Emerging Orthobiologics and Regenerative Medicine FAQ for Medical Professionals
How does regenerative medicine apply to musculoskeletal care?
The AAOS says it well in their 2018 consensus recommendations regarding the clinical use of biologics:
“The clinical use of biologics such as platelet-rich plasma and cell-based therapies to treat orthopaedic conditions has greatly outpaced the evidence.”
“Patient demand and clinical need along with the international experience support exploration of new pathways developed through the 21st Century Cures Act to accelerate clinical evaluation of the use of autogenous cell sources and culture-expanded cell-based therapies to treat musculoskeletal conditions.”
Musculoskeletal diseases include serious conditions for which conventional treatments are lacking. Misrepresentation of uncharacterized and unproven products as stem cells may erode public trust and compromise development of legitimate cell therapies. Pathways were recommended to improve accountability for biologics currently in general clinical use, including (1) redefining terminology to clearly distinguish cell therapy and ensure that treatments be clearly understood by practitioners and clearly communicated within the profession, to patients, and to the public, (2) standardization of reporting requirements, and (3) establishing registries for postmarket monitoring and quality assessments of biologic therapies.”
Currently, standard treatment options for musculoskeletal conditions remain limited to PRICE, conservative interventions such as exercise, therapy, and chiropractic, medications including NSAIDs, local corticosteroid injections, possibly viscosupplementation, and surgery. Public reporting of cost, quality, and outcomes information is lacking for many surgical procedures. Malanga says it well, that “historical and recent evidence increasingly refute the use of corticosteroid injections for most sports injuries, especially tendinopathies” (Malanga 2016, Coombs 2013). Ethically, the rising concern about potential harm from corticosteroid injections obligates our clinicians to investigate appropriate alternatives, including biological ones.
Swedish is committed to constantly innovating to find the best treatment options for our patients. The motivation to advance our knowledge about the effective use of orthobiologics is grounded in their potential as less expensive, less invasive and more effective treatment options than the current nonsurgical approaches to treating acute and chronic musculoskeletal injuries. We are also investigating their efficacy to delay or avoid surgical intervention. The hope is that regenerative medicine techniques will reduce the overall cost of care for musculoskeletal and orthopedic issues by reducing the need for surgery and ancillary costs, and reduce lost days at work.
Swedish is committed to the highest ethical standards in patient care and transparency. We partner with our patients to develop a treatment plan that is understandable, responsive to patient wishes, and strives for the least invasive options first. Most patients who seek orthobiological treatments do so because their symptoms do not respond to traditional treatments.
What is the Regenerative Medicine program at Swedish?
Cell therapies are also known as biologics or “orthobiologics,” and include growth factors, bone morphogenetic protein, mesenchymal stromal cells, platelets, and other factors. The Swedish Regenerative Medicine program offers two types of cell therapies – platelet-rich plasma (PRP) and Bone Marrow Concentrate Aspirate (BMAC).
What is platelet-rich plasma (PRP)?
Platelet-rich plasma (PRP) is a concentrate of platelets and plasma proteins derived from whole blood, centrifuged to remove erythrocytes. The remaining platelets and plasma in the centrifugate contain numerous growth factors that have multiple roles in tissue repair and healing. Numerous in vitro and in vivo studies have shown that the increased concentration of growth factors in PRP can improve cellular proliferation and repair and even healing in skeletal muscle, tendon, ligament (Middleton 2012).
What is BMAC?
Bone marrow aspirate concentrate (BMAC) is an orthobiologic harvested from bone marrow and centrifuged to remove erythrocytes and containing mononucleated white blood cells, mesenchymal stem cells, hematopoietic stem cells, and platelets. Progenitor cells, growth factors, and various mediators in BMAC play important roles in connective tissue repair in tendon, ligament, bone, and cartilage (Bashir 2015).
Clinical research involving PRP and BMAC in humans is currently underway, although lacking robust scientific rigor.
What does the evidence show about the safety and efficacy of PRP and BMAC?
