of stem cells to the brain

“…These niches may occur in the same location as the disorders, which would result in an inaccurate conclusion that stem cells migrate to injured areas. Some researchers [81] have used multi-potent astrocytic stem cells maintained in a hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper-capillary alginate gel and injected them into the brain of a neonatal rat pup. After a week in vivo, viable cells were retained within the injected scaffolds, and some delivered cells migrated into the surrounding brain tissue.…”