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Izolirana rekonstrukcija prednjeg križnog ligamenta (ACL) predstavlja zlatni standard u kirurškom liječenju rupture prednjeg križnog ligamenta. No, neuspjeh cijeljenja presatka i ostatna rotacijska nestabilnost koljena i dalje su česte postoperativne komplikacije. Anterolateralni ligament (ALL) i njegova uloga u kontroli rotacijske stabilnosti dobila je značajan interes 2013. nakon objave njegova „ponovnog otkrića”. Ta ligamentarna struktura, opisana još davne 1879., potječe od proksimalnog i stražnjeg dijela lateralnog epikondila bedrene kosti i hvata se na goljeničnoj kosti, na sredini između Gerdyjeva tuberkla i glavice fibule. Biomehanička ispitivanja pokazala su da anterolateralni ligament djeluje kao pasivni stabilizator koljena tijekom unutarnje rotacije koljena, i kod rupture ACL-a i lateralnih struktura koljena odgovoran je za nastanak pivot-shift fenomena. Pokazalo se da izolirana rekonstrukcija ACL-a u pacijenata s ozljedom ACL-a i ALL-a ne može vratiti normalnu kinematiku koljena, za razliku od njihove kombinirane rekonstrukcije. Uz to, dosadašnja literatura nudi brojne dokaze u smislu poboljšanja stabilnosti koljena nakon kombiniranog postupka rekonstrukcije ACL-a i ALL-a. Štoviše, nedavne kliničke studije pokazale su da ALL ima zaštitni učinak na očuvanje presatka ACL-a, kao i na brži ponovni povratak u sport i opće zadovoljstvo pacijenata s operativnim zahvatom. Ovaj pregledni rad ima za cilj dati pregled dosadašnjeg znanja anatomije, funkcije i učinka rekonstrukcije ACL-a i ALL-a u pacijenata s puknućem ACL-a., Isolated anterior cruciate ligament (ACL) reconstruction is the gold standard in surgical treatment of anterior cruciate ligament rupture. However, graft failure rates and residual rotational instability of the knee are still common post-operative complications. The anterolateral ligament (ALL) and its role in controlling rotational stability gained considerable interest in 2013 following the announcement of its ‟rediscovery”. This ligamentous structure, described back in 1879, originates just proximal and posterior of the lateral epicondyle of the femur and it ends on the tibia, midway between Gerdy's tubercle and the head of the fibula. Biomechanical studies have shown that the anterolateral ligament acts as a passive knee stabilizer during internal knee rotation and in the rupture of the ACL and lateral knee structures is responsible for the presence of a pivot-shift knee phenomenon. It has been shown that isolated ACL reconstruction in patients with ACL and ALL injury cannot restore normal knee kinematics unlike their combined reconstruction. In addition, recent literature shows evidence in terms of improving knee stability after a combined ACL and ALL reconstruction procedure. Moreover, recent clinical studies have shown that ALL has a protective effect on the preservation of ACL graft as well as on the faster return to sport and overall patient satisfaction. This review aims to give an overview of our current knowledge of the anatomy, function, and effect of combined ACL and ALL reconstruction in patients with ACL rupture.

Cushing's syndrome is an uncommon clinical condition most frequently presenting with central obesity, facial rounding, proximal muscle weakness, and skin thinning. The objective of this case report is to highlight an unusual presentation of Cushing's syndrome. A 35-year-old woman presented to the orthopedic clinic with a 1-year history of foot pain without any history of trauma. Radiography of the foot showed multiple metatarsal fractures. Evaluation for secondary causes of reduced bone strength revealed that the patient had Cushing's disease, although other typical signs and symptoms were not remarkable. It can be concluded that Cushing's syndrome should always be included in the differential diagnosis of foot fracture without any evidence of trauma.

