According to Dr. Bruce Gao, nature, including every biological system, builds objects generally through two procedures: adding parts together and/or subtracting parts from the whole. For example, our fingers are formed first through adding various cell types together during embryonic development to create a palm-like block, and then the block is carved into fingers through subtracting apoptotic cells in between the forming fingers.
Since the industrial revolution, human manufacturing activities have been mainly dependent on machining standard parts (subtractive procedure) and then assembling parts together (additive procedure) to produce industrialized products. Conventional machine tools are suitable to make standard parts only with regular shapes, such as circular or rectangular profiles. However, biomedical objects, such as animal organs, usually have irregular shapes and inhomogeneous compositions, so traditional manufacturing techniques are not suitable for the field of biomedicine.
To address this issue, layer-by-layer manufacturing techniques have been developed. By using either a 3D printer to add or a laser beam to subtract materials layer by layer at the microparticle level, irregularly shaped objects can be built. Based on these ideas, contemporary biofabrication technologies have been established.
“The worldwide growth of biofabrication,” stated Dr. Gao, “started at Clemson University in 2003 when Dr. Thomas Boland (assistant professor, Department of Bioengineering) filed a patent entitled Ink-jet printing of Viable Cells.” Dr. Boland’s invention was named one of the “Six Technologies That Will Change the World” by Business 2.0 Magazine in 2004; his research was featured on the Discovery Channel’s program “2057.”
Working in parallel with Dr. Boland, Dr. Gao and other Clemson Bioengineering faculty members established a biofabrication program in the Department of Bioengineering. Dr. Gao’s unique contribution to the field of biofabrication is the laser guidance-based cell micropatterning system. Worldwide, his is the only group that can use a laser beam to position various cell types to mimic specific in vivo-like cell-cell-ECM interactions at a spatiotemporal resolution on the submicron and millisecond level. His paper, “Laser-guidance-based cell deposition microscope for heterotypic single-cell micropatterning” was selected as one of eight highlighted articles for 2011 by Biofabrication, the only international journal specializing in biofabrication.
Dr. Gao, a world-caliber scholar in laser-based biofabrication, has been appointed to one of the South Carolina SmartState Endowed Chairs in Biofabrication Engineering to increase the dynamism of South Carolina’s work in biofabrication. Both a prime opportunity and a compelling need, this appointment is part of South Carolina’s effort to establish a SmartState Collaborative Center of Advanced Tissue Biofabrication. Three endowed chair positions, one each for Clemson University, University of South Carolina, and Medical University of South Carolina, were approved.
With Dr. Gao’s long-term vision to actuate South Carolina’s potential in biofabrication, he promises to vigorously champion, with the other endowed chairs in the center, South Carolina’s endeavor to extend its leadership in biofabrication to the international level. He said, “My short term goal is to reestablish Clemson’s leadership in biofabrication through technological advancement. The niche that exists in biofabrication research is Clemson’s area of strength — engineering-based technology.”
The endowed chair appointment will support the technological advancement required to occupy the niche while securing the preeminent position in the field. Specifically, Dr. Gao plans to contribute to South Carolina’s advanced tissue biofabrication program by developing the following:
1) A laser-based subtractive 3D microfabrication system. Current biofabrication techniques developed in South Carolina are additive: Using various printing methods to fabricate a designed structure. Clemson’s previous contribution to the field was the use of the biological cell as a building block to print biological tissue and organs. However, because building blocks do not exist for all materials, subtractive fabrication techniques are required. Dr. Gao and his collaborators at Clemson have developed numerous laser-based subtractive 3D micro/nanobiofabrication techniques such as a Raman laser biological gel microetching technique and a two-photon surface patterning technique that, at the nanoscale, can manipulate substrate for study of cell-extracellular matrix (ECM) interactions. With these developed techniques, Dr. Gao plans to establish a laser-based subtractive 3D micro/nanofabrication lab for a broad spectrum of materials—from glass to metal, from polymers to bioprosthetics.
2) A multibeam, laser guidance-based 3D additive cell manipulation system. Current printing-based additive microfabrication techniques lack temporospatial precision and thus cannot be used to study defined cell-ECM interactions, which are essential knowledge for achieving tissue/organ printing. Dr. Gao plans to further develop his current laser patterning system, using multiple beams to significantly increase throughput.
3) A 3D microfabrication digitization system. Dr. Gao’s previous research is in the forefront of the machine vision field; he will build on the techniques established in his research lab to develop an imaging system for digital design and assessment for 3D biofabrication.
Not only will the endowed chair funding enable the research advancement described above, the biofabrication techniques developed with the financial support will also enhance Clemson’s educational program. With conventional manufacturing techniques, students must undergo long-term training in mechanical design to be able to create their own design for a machine shop to make their research apparatus.
According to Dr. Gao, with biofabrication techniques, “students’ designs will not be restricted by a machine shop’s manufacturing capability, and a research apparatus can be made by the students themselves; thus, a student’s training can focus on solving actual biomedical problems.” For example, he said, “using a biochip designed and fabricated in my laboratory, my students recently found that stem cells had the potential to rescue damaged cardiac muscle cells by transferring mitochondria via nanotubes formed between the two cell types.”
To explore the mechanism, the students used the biofabrication techniques developed in Dr. Gao’s lab to fabricate biochips that confine nanotube formation between stem cells and cardiomyocytes and facilitate microscopic observation of mitochondrial transfer via formed nanotubes. The data Dr. Gao’s students obtained from the biochips enabled the interpretation of in vivo observed stem cell rescue effects in both animal and human heart models developed by Dr. Gao’s clinical collaborators.
