Within the last couple of decades, there has been a rapid influx of therapies called “orthobiologics” that try to leverage our bodies’ inherent capacity for healing (and biological processes) by utilizing either substances from our own bodies or substances that are derived from biologic origins (e.g., blood, bone marrow, stem cells etc.). These treatments are widespread in their applications and have been used to treat orthopedic conditions involving joint, tendon, and muscles among others.

In this post, I will talk about a few of the common treatments that fall under the umbrella category of “orthobiologics,” or “regenerative medicine,” such as PRP and stem cell therapy and then briefly discuss some of the evidence around their use for certain orthopedic conditions as well as what I have seen in the patients that I have worked with.

Orthobiologic Agents:

Orthobiologics are therapies that utilize biologic agents either from the patient’s own tissues or from other biologic sources (e.g., animal or lab bacteria grown preparations) to treat orthopedic injuries. Some Common Types of Orthobiologics are (Carr, 2019; Kruel, 2021; Le, 2018):

• Autologous Blood Injection (ABI): sample of whole blood that is harvested from the same individual it is used to treat (i.e., autologous); blood is drawn from one site and injected into another body site, without being processed.
• Bone Marrow Aspirate Concentrate (BMC or BMAC); (aka Bone Marrow Concentrate, BMC): autologous sample of bone marrow containing some progenitor cells (i.e., stem cells), healing factors, and growth factors. Commonly harvested from sites of superficial bone such as ASIS, PSIS, tibia, fibula. Usually processed with filtering and centrifuge to increase concentration of cells/growth factors in the sample.
• Hyaluronic Acid (HA) (a type of “Viscosupplementation”): HA is a viscous polysaccharide (i.e., glycosaminoglycan) that is made in the body by B-cells in the synovial membranes of joints, where it acts as a lubricant and shock absorber. When administered as an orthobiologic agent, it is commonly taken from animal sources or grown in a lab from bacteria sources.
• Platelet-Rich Plasma (PRP): autologous blood sample that is prepared in such a way so that it has a higher concentration of platelets and is proposed to have a higher concentration of growth factors and healing factors. Preparation is usually done by a one or two stage process to centrifuge (spin) and separate out the cells (red and white blood cells) and platelets from the plasma component of the blood. There are two types of PRP: Leukocyte-Rich PRP (LR-PRP) and Leukocyte-Poor PRP (LP-PRP). It is thought that white blood cells (leukocytes) may induce an inflammatory response from the body when reinjected into the body.
  • Leukocyte Rich PRP (LR-PRP): PRP sample that has been prepared to increase the concentration of leukoctyes (aka white blood cells). This type of PRP has been proposed to induce a greater inflammatory response because the added cells can “irritate” local tissues if injected
  • Leukocyte Poor PRP (LP-PRP):
• Mesenchymal Stem Cells (MSCs): mesenchymal stem cells (MSCs) are cells that can theoretically differentiate into different types of body tissue cells depending on the signals they get and the environment/body tissue in which they are placed. They can be found in and harvested from bone marrow or adipose tissue. MSCs also can affect nearby cells (i.e., “paracrine functions”) via release of chemicals that could stimulate new blood vessel formation, anti-inflammatory mechanisms, and wound healing.

Common Conditions Treated with orthobiologics include joint osteoarthritis (OA) (e.g., knee or hip OA), tendon or ligament injuries (e.g., Achilles’ tendinopathy, “tennis elbow”), and acute muscle strain injuries (e.g., hamstring strain injury). See sections below for brief reviews of each of these types of injuries and the evidence for or against the use of orthobiologic agents. 

Evidence For (Or Against) The Use of Orthobiologics

Hip and Knee Osteoarthritis (OA); Shoulder OA

Hip and knee OA could be treated with orthobiologic agents like HA, PRP, or stem-cell therapy. Most clinical practice guidelines (CPGs) for hip and knee OA recommend (with high-level evidence) first line treatments that include a combination of exercise and manual therapy such as in a physical therapy setting (Cibulka, 2017; Phillips, 2021; VA CPG). Other highly recommended treatments for these conditions include non-steroidal anti-inflammatory drugs (NSAIDs) and/or Tylenol.

Orthobiologics for hip and knee OA are not often recommended as first line treatments. However, most CPGs recommend viscosupplementation like HA as a second line treatment option with weak evidence if prior non-surgical treatment options have failed (Peck, 2021; Phillips, 2021; VA CPG) and use of HA could delay the need for surgical treatments such as knee replacement surgery (TKA) for greater than five years (Mordin, 2017). Studies on PRP treatment for OA conditions do not consistently find benefits (Bennell, 2021; Chang, 2014) such that there are not conclusive recommendations for or against its use for hip and knee OA (VA CPG). In a few low-quality studies, stem cell therapy could reduce pain and improved function in hip or knee OA, but again this data is from smaller studies or those with high risk of bias and strong evidence is lacking for this recommendation (Davatchi, 2016; Mardones, 2017; Pas, 2017). Furthermore, some clinical practice guidelines actually recommend AGAINST the use of stem cells for knee OA (weak evidence), and AGAINST the use of viscosupplementation like HA for hip OA (weak evidence).