During the past few decades, surgical techniques for anterior cruciate ligament (ACL) reconstruction have been developing significantly. To date, studies have shown that after ACL reconstruction, rotational stability has a greater impact on the patient's satisfaction, functional scores, and return to sports than translational stability. Although challenged by many authors in the literature, biomechanical studies on the anterolateral ligament (ALL) of the knee and clinical studies regarding ALL reconstruction have been revealing promising results. Thus, the potentially significant role of the ALL in biomechanical load sharing and improving rotational control of the knee has led to the development of various reconstruction techniques whose goal is to achieve simplicity and yield the best results possible. Guided by this idea, we have developed a modified ACL-ALL reconstruction surgical technique. In this article, our simple, bone-saving, anatomic technique to reconstruct both the ACL and ALL using hamstring tendon autograft is described., Technique Video Video 1 On the Graft Prep Station Base (Arthrex), the harvested semitendinosus tendon is marked every 8 cm and tripled over a TightRope on the tibial side, ensuring a graft length of 8 cm. The most distal suture (No. 2-0 Vicryl) is placed to stabilize the tripled semitendinosus graft and secure the length. The gracilis tendon is put inside the tripled semitendinosus graft, and the whole graft is then tagged with multiple sutures (No. 2-0 Vicryl) to secure the gracilis position and to tubularize the graft. A No. 2 FiberWire is placed on the femoral end of the anterior cruciate ligament (ACL) graft by going around and through the tendons to ensure secure further graft manipulation. The ACL graft is marked 3 cm from both the femoral and tibial sides, representing parts of the graft that will be placed inside the bone tunnels. An ACL graft consisting of 3 parts semitendinosus and 1 part gracilis is obtained, with a diameter of 8 to 10 mm and length of 8 cm. With the patient in the supine position and the left knee in 90° of flexion and in a leg holder, 3 bony landmarks are marked on the patient's left knee: the lateral epicondyle, the Gerdy tubercle, and the head of the fibula. Two convergent bony tunnels are drilled in the proximal part of the left tibia with a 4.5-mm drill bit, separated by roughly 2 cm and approximately 1 cm distal to the joint line. A suture (No. 2 Vicryl) is then passed through the tunnels in a retroverted fashion to create a loop for further anterolateral ligament (ALL) graft (gracilis tendon) passage. The tibial guidewire (outside-in jig) is placed 55° from the external medial tibial cortex into the ACL remnant. Subsequent reaming with the retro-drill is performed for 35 mm according to the previously measured ACL graft size, with preservation of the ACL remnant synovial cover and tibial attachment. A 2- to 3-cm incision is made along the lateral aspect of the thigh, extending proximal from the lateral epicondyle. A Kirschner wire is used to mark the femoral epicondyle. A guide is introduced through the anteromedial portal. The tip of the guide is anchored at the ACL femoral insertion. The guide sleeve is pushed onto the lateral cortex through the femoral stab incision underneath the iliotibial band (ITB) and into the incision made longitudinally through the ITB fibers to position a drill for femoral tunnel drilling roughly 1 cm proximal and 8 mm posterior to the Kirschner wire. Then, subsequent femoral bone drilling is performed to the appropriate measured ACL size. By use of a suture, the TightRope and graft are passed through the longitudinal incision of the ITB and the ACL femoral tunnel to the distal 3-cm mark inside the tibial tunnel. To ensure the exact length of the graft in the tibial bone tunnel (distal demarcation), tension on the graft from the femoral side is used and the correct graft and demarcation position is monitored arthroscopically. Subsequently, the TightRope is tightened on the tibial side and secured with the knee at 90° of flexion. The knee is then placed at 20° of flexion, and the femoral part of the ACL graft is tightened and secured with an outside-in bioabsorbable interference screw. With the use of a grasper or a shuttle suture, the suture tied to the gracilis is shuttled under the ITB through the incision made longitudinally through the ITB fibers and then through the skin incision made for the posterior end of the tibial bone tunnel. The ALL graft is shuttled through the tibial bone tunnel from posterior to anterior, using the previously passed suture loop (No. 2 Vicryl). The gracilis graft is brought back proximally again under the ITB and tied with FiberWire from the femoral end of the ACL graft with the patient's left knee in full extension and neutral rotation.

Objective Nasal septal pathologies requiring surgical intervention are common in the population. Additionally, nasal chondrocytes are becoming an important cell source in cartilage tissue engineering strategies for the repair of articular cartilage lesions. These procedures damage the nasal septal cartilage whose healing potential is limited due to its avascular, aneural, and alymphatic nature. Despite the high incidence of various surgical interventions that affect septum cartilage, limited nasal cartilage repair characterizations have been performed to date. Methods To evaluate the healing of the nasal septum cartilage perforation, a septal biopsy was performed in 14 sheep. Two and 6 months later, the tissue formed on the place of perforation was explanted and compared with the native tissue. Tissue morphology, protein and gene expression of explanted tissue was determined using histological, immunohistochemical and real-time quantitative polymerase chain reaction analysis. Results Tissue formed on the defect site, 2 and 6 months after the biopsy was characterized as mostly connective tissue with the presence of fibroblastic cells. This newly formed tissue contained no glycosaminoglycans and collagen type II but was positively stained for collagen type I. Cartilage-specific genes COL2, AGG, and COMP were significantly decreased in 2- and 6-month samples compared with the native nasal cartilage. Levels of COL1, COL4, and CRABP1 genes specific for perichondrium and connective tissue were higher in both test group samples in comparison with native cartilage. Conclusions Newly formed tissue was not cartilage but rather fibrous tissue suggesting the role of perichondrium and mucosa in tissue repair after nasal septum injury.

