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First, came platelet-rich plasma (PRP) treatments.  Then stem cell treatments became increasingly popular.  Most recently the term Orthobiologics is being used extensively.  What are Orthobiologics?  What are the different sources of Orthobiologics?  Why should I care about Orthobiologics.  Let’s dig in.

Making Sense of the Term “Orthobiologics”

This is an important term that is being used with increasing frequency in an expanding number of circles.  Let’s take a moment to dive deeper.  To better understand the term Orthobiologics lets break down the word.  Orthobiologics combines two words:  Ortho and Biologics.  The medical term “Ortho”  is from the Greek “orthos” which means straight or erect and is referencing bones, joints, muscles, and tendons.  Biologics has many different meanings.   In the context of Orthobiolgics it simply means that the substances are naturally derived substances from the body. These substances have the ability to heal bones, joints, muscles, and tendons.  They are different than the group of drugs also called “biologics” used by internal medicine and Rheumatologists to treat rheumatoid arthritis and other auto-immune conditions. These are drugs that are made by living organisms or parts of organisms and include genetically engineered proteins to target specific parts of the immune system.  Common examples include Humira and Enbrel.

What Are Orthobiologics?

Orthobiologics, therefore, are biological substances naturally found in the body that are used to promote quicker healing of muscle, tendon, and bone injuries (1).  Orthobiologics can further be categorized based upon where they come from and tissue type.

What Are the Different Sources of Orthobiolgics?

Orthobiolgics can come from one of two sources:  your own or someone else’s.  If the substance is your own it is referred to as AUTOLOGOUS.  An example of an autologous Orthobiologic is PRP where your own blood is drawn from your vein and processed and then re-injected.  If the substance is from another patient or pool of patients it is referred to as ALLOGENIC.  An example of an allogenic Orthobiologic is the use of birth tissue such  as Wharton’s Jelly or amniotic fluid.  These are products from other patients.  The distinction is important.  Autologous means substances that are from you whereas Allogenic means from others.

What Are the Different Tissue Types of Orthobiologics?

There are four different tissue types.  They include:

Blood-Derived

There are several different types of blood-derived Orthobiolgics.  The most common example is PRP ( platelet-rich plasma).  Blood is taken from a vein in the arm or hand and then is processed in a lab or centrifuge.  The red and white blood cells are removed and the platelets are concentrated.  Platelets are rich in growth factors. The PRP is then injected under x-ray or ultrasound guidance into the area of tissue damage.

Stem Cells

There are many different types of stem cells which include autologous, allogenic, and culture-expanded  The most common sources of autologous stem cells are from bone marrow and fat.  Autologous simply means patients own tissue. To obtain bone marrow stem cells a patient must undergo a bone marrow aspirate.  This is a medical procedure where a needle is placed into the hip bone and bone marrow is removed.  The bone marrow is then processed whereby the stem cells are concentrated (2). High-level research has demonstrated that the higher the number of stem cells the better the clinical results (3).

Allogenic “stem cells” are those that are derived from another person. Examples would include birth tissue products such as Wharton’s Jelly or amniotic fluid.  While these products are being marketed as having millions of stem cells, research laboratories at Cornell and University of California have proven no living stem cells are present in these products (4-6).

Culture Expanded Stem Cells  are another example of Orthobiolgics.  At present culture-expanded stem cells are not legal in the United States.  This involves isolating and growing stem cells from bone marrow, fat, or birth tissue to a much higher number.  This allows patients to undergo treatment in multiple areas.  In addition, culture-expanded stem cells are able to be frozen and used at a later time.  The biologic age of the cells is frozen until thawed and used clinically.  Culture expanded stem cells are used at the Regenexx Cayman Clinic in the Cayman Islands

Extra Cellular Matrix

Extracellular matrices (ECM) are Orthobiolgics that provide support to cells. They act as a scaffold for cells filling large gaps or holes in damaged or torn tissue.  They form a bridge of sorts that enables the cells to heal the damaged tissue.  ECM controls cell communication and regulates cellular processes such as growth, movement (7).  Examples of extracellular matrix include:

  1. Fat grafts AKA Lipogems (8)
  2. Birth Tissues derived from amniotic fluid (9)
  3. Birth Tissues derived from umbilical cords (10)
  4. Demineralized Bone Matrix ( DBM) which involves cadaver bone.  After the calcium is removed the matrix is used to recruit host cells to promote bone healing(11)

Conditioned Media

Exosomes are an example of an Orthobiologic conditioned media.  Exosomes have become highly visible on the internet and in the media and social media.  Physicians and chiropractors alike are promoting their regenerative and healing properties.  Exosomes are small packets of information excreted by living cells (12)  Exosomes are how cells communicate with one another.  They contain critical information for cells. This information may include how to reprogram a cell or how to accelerate cell growth.  Exosomes are present in most bodily fluids which include blood, urine, saliva, synovial fluid amniotic fluid, semen, and breast milk.  They are released in high quantities from rapidly growing cells. The FDA released a consumer alert in July regarding Exosomes because of serious adverse events.  They warned patients that many clinics across the country advertising Exosomes are using deceptive practices with unsubstantiated claims, putting patients at risk and there are no FDA approved Exosome products.  To better understand Exosomes  please click on the video below.

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Why Should I Care About Orthobiologics?