There are numerous clinical research studies currently underway to evaluate the effectiveness of PRP and BMAC treatments, and more than 1000 in the medical literature. Although preliminary results are promising and important advancements have been made in the field of orthobiologics, results remain inconclusive, and there are still areas of controversy. There remains no clear consensus on optimal protocols for PRP and BMAC. Many variables confound studies around efficacy, including varying harvest techniques, preparation methodologies, injection techniques, use of imaging guidance, cellular concentrations, presence/absence of adjunctive products (such as PRP with BMAC), post-procedural protocols (appropriate avoidance of anti-inflammatories), as well as rest and rehabilitation protocols. Furthermore, effectiveness of PRP can vary depending on the area of the body being treated, the overall health of the patient, and whether an injury is acute or chronic.
However, preliminary clinical studies of PRP’s efficacy for treating injuries to joints, tendons and ligaments show promising results. These treatments have a good safety profile, with few major complications. (Malanga 2014, Kon et al 2013, Sundman et al 2014, Chahla et al 2016, Riboh et al 2016, Fitzpatrick et al 2017, Campbell et al 2015, Pourcho et al 2014, and others).
BMAC studies have recently shown encouraging results for improved pain and function at 12 months for patients with chronic tendinopathy, chondral defects and osteoarthritis. Numerous studies demonstrate the safety of BMAC and potential to improve pain and activity level in patients with various knee pathologies (Moatshe 2017, Hauser and Orlofsky 2013, Centeno et al 2014, Kim et al 2014; Pascual-Garrido et al 2012, Chahla et al 2016, Gobbi et al 2015 and others).
Currently, PRP and BMAC have indications for mild to moderate degenerative joint disease (osteoarthritis/osteoarthrosis), tendinopathy, chondral defects, plantar fasciitis/fasciosis and ligament injuries.
How extensively is Swedish using PRP and BMAC to treat patients? What does their data show about the safety and efficacy of these procedures?
At Swedish, only a small proportion of our patients are treated with PRP and BMAC. Less than 5% of our patients at Swedish Spine Sports and Musculoskeletal Medicine chose treatment plans that include orthobiologic treatments such as PRP and BMAC (about 4% receive PRP, and less than one percent receive BMAC).
Swedish’s Sports Medicine subspecialists are fastidious about safety and technique. Our team participates in data collection along with several other academic and elite hospitals. The current major complication rate for PRP at Swedish is less than 1%. Of the 697 patients treated with PRP between 2015 and March 2019, there have been no reported infections, and only one reported synovitis reaction.
At Swedish, BMAC treatments may be offered as a last resort to avoid a potential surgical procedure, and a minority of patients are expected to progress to surgery. No complications have been reported to date as a result of the procedure. However, about 5% of patients treated thus far have progressed to surgery despite their BMAC procedure.
Approximately 60-80% of patients report improvements (depending on the treated area) in pain, function and quality of life after receiving PRP or BMAC.
Swedish only offers autologous treatments (using cells obtained from a person’s own blood or bone marrow), which avoids ethical concerns around the use of embryonic cells from fetal tissue as well as potential rejection and safety concerns associated with umbilical cord-derived products.
Several of Swedish’s Orthopedic colleagues are using orthobiologics as adjunctive therapy, primarily for intraarticular applications in the hip and knee and peritendinous applications in the elbow.
Additionally, sports medicine specialists at Swedish skilled and certified in the use of musculoskeletal ultrasound, which serves as imaging guidance to ensure accurate and safe delivery at the injection site (Malanga 2016).
Our subspecialty physicians may present these types of treatment alternatives to patients when several other treatment options have failed. Physicians discuss traditional and alternative treatments in full with each patient to ensure they understand their options and receive the best care possible. These treatment options are only considered when physicians and patients agree that the potential benefits outweigh the known risks.
What research is Swedish doing in the area of regenerative medicine?
Swedish is participating in ongoing data collection and clinical research on the efficacy and safety of regenerative treatments in musculoskeletal care.
We maintain a confidential patient registry documenting safety and outcomes data, as part of a larger multicenter collaborative data collection in partnership with several other leading academic institutions. Several of the group’s findings have already been published in peer-reviewed medical journals.
Swedish uses evidence-based patient reported outcomes (PRO) tools to track safety and quality outcomes for all of our patients treated with orthobiologics so that we continue to advance the evidence base around safety and efficacy of this treatment option.
Financial & competing interest disclosure
Authorship is by employed physicians of Swedish. The author(s) express no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this document.
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