Mayo Clinic Researchers Design 3D Printed Bioabsorbable Scaffold to Help Reconstruct ACL Ligaments and Deliver Time-Released Protein

Whenever I hear someone talk about the Mayo Clinic in Minnesota, I know the discussion will gear towards extremely innovative medical procedures, research, and surgical tactics. According to the most recent U.S. News & World Report rankings of top hospitals, the Mayo Clinic is the country’s #1 overall hospital, and is also #1 in more specialties, including nephrology, urology, and pulmonology, than any other hospital in America. We’ve written about the hospital’s work and research with 3D printing technology several times, from patient-specific medical models and a complex face transplant, to biocompatible enclosures for deep brain stimulation (DBS) electronic implants and even working with Google on a bathroom health monitoring system concept. Recently, Mayo Clinic researchers used 3D bioprinting to take on anterior cruciate ligament (ACL) reconstruction.

The researchers designed a 3D printed bioabsorbable, porous scaffold to help with the reconstruction of ACL ligaments in the knee. But what’s really special about this scaffold is that it’s been developed in such a way as to deliver a bone-promoting protein, in order to improve bone regeneration, over an extended period of time. Scaffolds, a crucial part of bioprinting, are pretty much what you’d expect from the name: they basically provide necessary structure to printed cells while they grow and develop. The additively manufactured creation of scaffolds can make or break a researcher’s work. The recent Mayo Clinic study described the 3D printed scaffold’s composition, and also compared various methods for delivering recombinant human bone morphogenetic protein 2 (rhBMP-2).

The study, “Three-Dimension-Printed Porous Poly(Propylene Fumarate) Scaffolds with Delayed rhMBP-2 Release for Anterior Cruciate Ligament Graft Fixation,” was published in the peer-reviewed journal Tissue Engineering, Part A, the flagship journal published 24 times each year. Tissue Engineering is the official journal of TERMIS, the Tissue Engineering & Regenerative Medicine International Society. The paper is available to read, for free, on the Tissue Engineering website until March 27; co-authors include Mahrokh Dadsetan, PhD; Sanjeev Kakar, MD; Maurits G.L. Olthof, MD; Joshua Alan Parry, MD; Kristen L. Shogren; Andre Van Wijnen, PhD; and Michael Yaszemski, MD, PhD, all with the Mayo Clinic’s Department of Orthopaedic Surgery, Tissue Engineering and Biomaterials Laboratory.

Load to failure testing setup on the servohydraulic testing MTS machine.

In the paper, the researchers compared four different release approaches, and how they reduced the initial rhBMP-2 burst release and extended it over time. Furthermore, they demonstrated how strong their porous, bioabsorbable scaffold was, using a rabbit ACL reconstruction model. The paper’s abstract explains that most ACL ruptures are reconstructed using bioabsorbable implants, but that the implants frequently suffer complication due to incomplete bone filling. The bone regeneration could potentially be enhanced through 3D printed scaffolds and tissue engineering techniques, so the researchers first designed a strong 3D poly(propylene fumarate) (PPF) porous scaffold, and then determined the rhBMP-2 release kinetics.

The abstract continues: “To determine the degree of scaffold porosity that maintained suitable pullout strength, tapered scaffolds were fabricated with increasing porosity (0%, 20%, 35%, and 44%) and pullout testing was performed in a cadaveric rabbit ACL reconstruction model. Scaffolds were coated with carbonate hydroxyapatite (synthetic bone mineral [SBM]), and radiolabeled rhBMP-2 was delivered in four different experimental groups as follows: Poly(lactic-co–glycolic acid) microspheres only, microspheres and collage (50:50), collagen only, and saline solution only. rhBMP-2 release was measured at day 1, 2, 4, 8, 16, and 32. The microsphere delivery groups had a smaller burst release and released a smaller percentage of rhBMP-2 over the 32 days than the collagen and saline only groups. In conclusion, a porous bioabsorbable scaffold with suitable strength for a rabbit ACL reconstruction was developed. Combining a synthetic bone mineral coating with microspheres had an additive effect, decreasing the initial burst release and cumulative release of rhBMP-2. Future studies need to evaluate this scaffold’s fixation strength and bone filing capabilities in vivo compared to traditional bioabsorbable implants.”

Porous wedge scaffold designs. (A) 20% porosity, (B) 35% porosity, and (C) 44% porosity.

The porous wedge scaffolds, measuring 3mm in diameter and 10mm in length, were designed using SOLIDWORKS, and were printed using the Viper si2 SLA 3D printer from 3D Systems. The implants had an acetone bath, and then were washed “extensively” with ethanol to get rid of any excess resin. Finally, the implants were post-cured in a 3D Systems UV oven for an hour. Testing ultimately determined that the 20% porous 3D printed PPF bioabsorbable scaffold maintained the proper amount of pullout strength in the ex vivo rabbit ACL graft fixation. However, the researchers say that further testing is necessary, to compare this scaffold’s subsequent in vivo bone filling and fixation strength.

Tissue Engineering co-editor-in-chief Peter C. Johnson, MD, Principal, MedSurgPI, and President and CEO, Scintellix, said about the study, “This work is a good example of the fusion of technologies – controlled release drug delivery and 3D printing.”

The research was funded by a grant, from the DePuy Synthes Joint Reconstruction and the Orthopaedic Research Education Foundation (OREF). Discuss in the Mayo Clinic forum at 3DPB.com.