What are orthobiologic injections, and what are they used for?
Orthobiologics are biological substances such as blood and tissues that are designed to promote bone, cartilage, and soft tissue (i.e. muscle, nerve, tendon, ligament etc.) healing and regeneration. Numerous orthopaedic diseases, including arthritis, strained muscles, and ligament tears, are treated with them. Clinical research has shown a significant potential for improved tissue healing in the presence of orthobiologics .
The injections have shown the potential to enhance muscle repair, particularly when using fluoroscopy or ultrasound-guided LR-PRP . They can be used as an adjunct in ligament healing following surgical repair . They can also be used to promote recovery of degenerative lesions, as proven by a systematic review which found eight out of nine studies showing how PRP gave a clinical and functional improvement in patients with meniscal tears .
Majority of Medical Studies Have Limitations
Though their common use started almost a decade ago and was formalized in the 1950s, most of the research conducted on these injections are recent; with no less than ten grade* 4 papers published only last year, and several of them published in the beginning of this year.
According to one review, a total of 474 articles were produced from 2009-2019, with the lot of these comprising of non-clinical trials, followed by clinical trials, and then reviews. From these more than half covered platelet-rich plasma, a third covered bone marrow aspirate, 15% covered adipose derived cells, and only 2.5% covered amniotic cells . Even so, the majority of these studies have a lot of limitations, so much of the information provided should be taken with a grain of salt.
What are the various types of orthobiologic injections?
The orthobiologic treatments include a range of injectable substances, which are basically autologous blood formulations, which means they are taken from one’s own body. These include platelet-rich plasma (PRP), isolated growth factors, as well as cell therapy techniques using cells derived from adipose tissue, amniotic sources, or bone marrow. Several orthobiologic products, ranging from blood derivatives to cellular therapies, are presently used in clinical practice as injectable treatments . These are shown below in TABLE 1.
TABLE 1: Types of orthobiologic products used in therapy
Platelet-rich plasma (PRP)
Uses a patient’s own blood cells to accelerate healing in a specific area
Autologous conditioned serum (ACS)
A blood product that is similar to PRP, but it is processed differently
Platelet-rich fibrin (PRF)
A fibrin matrix that contains platelets, leukocytes, and growth factors
Leukocyte-rich PRP (L-PRP)
Contains a higher concentration of white blood cells than PRP
Leukocyte-poor PRP (LP-PRP)
Contains a lower concentration of white blood cells than PRP
Gel-like substance within our connective tissue that promotes tissue integrity
Progenitor cells that can transform into a number of different tissues or organs. These include subtypes such as embryonic stem cells, bone marrow mesenchymal stem cells, neural stem cells, skin derived precursor stem cells, adipose stem cells and pluripotent stem cells.
How do these injections work?
It differs from product to product, but it is related to the innate healing potential of our body cells. For example, platelets are cells within our blood vessels that are involved in preventing blood loss by clotting up points of injury. They contain a high concentration of growth factors, cytokines, and other bioactive chemicals stored in granules, and these are involved in healing processes, immunoregulation, and inflammatory modulation. This is what makes platelet-rich plasma injections useful for therapy .
Stem cells, on the other hand, have the capacity for self-renewal and are flexible to transform into a wide variety of cell types depending upon the environment to which they are exposed. Because of this, they are efficacious in repairing and regenerating tissues. 
How effective are these injections? And how long do the effects last?
The effectiveness of orthobiologic injections is mostly towards reduction of pain, improvement in mobility, prevention of degeneration of tissue, and postponing the need for joint replacement. These benefits can be seen within the first six months and usually remain in follow-up periods .
PRP has been compared to bone marrow concentrate (BMC). The latter is more intrusive and has never been shown to be more effective than PRP. In comparison, patients experience a greater decrease in pain and greater activity level with just one PRP injection and can resume their daily activities at an optimal level. Only one injection of PRP is needed per year to treat conditions such as arthritis or tendonitis, and most patients report improvements two to six weeks after the procedure operation, and these effects are usually long-lasting . For example, in one study, 80% of patients responded to PRP, and 70% of patients who received a single injection reported a significant reduction in knee pain that lasted for about three years .
