Regenerative Medicine and Sports Injuries

Introduction

Sports injuries are highly prevalent, affecting athletes of all levels. A surveillance study done by Prieto-González et al. involving athletes in the age group of 14 to 21 concluded that 40.4% of athletes suffered injuries in the year 2019. Lumbar muscle strains, ankle sprains, and bone fractures were the most common injuries.(1) Another retrospective study done over 10 years, concluded that the lower extremity was very commonly involved in 68.71% of cases, out of which 29.79% cases included knee injuries.(1) Inflammation of the rotator cuff muscles of the shoulder due to overuse can lead to instability or dislocation of the joint if left untreated. Sports with overhead movements like swimming and tennis are most commonly affected.(2) Small tears in the tendons and ligaments around the elbow develop due to repetitive impact loading (Tennis elbow, Golfer’s elbow).(2) Ligament injuries in the knee (cruciate ligaments and the meniscus) are common in sports. It usually gets injured in sports like football involving high-speed sudden change of direction. Sports involving running and jumping like badminton involve injuries to the knee tendons.(2) Ankle sprain and injury to the Achilles tendon are the most common foot-related injuries in sports.(2)

Impact of Sports Injuries

Sports injuries impact athletes not only physically, but also psychologically, socially, and financially. According to the 2016-17 English Premier League (EPL) seasonal injury report, they lost an average of 1410 days due to various injuries and an injury-related wage bill cost the club 181 million pounds.(3) Injury not only affects the individual, but it also has an impact on their families, friends, teammates, coaches, support team, and also the larger communities, as described by Wiese-Bjornstal.(4)

Current concepts in the treatment of Sports Injuries 

The current first line of treatment for any sports injury, is to control the phase of pain and inflammation. This phase is followed by a functional rehabilitation program, and a gradual return to sports.(5) In severe injury cases the athlete undergoes a surgical intervention followed by a rehabilitation program.(5) Recently, the application of regenerative medicine in managing sports injuries is being tested. Regenerative medicine can be defined as the replacement or restoration of human tissue or organs to restore normal function.(6) This article summarises the present regenerative solutions for sports injury management. 

Regenerative Medicine

1. Stem cell therapy

Stem cells are precursor cells that have the ability for physiological cell death (apoptosis) and the formation of new cells (cell turnover).(7) The various types of stem cells are as follows:-

1. Totipotent cells have the capacity to regenerate an entire organism and differentiate into any cell in the body.(7)

2. Pluripotent stem cells are found after the stage of totipotent cells and have the capacity to differentiate into any of the three germ layers (basic building blocks of the body) as follows:-

• Ectoderm - the outer layer of the body, 

• Mesoderm - the middle layer of the body, 

• Endoderm - the inner layer of the body.(7)

1. Multipotent stem cells are capable of regenerating the middle layer cells: mesodermal cells. In sports injury, the tissues that get injured very frequently are cartilage, bones, and muscles which are derived from the mesenchymal stem cells (MSC) from the mesodermal layer of the body (middle layer).(7) The MSCs can be extracted from various sites in the body, but it is usually harvested from the bone marrow as it is associated with minimal complications. The application of stem cell therapy is still in the clinical trials phase, and further research is still needed to understand the long-term benefits. MSCs have the ability of cell differentiation and production of growth factors that stimulate neovascularisation and re-epithelialization, thereby facilitating wound healing.(8)

2. Platelet-rich-plasma (PRP)

A platelet concentration in the plasma higher than the baseline is required to induce a healing response.(5) A normal blood sample contains 94% of red blood cells (RBCs), 6% of platelets, and 1% of white blood cells. PRP contains 95% platelets and 5% of RBCs. This reversal of the RBC: platelet ratio is known to have high levels of proteins (growth factors and cytokines) that promote tissue restoration and healing.(8) Venous blood sample is collected and centrifuged to obtain three layers of the sample: a layer of RBCs,  the middle layer of platelets and white blood cells, and a top layer of plasma. The middle layer of platelet-rich plasma is used to treat various musculoskeletal injuries. PRP stimulates the formation of collagen, osteoblasts, and fibroblasts that stimulate structural formation of tissues. Acute hamstring strains are very prevalent and account for 29% of sports injuries. PRP has been shown to have favorable effects on hamstring strains.(8) Patellar tendinopathy and Achilles tendon injuries have also shown positive results in reducing inflammation and facilitating the healing of the tissues.(8) PRP utilizes an individual’s cells, thus making it less prone to infection and, safe and effective treatment. Few people have, however, reported scar tissue formation and calcification at the site of injection.(8) Further studies in this field will help us understand the long-term effects of PRP.

