Published online Oct 18, 2024. doi: 10.5312/wjo.v15.i10.908
Revised: August 31, 2024
Accepted: September 11, 2024
Published online: October 18, 2024
Processing time: 87 Days and 3.5 Hours
The field of orthopedic and regenerative medicine is rapidly evolving with the increasing utilization of orthobiologic. These biologically derived therapies, inc
Core Tip: Orthobiologics, including platelet-rich plasma, mesenchymal stem cells, bone marrow aspirate concentrate, stromal vascular fraction, and autologous chondrocyte implantation, show significant potential in enhancing musculoskeletal healing and reducing the need for invasive surgeries. Despite their growing popularity, inconsistencies in treatment protocols and evidence levels highlight the need for standardized, high-quality research. Future advancements in delivery systems, personalized medicine, and novel cell sources may further optimize their efficacy and safety.
- Citation: Jeyaraman M, Jeyaraman N, Ramasubramanian S, Balaji S, Muthu S. Evidence-based orthobiologic practice: Current evidence review and future directions. World J Orthop 2024; 15(10): 908-917
- URL: https://www.wjgnet.com/2218-5836/full/v15/i10/908.htm
- DOI: https://dx.doi.org/10.5312/wjo.v15.i10.908
The field of orthopedic and regenerative medicine is witnessing a surge in interest and application of orthobiologics. These biologically derived therapies, such as platelet-rich plasma (PRP), Adipose tissue-derived Mesenchymal Stem Cells (AD-MSCs), and Bone Marrow Aspirate Concentrate (BMAC), are being recognized for their potential to significantly improve the treatment outcomes of musculoskeletal injuries and degenerative conditions. The promise of these therapies lies in their ability to enhance the body's natural healing processes, offering a less invasive alternative to traditional surgical methods.
Orthobiologics is a dynamic and rapidly advancing field dedicated to the application of biologically derived substances and techniques to enhance healing and regeneration in musculoskeletal tissues. This domain encompasses a diverse range of therapies, including cell-based treatments such as MSCs and cultured chondrocytes, blood-derived products like PRP, tissue grafts, growth factors, hormones, and extracellular matrix components such as hyaluronic acid. While the focus of this paper is primarily on specific cell-based therapies and blood-derived products, it is crucial to recognize the broader and continually evolving nature of the orthobiologics landscape.
Orthobiologics involves using biological substances to promote the repair and regeneration of musculoskeletal tissues. These therapies are increasingly employed to address a wide array of conditions, including osteoarthritis, tendon and ligament injuries, cartilage defects, muscle injuries, and bone fractures[1-4]. To provide a comprehensive understanding of the field, it is essential to outline the major categories of orthobiologics currently in use or under investigation:
Utilized in the form of PRP, platelet-rich fibrin, platelet lysate, autologous conditioned serum, autologous protein solution, autologous conditioned plasma, hyperacute serum, growth factor concentrates, plasma rich in growth factors, and gold-indued cytokines.
These multipotent cells can be harvested from several sources namely: (1) Autologous (bone marrow, adipose tissue, umbilical cord, amniotic fluid, dental pulp, hair follicle, periosteum, menstrual blood, peripheral blood, and synovial fluid); and (2) allogenic.
Utilized in the form of BMA and BMAC.
Utilized in the form of adipose-derived stem cells, stromal vascular fraction (SVF), micro-fat, nano-fat, microvascular fragments, and exosomes.
The patient's chondrocytes are cultured and reimplanted.
Expanded under laboratory conditions to increase cell numbers.
Including bone morphogenetic proteins (BMPs), which are utilized to enhance bone healing.
Autologous or allogeneic grafts used for tissue repair and regeneration.
The clinical use of these orthobiologic techniques varies across the globe, influenced by differing regulatory frame
Despite the growing popularity and enthusiasm surrounding these therapies, the scientific validation of their efficacy and safety remains inconsistent and often controversial. Recent studies have shown promising results for the use of orthobiologics. For instance, PRP therapy has demonstrated significant potential in managing early knee osteoarthritis[5] and enhancing the healing process following rotator cuff repairs[6]. Similarly, stem cell therapies are being explored for their ability to regenerate cartilage in osteoarthritic joints[7] and improve recovery from tendon injuries[8]. However, the field faces challenges such as variability in treatment protocols, inconsistent outcomes, and regulatory concerns. The clinical application of orthobiologics also extends to chronic wound healing, where therapies like PRP have shown effectiveness in promoting tissue regeneration and reducing healing time[9]. Moreover, advancements in molecular biology and drug delivery systems are paving the way for more targeted and controlled release of bioactive molecules, enhancing the therapeutic potential of orthobiologics. This editorial aim to provide a concise overview of the current evidence levels in the field of orthobiologics.
