Why OrthoBiologics?

At the turn of the Millennium, the new century dawned with an evolution in the thinking process of many scientists involved in regenerative medicine specialities. Changing technology and the evolving understanding of healing processes led to a mindset change from a focus on fracture fixation and joint reconstruction to the possibility of regenerating damaged tissue, as well as stimulation of that regeneration. The term Orthobiologics was thus coined, referring to a class of regenerative medicine which uses natural substances derived from the body for healing of musculoskeletal injuries and degeneration. It is essentially a combination of two words- ‘Ortho’ referring to Orthopaedics and ‘biologics’ referring to substances derived from one's body (not to be confused with the terminology in pharma industry which refers to a category of drugs derived from living organism using recombinant DNA technology).¹ In the last 20 years, with significant hype and hope, along with some disappointments, Orthobiologics is emerging as a new subspeciality in Orthopaedics, with gradual acceptance.² Some procedures that were available earlier, especially cell culture based procedures like Autologous chondrocyte implantation (ACI) have shown a significant resurgence of interest³ The emergence of simpler procedures like PRP⁴ and BMAC⁵ has allowed ease of use, and better acceptance by clinicians and patients. The current symposium is an attempt at compiling the best data on the diverse category of Orthobiologic substances available, and the plethora of indications where these can be used.

Knee Osteoarthritis has been an area where significant interest has led to the extensive use of Orthobiologic products, not only to improve pain and quality of life, but also to try and delay the eventual progression.⁶ In this issue, articles ranging from basic science to clinical trials and systematic reviews are focussed on Orthobiologic use in OA Knee. The role of PRP as a chondroprotective agent by inhibiting apoptosis has been demonstrated in a guinea pig study by a team of researchers from PGIMER, Chandigarh. The role of stromal vascular fraction (SVF's) derived from adipose tissue in OA knee, the role of autologous and allogenic pooled MSC's in OA knee have also been discussed in two separate systematic reviews in this edition. A meta-analysis by Muthu et al. has looked at the ideal mesenchymal stromal cell count required for clinically significant effect in OA knee and the authors recommend a cell volume of 5–10 × 10⁷ cells to be delivered to the target site to obtain superior benefits out of the procedure. Another meta-analysis by Jeyaraman et al. has looked at the role of vehicle based delivery of MSC's to the target area, but did not notice added benefit of using a carrier as PRP or hyaluronic acid. An original research work on high molecular weight hyaluron by Acharya et al. has demonstrated improvement in Condition Specific and Generic Quality of Life Outcomes in Patients with Knee OA.

This issue also has publications focusing on chondral injuries in the knee, and another systematic review exclusively elucidating an evidence based update on chondral injuries to the hip. An interesting article comparing injection of cultured bone marrow derived mesenchymal cells with ACI for chondral knee defects has observed similar comparable results in their RCT at 6 years follow up. These are interesting findings, as such an approach can avoid a second stage surgery associated with ACI; the authors have administered cultured bone marrow derived mesenchymal cells by intra articular injections as it is known that the MSC's will home towards the zone of injury.

The hip is another joint that has generated significant interest for the application of Orthobiologic substances; since Avascular necrosis of Hip (AVN) remains a challenging situation, cellular therapies may provide an impetus to boost the existing surgical interventions, with improvement in joint preservation rates, provided these are used in the right stage of disease. In the current issue, two articles exploring BMAC and other cellular therapies as a treatment option in AVN of hip, as well as a scoping review combining cellular therapy with core decompression.

Nonunion and delayed fracture healing still remain clinically challenging situations; it is thus logical to use biological methods to enhance fracture healing. The gold standard autologous bone grafting, the oldest time established procedure, is perhaps the first understanding of orthobiologics and its potential role in fracture healing. We are all aware of the documented osteogenesis potential of the MSC's in the autograft. The current symposium includes a systematic review by Jamal et al. evaluating the role of PRP in augmenting fracture healing.

The question thus remains: Why Orthobiologics? Even today, despite huge advances in science in technology, some basic healing and repair processes are poorly understood. Surgeons are gaining insights by researchers looking at the cellular and micro-cellular levels of bone healing, and have realized that the power of healing actually lies within us. We just have to kick start some processes, or supplement some missing elements, and it maybe “signalling to initiate processes” that maybe the key to future methods. Orthopaedics in the 21st century may potentially be dominated by regenerative medicine experts, as there have been huge developments in the field. The thought process is clearly changing from being a pure mechanics oriented intervention to incorporating and respecting biology. Terms like mechanoregulation, instructive bone regeneration, and mRNA therapy have now become common place. With an increasing understanding of the subject, elucidating the right pathways, the right formulations, the right doses and right indications, we can expect more solutions to challenging orthopaedic problems. The new age orthopaedician should understand and master both mechanical aspect and biological aspect to give a holistic solution to complex problems.

So can we answer the question that we asked in the beginning- Why Orthobiologics? With current available evidence, we can try to start answering this question. We have now identified the needs and the gaps in our knowledge, we now know more about the signalling processes that regulate healing and we are also understanding how issues away from the bone and joint (co-morbidities etc) could influence the healing. Orthobiologics, as a hybrid concept fits right in, with basic science research being directly applied to situations needing healing and repair. But we have not yet crossed the threshold of understanding, and it is imperative that we do not jump the gun and use "ünder-cooked data”at too early a stage.

So Why OrthoBiologics? Because it maybe the next final frontier, and we all need to go there to improve Orthopaedic healing.