Fibrin glue improves osteochondral scaffold fixation: study on the human cadaveric knee exposed to continuous passive motion

SummaryObjectiveTo evaluate stability and integrity of bi-layer and three-layer collagen-hydroxyapatite (C-HA) osteochondral scaffolds in a human cadaveric knee exposed to continuous passive motion (CPM) with and without loading and the role of added fibrin glue to improve the press-fit fixation of C-HA scaffolds.DesignOsteochondral lesions (2.0 × 1.5 cm) were chiseled out on both condyles and trochlea in eight human cadaveric knees. A total of 24 bi-layer (5 mm, four in each condyle) or three-layer C-HA scaffolds (8 mm, eight in the trochlea, four in each condyle) were first press-fit implanted and underwent testing with CPM, 90 cycles, 0°–90°. The second set of 24 scaffolds was implanted in cleaned lesions with the addition of fibrin glue. Two knees with fibrin glue fixation were additionally exposed to 15 kg loading, with 30 cycles of CPM, 0°–30°. Then, the knees were reopened and the scaffolds were evaluated using semi-quantitative Drobnic and modified Bekkers scores.ResultsAll but two scaffolds remained in the lesions site throughout CPM. Two implants failed: both were bi-layer osteochondral scaffolds, press-fit implanted at the lateral femoral condyle (LFC). A statistically significant difference was obtained between press-fit and fibrin glue implants with both Drobnic (2.9 ± 0.7 vs 4.3 ± 0.1, P < 0.0005) and Bekkers (3.3 ± 1.0 vs 5.0 ± 0.1, P < 0.0005) scores. Additional knee loading did not affect fibrin glue scaffold fixation or integrity.ConclusionThis cadaveric study showed fibrin glue notably improved bi-layer or three-layer C-HA scaffold press-fit fixation regardless of lesion location. It is therefore recommended that fibrin glue be used during surgery to improve early post-operative C-HA scaffold stability and integrity

Basic science of osteoarthritis

Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.(undefined

Enhancing Biological and Biomechanical Fixation of Osteochondral Scaffold: A Grand Challenge

Osteoarthritis (OA) is a degenerative joint disease, typified by degradation of cartilage and changes in the subchondral bone, resulting in pain, stiffness and reduced mobility. Current surgical treatments often fail to regenerate hyaline cartilage and result in the formation of fibrocartilage. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bones in the early stage of OA and have shown potential in restoring the joint's function. In this approach, the use of three-dimensional scaffolds (with or without cells) provides support for tissue growth. Commercially available osteochondral (OC) scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, some controversial results are often reported from both clinical trials and animal studies. The objective of this chapter is to report the scaffolds clinical requirements and performance of the currently available OC scaffolds that have been investigated both in animal studies and in clinical trials. The findings have demonstrated the importance of biological and biomechanical fixation of the OC scaffolds in achieving good cartilage fill and improved hyaline cartilage formation. It is concluded that improving cartilage fill, enhancing its integration with host tissues and achieving a strong and stable subchondral bone support for overlying cartilage are still grand challenges for the early treatment of OA

Maioregen: Our Experience.

Different techniques have been proposed across the years to treat osteochondral diseases: minimally invasive bone marrow stimulation techniques aimed at favoring the healing process in the injured area through the migration of stem cells from the subchondral bone; on the other side, some more aggressive techniques are based on autologous or allogenic tissue transplant. Unfortunately, both the high specialization and the low healing potential of the cartilage tissue still make the treatment of cartilage defects a challenge for the orthopedic surgeon. Bioengineered scaffolds or polymeric matrices implanted in the injured area showed promising results. The range of scaffolds in use for chondral or osteochondral repair is very wide; they differ not only with respect to the type of the materials used for their realization but also for the presence or absence of one or more cell lines \u2013 either chondrogenic or osteogenic. When approaching big chondral lesions, the subchondral bone is often involved and it also needs to be treated in order to have a correct restoration of the most superficial layers of the joint. In our opinion the smartest treatment choice could be a cell-free osteochondral scaffold, an off-the-shelf product, thus immediately available, avoiding the double surgical time. Following this rationale, after preclinical in vitro and animal studies and under the approval of the local ethics committee, we introduced the use of a newly developed nanostructured biomimetic scaffold in a clinical pilot study to treat chondral and osteochondral lesions of the knee. Its safety and manageability, as much as the surgical procedure reproducibility and the clinical outcome, have been evaluated up to 36 months\u2019 follow-up in order to test its intrinsic potential without any cells culture aid

