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Novel Polyethylene Implant Material to Locally Release Therapeutic Agents for Pain and Infection Control

Next generation polymer material for joint implants to release antibiotics or analgesics as a prophylactic measure against periprosthetic joint infection and pain

Executive summary

Joint replacement surgery has revolutionized the treatment of debilitating arthritis, joint pain, and restoration of full joint function. However, these surgeries are extremely painful and are prone to infection due to significant surgical dissection and cutting of the bone.

Orhun Muratoglu, PhD, and Ebru Oral, PhD, together with their colleagues have developed a novel polyethylene implant material that can locally release therapeutic agents (analgesics, antibiotics) to control pain and prevent infection of the joint. Once in vivo, the analgesic first quickly elutes from the implant, bathing the joint and surrounding tissues and providing complete pain relief for the first few days post- surgery, when the pain is the most severe. The analgesic then slowly continues to elute from the polymer for several weeks, providing relief until the tissues are healed. 

This invention can also take advantage of a synergistic anti-bacterial effect when combining multiple analgesics or analgesics with antibiotics. As such, these eluted agents provide a prophylactic against bacterial infection.

This invention is based on previous work from Drs. Muratoglu and Oral, where they have developed novel methods of synthesizing degradable polymeric material containing therapeutic agents, synthesizing using microwave radiation, and methods of photo-crosslinking of ultra-high molecular weight polyethylene (UHMWPE) for fatigue resistance of the implant surface.

Unmet need

Current practice does not adequately treat all pain or eliminate all cases of infection. Treatment for post-operative pain is systemic drug administration, but to treat a local problem, which results in inadequate treatment of the pain. Therefore, the medication doses that patients need to feel relief often come with significant side effects, such as delirium, nausea, vomiting, prolonged hospital stays, and others.

A sustained and appropriate level of analgesic locally within the joint would eliminate the need for pain medications and therefore eliminate the side effects from those drugs. Additionally, post-surgical opioid abuse is a growing concern, and this technology would eliminate patients being prescribed those substances.

Medical devices are susceptible to bacterial colonization. Adhesion of bacteria to the surface of a medical device can then induce formation of bacterial biofilms that are much less accessible to antibiotics. Alone, administration of antibiotics is not effective for treating medical device-associated infections because the antibiotic penetration to the site of infection depends on the blood flow to the infected site. Areas with relatively low blood flow (e.g., bone, cartilage, immediate area surrounding medical implants) will have low local concentration of antibiotics.

Value proposition

The combination of therapeutic agents and the speed at which the agents elute from the polymer can be adjusted. Therefore, this treatment can be tailored to each implant or procedure, improving patient prognosis and recovery from surgery.

The pain relief should be immediate and sustained for several weeks after surgery, allowing patients to be discharged from the hospital earlier. This would provide patients with appropriate post-surgical pain management, particularly during the critical physiotherapy sessions, facilitating and optimizing the gain from those sessions, and reducing post-operative stiffness and pain. A local analgesic would not interfere with muscle function or strength, a common problem with regional anesthetics and nerve blocks.

Above all, this would reduce the morbidity associated with the otherwise highly successful surgical procedure of joint replacement surgery. Sustained, high concentration delivery of antibiotics at the surgical site aims to prevent infections, the development of pathogenic biofilms on the implants, and resistant bacterial strains. By preventing infection, patients will avoid additional long term medical management, which often includes additional operations to remove infected implants, disinfect and stabilize the joint with drug-eluting spacers, and install a new implant.


Orhun Muratoglu, PhD

Orhun Muratoglu, PhD, is a professor of orthopedic surgery at Harvard Medical School, the director of the Harris Orthopaedics Laboratory and the Technology Implementation Research Center (TIRC), and the vice chair, clinical innovation in the orthopedic surgery at Massachusetts General Hospital. His research interests include materials development, materials testing, ultra-high molecular weight polyethylene, among others. He has published over 145 peer-reviewed articles and holds 118 issued patents. He received his PhD from MIT in the program for polymer science and technology.


Ebru Oral, PhD

Ebru Oral, PhD, is an associate professor of orthopaedics at Harvard Medical School. She is also the associate director at the Harris Orthopaedics Laboratory and is the associate director of the Preclinical Research Support Core at Mass General. She has over 60 peer-reviewed publications and is an inventor on over 40 international patents on material technologies for joint replacements. Dr. Oral received her PhD in chemical engineering from Purdue University.

