New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small building blocks, artificial ECM networks from protein polymers or peptide-conjugated synthetic polymers that present bioactive ligands and respond to cell-secreted signals to enable proteolytic remodeling. These materials have already found application in differentiating stem cells into neurons, repairing bone and inducing angiogenesis. Although modern synthetic biomaterials represent oversimplified mimics of natural ECMs lacking the essential natural temporal and spatial complexity, a growing symbiosis of materials engineering and cell biology may ultimately result in synthetic materials that contain the necessary signals to recapitulate developmental processes in tissue- and organ-specific differentiation and morphogenesis.

https://sisu.ut.ee/sites/default/files/quantum/files/synthetic_biomaterials_as_instructive_extracellular_microenvironments_for_morphogenesis_in_tissue_engineering_lutolf_m.p_hubbell_j.a_2005_0.pdf

Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering

During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.

/pdf/myofibroblasts-and-mechano-regulation-of-connective-tissue-nzvxuu0xbh.pdf

Myofibroblasts and mechano-regulation of connective tissue remodelling

Biomaterials have played an enormous role in the success of medical devices and drug delivery systems. We discuss here new challenges and directions in biomaterials research. These include synthetic replacements for biological tissues, designing materials for specific medical applications, and materials for new applications such as diagnostics and array technologies.

Designing materials for biology and medicine

Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

A tissue engineering approach was developed to produce arbitrary lengths of vascular graft material from smooth muscle and endothelial cells that were derived from a biopsy of vascular tissue. Bovine vessels cultured under pulsatile conditions had rupture strengths greater than 2000 millimeters of mercury, suture retention strengths of up to 90 grams, and collagen contents of up to 50 percent. Cultured vessels also showed contractile responses to pharmacological agents and contained smooth muscle cells that displayed markers of differentiation such as calponin and myosin heavy chains. Tissue-engineered arteries were implanted in miniature swine, with patency documented up to 24 days by digital angiography.

https://science.sciencemag.org/content/sci/284/5413/489.full.pdf

Functional arteries grown in vitro.

Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the concentration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immunologically tolerated "tissue" for wound healing and as a model for studying fibroblast function are discussed.

https://www.pnas.org/content/pnas/76/3/1274.full.pdf

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro.

A model of a blood vessel was constructed in vitro. Its multilayered structure resembled that of an artery and it withstood physiological pressures. Electron microscopy showed that the endothelial cells lining the lumen and the smooth muscle cells in the wall were healthy and well differentiated. The lining of endothelial cells functioned physically, as a permeability barrier, and biosynthetically, producing von Willebrand's factor and prostacyclin. The strength of the model depended on its multiple layers of collagen integrated with a Dacron mesh.

https://science.sciencemag.org/content/sci/231/4736/397.full.pdf

A blood vessel model constructed from collagen and cultured vascular cells

Living skin-equivalent grafts consisting of fibroblasts cast in collagen lattices and seeded with epidermal cells were successfully grafted onto the donors of the cells. The grafts were vascularized, did not evoke a homograft reaction, inhibited wound contraction, filled the wound space, and persisted.

https://science.sciencemag.org/content/sci/211/4486/1052.full.pdf

Eugene Bell

Papers

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

A blood vessel model constructed from collagen and cultured vascular cells

Living tissue formed in vitro and accepted as skin-equivalent tissue of full thickness

The reconstitution of living skin.