Unconventional Biomaterials for Regenerative Engineering

Across different areas of regenerative engineering, there are limitations with controlling cell adhesion, viability, growth, differentiation, biocompatibility. Conversion of simple and abundant items to advanced cell culture substrates addresses some of the limitations in regenerative engineering. Departure from complex fabrication processes to the applications of unusual materials provides another dimension to the engineering of viable multifunctional tissue constructs and regenerative can increase access to regenerative engineering technologies on a global scale. In this work, we used unconventional biomaterials such as eggshells and paper for tissue regeneration.<br/><br/>We fabricated eggshell micro/nanoparticle (ESP) reinforced protein-based scaffolds to produce mechanically stable and biologically active three-dimensional (3D) scaffolds that can differentiate stem cells into osteoblasts. The ESP-reinforced constructs were then implanted in a rat model to determine their biocompatibility and degradation behaviors. In addition, these composite scaffolds were used to regenerate critical sized cranial defects in a rat model. We also used mineralized paper scaffolds with hydrogels through an origami-inspired approach to test their osteoinductivity and potential for tissue repair in <i>in vitro</i> and <i>in vivo</i> studies.^1-6<br/><br/>The ESP-reinforced scaffolds enabled the differentiation of stem cells into osteogenic lineage. The constructs showed significant enhancement in mineralization by the cells. The ESP composites demonstrated superior mechanical properties and showed favorable <i>in vivo</i> responses by subcutaneous implantation in a rat model. The scaffolds were responsive to cells and did not elicit inflammatory responses <i>in vivo</i>. The implants were easily accepted by the host, allowed for cellular infiltration and migration in 3D, and highly vascularized. Implantation of ESP-reinforced scaffolds into critical sized cranial defects in a rat model resulted in significant bone regeneration in 12 weeks. The resulting bone volume and bone density were as high as the native bone using these composite scaffolds as determined by micro-computed tomography assessment.<br/><br/>We also fabricated origami-inspired paper-based scaffolds for biomineralization. Material properties of the paper-based mineralized scaffolds were highly tunable. The tensile modulus of the scaffolds increased significantly after the mineralization process. Gene expression results for the osteogenic differentiation markers revealed the osteoinductivity of the mineralized paper scaffolds. Subcutaneous implantation of the samples in rats demonstrated biocompatibility, vascularization, and integration <i>in vivo</i>.<br/><br/>Unconventional scaffolds that are readily available and adapted from nature demonstrated biomimetic characteristics including porosity, structure, and bioactivity resulting in physiologically relevant constructs. The use of existing naturally derived materials in combination with hydrogels for regenerative engineering provides an inexpensive and sustainable approach that benefits the economy and environment while providing unique solutions to unmet clinical needs. Many of the unconventional biomaterials are overlooked and under-studied for biomedical applications, partly for their simplicity as mundane items.<br/><br/><b>References: </b>¹Nguyen, M.A., Camci-Unal, G., Trends in Biotechnology, 38(2): 178-190, 2020. ²Suvarnapathaki, S., Wu, X., Lantigua, D., Nguyen, M.A., Camci-Unal, G., Nature Asia Materials, 11(1): 1-18, 2019. ³Wu, X., Stroll, S.I., Lantigua, D., Suvarnapathaki, S., Camci-Unal, G., Biomaterials Science, 7, 2675-2685, 2019. ⁴Wu, X., Gauntlett, O., Zhang, T., Suvarnapathaki, S., McCarthy, C., Wu, B., Camci-Unal, G., “ACS Applied Materials & Interfaces, 13, 51, 60921-60932, 2021. ⁵Wu, X., Walsh, K., Suvarnapathaki, S., Lantigua, D., McCarthy, C., Camci-Unal, G., Biotechnology and Bioengineering, 118, 1411-1418, 2020. ⁶Ahmed, A.R., Gauntlett, O., Camci-Unal, G., ACS Omega, 6(1): 46-54, 2021.