Surgical Treatment of Patients with Bone and Cartilage Tissue Defects Using Autologous Platelet-Rich Plasma

The dissertation is devoted to the surgical treatment of bone and cartilage tissue defects using autologous platelet-rich plasma (aPRP). The relevance of the research is determined by the high prevalence of trauma leading to significant bone and cartilage defects, as well as the insufficient effectiveness of existing surgical treatment methods, including internal fixation, distraction osteogenesis, and the use of xenomaterials. The work proposes a method for restoring defects of long tubular bones and intra-articular cartilage through stimulation of osteo- and chondrogenesis using aPRP obtained on domestic equipment. The properties of aPRP, its influence on reparative regeneration, and the immediate and long-term results of surgical treatment in comparison with standard plastic methods have been investigated. The work has scientific and theoretical, medical-social, and economic significance.

RELEVANCE OF THE PROBLEM. Currently, the problem of trauma — an "epidemic of injuries" (Mironov S.P., Trozhenko V.V. et al., 2006), has acquired enormous medical and social significance. This is primarily associated with the rapid pace of socio-economic development of society and its urbanization. Trauma, predominantly domestic and traffic-related (85% of all injuries — according to Konovalov A.N. and Likhterman I.B., 1991), has increased 4–5 times and firmly holds leading positions in the structure of morbidity and mortality (first place among men of working age and third in the overall structure — after cardiovascular and oncological diseases). At the same time, the occupational component has decreased accordingly. Of course, particular attention is given to the increase in gunshot wounds (Miller M. 1996, Keyevsky V.V., 2004, Ataev A.R. et al. 2006).

All of the above types of trauma are characterized by "high energy" of injury with significant destruction of organs and tissues, both at the site of the injurious agent and throughout the zone of molecular concussion. Naturally, the number of complications (delayed consolidation, non-healing bone and cartilage defects, pseudoarthrosis, osteomyelitis, etc.) has increased, related both to the nature of the kinetic component of the injurious agent and to changes in the body's response reaction, manifesting as prolonged repair periods and the development of severe forms of "traumatic disease" (Okhotsky V.P., Lavrishcheva G.I., 1967). Despite significant development of methods and approaches to surgical treatment of bone and cartilage tissue defects, such as AO (Miller M. et al. 1986, 1996), Ilizarov method (Ilizarov G.A. et al., 1980, Devyatov A.A. 1987), and minimally invasive and endoscopic surgery — the problem of significantly reducing treatment duration and costs remains substantial (Shevchenko S.B., 2006).

For decades, experimental and clinical studies of the mechanisms of reparative regeneration of bone and cartilage have been ongoing, and questions raised by the first investigators of osteogenesis over a hundred years ago continue to remain debatable and largely unresolved (Vinogradova T.P., Lavrishcheva G.I., Onoprienko G.A., 1974–1996, Akhpashev F.F., Zagorodny N.V., 2005, Dyachkov A.N. et al., 2006).

It appears that the limit of application of modern implants, both innovative and technological, is sufficiently close. In any case, the use of AO, Ilizarov method, and similar methods cannot in itself be considered sufficient for complete repair of cartilage and bone tissues subjected to high-energy destruction with the formation of significant defects causing disruption of bone continuity. Moreover, numerous xenomaterials proposed at various times by various authors (from foam to "Norian") for filling bone and cartilage tissue defects either do not incorporate at all or have weak connectivity with surrounding tissues (Zagorodny N.V., Makunin V.I. et al. 2005).

Works by classical surgeons have repeatedly indicated that the most important part of the physiological process of reparative chondro- and osteoregeneration is adequate blood supply to the trauma site (Petrov N.I. 1913, Rusanov A.A., 1959, Stetsula V.I., 1965, Devyatov A.A., Kamerin V.K., 1987, Collier, 1911, Kuncher, 1967, Truet, 1974, Miller, 1986 et al.). However, only from the mid-1950s (in connection with the development of "narrow" medical-biological specialties and the application of refined experimental technologies) did understanding begin to emerge of the essence of phenomena and processes occurring directly in osteogenic precursor cells ("DOCP and IOCP — determined osteogenic precursor cells" and "inducible osteogenic precursor cells" (Fridenshtein A.Ya., Lalykina K.S., 1973, 1980)).

