Professor Ben Wu has published >230 peer-reviewed articles with >13,000 citations (https://goo.gl/GS1GHM), ~20 patents, and received numerous research awards for his cutting-edge research in the formation of biomimetic apatites, development of bioinspired growth factors, mathematical modeling of in vivo moving boundary diffusion-reaction problems during tissue engineering and cancer survival, and engineering of biomimetic microenvironment to deliver cells, proteins, and genes to promote repair and regeneration of hard and soft tissues. His work has impacted clinical disciplines ranging from Dentistry, Orthopedics, Radiology, Interventional Radiology, Urology, Pediatric Surgery, Ophthalmic Surgery, Plastic and Reconstructive Surgery. His current research focuses on advanced biomanufacturing of medical/dental devices for preventive diagnostics and therapeutics, biomolecular engineering of orthobiologics, development of interactive materials to control microbiome-host interactions, and incorporation of machine learning in medical decision making.
Dr. Wu’s team have been extensively investigating the natural formation of a biological apatite during bone wound healing and developed a materials processing strategy to mimic this natural interface and confer uniform, bioactive apatite coating throughout the pores of complex three dimensional scaffolds. By controlling specific stages of the self-assembly process, they’ve extended the classic structure-processing-property-performance paradigm and demonstrated that materials engineering parameters can produce distinct apatite structures that directly affect osteoblastic gene expression and bone formation.
Dr. Wu’s team has developed a scalable engineering strategies to modify and deliver Nell-1, a natural human growth factor that is naturally expressed at the osteogenic front of a premature cranial suture fusion associated with craniosynostosis. Unlike bone morphogenetic proteins which signal non-specifically upstream of core-binding factor Cbfa1/Runx2 and are responsible for numerous clinical complications in human cervical spinal fusion, Nell-1 appears to signal downstream of Cbfa1/Runx2 and may therefore potentially yield fewer complications. After many years of developing vehicles to deliver Nell-1 for bone and cartilage repair, his team joined forces with a large multidisciplinary project to bioconjugate a protective coating and a bone-specific motif, thereby extending the long-term blood circulation and bone targeting in vivo. The modified NELL-1 showed the ability to treat osteoporotic mice on earth, and on severe microgravity conditions aboard international space station.
3-D mass transport
In 3D, mass transport limitations of nutrients and waste products remain a major obstacle to the survival, proliferation, and differentiation of the stem cells in large clinical size defects. Dr. Wu and his team previously showed experimentally and theoretically that controlling spatial distribution of cells can impact cell proliferation in 3D based on oxygen transport limitation and heterogeneous consumption. They subsequently showed theoretically and confirmed experimentally that acidosis is actually the most serious consequence. They recently expanded this understanding to the 3D hypoxic effects on increased drug resistance by cancer cells. Their in-vitro 3D models acquired higher apoptosis resistance via up-regulation of anti-apoptotic proteins, and that the precise mechanism depends on each 3D microenvironment. Based on these preliminary findings, the 3D/3D model offers the critical features of 3D cell-cell adhesion, and mass-transport limitation that cannot be easily replicated by 2D models.
Cancer, trauma, and congenital defects of the maxillofacial area that are too extensive for surgical reconstruction are often treated by maxillofacial prosthodontists with custom‐made prosthetics to restore orofacial disfiguration and defects. These lifechanging prostheses restore speech, facial form, function, and most importantly, dignity, and return quality of life for the patients. The benefits are critical to restoring the patient’s mental health and reengaging them with society. Dr. Wu’s team is committed to developing advanced, printable biomaterials “bioinks” to support 3D printing of functionally graded maxillofacial prostheses that offer the touch and feel of natural tissues, beautiful esthetics to restore self esteem, and biocompatibility to ensure safety. Our team is developing materials for two major printing strategies to meet the diverse, complex needs of our patients. The focused objective of this proposal is to develop novel silicone powder materials.
3D Pharming bioinks
The goal of the 3D Pharming research is to develop photo-polymerizing material systems for rapid on-demand manufacturing of patient specific oral solid dosages (OSD) in local compounding pharmacies. Additive manufacturing is an attractive strategy for fabricating oral dosage forms because it can offer precise control over drug dose, release kinetics, and has the potential to combine multiple drugs into a single tablet. The focus has been to develop photo-curable bioinks suitable for inkjet printing, and capable of dispensing hydrophilic and hydrophobic active pharmaceutical ingredients (API). Inkjet printing offers fast printing speeds and the ability to print at room temperature for the preservation of temperature labile APIs, which is an advantage over 3D printing techniques previously used for 3D Pharming, such as powder bed printing and fused deposition modelling (FDM), respectively.
To date, a hydrophilic bioink has been successfully engineered by chemically conjugating norbornene moieties onto the backbone of hyaluronic acid, which creates a photo-curable, biocompatible polymer that can be used as the main bioink component. Additionally, a poly(ethylene glycol)-based photo-curable formulation has been developed for the dispensing of hydrophobic APIs. The ability of these bioinks to form droplets has been analyzed by calculating the inverse of the Ohnesorge number and the mechanical properties of the polymerized gels have been assessed. Immediate and sustained API release profiles were achieved for hydrophilic and hydrophobic APIs, respectively; thereby demonstrating control over drug release kinetics. Additionally, both bioinks have been used to fabricate combination therapies by creating a polypill that contains two drugs for the treatment of hypertension. The current work is compatible with APIs that achieve their pharmacological effect at low dosages.