Orthobiologics are increasingly being utilized in various clinical scenarios to promote the healing and regeneration of musculoskeletal tissues. They are particularly prominent in the treatment of sports injuries, osteoarthritis, and spinal disorders. PRP, in particular, has demonstrated effectiveness in treating tendinopathies like tennis elbow and patellar tendinitis. It achieves this by delivering growth factors that promote healing and reduce inflammation. Similarly, stem cell therapies, especially those involving MSCs, are being explored for their potential to repair and regenerate damaged ligaments and tendons. These therapies show promise in accelerating recovery and reducing the necessity for surgical in
The popularity and market growth of orthobiologics are driven by several factors, including the increasing prevalence of musculoskeletal conditions, advancements in biological therapies, and a growing preference for minimally invasive treatments. The global orthobiologics market is projected to surpass USD 11.4 billion by 2032. This expansion is fueled by the increasing prevalence of musculoskeletal conditions and sports injuries, advancements in biologic therapies, a gro
Table 1 summarizes the indications for orthobiologic products and the level of evidence supporting their usage across various musculoskeletal conditions. We used the Level of Evidence table to ascertain the level of evidence of the studies available for a given orthobiologic[15]. Further, we graded the studies for their quality, based on the bias in their study design into high, moderate, and low[16,17]. For example: Despite the availability of randomized controlled trials (RCTs) for a given orthobiologic if the quality parameters are not satisfied they are downgraded by one level. Orthobiologics such as PRP, BMAC/Microfragmented Adipose Tissue/(SVF/MFAT/AD-MSC), allogeneic MSC, and cultured cho
Indication | Orthobiologic product | Level of evidence | Ref. |
Knee osteoarthritis | PRP | 1 | [18-20] |
BMAC | 1 | [21,22] | |
SVF/MFAT/AD-MSC | 1 | [23-25] | |
Allogeneic MSC | 1 | [26-28] | |
Cultured chondrocytes (ACI/MACI) | 1 | [29] | |
Avascular necrosis of femoral head | BMAC | 1 | [30-32] |
SVF/MFAT/AD-MSC | 4 | [33,34] | |
Cultured osteoblasts | 4 | [35-37] | |
Lateral epicondylitis | PRP | 1 | [1,38] |
BMAC | 1 | [39] | |
Achilles tendinopathy | PRP | 1 | [40,41] |
BMAC | 1 | [39] | |
Patellar tendinopathy | PRP | 1 | [42,43] |
BMAC | 1 | [39] | |
Adhesive capsulitis | PRP | 1 | [44,45] |
Plantar fasciitis | PRP | 1 | [46,47] |
SVF | 4 | [48] | |
Degenerative disc disease | PRP | 1 | [49,50] |
BMAC | 1 | [51-53] | |
Fracture | PRP | 1 | [54-56] |
BMAC | 1 | [57-59] | |
ACL augment | PRP | 1 | [60,61] |
BMAC | 1 | [62] | |
Meniscus repair | PRP | 1 | [63-65] |
BMAC | 4 | [66,67] | |
MFAT | 1 | [68] | |
Rotator cuff repair augment | PRP | 1 | [69,70] |
BMAC | 1 | [39,71,72] | |
Ankle sprain | PRP | 1 | [73] |
Acute muscle injuries | PRP | 1 | [74] |
Ankle osteoarthritis | PRP | 1 | [75,76] |
Carpal tunnel syndrome | PRP | 1 | [77,78] |
For knee osteoarthritis, multiple orthobiologics such as PRP, BMAC, SVF/MFAT/AD-MSC, allogeneic MSC, and cultured chondrocytes demonstrate a high level of evidence (Level 1). Similarly, PRP and BMAC show strong support (Level 1) in the treatment of conditions like lateral epicondylitis, Achilles tendinopathy, patellar tendinopathy, adhesive capsulitis, plantar fasciitis, degenerative disc disease, fractures, ACL augmentation, and meniscus repair (with MFAT also showing Level 1 evidence). In contrast, avascular necrosis of the femoral head shows high-level evidence (Level 1) for BMAC, but a lower level of evidence (Level 4) for SVF/MFAT/AD-MSC and cultured osteoblasts. Other conditions like plantar fasciitis treated with SVF and meniscus repair with BMAC exhibit Level 4 evidence, suggesting the need for further research to validate their efficacy. The data suggest that PRP and BMAC are extensively supported by high-qua
The development and application of orthobiologics face significant regulatory challenges. Regulatory bodies like the European Medicines Agency and the United States Food and Drug Administration require extensive clinical data to ensure safety and efficacy, but the rapid advancement of these therapies often outpaces regulatory frameworks. This mismatch can lead to delays in approval and commercialization[79-81]. Ethically, the use of stem cells and other bio
Despite the promising potential of orthobiologics, several research gaps need to be addressed. One of the key gaps is the lack of standardized protocols for the preparation and application of these therapies. The variability in methods for isolating and concentrating biological materials, such as PRP and stem cells, leads to inconsistent results across studies, making it challenging to draw definitive conclusions about their efficacy. Moreover, long-term safety and efficacy data are scarce. Most studies focus on short-term outcomes, and there is a need for longitudinal studies that follow patients over several years to understand the durability of the benefits and any potential long-term adverse effects. There is also a need for more high-quality RCTs to provide robust evidence that can guide clinical practice.
The future of orthobiologics is promising, driven by advancements in biotechnology and personalized medicine. One exciting prospect is the development of more sophisticated delivery systems that can target biological materials precisely to the site of injury or disease. For instance, advances in nanotechnology and drug delivery systems could enhance the efficacy of growth factors and stem cells by ensuring sustained and controlled release. Personalized medicine also holds great potential for orthobiologics. By leveraging genomic and proteomic data, clinicians can tailor biologic therapies to the individual patient’s biological profile, improving outcomes and reducing the risk of adverse reactions. This approach aligns with the broader trend in medicine towards more personalized and precision-based treatments.
iPSCs represent a promising frontier for future orthobiologic therapies, offering several key advantages that could revolutionize the field. Derived from adult somatic cells, iPSCs circumvent the ethical concerns associated with em
The field of orthobiologics shows immense potential in enhancing musculoskeletal healing and regeneration. Despite pro
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