With respect to the choice of injection, LP-PRP may be preferable to LR-PRP when treating knee osteoarthritis. Hyaluronic acid combined with PRP has shown a greater synergistic effect, but the result may vary in different individuals .
However, it should be noted that, despite ongoing research, there is no evidence that these formulations slow down or completely stop the course of diseases like osteoarthritis. Moreover, most of the benefit is derived from younger people with milder diseases, and this is limited to symptomatic improvement only .
The site of injection can also affect outcomes, as a study has shown how subchondral bone (bone that sits underneath cartilage in a joint) injections of orthobiologics may be preferable to intra-articular injections for the treatment of osteoarthritis (OA). 
What types of diseases have these proven effective?
The treatment has been shown effective for some diseases, such as:
- Hip and knee Osteoarthritis (OA); inflammation of the joints usually due to friction (reduced synovial fluid) or wear and tear of cartilage covering bones .
- Lesions in the bone marrow; these can happen due to arthritis reaching the inside of a bone .
- Focal knee cartilage lesions; these happen when only the cartilage covering the bone is damaged .
- Subchondral Fractures of the Knee; these happen when only a portion of the tibia bone underlying the cartilage at the end is damaged .
- Myotendinous injury; any injury involving the muscle or its tendon .
- Patellar tendinopathy, also referred to as “jumper’s knee” at it occurs commonly in athletes .
- Plantar Fasciopathy; this is inflammation of the fibrous covering of the sole of the foot that lies beneath the skin but covers the muscles .
The treatment has also shown good results in the treatment of nerve injuries, specifically carpal tunnel syndrome, lumbar radiculopathy, and diabetes induced neuropathy . What’s great is that none of the studies reported any severe nerve scarring due to injections. One study even reported how use of stem cells increased the success of implanting tissue engineered nerve grafts in patients with nerve injuries.
What about cervical injuries or pain? Do these injections offer any benefit?
As a matter of fact, one case series has shown how PRP, when combined with other products such as platelet lysate and prolotherapy, significantly reduced pain and improved movement in 14 patients with pain that remains localized to the neck and immediate surrounding structures and does not involve dysfunction of the arms, hands, fingers, or other body regions (axial neck pain). The injection given was fluoroscopic guided into cervical facets, and depending upon the severity of symptoms, the amount was adjusted accordingly, but the effects were noted for up to 2 years on follow-up .
Read about Biomechanical Failures and the most important stabilizing ligaments of the Craniocervical Junction
Anything I should know before getting this injection, like side effects?
- PRP injections are a low-risk therapy due to the fact it is an autologous product, so there is less chance of reactions.
- Bleeding, tissue damage, infection, and nerve injury are less frequent hazards associated with PRP injections post-operation.
- Fluoroscopy-guided spine injections are considered best practice as they provide adequate imaging of the bony structures for improved injection precision.
- Make sure that you find a trained and experienced Physician such as an Interventional Radiologist, Orthopaedic Surgeon or a Pain or Sports Medicine Physician with certification and experience injecting areas of the spine.
- The most common complaint by patients is a temporary increase in pain, but this was mostly associated with LR-PRP and not LP-PRP. Otherwise, there was no difference in complications arising from PRP, Hyaluronic acid, or placebo .
What is the difference between ultrasound-guided and fluoroscopic-guided injections?
Despite best efforts, blind injections—those carried out without imaging—are not always accurate, with some joints having an accuracy as low as 30%.
Injections that are guided by ultrasound ensure that the medication is correctly injected at the desired location, with accuracy always above 90% . It has also been shown that ultrasound-guided injections hurt less than blind injections. Another benefit of ultrasound injections is that they provide “real-time” and “dynamic” feedback that the patient and the clinician can see and use right away .