Background Matrix metalloproteinases (MMPs) play an important role in matrix remodelling, as well as in tendon integrity. Due to overuse, athletes often develop chronic tendinopathies. If not treated, they lead to severe impairment, even complete tendon ruptures. Aim The main purpose of this study was to investigate whether three functional polymorphisms within the MMP3 gene are associated with increased risk of developing tendinopathies in high-level Croatian athletes. Methods We have recruited one hundred fifty- five (63 high-level athletes with diagnosed tendinopathies and 92 asymptomatic controls) unrelated Caucasians for this case- control genetic study. All participants were genotyped for three single nucleotide polymorphisms (SNP) within the MMP3 gene: rs591058 C/T, rs650108 A/G and rs679620 G/A using the pyrosequencing method. Results The MMP3 rs650108 GG (P = 0.0074) and rs679620 AA (P = 0.0119) genotypes were significantly over-represented in cases compared with controls, while rs591058 TT (P = 0.0759), as well as haplotype variant T - G - A (P = 0.06), implicated that there is an indication of predisposition for tendinopathies. Conclusion These results support association between functional variants within the MMP3 gene and the risk of tendinopathies in high-level athletes. Further research is needed to replicate these results in a larger population.

Orthopedic surgeons sometimes combine recombinant, human BMP-2 with autograft bone when dealing with problematic osseous fractures. Although some case reports indicate success with this off-label strategy, there have been no randomized controlled trials. Moreover, a literature search revealed only one pre-clinical study and this was in a cranial defect model. The present project examined the consequences of combining BMP-2 with particles of living bone in a rat femoral defect model. Human bone particles were recovered with a reamer-irrigator-aspirator (RIA). To allow acceptance of the xenograft as surrogate autograft, rats were administered an immunosuppressive cocktail that does not interfere with bone healing. Implantation of 200 µg living bone particles generated a small amount of new bone and defects did not heal. Graded amounts of BMP-2 that alone provoked no healing (1.1 µg), borderline healing (5.5 µg), or full healing (11 µg) were added to this amount of bone particles. Addition of BMP-2 (1.1 µg) increased osteogenesis, and produced bridging in 2 of 7 defects. The combination of BMP-2 (5.5 µg) and bone particles made healing more reliable and advanced the maturation of the regenerate. Bone formation with BMP-2 (11 µg) and bone particles showed improved maturation. Thus, the combination of autograft and BMP-2 may be helpful clinically under conditions where the healing response is suboptimal. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2137-2145, 2016. Clinical significance These data support the clinical use of recombinant, human BMP-2 with autograft bone when treating large segmental osseous defects. The combination leads to greater bone formation and accelerates the maturation of the regenerate.

The aim of this study is to examine the capacity of muscle tissue preserved on hamstring tendons forming candy-stripe grafts in order to improve tendon to bone ingrowth and ligamentization. We hypothesized that muscle tissue does possess a stem cell population that could enhance the healing process of the ACL graft when preserved on the tendons. Human samples from gracilis and semitendinosus muscles were collected during ACL surgery from ten patients and from these tissue samples human muscle-derived stem cells and tendon- derived stem cells were isolated and propagated. Both stem cell populations were in- vitro differentiated into osteogenic lineage. Alkaline phosphatase activity was determined at days zero and 14 of the osteogenic induction and von Kossa staining to assess mineralization of the cultures. Total RNA was collected from osteoblast cultures and real time quantitative PCR was performed. Western-blot for osteocalcin and collagen type I followed protein isolation. Immunofluorescence double labeling of pericytes in muscle and tendon tissue was performed. Mesenchymal stem cells from muscle and tendon tissue were isolated and expanded in cell culture. More time was needed to grow the tendon derived culture compared to muscle derived culture. Muscle derived stem cells exhibited more alkaline phosphatase actvity compared to tendon derived stem cells, whereas tendon derived stem cells formed more mineralized nodules after 14 days of osteoinduction. Muscle derived stem cells exhibited higher expression levels of bone sialoprotein, and tendon derived stem cells showed higher expression of dental-matrix- protein 1 and osteocalcin. Immunofluorescent staining against pericytes indicated that they are more abundant in muscle tissue. These results indicate that muscle tissue is a better source of stem cells than tendon tissue. Achievement of this study is proof that there is vast innate capacity of muscle tissue for enhancement of bone-tendon integration and ligamentization of ACL hamstring grafts and consequently muscle tissue should not be treated as waste after harvesting.

