Richard Oreffo, a professor of Musculoskeletal Science at the University of Southampton in England, and colleagues developed 3-D biocompatible hydrogels by formulating two cationic polymers, chitosan (derived from shrimp shells) and poly-L-lactide (PLA) with polyvinyl acetate (PVA). The hydrogels proved stable under cell‐culture conditions, and facilitated skeletal cell proliferation into fibroblasts leading to skeletal tissue regeneration. This promising chitosan-based 3-D scaffold material can accommodate a variety of materials, such as DNA, proteins, and peptides.
Skeletal tissue regeneration is often required following trauma, where bone and/or cartilage loss may be experienced. This continues to be a significant driver for the development of biomaterials with a 3D structural network that is biocompatible and biodegradable. Biopolymer or solvent blending processing can avoid complications associated with conventional thermal or mechanical polymer blending or synthesis. This can open up large areas for these materials in simplifying regulatory pathways towards in vivo application and translation into clinical use.
The research group tested hundreds of combinations of plastics and biomaterials, to identify a blend that was biocompatible, robust, lightweight, and able to support bone stem cell proliferation. Results from in vitro and animal in vivo testing unveiled the optimal formulation of the chitosan + PLA + PVA blended 3-D hydrogel scaffold. The material resulted in a tough yet highly porous scaffold material. This may make it an ideal scaffold for a broken bone – a placeholder structure that can be replaced with real bone tissue as the body heals.
The research group tested hundreds of combinations of plastics and biomaterials, to identify a blend that was biocompatible, robust, lightweight, and able to support bone stem cell proliferation. Results from in vitro and animal in vivo testing unveiled the optimal formulation of the chitosan + PLA + PVA blended 3-D hydrogel scaffold. The material resulted in a tough yet highly porous scaffold material. This may make it an ideal scaffold for a broken bone – a placeholder structure that can be replaced with real bone tissue as the body heals.
The material is a honeycomb-like scaffold structure that allows blood to flow through it, enabling stem cells from the subjects’ bone marrow to attach to the material and grow new bone. The implanted material then slowly biodegrades as it is replaced by newly grown bone. The polymer “has this lovely honeycomb structure,” Oreffo said. That allows living cells to “crawl all over it. Blood vessels can penetrate it. So it’s really nice.”
Chitosan is a linear polysaccharide composed of randomly distributed β-(1→4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). It is made by treating the chitin shells of shrimp and other crustaceans with an alkaline substance, like sodium hydroxide.
Poly(vinyl acetate) is known as wood, white, carpenter’s, school, PVA, or Elmer’s glue . Its an aliphatic rubbery synthetic polymer with the formula (C4H6O2)n. It belongs to the polyvinyl ester family, with formula [RCOOCHCH2]. It is a type of thermoplastic.
Polylactic acid or polylactide (PLA) is a thermoplastic aliphatic polyester derived from renewable resources. It is considered a bioplastic. In 2010, PLA had the second highest consumption volume of any bioplastic of the world.
Oreffo’s team tested the polymer in mice that had parts of their femur bones removed. The resulting hole was a size “that won’t heal normally,” Oreffo said. “We put these scaffolds into that [gap] and seen their repair over four to eight weeks.” Further, when the scaffold was seeded with human bone stem cells, the bone healed faster, but even without the stem cells, the mice’s bones began to fill in along the scaffolding structure.
In humans, the structure should serve to repair bone breaks that are too severe to heal on their own. “If you’ve had a car accident where you’ve had significant bone breaks … ideally, you want your own stem cells in there,” Oreffo said. “This is a real opportunity: A scaffold that can be colonized with the patient’s own stem cells.”
Researchers worldwide are pursuing approaches to healing bones using various hydrogels to make up 3-D scaffolds and combine them with stem cells. For example researchers are using methods to include nanoparticles with chitosan in bone and tissue regeneration.