In 1965, M.R. Urist of the University of California first used platelet-rich plasma for stimulation of osteogenesis in facial bone defects, as a factor promoting an increase in osteoinductive morphogenetic protein ("BMP — bone morphogenetic protein"). He proceeded from the work of predecessors in which data on pronounced osteogenic and chondrogenic activity of substances contained in platelet alpha granules already existed.

These substances ("PDGF — platelet-derived growth factor", "VEGF — vascular endothelial growth factor", "TGF — tissue growth factor", and others) have an oligopeptide structure and belong to the group of so-called "growth factors", to which epidermal growth factor, insulin, and others also belong, the characteristic feature of which is a high degree of affinity and relatively prolonged duration of primary action on IOCP receptors (Miyazono K., et al., 1994). Unlike true mutagens (ionizing radiation, carcinogens, under-oxidized radical groups, and others), "growth factors" act not on the hereditary chromosomal apparatus of the cell but on membrane cell receptors of the first and second type, causing acceleration of growth and differentiation of healthy precursor cells. The practical result of research in this area of osteology was the widespread use of platelet-rich plasma in the treatment of bone defects of the maxillofacial region — "implant engraftment" (Tyapongsak R. et al., 1998).

The speed of reparative regeneration of bone defects increased 2–2.5 times, which affected the reduction in duration and, naturally, the cost of treatment. However, we have no information about any research works in which platelet-rich autologous plasma was used for filling bone-cartilage defects of long tubular bones (either isolated or in combination with implants).

Numerous techniques applied for stimulation of osteo- and chondrogenesis processes for closing bone-cartilage tissue defects (ozone therapy, barotherapy; auto- and xenotransplantation as one of the optimal options) have their own positive and negative aspects, both in the medical-social and economic aspects. This state of affairs indicates less the success of modern surgery in this area than it reflects the great diversity of views and the absence of a unified "golden" standard for the treatment of bone and cartilage tissue defects.

Currently, opportunities for treating patients with bone and articular cartilage defects have become much greater. However, a definitive solution to this important problem of surgery and traumatology has not yet been achieved, as evidenced by the materials of international symposia "Bioimplantology at the Threshold of the XXI Century" — Moscow, 2001, Samara, 2004, the VIII All-Russian Congress of Traumatologists-Orthopedists (Samara, 2006), and others.

GOAL OF THE STUDY:

Improvement of surgical treatment outcomes for patients with cartilage and bone tissue defects through the implementation of a method for stimulation of osteo- and chondrogenesis using autologous platelet-rich plasma (PRP).

TASKS:

1. To develop an accessible method for obtaining autologous platelet-rich plasma (PRP) in the conditions of a surgical hospital.

2. To study the possibilities of using autologous PRP in the surgical treatment of patients with defects of long tubular bones (with disruption of bone continuity) and articular cartilage.

3. To investigate the properties of autologous PRP obtained and used in the conditions of a surgical hospital and the associated changes in the process of reparative osteo- and chondrogenesis.

4. To study the immediate and long-term results of surgical treatment of patients with bone and cartilage tissue defects as a result of the effect of autologous PRP.

5. To determine the effectiveness of autologous PRP application in patients with bone defects (with disruption of continuity) and articular cartilage compared with those operated on by standard methods.

SCIENTIFIC NOVELTY:

1. A method is proposed for restoration of long tubular bone defects (with disruption of bone continuity) and intra-articular cartilage through stimulation of osteo- and chondrogenesis processes using autologous platelet-rich plasma obtained on domestic equipment.

