Introduction

Osteoarthritis is a major cause of disability and is a source of substantial expense to the medical system. Due to early development of osteoarthritis in young athletes, and increased overall lifespan, early diagnosis and treatment of osteoarthritis is critical. Also critical is the need for therapies that can prolong functional joint health and perhaps eventually, therapies that can reverse the disease process. There has been great enthusiasm by many for othobiologics to fill this need. Orthobiologic therapies rely upon the actions of substances that are normally present in the body that aid in tissue repair.¹ Examples of orthobiologic therapies include platelet-rich plasma (PRP), autologous conditioned serum (ACS), autologous protein solution (APS), culture expanded stromal cells from a variety of tissue sources, and minimally manipulated cell-based therapies such as bone marrow aspirate concentrate (BMAC) and stromal vascular fraction (SVF). Evidence from basic science and animal model studies of various orthobiologics frequently support the rationale for the use of these modalities as a component of the treatment paradigm for osteoarthritis. However, these therapies are inherently more complex than traditional pharmaceuticals and there is wide variability that contributes to confusing and conflicting results in the scientific literature. A systematic approach is essential to determine, for each therapy: the constituents of each product, patient effects (ie. age, systemic health), administration factors (timing, frequency, dose, route), and confounding factors such as systemic drug effects on the behavior of cells and platelets.

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Platelet-rich plasma is prepared from blood and has an increased platelet concentration compared to whole blood. Growth factors in the alpha granules of platelets are credited as the bioactive factors of interest in PRP, however the leukocytes, plasma proteins, and red cells also play a role. Based on systematic review of the literature, in vitro studies consistently demonstrate PRPs ability to increase cell viability, proliferation and migration.² In this same study, in vivo animal model results were less consistent although there is evidence to support anti-inflammatory effects in osteoarthritic joints. An interesting recent study in dogs challenges the paradigm of non-steroidal anti-inflammatory avoidance prior to collection of blood for PRP preparation as no effect was found on platelet degranulation.³ Despite calls for consistency in reporting, the PRP literature continues to be plagued by incomplete characterization of the product used which has been detrimental to the progress of this promising therapy.²

The fundamental concept of BMAC is to gain the best of both worlds in one patient-side therapy: platelet growth factors and MSC. The basic scientific literature with respect to BMAC is still in its infancy and is outweighed by small clinical studies. In a recent equine cartilage defect model, defects grafted with BMAC were not different in repair quality compared to microfracture.⁴ In addition, MSC in BMAC underwent chondrogenic differentiation in vitro but not in vivo. However, in a goat osteoarthritis model, injection of BMAC had increases in measured growth factors, reduced inflammatory cytokines in joint fluid, and had less matrix loss compared to control.⁵ This may support the role of growth factors and paracrine effects of MSC to modulate inflammation and catabolism in osteoarthritis in the absence of the ability of MSC engraftment and differentiation. Multisite aspiration should theoretically increase the fraction of MSC, however Oliver et al. found no difference with single vs multisite aspiration.⁶ Given that preparation is similar to PRP, BMAC is troubled by many of the same variables as PRP necessitating standardization of reporting.⁷

Stromal vascular fraction is an attractive therapeutic because of ease and speed of collection and processing. As a cell-based therapy, it is heterogeneous in nature. The advantages and disadvantages of this heterogeneity have yet to be fully elucidated as is also true for the basic mechanism of action in osteoarthritis.⁸

Culture expanded MSC provide a more homogeneous cell population and greater cell numbers at the time of injection, but require greater time between harvest and delivery, expense, and complexity of regulatory control. Numerous questions remain to be answered including the best cell source, dose, timing of therapy, culture optimization including avoidance of xenogeneic proteins, specific indications, and safety of allogenic therapy. Culture expanded cells from a variety of sources have been studied for their immunomodulatory potential including bone marrow-derived, adipose-derived, amniotic, and peripheral blood MSC, among others.^9,10 An important discovery in the concept of MSC as a treatment for osteoarthritis was the anti-inflammatory and immunomodulatory phenotype adopted by the cells after exposure to synovial fluid from osteoarthritic joints or inflammatory cytokines prominent in the pathophysiology of osteoarthritis and recent work has demonstrated differences in the secretome of MSC exposed to synovial fluid from early vs late osteoarthritic joints.^11,12

Overall, the orthobiologics are generally considered safe for the purpose of joint injection and the rationale for the utility of many of these therapies is strong and supported by basic mechanistic evidence. However, many questions remain that can only be answered by well controlled studies with complete characterization of the therapy being used.

References

1. Huebner K and Getgood A. Ortho-biologics for osteoarthritis. Clin Sports Med. 38:123-141, 2019.

2. Fice MP, Miller JC, Christian R, et al. The role of platelet-rich plasma in cartilage pathology: An updated systematic review of the basic science evidence. Arthroscopy. 35(3):961-976, 2019.

3. Ludwig HC, Birdwhistell KE, Breainard BM, Franklin SP. Use of cyclooxygenase-2 inhibitor does not inhibit platelet activation or growth factor release from platelet-rich plasma. Am J Sports Med. 45(14):3351-3357, 2017.