Orthobiologics are the future for orthopedic and musculoskeletal medicine. A common example includes the use of bone marrow-derived stem cells in the treatment of ACL tears in the knee.  At the Centeno-Schultz Clinic, we pioneered the technique whereby patients can successfully use their own stem cells and avoid the risks and downtime of conventional ACL surgery.  Another example is the use of PRP for small Rotator Cuff tears in the shoulder.  Instead of surgical repair patients are now able to have ultrasound-guided injections of their own PRP into the areas of tissue damage.  PRP is rich in growth factors which allow for an increase in blood flow and reduction in inflammation.  As Orthobiologics get more advanced it is likely that more invasive, larger orthopedic surgeries will be replaced by Orthobiologic injections.  Why?  Orthobiologics have the ability to heal areas of tissue damage without the risks, complications, and downtime associated with traditional orthopedic surgery.  To learn more about Orthobiologics please click on the video below.

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In Conclusion

Orthobiologics are biological substances naturally found in the body that are used to promote quicker healing of muscle, tendon, and bone injuries. Orthobiologics come from two sources:  Autologous and Allogenic.  Autologous means the substances are your own whereas allogenic refers to products that are from another patient or pool of patients.  There are four different tissue types:  blood-derived such as PRP, stem cells, extra cellular matrix, and conditioned media.  Orthobiologics are important as they will change the practice of orthopedic and musculoskeletal medicine.  They offer patients the opportunity to use their own cells to heal injury while avoiding tissue injury, risks, and downtime associated with surgery.

If you are scheduled for a steroid injection or surgery know that there are other viable options. Your body has the ability to promote and accelerate healing.  Schedule a Telemedicine consultation with a board-certified, fellowship-trained physician from the comfort of your backyard or home to learn whether an Orthobiologic can help you.

 


1.Dhillon MS, Behera P, Patel S, Shetty V. Orthobiologics and platelet rich plasma. Indian J Orthop. 2014;48(1):1-9. doi:10.4103/0019-5413.125477

2..Gianakos AL, Sun L, Patel JN, Adams DM, Liporace FA. Clinical application of concentrated bone marrow aspirate in orthopaedics: A systematic review. World J Orthop. 2017;8(6):491–506. Published 2017 Jun 18. doi:10.5312/wjo.v8.i6.491.

3. Harrell DB, Caradonna E, Mazzucco L, et al. Non-Hematopoietic Essential Functions of Bone Marrow Cells: A Review of Scientific and Clinical Literature and Rationale for Treating Bone Defects. Orthop Rev (Pavia). 2015;7(4):5691. Published 2015 Dec 28. doi:10.4081/or.2015.5691

4.Burke J, Kolhe R, Hunter M, Isales C, Hamrick M, Fulzele S. Stem Cell-Derived Exosomes: A Potential Alternative Therapeutic Agent in Orthopaedics. Stem Cells Int. 2016;2016:5802529. doi:10.1155/2016/5802529

5.Dustin R. Berger, Nicolette F. Lyons, and Neven J. Steinmetz. In Vitro Evaluation of Injectable, Placental Tissue-Derived Products for Interventional Orthopedics. Interventional Orthopedics Foundation Annual Meeting. Denver, 2015. https://interventionalorthopedics.org/wp-content/uploads/2017/08/AmnioProducts-Poster.pdf

6.Liliya Becktell, Andrea Matuska, PhD, Stephanie Hon, DVM, Michelle L. Delco, DVM, PhD, Brian J. Cole, MD, Lisa A. Fortier, DVM, PhD. Proteomic analysis and cell viability of nine amnion-derived biologics. Orthopedic Research Society Annual Meeting, New Orleans, 2018. https://app.box.com/s/vcx7uw17gupg9ki06i57lno1tbjmzwaf

7.Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123(Pt 24):4195-4200. doi:10.1242/jcs.023820

8. Russo A, Condello V, Madonna V, Guerriero M, Zorzi C. Autologous and micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis. J Exp Orthop. 2017;4(1):33. Published 2017 Oct 3. doi:10.1186/s40634-017-0108-2.

9.Woodall BM, Elena N, Gamboa JT, et al. Anterior Cruciate Ligament Reconstruction With Amnion Biological Augmentation. Arthrosc Tech. 2018;7(4):e355–e360. Published 2018 Mar 19. doi:10.1016/j.eats.2017.10.002.

10.Jadalannagari S, Converse G, McFall C, et al. Decellularized Wharton’s Jelly from human umbilical cord as a novel 3D scaffolding material for tissue engineering applications [published correction appears in PLoS One. 2017 Mar 7;12 (3):e0173827]. PLoS One. 2017;12(2):e0172098. Published 2017 Feb 21. doi:10.1371/journal.pone.0172098

11.Drosos GI, Touzopoulos P, Ververidis A, Tilkeridis K, Kazakos K. Use of demineralized bone matrix in the extremities. World J Orthop. 2015;6(2):269–277. Published 2015 Mar 18. doi:10.5312/wjo.v6.i2.269.

12.Vakhshiteh F, Atyabi F, Ostad SN. Mesenchymal stem cell exosomes: a two-edged sword in cancer therapy. Int J Nanomedicine. 2019;14:2847–2859. Published 2019 Apr 23. doi: 10.2147/IJN.S200036