Additive Manufacturing and Natural Medicine in Bone Regeneration: Opportunities and Challenges

An estimated one million bone grafting procedures are performed annually in the U.S. and a few million worldwide to repair fractures, cysts, bone defects, tumors, and hip and knee replacements. An increase in the number of procedures is strongly tied to increased musculoskeletal disorders, the aging population segment, and sports-related injuries. Sometimes, patient-matched devices are necessary for patients with special anatomical needs or concerns related to specific defect size complexity.<br/>3D printing (3DP) or additive manufacturing (AM) is becoming essential in patient-matched implants due to lower cost and shorter manufacturing lead time. Additively manufactured components must be controlled and optimized carefully for their reproducibility, machine-to-machine part quality variations, and process-specific material properties. Establishing process property relationships for different AM techniques is vital to successfully implementing these manufacturing practices in biomedical devices. Complex biomaterials, e.g., calcium phosphate (CaP) ceramics compositionally similar to the inorganic part of the bone, show significant promise toward implant applications in both 3DP tissue engineering scaffolds and surface-modified hip and knee implants. It is worth noting that even with all the excitement on 3DP in recent years, <i><u>reliable and reproducible 3DP</u></i> ceramic <i><u>scaffold</u></i> manufacturing <i><u>is</u></i> <i>rare compared to</i> porous polymeric or metallic structures due to their ease of processability.<br/>We have used extrusion-based and commercial binder jetting 3D Printing machines (ExOne, PA) with various ceramic powders for the past 25 years to critically identify and understand the effects of process-property variations on 3DP CaP scaffolds. Our CaP scaffolds using 3DP have an average designed pore size of 300-400 microns, with 40 volume % porosity and compressive mechanical strength of &gt;15 MPa, followed by NMC loading on those CaP scaffolds. We have designed and built a 3DP machine capable of printing high-viscosity slurry to directly print doped CaP–polymer scaffolds with similar inorganic composition as bone. 3D interconnected channels in CaP scaffolds provide pathways for micronutrients, improved cell-material interactions, and increased surface area, allowing improved mechanical interlocking between scaffolds and surrounding bone.<br/><i>In vivo</i> studies show improved osteogenesis, angiogenesis, and controlled drug delivery using natural medicinal compounds (NMCs) in these 3D-printed scaffolds and coatings. The use of NMCs in CaP or CaP-polymer composites can eliminate the need for autografts and related second-site surgery for harvesting. NMCs can also replace growth factors (GFs) and proteins for faster healing. NMCs work with CaPs and other materials, such as titanium metals, to enhance early-stage bone tissue ingrowth for applications in load-bearing or non-load-bearing implants. These systems show promise for use in orthopedic and dental devices while eliminating the need for autografts and the second site surgery for harvesting and improving current hip/knee implant lifetime. The presentation will address the design of next-generation bone tissue engineering scaffolds and hip/knee devices based on clinical needs in the fixation of bone disorders and scientific challenges.