New scaffold\u2013based one step procedure

The use of scaffolds in combination with autologous chondrocytes is well established in clinical practice in Europe (even if not yet available in the US). The rationale for using a scaffold is to have a temporary three dimensional structure of biodegradable polymers for the growth of living cells. An ideal scaffold should mimic biology and the architectural and structural properties of the native tissue, thus facilitating cell infiltration, attachment, proliferation and differentiation. Other important properties include biocompatibility and biodegradability through safe biochemical pathways at suitable time intervals to support the first phases of tissue formation and gradual replacement by regenerating tissue. There is increasing interest in utilising various biomaterials in clinical practice, not only to deliver expanded autologous chondrocytes for tissue regeneration, but also as a new treatment approach, which involves the implant of various biomaterials for "in situ" cartilage repair exploiting bone marrow stem cell differentiation induced by the scaffold properties. In fact, some scaffolds may have a potential themselves to promote chondral or osteochondral regeneration by exploiting the self-regenerative potential of the body. An ideal graft would be an off-the-shelf product from both a surgical and commercial standpoint. The possibility to produce a cell-free implant that is "smart" enought to provide the joint with the appropriate stimuli to induce orderly and durable tissue regeneration is realy attractive, and new, different biomaterials have recently been proposed to induce "in situ" cartilage regeneration after direct transplantation onto the defect site both in research and in clinical practice

Biomaterials for Osteochondral reconstruction

The modern regenerative procedures demonstrated to offer the replacement of the articular surface with a hyaline-like tissue, but the properties of healthy cartilage tissue are still unmatched by any available substitute. Moreover, the treatment of osteochondral lesions is even more biologically challenging since two different tissues are involved (bone and articular cartilage) with a distinctly different intrinsic healing capacity. For the repair of the entire osteochondral unit, several authors have highlighted the need for biphasic scaffolds, to reproduce the different biological and functional requirements for guiding the growht of the two tissues, and different specific scaffolds have been developed for the treatment of large chondral or osteochondral articular defects. At the time being, among these only two scaffols used for osteochondral regeneration are commercialized for clinical application. One is a bilayer porous PLGA-calcium-sulphate biopolymer. The second osteochondral scaffold is a nanostructured biomimetic HA-collagen scaffold with a porous 3-D tri-layer composite structure, mimicking the whole osteochonfral anatomy. Other osteochondral scaffolds are still under preclinical investigation. In this chapter we focus on reviewing the available evidence on the clinical outcome of these osteochondral scaffolds, as well as on reporting the new biomaterials developed and tested in preclinical studies that show to be promising for osteochondral regeneration

Tibial plateau lesions. Surface reconstruction with a biomimetic osteochondral scaffold: Results at 2 years of follow-up.

Abstract INTRODUCTION: Tibial plateau articular pathology caused by post-traumatic or degenerative lesions is a challenge for the orthopaedic surgeon and can lead to early osteoarthritis. The aim of the present study was to evaluate the results of treatment of these complex defects with implantation of an osteochondral scaffold, which is designed to target the cartilage surface and to reconstruct joint anatomy by addressing the entire osteochondral unit. MATERIALS AND METHODS: Eleven patients (5 female and 6 male) with a mean age of 37.3\ub111.0 years and osteochondral lesions of the tibial plateau (mean 5.1\ub12.7cm(2); range 3.0-12.5cm(2)) were treated with the implantation of an osteochondral biomimetic collagen-hydroxyapatite scaffold (Maioregen(\uae), Fin-Ceramica, Faenza, Italy). Comorbidities were addressed taking care to restore the correct limb alignment. Patients were evaluated pre-operatively and prospectively followed-up for 2 years using the International Knee Documentation Committee (IKDC) subjective and objective scores; activity level was documented using the Tegner score. RESULTS: Three patients experienced minor adverse events. No patients required further surgery for treatment failure during the study follow-up period, and 8 patients (72.7%) reported a marked improvement. The IKDC subjective score improved from 42.5\ub110.2 before treatment to 69.8\ub119.0 at 12 months (p<0.05), with stable results at 24 months. The IKDC objective score increased from 27.3% normal and nearly normal knees before treatment to 85.7% normal and nearly normal knees at 24 months of follow-up. The Tegner score increased from 2.3\ub12.1 before treatment to 4.8\ub12.4 at 12 months (p<0.05), and was stable at the final follow-up. CONCLUSION: The present study on the implantation of an osteochondral scaffold for the treatment of tibial plateau lesions showed a promising clinical outcome at short-term follow-up, which indicates that this procedure can be considered as a possible treatment option, even in these complex defects, when comorbidities are concomitantly addressed

Acellular matrix-based cartilage regeneration techniques for osteochondral repair

The aim of the present review is to illustrate the clinical state of the art of cell-free scaffolds application as regeneration techniques for the treatment of osteochondral lesions

PRP-Augmented Scaffolds for Cartilage Regeneration: A Systematic Review

Moderne regenerative procedures fo articular cartilage defects have proved to provide good replacement of damaged cartilage, although, at present, the properties of a native healthy cartilage are still not achievable by any substitute