Background:Proximal diaphyseal stress fractures of the fifth metatarsal are common in athletes. Conservative treatment has been shown to result in high rates of delayed union, nonunion, and refracture, so internal fixation has become the treatment of choice in competitive athletes.Methods:Twenty top-level athletes with diaphyseal stress fractures fixed with intramedullary malleolar screws were evaluated. Functional outcome was assessed by American Orthopaedic Foot and Ankle Society midfoot score. Static and dynamic maximum vertical force and peak plantar pressures were evaluated with a computerized pedobarograph.Results:Mean follow-up from surgery to interview was 10.3 years (range, 3.5–19.0 years). Clinical healing was 95%, and there has been one refracture (5%). The mean time from surgery to return to sport was 9 weeks (range, 5–14 weeks). Twelve athletes (60%) returned to a higher level of training, 7 (35%) to the same level, and 1 (5%) to a lower level compared with the level of training before injury. Average American Orthopaedic Foot and Ankle Society midfoot score was 93.8 (range, 85–100). During the computerized pedobarographic evaluations, 18 patients (90%) presented with varus of the metatarsus and the midfoot and 2 (10%) presented with a normal plantigrade foot.Conclusions:Intramedullary malleolar screws can yield reliable and effective healing of fifth metatarsal stress fractures in athletes. Varus of the metatarsus and the midfoot were predisposing factors for stress fractures in this population of competitive athletes, and all were recommended to wear orthoses until their competitive careers were completed. (J Am Podiatr Med Assoc 101(6): 517–522, 2011)

The aim of this study was to present long-term results of sagittal osteotomy of the patella after Morscher. The study included 70 patients treated for patellar dysplasia with a postoperative follow-up from nine to 20 years. There were 59 females and 11 males with an average age of 21 years at the time of operation. Results were evaluated for the entire group of 70 patients and then presented separately for the 30 patients in whom sagittal osteotomy of the patella was performed as a single procedure and 40 patients in whom, in addition to sagittal osteotomy of the patella, medialisation and ventralisation or distalisation of the tibial tuberosity were also performed. The mean value of the Wiberg patellar angle was 112 degrees preoperatively and 140 degrees postoperatively. In the whole group of patients excellent results were obtained in 24 (35%), good results in 30 (42%), fair results in 13 (19%) and poor results in three (4%) patients. In 30 patients with sagittal osteotomy as a single operation excellent results were obtained in 13 (43%), good results in 14 (47%) and fair results in three (10%) patients, while in the 40 patients with sagittal osteotomy and additional surgical procedures, 11 (27%) were excellent, 16 (40%) good, ten (25%) fair and three (8%) had poor results. Sagittal osteotomy of the patella after Morscher is an enrichment of the spectrum of the secondary-causal and preventive procedures for the treatment of patello-femoral disorders.

The last three decades have witnessed a tremendous increase in female sports participation at all levels. However, increased sports participation of female athletes has also increased the incidence of sport-related injuries, which can be either acute trauma or overuse injuries. Overuse injuries may be defined as an imbalance caused by overly intensive training and inadequate recovery, which subsequently leads to a breakdown in tissue reparative mechanisms. This article will review the most frequent overuse injuries in female athletes in the context of anatomical, physiological, and psychological differences between genders.

The localized form of pigmented villonodular synovitis (LPVS) is a lesion characterized by focal involvement of the synovial membrane. The knee is the most commonly affected joint. We report three cases of LPVS of the knee which were not diagnosed upon clinical evaluation. The aim is to bring the attention of clinicians to this pathological entity, which is often regarded as extremely rare and is therefore not considered in the early differential diagnosis of various knee derangements. Diagnostic and therapeutic arthroscopy was performed. The lesions were completely resected and patohistological findings confirmed the diagnosis of LPVS. All of our three patients have remained asymptomatic at 8, 10, and 12-month follow-ups.