See chart below for CPG evidence for the use of Hyaluroic Acid (HA) to treat knee OA (from Phillips, 2021):

From my research, there are a few studies supporting the use (weak evidence) that BMAC PLUS PRP could help improve function in those with knee OA or shoulder (glenohumeral joint) OA (Centeno, 2015; Centeno, 2018).

Clinical Bottom Line: Orthobiologics for Hip or Knee OA

+ Could use HA for knee OA, if other first line treatments have failed (e.g., NSAIDs, Tylenol, Physical Therapy)

+ Could use BMAC + PRP for knee OA, could use BMAC + PRP for glenohumeral joint (shoulder) OA

+/- Not enough evidence to recommend PRP or Stem Cells (BMAC or MSCs) as isolated treatments for Hip or Knee OA, may be recommended against!

Tendon or Ligament Injuries

Tendinopathies are some of the most common conditions in which treatments such as PRP are recommended. As I’ve written about extensively, tendon pain is notoriously tough to treat because of its multifactorial nature, often long-standing duration, and the time that it may take for exercise-based treatments to see lasting results. A few of my posts on tendinopathy are here:

• “Greater Trochanteric Pain Syndrome”
• Lower Extremity Tendinopathy “Loading” CHEAT SHEET! Quick Reference for treatments and goals!
• Tendinopathy Treatment Tips for the Lower Body
• Tips for Treating Lower Extremity Tendinopathies: Part 1: ASSESSMENT
• Tips for Treating Lower Extremity Tendinopathies: Part 2: EXERCISE PRESCRIPTION
• Tips for Treating Lower Extremity Tendinopathies: Part 3: INDIVIDUALIZING TREATMENT (CASE EXAMPLES)

Areas of tendinopathy that have been recommended for treatment with PRP therapy or other orthobiologics could include rotator cuff tendons, lateral elbow common extensor tendon, patellar tendon, gluteus medius tendon, Achilles’ tendon and plantar fascia. Though more research exists in this area, there are no conclusive recommendations due to different studies often finding conflicting results (e.g., benefit from PRP vs. no benefit from PRP). These inconclusive findings are true for lateral elbow pain with some studies finding a benefit of PRP (Kwapisz, 2018) and some not (Cochrane Review of 32 studies; Karjalainen, 2021); also in non-operative rotator cuff tendon pathology, some studies show a benefit of PRP (O’Dowd, 2022), while others do not (Carr, 2019); and finally mixed results were found for biceps’ tendon injury, with some studies finding benefits of PRP (Barker, 2015) and others not finding benefits (Kwapisz, 2018).

For Lower body tendon or ligament injuries, it seems that PRP is NOT indicated for Achilles’ tendinopathies (Arthur, 2023; O’Dowd, 2022) but may have promise for plantar fascia injuries (O’Dowd, 2022). Furthermore, there seems to be no conclusive evidence to recommend the use of stem cell therapy to treat tendon pain (Pas, 2017).

Clinical Bottom Line: Orthobiologics for tendon or ligament injuries

-Do NOT use PRP for Achilles’ tendon, intra-operative rotator cuff tendon, or with ACL surgery

+ LOW Quality or Insufficient (+/-) evidence to recommend PRP for lateral elbow pain (aka, “tennis elbow”), biceps’ tendon, or non-operative rotator cuff tendon pathology+/- No evidence to recommend HA, BMAC, or MSCs for tendon or ligament injuries

Muscle Injuries

Research on the use of orthobiologics for acute muscle injuries is very limited. However, in one review looking at findings from 6 studies on PRP for acute muscle injuries (majority of the studies looked at PRP to treat acute hamstring injury), there was low evidence that PRP injections could improve pain and function (O’Dowd, 2022), and possibly reduce time for return to sport (Grassi, 2018).

Clinical Bottom Line: Orthobiologics for acute muscle injuries

+/- Not enough evidence to recommend PRP, HA, or MSCs for acute muscle injuries

(though, low level evidence says they may help and could reduce time to return to sport)

Hopefully, this look at evidence for and against the use of orthobiologic treatments provides some utility in your clinical practice. References are cited below and I want to reiterate that this is in no way a recommendation for individual treatment decisions which can vary widely based on the person and medical team’s recommendations. This is just my perspective on what the evidence to date suggests and overall, I would say that I’ve seen outcomes with many of the patients that I’ve worked with that seem to parallel the evidence base to date. For example, in my clinical practice I tend to see:

• Variable success with HA injections for Knee OA
• Not much benefit from PRP or injection therapy for lateral elbow pain
• Some success with stem cell injections though this tends to be inconsistent across diagnoses and patients and some patients have no benefit from these injections

References:

