Orthobiologics

Abstract:

The orthopedic sports medicine profession experienced a pivotal shift with the acceptance and application of the arthroscope. The next leap forward will hinge on the acceptance, application, and regulation of biologic therapies, and a sentinel event will be the US Food and Drug Administration approval of a stem cell technology. While the arthroscope was developed in the hands of our sports medicine mentors, the current history of biologics has been mostly written by basic scientists. The baby steps of these technologies have involved benchtop laboratory studies and preclinical animal trials, clearly illustrating great potential. Clinical progress has struggled forward but stalled. Regulatory constraints and our inability to establish safety and efficacy are the major hurdles, with disconnect between the basic scientist, clinician, and regulatory bodies to blame. While the development of the arthroscope was barely influenced by governmental regulation, this will control and model the future of stem cell technologies. With current legislation before Congress concerning stem cell regulation, the next steps are dependent upon the clinician’s understanding and participation in this regulation.

Abstract:

PURPOSE:

To examine the number of viable stem cells contained in the postinjury effusion fluid and the waste byproducts of arthroscopic cruciate ligament surgery.

METHODS:

This study included patients older than 18 years of age with acute (<5 weeks old) cruciate ligament injuries requiring arthroscopic surgery. The postinjury effusion fluid (effusion fluid), fat pad and cruciate ligament stump debridement tissue (byproduct tissue), and arthroscopic fluid collected during fat pad and/or stump debridement (byproduct fluid) were collected at the time of surgery from 30 individuals. Specimens were analyzed, investigating cell viability, nucleated cell counts, cell concentrations, colony-forming unit assays, and flow cytometry. Samples from the first 20 individuals were collected in small specimen containers, and samples from the last 10 individuals were collected in larger specimen containers.

RESULTS:

Cells of the injury effusion exhibited the greatest viability (86.4 ± 1.31%) when compared with the small volume harvest byproduct tissue (50.2 ± 2.5%, P = .0001), small volume harvest byproduct fluid (48.8 ± 1.88%, P = .0001), large volume harvest byproduct tissue (70.1 ± 5.6%, P = .0001), and large volume harvest byproduct fluid (60.3 ± 3.41%, P = .0001). The culture analysis of fibroblast colony-forming units found on average 1916 ± 281 progenitor cells in the effusion fluid, 2488 ± 778 progenitor cells in the byproduct tissue, and 2357 ± 339 progenitor cells in the byproduct fluid. Flow cytometry confirmed the presence of immature cells and the presence of cells with markers typically expressed by known stem cell populations.

CONCLUSIONS:

Viable stem cells are mobilized to the post injury effusion at the time of cruciate ligament injury and can be found in the byproduct waste of cruciate ligament surgery.

CLINICAL RELEVANCE:

The methodology around effusion fluid and byproduct tissue capture during cruciate ligament surgery should be investigated further. Cell amounts available from these tissues with current technologies are not sufficient for immediate evidence-based clinical application.

Abstract:

Regenerative medicine is emerging with great interest and hope from patients, industry, academia, and medical professionals. Cartilage regeneration, restoration, or repair is one of the prime targets that remains largely unsolved, and many believe that regenerative medicine can possibly deliver solutions that can be widely used to address the current gap(s) in treatment. In the United States, Europe, Australia, and India the regulation of regenerative based treatments has become a big debate. Although the rules and regulations remain unclear, clinicians that are interested should carry-on with the best available guidelines to ensure safety and compliance during delivery in clinical practice to avoid regulatory infraction. Many have made significant investment of time, resources, and facilities in recent years to provide new regenerative treatment options and advance medical care for patients. Instead of reinventing the wheel, it would be more efficient to adopt currently accepted standards and nomenclature borrowed from transplantation science, and cord blood storage industries. The purposes of this article are to provide some historical background to the field of regenerative medicine as it applies to cartilage, and how this field has developed. This will be followed by a separate discussion on regulatory oversight and input and how it has influenced access to care. Furthermore, we discuss current clinical techniques and progress, and ways to deliver these treatments to patients safely, effectively, and in a cost sensitive manner, concluding with an overview of some of the promising regenerative techniques specific to cartilage.

Abstract:

The future of orthopedic surgery appears to be intimately associated with the development of orthobiologics to facilitate healing and the treatment of multiple disease processes. The orthopedic community should understand developmental processes to ensure that products are adequately studied and the effects are fully known before widespread implementation in the clinical setting. Technologies that embrace this paradigm will impact the field the most.

Abstract:

PURPOSE:

To histologically evaluate the quality of articular cartilage regeneration from the medial compartment after arthroscopic subchondral drilling followed by postoperative intra-articular injections of autologous peripheral blood stem cells (PBSCs) and hyaluronic acid with concomitant medial open-wedge high tibial osteotomy (HTO) in patients with varus deformity of the knee joint.