Fluoroscopy is most frequently used in the field of pain management for peripheral joint surgeries (such as hips and knees), epidural steroid injections, nerve blocks, spinal joint injections, and other similar therapies. It is more commonly used for spinal injections because of the ability to visualize bone better. Though, ultrasound has the benefit of ease and less exposure to ionizing radiation. Otherwise, there is little to no difference in outcomes of pain relief and adverse effects .
New Upper Cervical Orthobiological Injection Clinical Trial
CCI and PICL
“CCI stands for cranial cervical instability which means that the ligaments that hold the head on are too loose. To help that problem, we developed a new procedure called PICL which stands for Percutaneous Implantation of the CCJ Ligaments. This is still an investigational procedure that has already changed many lives and helped patients avoid a complication-laden upper cervical fusion…..”(cont’d). Reference. The Clinical Trial is supposed to end in 2024.
You can read more on the PICL Study here. Dr. Centeno reviews research data collected on the PICL procedure when used to treat craniocervical instability (CCI).
Is PICL effective or placebo effect? Long lasting or temporary? Transiently reducing inflammation? …. we’ll have to wait for the clinical trial to end and its publication to get information on this treatment.
- Zhu Y, Yuan M, Meng H, et al. Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review. Osteoarthritis Cartilage. 2013;21(11):1627-1637.
- Stephens PM, Nussbaum RP, Onishi K. Orthobiologic Interventions for Muscle Injuries. Phys Med Rehabil Clin N Am. 2023 Feb;34(1):181-198. doi: 10.1016/j.pmr.2022.08.012. PMID: 36410882.
- Podesta L, Honbo ES, Mattfeld R, Khadavi M. Orthobiologic Treatment of Ligament Injuries. Phys Med Rehabil Clin N Am. 2023 Feb;34(1):135-163. doi: 10.1016/j.pmr.2022.08.010. PMID: 36410880.
- Conte P, Anzillotti G, Di Matteo B, Gallese A, Vitale U, Marcacci M, Kon E. Orthobiologic injections for treating degenerative meniscus lesions: a matter of facts? Ten years of clinical experience in a systematic review. Journal of Cartilage & Joint Preservation. 2023 Jan 13:100104.
- Obana KK, Schallmo MS, Hong IS, Ahmad CS, Moorman III CT, Trofa DP, Saltzman BM. Current trends in orthobiologics: an 11-year review of the orthopaedic literature. The American Journal of Sports Medicine. 2022 Sep;50(11):3121-9.
- Spencer W Sullivan, Oluwatobi M Aladesuru, Anil S Ranawat, Benedict U Nwachukwu, The use of biologics to improve patient-reported outcomes in hip preservation, Journal of Hip Preservation Surgery, Volume 8, Issue 1, January 2021, Pages 3–13, https://doi.org/10.1093/jhps/hnab028
- Cavallo, C., Boffa, A., Andriolo, L. et al. Bone marrow concentrate injections for the treatment of osteoarthritis: evidence from preclinical findings to the clinical application. International Orthopaedics (SICOT) 45, 525–538 (2021). https://doi.org/10.1007/s00264-020-04703-w
- Cole BJ, Gilat R, DiFiori J, Rodeo SA, Bedi A. The 2020 NBA orthobiologics consensus statement. Orthopaedic journal of sports medicine. 2021 May 4;9(5):23259671211002296.
- Centeno C, Cartier C, Stemper I, Dodson E, Freeman M, Azuike U, Williams C, Hyzy M, Silva O, Steinmetz N. The treatment of bone marrow lesions associated with advanced knee osteoarthritis: comparing intraosseous and intraarticular injections with bone marrow concentrate and platelet products. Pain Physician. 2021;24(3):E279.
- Baria, M., Luke, W. How orthobiologics uses the body’s own cells to promote healing. (2022). https://health.osu.edu/health/bone-and-joint/promote-healing-with-orthobiologics (Accessed: 25/03/2023)
- Jain, R. (2021). Orthobiologics: utilising the healing power of the human body.https://www.topdoctors.co.uk/medical-articles/orthobiologics-utilising-the-healing-power-of-the-human-body (Accessed: 25/03/2023)
- Gardner JE, Williams CW, Bowers RL. Subchondral versus intra-articular orthobiologic injections for the treatment of knee osteoarthritis: a review. Regenerative Medicine. 2022 Jun;17(6):389-400.