Background: Femoral shaft stress fractures in athletes are not common but pose a great diagnostic challenge to clinicians. Because of few clinical signs, diagnosis and treatment are often delayed. Furthermore, if not treated correctly, these fractures are well known for complications and difficulties. Objective: To develop a well structured and reproducible treatment algorithm for athletes with femoral shaft stress fractures. Methods: The proposed algorithm is carried out in four phases, each lasting three weeks, and the move to the next phase is based on the result of the tests carried out at the end of the previous phase. Over nine years, we treated seven top level athletes, aged 17–21. In all athletes, diagnosis was based on physical examination, plain radiographs, and bone scan. Results: As a result of the treatment method, all the athletes were fully engaged in athletic activity 12–18 weeks after the beginning of treatment. After completion of the treatment, the athletes were followed up for 48–96 months. During the follow up, there was no recurrence of discomfort or pain, and all the athletes eventually returned to competition level. Conclusion: These results and data available from the literature suggest that the algorithm is the optimal treatment protocol for femoral shaft stress fractures in athletes, avoiding the common complications and difficulties.

We report on 2 cases of hyperextension/valgus elbow injuries in two adult male national team water polo goalkeepers. Both were healthy and had never sustained any major injuries of the elbow. Mechanism and type of injury in both of them was identical. Different medical treatment protocols of these injuries possibly have led to different outcomes, with one of them developing osteochondritis dissecans (OCD). Inadequate medical treatment of acute impact elbow injuries could lead to osteochondritis disecans of the elbow in top-level adult male water polo goalkeepers.

Background: Large segmental defects in bone do not heal well and present clinical challenges. This study investigated modulation of the mechanical environment as a means of improving bone healing in the presence of bone morphogenetic protein (BMP)-2. Although the influence of mechanical forces on the healing of fractures is well established, no previous studies, to our knowledge, have described their influence on the healing of large segmental defects. We hypothesized that bone-healing would be improved by initial, low-stiffness fixation of the defect, followed by high-stiffness fixation during the healing process. We call this reverse dynamization. Methods: A rat model of a critical-sized femoral defect was used. External fixators were constructed to provide different degrees of stiffness and, importantly, the ability to change stiffness during the healing process in vivo. Healing of the critical-sized defects was initiated by the implantation of 11 mg of recombinant human BMP (rhBMP)-2 on a collagen sponge. Groups of rats receiving BMP-2 were allowed to heal with low, medium, and high-stiffness fixators, as well as under conditions of reverse dynamization, in which the stiffness was changed from low to high at two weeks. Healing was assessed at eight weeks with use of radiographs, histological analysis, microcomputed tomography, dual x-ray absorptiometry, and mechanical testing. Results: Under constant stiffness, the low-stiffness fixator produced the best healing after eight weeks. However, reverse dynamization provided considerable improvement, resulting in a marked acceleration of the healing process by all of the criteria of this study. The histological data suggest that this was the result of intramembranous, rather than endochondral, ossification. Conclusions: Reverse dynamization accelerated healing in the presence of BMP-2 in the rat femur and is worthy of further investigation as a means of improving the healing of large segmental bone defects. Clinical Relevance: These data provide the basis of a novel, simple, and inexpensive way to improve the healing of critical-sized defects in long bones. Reverse dynamization may also be applicable to other circumstances in which bonehealing is problematic.

Clinical management of delayed healing or nonunion of long bone fractures and segmental bone defects poses a substantial orthopaedic challenge. Surgical advances and bone tissue engineering are providing new avenues to stimulate bone growth in cases of bone loss and nonunion. The reamer-irrigator-aspirator (RIA) device allows surgeons to aspirate the medullary contents of long bones and use the progenitor-rich “flow-through” fraction in autologous bone grafting. Dexamethasone (DEX) is a synthetic steroid that has been shown to induce osteoblastic differentiation. A series of 13 patients treated with RIA bone grafting enhanced with DEX for nonunion or segmental defect was examined retrospectively to assess the quality of bony union and clinical outcomes. Despite the initial poor prognoses, promising results were achieved using this technique ; and given the complexity of these cases the observed success is of great value and warrants controlled study into both standardisation of the procedure and concentration of the grafting material.

