Biomineralized Polysaccharide Capsules for Encapsulation, Organization, and Delivery of Human Cell Types and Growth Factors

Abstract

The construction of biomimetic microenvironments with specific chemical and physical cues for the organization and modulation of a variety of cell populations is of key importance in tissue engineering. We show that a range of human cell types, including promyoblasts, chondrocytes, adipocytes, adenovirally transduced osteoprogenitors, immunoselected mesenchymal stem cells, and the osteogenic factor, rhBMP‐2 (BMP: bone morphogenic protein), can be successfully encapsulated within mineralized polysaccharide capsules without loss of function in vivo. By controlling the extent of mineralization within the alginate/chitosan shell membrane, degradation of the shell wall and release of cells or rhBMP‐2 into the surrounding medium can be regulated. In addition, we describe for the first time the ability to generate bead‐in‐bead capsules consisting of spatially separated cell populations and temporally separated biomolecule release, entrapped within alginate/chitosan shells of variable thickness, mineralization, and stability. Such materials offer significant potential as multifunctional scaffolds and delivery vehicles in tissue regeneration of hard and soft tissues.

Crosslink Effect and Albumin Adsorption onto Chitosan/Alginate Multilayered Systems: An in situ QCM‐D Study

“…[22] ALG is an anionic biopolymer extracted from marine brown algae and one of the natural origin polymers with more use in tissue engineering, especially for growth factor delivery and cell encapsulation. [23] The potential of the quartz crystal microbalance with dissipation monitoring (QCM-D), as an important tool for following in situ the build-up of multilayer assemblies composed by CHI and ALG, will be investigated. Afterwards, the adsorption behavior of human serum albumin (HSA), the major protein constituent of human blood plasma, will also be assessed in real time.…”

Skeletal stem cells: Phenotype, biology and environmental niches informing tissue regeneration

“…Further requirements for tissue regeneration are a supportive scaffold and alginate polysaccharide capsules offer a 3D structure for the encapsulation and organization of cells exploiting this paradigm and can not only support a range of cell skeletal cell types but allow presentation of specific stimuli to direct the formation of a desired tissue as well as allowing mechanical integrity to a cell-tissue construct (Caterson et al, 2001;Alsberg et al, 2002;, Green et al, 2005). We have used human skeletal progenitors encapsulated within alginate/chitosan polysaccharide templates to promote chondrogenesis and looked at the potential to begin to create artificial microenvironments (Pound et al, 2006(Pound et al, , 2007.…”

Biomineralized Polysaccharide Beads for Dual‐Stimuli‐Responsive Drug Delivery

“…[10] Previous studies demonstrated that inorganic/organic hybrid materials [11][12][13][14] were likely to be of generic importance in the design of biocompatible microcapsules because they often exhibit complementary properties, and, in this regard, synthetic approaches based on mimicking natural processes such as biomineralization should be promising. [15][16][17] Biomineralization often involves a diffusioncontrolled deposition of inorganic minerals within porous organic polymeric matrices. Biomineralized polysaccharide capsules have potential applications for cell growth, [15,18] release of functional biomolecules, [17] gene delivery, [19] and the implications therein for tissue engineering.…”

“…[15][16][17] Biomineralization often involves a diffusioncontrolled deposition of inorganic minerals within porous organic polymeric matrices. Biomineralized polysaccharide capsules have potential applications for cell growth, [15,18] release of functional biomolecules, [17] gene delivery, [19] and the implications therein for tissue engineering. [20] For example, Green et al [15] demonstrated both in vitro and in vivo a number of human cell types and immortalized cell lines encapsulated within mineralized polysaccharide capsules, including adipocytes, chondrocytes, bone marrow cells, and mesenchymal stem cells.…”

“…Biomineralized polysaccharide capsules have potential applications for cell growth, [15,18] release of functional biomolecules, [17] gene delivery, [19] and the implications therein for tissue engineering. [20] For example, Green et al [15] demonstrated both in vitro and in vivo a number of human cell types and immortalized cell lines encapsulated within mineralized polysaccharide capsules, including adipocytes, chondrocytes, bone marrow cells, and mesenchymal stem cells. The same group [19] demonstrated that mineralized polysaccharide microcapsules could be used successfully for temporal and spatial delivery of cells and biomolecules for skeletal tissue engineering.…”