- Zaffagnini M, Boffa A, Andriolo L, Raggi F, Zaffagnini S, Filardo G. Orthobiologic Injections for the Treatment of Hip Osteoarthritis: A Systematic Review. Journal of Clinical Medicine. 2022 Nov 10;11(22):6663.
- Kunze KN, Hussain ZB, Sánchez M, Chahla J. Injectable orthobiologics for the treatment of subchondral insufficiency fractures of the knee (SIFK) and related pathogenic processes. Orthobiologics: Injectable Therapies for the Musculoskeletal System. 2022:349-59.
- Williams C, Jerome M, Fausel C, Dodson E, Stemper I, Centeno C. Regenerative Injection Treatments Utilizing Platelet Products and Prolotherapy for Cervical Spine Pain: A Functional Spinal Unit Approach. Cureus. 2021 Oct 8;13(10):e18608. doi: 10.7759/cureus.18608. PMID: 34659923; PMCID: PMC8500543.
- Rodríguez-Merchán EC. Intra-Articular Platelet-Rich Plasma Injections in Knee Osteoarthritis: A Review of Their Current Molecular Mechanisms of Action and Their Degree of Efficacy. Int J Mol Sci. 2022 Jan 24;23(3):1301. doi: 10.3390/ijms23031301. PMID: 35163225; PMCID: PMC8836227.
- Cluett, J. (2022) The pros and cons of ultrasound guided injectionshttps://www.verywellhealth.com/ultrasound-guided-injections-2549577 (Accessed: 25/03/2023)
- Daniels EW, Cole D, Jacobs B, Phillips SF. Existing evidence on ultrasound-guided injections in sports medicine. Orthopaedic journal of sports medicine. 2018 Feb 15;6(2):2325967118756576.
- Fluoroscopic and Ultrasound Guided Injections. Piedmont Physical Medicine and Rehabilitation.https://piedmontpmr.com/fluoroscopic-ultrasound-guided-injections/ (Accessed: 25/03/2023)
- Hofmeister M, Dowsett LE, Lorenzetti DL, Clement F. Ultrasound- versus fluoroscopy-guided injections in the lower back for the management of pain: a systematic review. Eur Radiol. 2019 Jul;29(7):3401-3409. doi: 10.1007/s00330-019-06065-3. Epub 2019 Mar 18. PMID: 30887198.
- Senna MK, Shaat RM, Ali AAA. Platelet-rich plasma in treatment of patients with idiopathic carpal tunnel syndrome. Clin Rheumatol. 2019 Dec;38(12):3643-3654. doi: 10.1007/s10067-019-04719-7. Epub 2019 Aug 16. PMID: 31420812.
- Kubrova E, Martinez Alvarez GA, Her YF, Pagan-Rosado R, Qu W, D’Souza RS. Platelet Rich Plasma and Platelet-Related Products in the Treatment of Radiculopathy-A Systematic Review of the Literature. Biomedicines. 2022;10(11):2813. Published 2022 Nov 4. doi:10.3390/biomedicines10112813
- Hassanien M, Elawamy A, Kamel EZ, Khalifa WA, Abolfadl GM, Roushdy ASI, El Zohne RA, Makarem YS. Perineural Platelet-Rich Plasma for Diabetic Neuropathic Pain, Could It Make a Difference? Pain Med. 2020 Apr 1;21(4):757-765. doi: 10.1093/pm/pnz140. PMID: 31298289.
- Yi S, Zhang Y, Gu X, Huang L, Zhang K, Qian T, Gu X. Application of stem cells in peripheral nerve regeneration. Burns & trauma. 2020 Jan 1;8.
SBA Ref. Prof. AB April 2023