Orthobiologics in Musculoskeletal Medicine: An Evidence-Based Patient Guide

What Are Orthobiologics?

Orthobiologics refer to a group of therapies that use naturally occurring cells, proteins, and biological molecules to promote healing and reduce inflammation in injured or degenerative tissues. These therapies may help with:

• Slowing joint degeneration.
• Supporting tendon, ligament, and soft tissue repair.
• Modulating inflammation and immune responses.
• Reducing chronic pain.
• Enhancing the body’s natural regenerative capacity.

Orthobiologics work differently from traditional medications. Rather than suppressing symptoms alone, they aim to restore biological balance and activate the body’s intrinsic healing abilities.

Types of Orthobiologic Therapies (With Scientific Evidence)

1. Platelet-Rich Plasma (PRP)

What Is PRP?

PRP is derived from a small sample of the patient’s own blood. The blood is processed using specialized centrifugation to isolate and concentrate platelets. This concentrated platelet-rich portion is then injected into the affected joint, tendon, or soft tissue.

How Does PRP Work?

Platelets release multiple growth factors that stimulate healing:

• Platelet-derived growth factor (PDGF)
• Transforming growth factor-beta (TGF-β)
• Vascular endothelial growth factor (VEGF)
• Insulin-like growth factor (IGF)

These growth factors promote collagen synthesis, tissue repair, angiogenesis (new blood vessel formation), and modulate inflammation.

Clinical Evidence:

• Knee OsteoarthritisBennell et al. (2021) demonstrated that PRP led to improved symptoms at 12 months compared to placebo in patients with knee osteoarthritis.(Bennell KL et al., JAMA. 2021;326(20):2021-2030)Shen et al. (2017) concluded that PRP is superior to hyaluronic acid for both pain relief and function improvement.(Shen L et al., Arthroscopy. 2017;33(3):659-670)
• Tendinopathy (Tennis Elbow, Rotator Cuff, Achilles)Fitzpatrick et al. (2017) showed significant pain reduction in tendinopathy compared to placebo and corticosteroid injections.(Fitzpatrick J et al., Am J Sports Med. 2017;45(1):226-233)
• Rotator Cuff TendinopathyHurley et al. (2021) found PRP to improve both pain and function in rotator cuff injuries.(Hurley ET et al., Arthroscopy. 2021;37(3):1193-1205)

Summary:

PRP remains the most extensively studied orthobiologic, with strong scientific support in osteoarthritis and various tendon injuries.

2. Alpha-2-Macroglobulin (A2M) and Cytokine-Enriched Plasma

What Is A2M?

A2M is a large plasma protein that neutralizes destructive enzymes (matrix metalloproteinases – MMPs) and inflammatory cytokines (IL-1, TNF-α) that contribute to cartilage breakdown in osteoarthritis.

Clinical Evidence:

• Kraus et al. (2017) demonstrated that elevated proteolytic enzymes in osteoarthritis can be neutralized by A2M in preclinical models.(Kraus VB et al., Osteoarthritis Cartilage. 2017;25(8):1233-1240)
• Lodhia et al. (2021) reviewed A2M as a promising adjunctive treatment for early osteoarthritis.(Lodhia P et al., Am J Orthop. 2021;50(6):279-285)

Summary:

A2M offers a highly targeted mechanism to slow cartilage breakdown, particularly in early-stage osteoarthritis.

3. Bone Marrow Aspirate Concentrate (BMAC)

What Is BMAC?

Bone marrow is aspirated from the iliac crest and processed to concentrate mesenchymal stem cells (MSCs), progenitor cells, platelets, and growth factors. The concentrate is then injected into the area of tissue damage.

How Does It Work?

BMAC delivers MSCs that support:

• Cartilage regeneration.
• Anti-inflammatory modulation.
• Immune system regulation.
• Tissue healing.

Clinical Evidence:

• Centeno et al. (2018) reported improvement in pain and function in patients with knee osteoarthritis treated with BMAC.(Centeno CJ et al., Stem Cells Int. 2018;2018:6150987)
• Kim et al. (2014) demonstrated cartilage repair potential using BMAC for early osteoarthritis.(Kim JD et al., Am J Sports Med. 2014;42(8):1764-1773)
• Chahla et al. (2016) reviewed BMAC’s clinical potential while emphasizing the need for further standardization.(Chahla J et al., Arthroscopy. 2016;32(6):1151-1167)

Summary:

BMAC holds strong promise for cartilage repair and advanced osteoarthritis, but requires careful expert technique for optimal results.

4. Adipose-Derived Stem Cells (AD-MSCs)

What Is AD-MSC Therapy?

Adipose (fat) tissue is rich in regenerative cells. Fat is harvested, minimally processed (micro-fragmented) or culture-expanded to isolate MSCs, which are then injected into affected tissues.

How Does It Work?

AD-MSCs possess powerful:

• Anti-inflammatory properties.
• Cartilage protective effects.
• Immunomodulatory functions.

Clinical Evidence:

• Freitag et al. (2019) demonstrated significant improvement in pain and function in knee osteoarthritis using AD-MSCs.(Freitag J et al., Stem Cells Int. 2019;2019:4313565)
• Jo et al. (2014) showed cartilage regeneration in severe OA patients receiving AD-MSC injections.(Jo CH et al., Stem Cells. 2014;32(5):1254-1266)
• Lee et al. (2019) reported long-term benefit in severe knee OA with adipose stem cell therapy.(Lee WS et al., Stem Cells Int. 2019;2019:2715291)

Summary:

AD-MSC therapy offers an advanced regenerative option for moderate to severe osteoarthritis, particularly in patients aiming to delay joint replacement.

5. Exosomes & Birth Tissue-Derived Products (Experimental Stage)

What Are Exosomes?

Exosomes are microscopic extracellular vesicles secreted by cells, carrying signaling molecules (proteins, lipids, RNA) that may influence tissue repair.

Current Research Status:

• Mendt et al. (2019) reviewed the emerging potential of exosomes in regenerative medicine, though human trials remain limited.(Mendt M et al., Cell Stem Cell. 2019;25(5):724-740)

Summary:

Exosome-based therapies remain in the experimental phase, with ongoing research necessary before routine clinical use.

Why Orthobiologics Matter

Orthobiologic medicine does not replace surgical care but aims to:

• Delay surgery where possible.
• Improve pain control and mobility.
• Slow down tissue degeneration.
• Activate biological healing.

Each treatment must be carefully selected based on:

• Severity of the condition.
• Individual patient profile.
• Evidence-based protocols.
• Safety and regulatory guidelines.

References

1. Bennell KL et al., JAMA. 2021;326(20):2021-2030.
2. Shen L et al., Arthroscopy. 2017;33(3):659-670.
3. Fitzpatrick J et al., Am J Sports Med. 2017;45(1):226-233.
4. Hurley ET et al., Arthroscopy. 2021;37(3):1193-1205.
5. Kraus VB et al., Osteoarthritis Cartilage. 2017;25(8):1233-1240.
6. Lodhia P et al., Am J Orthop. 2021;50(6):279-285.
7. Centeno CJ et al., Stem Cells Int. 2018;2018:6150987.
8. Kim JD et al., Am J Sports Med. 2014;42(8):1764-1773.
9. Chahla J et al., Arthroscopy. 2016;32(6):1151-1167.
10. Freitag J et al., Stem Cells Int. 2019;2019:4313565.
11. Jo CH et al., Stem Cells. 2014;32(5):1254-1266.
12. Lee WS et al., Stem Cells Int. 2019;2019:2715291.
13. Mendt M et al., Cell Stem Cell. 2019;25(5):724-740.