Reclaiming a Natural Beauty: Whole-Organ Engineering with Natural Extracellular Materials

Abstract

The ability to engineer whole organs as replacements for allografts and xenografts is an ongoing pursuit in regenerative medicine. While challenges remain, including systemic tissue integration with angiogenesis, lymphatiogenesis and neurogenesis, ongoing efforts are working to develop novel technologies to produce implantable engineered scaffolds and potentially engineered whole organs. Natural extracellular matrix materials, commonly utilized in vitro, are now being used as effective, natural, acellular allografts, and are being integrated into nanoscale scaffolds and matrices with programmable responsiveness. Based on the significant use of natural scaffolds for tissue regeneration and bioengineering strategies, this review focuses on recent and ongoing efforts to engineer whole organs, such as the tooth, featuring natural extracellular matrix molecules. Keywordsdecellularization; electrospinning; functional scaffolds; natural extracellular matrices; smart materials; tissue and organ engineering Since the advent of the auricular implant grown on a mouse's back [1,2], whole-organ engineering has been proof-of-concept and a growing pursuit in the field of regenerative medicine. Whole-organ engineering endeavors to create functional organs, in addition to furthering our understanding of the composition of individual tissues, and the interfaces between tissue types. The extracellular matrix (ECM) offers not only a physical structure to house the cells within tissue, but also supplies directions for the morphogenetic process integrated into the tissue. Proliferation, differentiation, adhesion, migration and survival are all intrinsically linked to cell-surface receptor binding sites found on ECM molecules. Natural ECMs consist of proteins and polysaccharides secreted by cells. Many are 'multimodal' molecules with areas for both cell and ECM protein binding sites [3]. Others have written comprehensively on specific natural ECM molecules' and respective functions [4][5][6][7][8]. The two major components to the ECM in organ systems include the basal lamina and the stromal matrix. While the ECM composition can vary from tissue to tissue, the basal lamina, found bordering epithelial sheets, primarily consists of collagen IV and laminins; stromal or interstitial matrices include diverse compositions such as fibrillar collagen I or hyaluronic acid [3]. There are many benefits to incorporating natural materials into engineered tissues and organs. In addition to functional cell and ECM adhesion sites, natural ECM molecules offer improved biocompatibility over synthetic alternatives as well as genetic conservation in terms of use with xenogenic products [8,9]. Over the years, biomaterials have advanced from incorporating inert materials into the body, to creating bioactive and bioresponsive material implantations, in the pursuit of repairing organ functionality or regenerating tissue. The use of natural ECM materials spans these efforts. The main focus of this review is to showcase the latest developments in whole-...

Successful Periodontal Ligament Regeneration by Periodontal Progenitor Preseeding on Natural Tooth Root Surfaces

“…To differentiate DF, PDL, DP, and MSCs toward an osteogenic lineage, cells were seeded at a density of 3,500 cells/cm 2 …”

“…Although theoretically any type of stem cells, matrices, or factors might be suitable for the regeneration of any type of tissue, recent studies have emphasized the benefits of natural extracellular matrices (ECMs) and tissue-specific progenitors for tissue engineering purposes [2]. Examples for the instructive abilities of natural, tissue-specific ECMs include successful cardiac muscle regeneration using a decellularized heart [3], trachea regeneration using cadaveric trachea and stem cell population [4], and induction of lungspecific lineages by acellular natural lung matrix [5].…”

Apatite Microtopographies Instruct Signaling Tapestries for Progenitor-Driven New Attachment of Teeth

“…2 In recent years, the ability of natural ECMs to aide whole organ regeneration has become increasingly important. 3 While most natural ECM scaffolds rapidly disintegrate once removed from the body, the mineralized matrices of bones and teeth remain intact, often for hundreds or thousands of years after the surrounding organism is deceased. On a microenvironmental scale, the surface of these inorganic biological minerals retains a topographic impression of the cells and proteins that once contributed to their formation and contour, providing retrospective witness to the molecular interactions that helped to shape them.…”

Whole-organ engineering with natural extracellular materials

“…Similarly, preliminary analyses in a 5.5 month old porcine molar model have demonstrated some ECM fiber organization within the bioengineered tooth-bud and surrounding alveolar bone. Areas of collagen, keratin and fibronectin were shown to co-localize within vascular regions of the dental pulp as well as in enamel epithelium [98]. Future studies will elucidate further ECM organization and composition in these bioengineered teeth.…”