Dan Currie

Associate Director, Business Development and Licensing, Mass General Brigham Innovation


Background and proof of concept

The inventors have shown proof of concept in different aspects of the invention. They have shown that:

  • Anesthetics, such as bupivacaine hydrochloride or ropivacaine hydrochloride powder, can be mechanically mixed with polyethylene powder prior to consolidation and then elute out when placed in water
  • Anesthetics ,such as lidocaine or bupivacaine, diffuse into polyethylene at elevated temperatures and then elute out when placed in water at body temperature
  • Bupivacaine can be blended with UHMWPE powder and compression molded without damaging the drug
  • Bupivacaine can be released at clinically relevant rates for several days
  • In vivo rat models: UHMWPE loaded with bupivacaine, an anesthetic is effective at managing pain and bacterial growth post total joint replacement
  • In vivo rabbit models: UHMWPE loaded with vancomycin is effective at treating infection post total joint replacement
  • There is synergy between analgesics and antibiotics; per experiments against 52 strains of MSSA, the most common pathogenic organism causing periprosthetic joint infections
  • In vivo rabbit models, therapeutic UHMWPE bearing surfaces are effective against periprosthetic infection
  • In vivo rabbit models, treatment of lapine knees infected with Staphylococcus aureus with the antibiotic-eluting UHMWPE led to complete bacterial eradication and the absence of detectable systemic effects

Advantages and progress

This invention has several advantages over existing pain management and infection control strategies after joint replacement surgery. Patients will have shorter hospital stays, fewer side effects, and effective antibacterial treatment after surgery. Delivery of the agents may be designed in different ways: (i) elution from UHMWPE, with the therapeutic agents encapsulated in the manufactured polymer, or (ii) via degradable hydrogels that can be manufactured in the operating room.

Most current commercially available drug-eluting polymers are pre-manufactured with the drug, and therefore medical professionals are unable to select a specific drug for the patient. The hydrogel method allows for greater customization and flexibility in using the desired drug or combination of drugs, as may be desired when using antibiotics to treat peri-prosthetic implant infections.

The inventors have recently developed a temporary spacer that consists of a cobalt-chrome (CoCr) femoral component and an UHMWPE tibial insert that elutes gentamicin, an antibiotic.


The polyethylene (a polymer) piece of the prosthetic device can be engineered to contain clinically relevant levels of an anesthetic (AT), such as lidocaine, bupivacaine, ropivacaine, or others, or a mixture of anesthetics and antibiotics embedded within the polymer. Notably, the inventors have published on the synergistic antibacterial effect of analgesics/anesthetics and antibiotics. This would enable pain relief and protection from infection simultaneously post-operation.

Once in vivo, the AT and/or antibiotics slowly and predictably elute from the material, bathing the joint and local tissues, thus providing relief from pain and protection from infection after the procedure. The polyethylene polymer is manufactured and designed in such a way that AT and antibiotics elute relatively quickly in the first few days after surgery, when the pain is most severe. In addition, the AT and antibiotics continue to elute from the material more slowly for a period of several weeks until most or all of the drug is eluted from the polymer, thus providing sustained pain relief until most tissues have healed.

Competitive advantages

This invention can address major complications post joint replacement surgery. These surgeries are very painful and present a risk of surgical site infection. Prosthetic-joint infections (PJI) are serious complications, due to the need for aggressive revision surgeries and long-term use of systemic antibiotics. Survival rate at five years for PJI is 87.3%, which is worse than three of the five most common cancers (prostate- 99%, melanoma-91%, breast-89%).

With this novel polymeric material, pain and infection are addressed at the site of the surgery. Patients will therefore have lower morbidity, shorter hospital stays, and may avoid the side effects of opioids. The prognosis of patients will be better, with the risk of infection being significantly decreased, and allowing patients to fully reap the benefits of regaining function of their affected joint.

The global joint replacement market size was valued at $17.1 billion in 2020 and is expected to expand at a compound annual growth rate (CAGR) of 3.4% from 2021 to 2028. The market is being driven by the increasing prevalence of orthopedic disorders, osteoporosis, and arthritis. Over time, the need for joint replacement surgeries is going to increase, as well as the need for more effective pain management and infection control post-operation.


MGH 2020-132:  
United States Provisional Application 62/969,247  
WIPO PCT Application PCT/US2021/016475  
United States PCT Application 17/796,925  
Publication Number: WO2021158704A1

MGH 24829:  
United States Provisional Application 62/551,440  
WIPO PCT Application PCT/US2018/048256  
United States PCT Application 16/635,105  
Publication Number: US20210395472A1

MGH 23975:  
United States Provisional Application 62/330,478  
WIPO PCT Application PCT/US2017/029789

United States PCT Application 16/098,233  
Publication Number: US20190160207A1


Zmistowski B, Karam JA, Durinka JB, Casper DS, Parvizi J. Periprosthetic joint infection increases the risk of one-year mortality. J Bone Joint Surg. 2013;95:2177–2184.