Courtesy: Prof Deiary Kader, London, UK

Overview

This discussion focuses on three major orthobiologic therapies:

Hyaluronic Acid (Viscosupplementation)
Platelet-Rich Plasma (PRP)
Cell-Based Therapies (Stem Cells / Mesenchymal Cells)

These therapies aim to enhance biological healing and tissue regeneration, but their clinical effectiveness varies.

Concept of Biological Regeneration

Natural Regenerative Capacity

The human body has an inherent ability to regenerate tissues.

Examples

Approximately 3 million red blood cells are replaced every second
Stem/progenitor cells contribute to:
- Tissue repair
- Tendon and soft tissue regeneration

Clinical Observation

Around 70% of patients show hamstring tendon regeneration after ACL graft harvest

Commercialization of Orthobiologics

Growth of the Industry

There has been rapid commercialization of:

PRP
Stem cell therapy
Biologic injections

Claims in Clinical Practice

Orthobiologics are marketed for:

Arthritis
Sports injuries
Hair loss
Diabetes
Neurological disorders

Concerns

Lack of regulation
Limited high-quality evidence
High treatment cost

Hyaluronic Acid (Viscosupplementation)

Background

Widely used for knee osteoarthritis, with multiple commercial formulations available.

Key Principle

Hyaluronic acid preparations are not identical.

Differences Include

Molecular weight
Preparation techniques
Injection protocols

Evidence from Literature

Cochrane Review (2006)

Demonstrated some effectiveness
Effect size was small

Meta-analysis (54 RCTs)

Onset of benefit: ~4 weeks
Peak effect: ~8 weeks

Other Meta-analyses

Some show minimal benefit
Others report moderate improvement

Guideline Recommendations

NICE – Does not recommend routine use
OARSI – No strong support
AAOS – Previously recommended against routine use

Clinical Takeaway

Provides short-term symptom relief
Best suited for early osteoarthritis

Duration of Effect

Typically 2–3 months

Limitation

Reduced effectiveness in advanced arthritis

Platelet-Rich Plasma (PRP)

Composition

PRP contains:

Platelets
Growth factors
Cytokines
Clotting factors
Prostaglandins
Electrolytes

More than 1100 proteins have been identified

Types of PRP

Leukocyte-rich PRP
Leukocyte-poor PRP

Preparation Methods

Soft spin
Hard spin

Key Difference

Leukocyte-rich PRP ? More inflammatory response

Evidence in Knee Osteoarthritis

Findings

Some studies – Small clinical benefit
Some RCTs- PRP superior to hyaluronic acid
Some meta-analyses ? No significant benefit

PRP in Tendinopathy

Conditions Studied

Patellar tendinopathy

Comparisons

Dry needling
Shockwave therapy
Physiotherapy

Conclusion

Most high-quality studies show no clear benefit

Limitations of PRP

Major Issue: Lack of Standardization

40 preparation systems exist
Variability in:
- Platelet concentration
- Growth factor levels
- Leukocyte count
- Preparation techniques

Additional Influencing Factors

Time of day
Patient-specific variables

Stem Cell and Cell-Based Therapies

Definition of Stem Cells

According to NIH, stem cells:

Can self-renew
Are undifferentiated
Can differentiate into specialized cells

Types of Stem Cells

1. Embryonic Stem Cells

Pluripotent
Can form any tissue

2. Adult (Somatic) Stem Cells

Multipotent
Found in various tissues

3. Induced Pluripotent Stem Cells

Reprogrammed adult cells
Nobel Prize-winning discovery

Mesenchymal Stem Cells (MSC)

Originally described by Arnold Caplan

Updated Concept

Not true stem cells
Renamed as:
- Medicinal signaling cells

Mechanism of Action

MSCs act primarily through:

1. Paracrine Effects

Cytokine secretion
Growth factor release

2. Immunomodulation

Regulation of immune response

3. Trophic Effects

Promote local tissue healing

4. Anti-inflammatory Effects

Reduce joint inflammation

Sources of MSCs

Bone marrow
Adipose tissue
Perivascular cells (pericytes)

Clinical Applications of Stem Cells

ACL Injuries

No significant benefit in high-quality studies

Meniscal Injuries

Some MRI studies show increased volume
Reliability of measurement is questionable

Tendinopathy

Small studies suggest possible benefit
Evidence remains weak

Knee Osteoarthritis

Case series – cartilage improvement
RCTs – no difference vs saline

Overall Conclusion

Evidence remains insufficient

Limitations of Stem Cell Therapy

Lack of standardization
Unknown composition
Unclear mechanism
Poor-quality trials
High risk of bias

Placebo Effect in Orthopaedics

Key Insight

Up to 50% of perceived treatment benefit may be placebo

Applies To

Injections
Certain surgical interventions

Future Directions

Exosomes

Definition

Small extracellular vesicles (30–100 nm)

Function

Carry signaling molecules
Facilitate cell-to-cell communication

Potential Applications

Targeted regenerative therapy
Delivery of biological signals to tissues

Key Conclusions

Orthobiologics show promising potential, but evidence is limited
Hyaluronic acid – short-term benefit in early OA
PRP – inconsistent and variable outcomes
MSCs – function mainly as signaling cells, not true stem cells

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