2. A method of applying autologous PRP for surgical treatment of patients with bone and cartilage tissue defects has been developed, with indications and contraindications for its use determined.

3. Immediate and long-term results of applying methods for restoration of articular cartilage and bone tissue defects using autologous PRP have been studied through comprehensive, objective investigation.

4. The effectiveness of the proposed method for restoration of bone and cartilage tissue defects using autologous PRP has been demonstrated on the basis of analysis of immediate and long-term treatment outcomes.

IMPLEMENTATION OF RESEARCH RESULTS:

The developed method of surgical treatment of patients with bone and cartilage tissue defects has been implemented for practical use in the departments of traumatology and burn surgery of GUZ VOKB No. 1, GKB No. 15 in Moscow, Krasnogorsk Central District Hospital of Moscow Oblast, and BSMP in Voronezh.

APPROVAL OF THE WORK:

Materials of the dissertation were reported and discussed at the Second International Congress "Modern Technologies in Traumatology and Orthopedics" in October 2005 (Moscow), at the Second Scientific-Practical Conference of Traumatologists-Orthopedists of the Federal Medical-Biological Agency in December 2005 (Moscow), at the International Surgeon Seminar "Weill-Cornell Seminar in Salzburg: Bone and Joint Surgery," November 6–11, 2005 (Salzburg, Austria), at a session of the Voronezh Regional Scientific Society of Surgeons in May 2006, at the VIII All-Russian Congress of Traumatologists-Orthopedists in June 2006 (Samara), at sessions of the departments of traumatology, orthopedics, military-field surgery, and general surgery of the VMA named after N.N. Burdenko (October 2006), and at the Third Scientific-Practical Conference of Traumatologists-Orthopedists of the Federal Medical-Biological Agency in December 2006 (Moscow). The main provisions and conclusions are presented in 11 printed works on the dissertation topic, of which 1 was published in a journal registered in VAK. As a result of the conducted research, a patent for invention No. 2283043 dated 10.09.2006 and a patent for invention No. 2305563 dated 10.09.2007 were obtained.

PRACTICAL SIGNIFICANCE:

1. Scientific and theoretical effect: a new method for treating defects of long tubular bones (with disruption of bone continuity) and articular cartilage using autologous PRP has been developed, and its effectiveness in stimulating chondro- and osteogenesis processes has been determined.

2. Medical and social effect: implementation of the developed method in clinical practice reduces the number of nonunions and pseudoarthroses in patients with bone and cartilage tissue defects, decreases the number of surgical interventions for harvesting autologous bone transplants, resulting in reduced surgical trauma and improved quality of life for patients with this pathology.

3. Economic effect: reduction of hospital stay duration, decrease in the period of temporary disability, reduction in the percentage of disability in this group of patients, and savings on medications.

SCOPE AND STRUCTURE OF THE WORK:

The work is presented in 113 pages and consists of an introduction, a literature review, a chapter on materials and research methods, three chapters of original research, conclusions, findings, practical recommendations, and a reference list containing 217 sources, of which 158 are domestic and 59 are foreign.

Demonstration material is presented in the form of 9 tables and 34 figures.

MAIN PROVISIONS FOR DEFENSE:

1. The developed method of applying autologous platelet-rich plasma to enhance stimulation of chondro- and osteogenesis allows improvement of surgical treatment outcomes for patients with bone and cartilage tissue defects.

2. The use of autologous PRP eliminates the use of xenografts and significantly reduces the number of autologous bone transplants, leaving them the role of a "regeneration focus" in cases with significant volumes of bone defect.

3. Analysis of the obtained results demonstrates the pronounced effectiveness of the proposed method of surgical treatment of bone and cartilage tissue defects.

4. The method of treatment using autologous platelet-rich plasma surpasses standard methods of treatment for patients with defects of long tubular bones of various locations (with disruption of bone continuity) and articular cartilage.