METHODS:

Eight patients with varus deformity of the knee joint underwent arthroscopic subchondral drilling of International Cartilage Repair Society (ICRS) grade 4 bone-on-bone lesions of the medial compartment with concomitant HTO. These patients were part of a larger pilot study in which 18 patients underwent the same procedure. PBSCs were harvested and cryopreserved preoperatively. At 1 week after surgery, 8 mL of PBSCs was mixed with 2 mL of hyaluronic acid and injected intra-articularly into the knee joint; this was repeated once a week for 5 consecutive weeks. Three additional intra-articular injections were administered weekly at intervals of 6, 12, and 18 months postoperatively. Informed consent was obtained at the time of hardware removal for opportunistic second-look arthroscopy and chondral biopsy. Biopsy specimens were stained with H&E, safranin O, and immunohistochemical staining for type I and II collagen. Specimens were graded using the 14 components of the ICRS Visual Assessment Scale II, and a total score was obtained.

RESULTS:

Second-look arthroscopy showed satisfactory healing of the regenerated cartilage. Histologic analysis showed significant amounts of proteoglycan and type II collagen. The total ICRS Visual Assessment Scale II histologic scores comparing the regenerated articular cartilage (mean, 1,274) with normal articular cartilage (mean, 1,340) indicated that the repair cartilage score approached 95% of the normal articular cartilage score. There were no infections, delayed unions, or nonunions.

CONCLUSIONS:

Chondrogenesis with stem cells in combination with medial open-wedge HTO for varus deformity correction of the knee joint regenerates cartilage that closely resembles the native articular cartilage.

LEVEL OF EVIDENCE:

Level IV, therapeutic case series.

Abstract:

In orthopedic surgery there has been a never-ending quest to improve surgical outcome and the patient’s experience. Progression has been marked by the refinement of surgical techniques and instruments and later by enhanced diagnostic imaging capability, specifically magnetic resonance. Over time implant optimization was achieved, along with the development of innovative minimally invasive arthroscopic technical skills to leverage new versions of classic procedures and implants to improve short-term patient morbidity and initial, mid-term, and long-term patient outcomes. The use of regenerative and/or biological adjuncts to aid the healing process has followed in the drive for continual improvement, and major breakthroughs in basic science have significantly unraveled the mechanisms of key healing and regenerative pathways. A wide spectrum of primary and complementary regenerative treatments is becoming increasingly available, including blood-derived preparations, growth factors, bone marrow preparations, and stem cells. This is a new era in the application of biologically active material, and it is transforming clinical practice by providing effective supportive treatments either at the time of the index procedure or during the postoperative period. Regenerative treatments are currently in active use to enhance many areas of orthopedic surgery in an attempt to improve success and outcome. In this review we provide a comprehensive overview of the peer-reviewed evidence-based literature, highlighting the clinical outcomes in humans both with preclinical data and human clinical trials involving regenerative preparations within the areas of rotator cuff, meniscus, ligament, and articular cartilage surgical repair.

Abstract:

PURPOSE:

To evaluate the effects of vigorous short-term exercise on the platelet and other cellular components of 2 point-of-care blood-processing devices: a buffy coat-based platelet-rich plasma (PRP) product and a plasma-based PRP product.

METHODS:

Twenty healthy subjects (aged 21-45 years) participated in a 20-minute vigorous exercise regimen on an upright stationary bike at 70% to 85% of maximum target heart rate. Pre- and post-exercise blood was processed in either a plasma-based or automated buffy coat-based PRP system. Complete blood counts were used to compare the cellular components in whole blood and the PRP products.

RESULTS:

Exercise significantly increased the concentrations of platelets by over 20% in whole blood (P < .001) and in both PRP products (P = .002 and P = .018). Both devices performed consistently with pre- and post-exercise blood. Buffy coat-based PRP prepared after exercise was also significantly larger in volume and had a significantly higher concentration of mobilized hematopoietic stem cells (hematopoietic progenitor cells [HPCs], from 1.7/μL to 2.7/μL, P = .043). The concentrations of all white blood cell types were increased, which could be differentially collected in the devices studied.

CONCLUSIONS:

Exercise can be used to consistently alter the composition of PRP. Twenty minutes of vigorous exercise can increase platelet concentrations in plasma-based and buffy coat-based PRP products and can increase HPC concentrations and volume in buffy coat-based PRP.

CLINICAL RELEVANCE:

This study shows a nonpharmacologic method to increase platelet and HPC harvests from peripheral blood. This is important because it highlights a method for altering biological therapies with limited comorbidity.