A Three-Dimensional-Printed, Stem Cell Implant Repairs a Hip

Physicians and stem cell scientists at Southampton, UK have completed a hip surgery in which a 3D printed implant and stem cell graft were used to replace a diseased hip.

The 3D printed hip was made from titanium but it was designed using the patient’s CT scan and CAD CAM (computer aided design and computer aided manufacturing) technology. By printing the hip bone by means of CAD CAM technology the manufactured hip was designed to the patient’s exact specifications and measurements.

This implant will provide a new socket into which the ball of the femur bone is inserted. Between the titanium implant and the pelvis bone, the surgeons inserted a graft containing bone-making stem cells.

The stem cell graft should act as a filler for the loss of bone. The patient’s own bone marrow stem cells were added to the graft in order to provide a source of bone-making stem cells to encourage bone regeneration behind and around the metal implant.

Douglas Dunlop, a consultant orthopedic surgeon, who conducted this operation at the Southampton General Hospital, thinks that this type of procedure could be a genuine game changer. “The benefits to the patient through this pioneering procedure are numerous. The titanium used to make the hip is more durable and has been printed to match the patient’s exact measurements – this should improve the fit and could rescue the risk of having to have another surgery. The bone graft material that has been used has excellent biocompatibility and strength and will fill the defect behind the bone well, fusing it all together.”

Over the past decade Dr. Dunlop and University of Southampton scientist Professor Richard Oreffo have developed a translational research program that aims to use a patient’s own skeletal stem cells to replace damaged or lost bone during orthopedic procedures.  For example, see A Aarvold, et al., J Tissue Eng Regen Med. 2012 Oct 5. doi: 10.1002/term.1577; JO Smith, et al., J Tissue Eng Regen Med. 2014 Apr;8(4):304-13; ER Tayton, et al., J Bone Joint Surg Br. 2012 Jun;94(6):848-55; E Tayton, et al., Acta Biomater. 2012 May;8(5):1918-27; A Aarvold, et al., Regen Med. 2011 Jul;6(4):461-7. doi: 10.2217/rme.11.33; and JO Smith, et al., Tissue Eng Part B Rev. 2011 Oct;17(5):307-20.

In this particular operation, the graft is made up of a bone scaffold that allows blood to flow through it. Stem cells from the bone marrow attach to this material and grow new bone. This implant will support the 3D printed hip implant.

Professor Oreffo comments: “The 3D printing of the implant in titanium, from CT scans of the patient and stem cell graft is cutting edge and offers the possibility of improved outcomes for patients.

“Fractures and bone loss due to trauma or disease are a significant clinical and socioeconomic problem. Growing bone at the point of injury alongside a hip implant that has been designed to the exact fit of the patient is exciting and offers real opportunities for improved recovery and quality of life.”

For the patient, Meryl Richards, from Hampshire, the procedure means an end to her hip troubles. In 1977 she was involved in a traffic accident and since then has had to have six operations to repair her injured hip.

She says: “The way medicine has evolved is fantastic. I hope that this will be the last time that I have to have a hip operation. I feel excited to have this pioneering surgery and I can see what a benefit it will have to me.”

Pluristem’s Phase I/II Muscle Injury Trial Shows that Placental Stem Cells Augment Muscle Healing After Surgery

Pluristem Therapeutics Inc. a leading developer of placenta-based cell therapies, has announced top-line results from its Phase I/II clinical trial that accesses the safety and efficacy of PLacental eXpanded (PLX-PAD) cells in the treatment of muscle injury. This clinical trial showed that PLX-PAD cells were safe and effective. These results provide evidence that PLX cells may be efficacious in the treatment of orthopedic injuries including muscles and tendons.

This Phase I/II trial was a randomized, placebo-controlled, double-blinded study conducted at the Orthopedic Clinic of the Charité University Medical School under the auspices of the Paul-Ehrlich-Institute (PEI), Germany’s health authority. The injured muscle studied was the gluteus medius muscle in the buttock. Hip-replacement patients undergo a surgical procedure that injuries the gluteus medius muscle healing of this muscle after hip replacement surgery is crucial for joint stability and function.

Gluteal Muscles

The 20 patients in the study were randomized into three treatment groups. Each patient received an injection in the gluteal muscle that had been traumatized during surgery. One group was treated with 150 million PLX-PAD cells per dose (n=7), the second was administered 300 million PLX-PAD cells per dose (n=6), and the third received placebo (n=7).

The primary safety endpoint was clearly met since no serious adverse events were reported at either dose level. The study showed that PLX-PAD cells were safe and well tolerated.

The primary efficacy endpoint of the study (how well the stem cells worked) was the change in maximal voluntary isometric contraction force of the gluteal muscle at six months after surgery. Efficacy was shown in both PLX-PAD-treated patient groups. The group that received a dose of 150 million cells showed a statistically significant 500% improvement over the placebo group in the change of the maximal contraction force of the gluteal muscle (p=0.0067). Patients who received the lower dose (300 million cells) showed a 300% improvement over the placebo (p=0.18).

An analysis of the overall structure of the gluteal muscle using magnetic resonance imaging (MRI) indicated an increase in muscle volume in those patients treated with PLX-PAD cells versus the placebo group. The patients who had received the 150 million cell dose displayed a statistically significant superiority over the placebo group. Patients treated at the 150 million cell dose showed an approximate 300% improvement over the placebo in the analysis of muscle volume (p=0.004). Patients treated at the 300 million cell dose showed an approximate 150% improvement over the placebo in the change of muscle volume (p=0.19).

The study’s Senior Scientist, Dr. Tobias Winkler of the Center for Musculoskeletal Surgery, Julius Wolff Institute Berlin, Charité – Universitaetsmedizin Berlin, Germany, commented, “I am very impressed with the magnitude of the efficacy results seen in this trial. PLX cells demonstrated safety and suggested that the increase in muscle volume could be a mechanism for the improvement of contraction force.”

Zami Aberman Chairman and CEO stated, “This was a very important study not only for Pluristem but for the cell therapy industry in general. The study confirms our pre-clinical findings that PLX-PAD cell therapy can be effective in treating muscle injury. Having a statistically significant result for our primary efficacy endpoint is very encouraging and consistent with our understanding of the mechanism of action associated with cell therapy. Based on these results, we intend to move forward with implementing our strategy towards using PLX cells in orthopedic indications and muscle trauma.”