3. Prolotherapy (PrT)

The basic principle of prolotherapy is to create a controlled injury to the affected site which triggers an inflammatory response that leads to stimulation of macrophages and fibroblasts and ultimately collagen deposition for structural formation of the tissues. This assists in strengthening the damaged cartilage, tendons, and ligaments. The commonly used solution in PrT is hyperosmolar dextrose. The mechanism of action of this dextrose solution involves chemical and mechanical pathways, which ultimately trigger an inflammatory response, resulting in collagen deposition.(9) Dextrose solution also acts on the sensorineural pathways thus modulating pain sensations.(9) PrT has shown positive results in treating common sports injuries like lateral epicondylitis, (Tennis elbow), rotator cuff tendinopathy (inflammation of shoulder tendons), plantar fasciitis (patient often complains of heel pain), Osgood- Schlatter disease (pain around the knee).(9) Mengting Zhu et al. conducted a systematic review and meta-analysis to investigate the effects of hypertonic dextrose injection (DPT) in lateral elbow tendinosis.  Data from eight studies included in the study concluded that DPT is superior to non-surgical treatments in reducing pain and improving function in lateral elbow tendinosis.(10)

4. Tissue engineering with Biomaterials

A material, construct, or surface that interacts with the biological system is a biomaterial.(11) Biomaterials are obtained naturally or can be made synthetically. The three important properties that make them useful for tissue engineering are: biocompatible (does not trigger an immune response), biodegradable (degrades in the body after fulfilling the function), and bioactive (influence biological response).(11) Chitosan, collagen, and cellulose are natural biomaterials and polylactic acid is an example of synthetic biomaterials. These biomaterials are used to prepare scaffolds which are placed in the injured tissues.(11) Clinical studies are currently underway to investigate the effects of implantation of synthetically engineered cartilage created from scaffolds, at the affected site.(12)

Way ahead with Regenerative Medicine

Regenerative medicine has a great potential to revolutionise the treatment of sports injuries offering alternatives to long recovery time and the use of medications for infection control and pain management. These new methods of treatment are proving to accelerate the physiological healing of the tissue and reduce inflammation which is very important for an injured athlete. Extensive research is still required, in the context of sports injuries, for such methods to be accepted on a larger scale.(12)

References

1. Al-Qahtani MA, Allajhar MA, Alzahrani AA, et al. Sports-Related Injuries in Adolescent Athletes: A Systematic Review. Cureus. 2023;15(11):e49392. Published 2023 Nov 25.

2. Sports Injuries (2024) National Institute of Arthritis and Musculoskeletal and Skin Diseases. Available at: https://www.niams.nih.gov/health-topics/sports-injuries#:~:text=Injuries%20to%20the%20musculoskeletal%20system,Bone%20fracture. (Accessed: 12 November 2024).

3. Eliakim E, Morgulev E, Lidor R, Meckel Y. Estimation of injury costs: financial damage of English Premier teams' underachievement due to injuries [published correction appears in BMJ Open Sport Exerc Med. 2020 Jun 15;6(1):e000675corr1. doi: 10.1136/bmjsem-2019-000675corr1]. BMJ Open Sport Exerc Med. 2020;6(1):e000675. Published 2020 May 20.

4. Podlog, L., Wagnsson, S., & Wadey, R. (2023). The impact of competitive youth athlete injury on parents: a narrative review. Sport in Society, 27(8), 1332–1355.

5. Malanga G, Nakamura R. The role of regenerative medicine in the treatment of sports injuries [published correction appears in Phys Med Rehabil Clin N Am. 2015 May;26(2):xix. Nakamurra, Reina [corrected to Nakamura, Reina]]. Phys Med Rehabil Clin N Am. 2014;25(4):881-895.

6. Sampogna G, Guraya SY, Forgione A. Regenerative medicine: Historical roots and potential strategies in modern medicine. J Microsc Ultrastruct. 2015;3(3):101-107.

7. Ajibade DA, Vance DD, Hare JM, Kaplan LD, Lesniak BP. Emerging Applications of Stem Cell and Regenerative Medicine to Sports Injuries. Orthop J Sports Med.

8. Ramaswamy Reddy SH, Reddy R, Babu NC, Ashok GN. Stem-cell therapy and platelet-rich plasma in regenerative medicines: A review on pros and cons of the technologies. J Oral Maxillofac Pathol. 2018;22(3):367-374.

9. Nazemi A, Komatsu D, Penna J, Capotosto S. Poster 361: Prolotherapy in the Treatment of Sports-Related Tendinopathies: A Systematic Review. Orthop J Sports Med. 2023;11(7 suppl3):2325967123S00324. Published 2023 Jul 31.

10. Zhu M, Rabago D, Chung VC, Reeves KD, Wong SY, Sit RW. Effects of hypertonic dextrose injection (Prolotherapy) in lateral elbow tendinosis: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2022;103(11):2209–18.

11. Eldeeb AE, Salah S, Elkasabgy NA. Biomaterials for Tissue Engineering Applications and Current Updates in the Field: A Comprehensive Review. AAPS PharmSciTech. 2022;23(7):267. Published 2022 Sep 26.

12. Abdolmaleki, A., Zahri, S., Asadi, A., Wassersug, R. Role of Tissue Engineering and Regenerative Medicine in Treatment of Sport Injuries. Trauma Monthly, 2020; 25(3): 106-112.