Orthopedic surgery is going through a serious paradigm shift ; instead of simply replacing damaged tissues with prosthetic or allograft material, the aim is to regenerate them. This endeavor has generated the field of regenerative orthopaedics, an increasingly expanding area of research with hopes of providing new and better treatments for diseases and injuries affecting the musculoskeletal system. As part of this process, we are witnessing a substantial accumulation of new cellular and molecular insights into connective tissue function, coupled with emerging new concepts in stem cell biology and scaffolding technologies. Indeed, any successful strategy to regenerate musculoskeletal tissues can be portrayed as an intricate interplay between the three main constituents of the regenerative system: cells, environment and scaffolds. This review is not meant to be exhaustive and comprehensive, but aims to highlight concepts and key advances in the field of regenerative orthopaedics and tissue engineering, as well as to present current possibilities for clinical translation.

The aim of this paper is to report on three cases of symptomatic osteochondritis dissecans of the humeral capitellum in adolescent gymnasts, two females and one male. In all the cases arthroscopic surgery was performed. During arthroscopy, loose osteochondral fragments were removed, the defect was debrided and microfractures were performed. All the three patients regained the full range of motion of the affected elbow, and returned to the high-level gymnastics within a period of 5 months. At 12 months follow-up, all the three patients remained symptomless and were participating in high-level gymnastics. A combination of arthroscopy and the microfracture technique is a reliable method with excellent short-term results in the treatment of the osteochondritis dissecans of the elbow.

The authors report a case of a 21-year-old woman with osteoid osteoma of the talar neck that was treated with arthroscopic resection. The nidus was removed in one piece with grasping forceps, and histopathologic findings confirmed the preoperative diagnosis of osteoid osteoma. Postoperatively, the patient was immediately relieved of ankle pain and there was no recurrence at the 1-year follow-up. If possible, the nidus should be removed without the use of a motorized instrument to ensure the correct histolologic diagnosis.

Dear Editor, With great interest and enthusiasm, we read the article “Orthopaedic applications of gene therapy“ [1]. The authors should be congratulated for their concise yet very thorough and excellent coverage of the gene therapy applications in orthopaedics. However, it is our opinion that articular cartilage deserved more of their attention. Primarily, we think that the subsection heading “Cartilage repair” should be expanded to “Cartilage repair and regeneration”, particularly since the authors did mention “stimulation of cartilage regeneration” which implies the possibility of inducing intrinsic healing of the damaged cartilage by hyaline cartilage formation. When treating localised cartilage defects we should ask ourselves: What kind of new tissue formation inside the defect do we want to induce? Ideally we aim for articular cartilage regeneration, not repair, which would mean formation of hyaline cartilage, not fibrocartilage. Treatment options published in the literature can be roughly divided into two concepts—reparative and restorative. The end result of the first concept is fibrocartilage, and the microfracture technique is the most popular representative. In contrast, the restorative concept aims for hyaline cartilage implantation/formation and includes implantation of osteochondral plugs with perfectly organised cartilage and matrix and/or cell therapy, namely autologous chondrocyte transplantation. Anabolic factors including members of the TGF-beta superfamily, such as BMPs, have proven their potential to stimulate chondrogenesis and synthesis of cartilage-specific matrix components in animal models [2, 3]. However, those proteins have short half-lives and it is difficult to maintain adequate in situ concentrations necessary for their proper functioning. Furthermore, many proteins act intracellularly and because cells cannot normally import these proteins, they cannot be used in soluble forms. These problems are the reason why gene therapy has attracted so much attention lately. The transfer of the respective genes into the joint, possibly in combination with the supply of chondroprogenitor cells, might be an elegant method to achieve a sustained delivery of such therapeutic factors at the required location in vivo [4]. Pascher et al. [5] developed a novel ex vivo method by using coagulated bone marrow aspirate as a mean of gene delivery to cartilage. Vector-seeded and cell-seeded bone marrow clots (“gene plugs”) were found to maintain their structural integrity following extensive culture and maintained transgenic expression for several weeks. Therefore, we conclude that there is a huge potential for new tissue formation by gene therapy trandsuction of cells of different origin. Cells originating subchondrally, in combination with gene therapy, may form tissue of higher quality than is achieved with the classical microfracture technique. On the other hand, hyaline cartilage formation by gene therapy induction in combination with cell implantation (possibly on biodegradable scaffolds) might be the answer to the current limitations of cartilage treatment modalities, and may provide permanent solution for the patients. Many animal studies are currently underway to investigate gene therapy-induced cartilage regeneration of chondral and osteochondral defects, and some of these investigations can be expected to lead to clinical trials and yield answers to these open questions.