• Arthur Vithran DT, Xie W, Opoku M, Essien AE, He M, Li Y. The Efficacy of Platelet-Rich Plasma Injection Therapy in the Treatment of Patients with Achilles Tendinopathy: A Systematic Review and Meta-Analysis. JCM. 2023;12(3):995.
• Barker SL, Bell SN, Connell D, Coghlan JA. Ultrasound-guided platelet-rich plasma injection for distal biceps tendinopathy. Shoulder & Elbow. 2015;7(2):110-114.
• Bennell KL, Paterson KL, Metcalf BR, et al. Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial. JAMA. 2021;326(20):2021-2030.
• Carr JB, Rodeo SA. The role of biologic agents in the management of common shoulder pathologies: current state and future directions. Journal of Shoulder and Elbow Surgery. 2019;28(11):2041-2052.
• Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis. J Pain Res. 2015 Jun 5;8:269-76.
• Centeno C, Sheinkop M, Dodson E, Stemper I, Williams C, Hyzy M, Ichim T, Freeman M. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. J Transl Med. 2018 Dec 13;16(1):355.
• Chang KV, Hung CY, Aliwarga F, Wang TG, Han DS, Chen WS. Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2014 Mar;95(3):562-75.
• Cibulka MT, Bloom NJ, Enseki KR, Macdonald CW, Woehrle J, McDonough CM. Hip Pain and Mobility Deficits—Hip Osteoarthritis: Revision 2017: Clinical Practice Guidelines Linked to the International Classification of Functioning, Disability and Health From the Orthopaedic Section of the American Physical Therapy Association. J Orthop Sports Phys Ther. 2017;47(6):A1-A37.
• Davatchi F, Sadeghi Abdollahi B, Mohyeddin M, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis. 2016;19(3):219-225.
• Grassi A, Napoli F, Romandini I, et al. Is Platelet-Rich Plasma (PRP) Effective in the Treatment of Acute Muscle Injuries? A Systematic Review and Meta-Analysis. Sports Med. 2018;48(4):971-989.
• Karjalainen TV, Silagy M, O’Bryan E, Johnston RV, Cyril S, Buchbinder R. Autologous blood and platelet-rich plasma injection therapy for lateral elbow pain. Cochrane Musculoskeletal Group, ed. Cochrane Database of Systematic Reviews. 2021;2021(9).
• Krishnamurthy A, Lang AE, Pangarkar S, Edison J, Cody J, Sall J. Synopsis of the 2020 US Department of Veterans Affairs/US Department of Defense Clinical Practice Guideline: The Non-Surgical Management of Hip and Knee Osteoarthritis. Mayo Clin Proc. 2021 Sep;96(9):2435-2447.
• Kruel AVS, Ribeiro LL, Gusmão PD, Huber SC, Lana JFSD. Orthobiologics in the treatment of hip disorders. World J Stem Cells. 2021 Apr 26;13(4):304-316.
• Kwapisz A, Prabhakar S, Compagnoni R, Sibilska A, Randelli P. Platelet-Rich Plasma for Elbow Pathologies: a Descriptive Review of Current Literature. Curr Rev Musculoskelet Med. 2018;11(4):598-606. doi:10.1007/s12178-018-9520-1.
• Le ADK, Enweze L, DeBaun MR, Dragoo JL. Current Clinical Recommendations for Use of Platelet-Rich Plasma. Curr Rev Musculoskelet Med. 2018;11(4):624-634.
• Mardones R, Jofré CM, Tobar L, Minguell JJ. Mesenchymal stem cell therapy in the treatment of hip osteoarthritis. Journal of Hip Preservation Surgery. 2017;4(2):159-163.
• Miller LE, Parrish WR, Roides B, Bhattacharyya S. Efficacy of platelet-rich plasma injections for symptomatic tendinopathy: systematic review and meta-analysis of randomised injection-controlled trials. BMJ Open Sport Exerc Med. 2017 Nov 6;3(1):e000237.
• Pas HI, Winters M, Haisma HJ, Koenis MJ, Tol JL, Moen MH. Stem cell injections in knee osteoarthritis: a systematic review of the literature. Br J Sports Med. 2017;51(15):1125-1133.
• Pas HIMFL, Moen MH, Haisma HJ, Winters M. No evidence for the use of stem cell therapy for tendon disorders: a systematic review. Br J Sports Med. 2017;51(13):996-1002..
• Peck J, Slovek A, Miro P, Vij N, Traube B, Lee C, Berger AA, Kassem H, Kaye AD, Sherman WF, Abd-Elsayed A. A Comprehensive Review of Viscosupplementation in Osteoarthritis of the Knee. Orthop Rev (Pavia). 2021 Jul 10;13(2):25549.
• Phillips M, Bhandari M, Grant J, et al. A Systematic Review of Current Clinical Practice Guidelines on Intra-articular Hyaluronic Acid, Corticosteroid, and Platelet-Rich Plasma Injection for Knee Osteoarthritis: An International Perspective. Orthopaedic Journal of Sports Medicine. 2021;9(8):232596712110302.