4. Chu CR, Fortier LA, Williams A, et al. Minimally manipulated bone marrow concentrate compared with microfracture treatment of full-thickness chondral defects: A one year study in an equine model. J Bone Joint Surg Am. 100(2):138-146, 2018

5. Wang Z, Zhai C, Fei H, et al. Intraarticular injection autologous platelet-rich plasma and bone marrow concentrate in a goat osteoarthritis model. J Orthop Res. Feb 21, 2018. Doi: 10.1002 [epub ahead of print]

6. Oliver K, Awan T, Bayes M. Single- versus multiple-site harvesting techniques for bone marrow concentrate: Evaluation of aspirate quality and pain. Orthop J Sports Med. 5(8):2325967117724398, 2017.

7. Gaul F, Bugbee WD, Hoenecke HR, D’Lima DD. A review of commercially available point-of-care devices to concentrate bone marrow for the treatment of osteoarthritis and focal cartilage lesions. Cartilage. Apr 1, 2018:1947603518768080. [epub ahead of print]

8. Shimozono Y, Fortier LA, Brown, D, et al. Adipose-based therapies for knee pain-fat or fiction. J Knee Surg. 32(1):55-64, 2019.

9. de Girolamo L, Kon E, Filardo G, et al. Regenerative approaches for the treatment of early OA. Knee Surg Sports Traumatol Arthrosc. 24:1826-1835, 2016.

10. Longhini ALF, Salazar TE, Vieira C, et al. Peripheral blood-derived mesenchymal stem cells demonstrate immunomodulatory potential for therapeutic use in horse. PLoS One. 14(3):e0212642, 2019.

11. McKinney JM, Doan TN, Wang L, et al. Therapeutic efficacy of intra-articular delivery of encapsulated human mesenchymal stem cells on early stage osteoarthritis. 37:42-59, 2019.

12. Gomez-Aristizabal A, Sharma A, Bakooshli MA, et al. Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid. Osteoarthritis Cartilage 25(5):737-741, 2017.

Introduction

There is a large variety of musculoskeletal diseases and injuries that could benefit from developing new technologies in regenerative medicine. Regenerative engineering can be defined as the convergence of advanced materials science, stem cell science, developmental biology, and clinical translation [1]. Stem cells (SCs) treatment hold great repair potential through systemic and local delivery [2-4]. However, the major challenge is to improve therapeutic cells’ delivery and targeting using standard protocols easily scalable.

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Biomaterials are fundamental tools for several regenerative medicine approaches, and they can either being use alone or in combination with SCs. Scaffolds – natural, synthetic or hybrid - have shown substantial promise for maintaining an organized space for tissue growth, providing mechanical stability, and superior support for cells’ adhesion and migration efficiently mimicking all the desired features of a host extracellular matrix. However, during the implantation of scaffolds, an injury occurs generating complex processes that stimulate the host’s inflammatory response to the implanted material can negatively impact the environment ultimately resulting in fibrosis (foreign body reaction) and scar formation. Scars are areas of fibrous tissue characterized by disorganized collagen deposition that seals off the damaged tissue. Despite this primary function, scars prevent the process of functional tissue recovery. On the contrary, most of the processes of functional healing are scar-free. Understanding these processes would allow the development of new therapeutic strategies based on the driving molecular mechanisms that improve the regenerative process.

On this porpoise, the surface of the biomaterial can be chemically functionalized with bioactive signals to tune the implanted or the infiltrating cells’ response to trigger functional tissue regeneration rather than scar formation.

A tissue engineering approach based on tuning the immune-response is still lacking in clinic as a regenerative therapy. The chemistry and architecture of biomaterials can be manipulated to prevent a pro-inflammatory response as well as boost the immunosuppressive potential of SCs ensuring a promotion of tissue regeneration. We are able to bestow on the surface of biomaterials active signals to efficiently reduce the inflammatory response promoting tissue regeneration rather than unfunctional scar formation.

We used SCs from classic bone marrow and cartilage tissue resident SCs to study and improve their stemness and therapeutic characteristics. We developed treatments to improve their homing ability [5], and created functionalized biomimetic materials to increase their immune-suppressive potential and support in situ proliferation and differentiation [6], showing osteoinductive and chondroinductive properties both in vitro and in vivo [7, 8].

We believe these treatments to be the new direction in order to develop cellular therapies to treat musculoskeletal inflammatory conditions. The transient enhancing of SCs potential induced by different substrates could be a new tool for new therapies with limited side effects. There is a clinical need for biomaterials that will give another strategy to treat patients with defects in their weight bearing joints as well as for critical size defects in bone. Right now, it is still debating if cellular or acellular scaffolds are most likely to be successful. We want to focus the attention that no matter the strategy, rather the target should be tuning the inflammatory response to enhance reparative pathways that presently lead to scar formation, failure of integration, and failure to generate native tissue.

References

References.

1. Taraballi, F., et al., Concise Review: Biomimetic Functionalization of Biomaterials to Stimulate the Endogenous Healing Process of Cartilage and Bone Tissue. Stem cells translational medicine, 2017. 6(12): p. 2186-2196.

2. Fernandez-Moure, J.S., et al., Not all stem cells are created equal: a comparative analysis of osteogenic potential in compact bone and adipose-derived mesenchymal stem cells. Journal of the American College of Surgeons, 2013. 217(3): p. S99.

3. Corradetti, B., et al., Osteoprogenitor cells from bone marrow and cortical bone: understanding how the environment affects their fate. Stem cells and development, 2014. 24(9): p. 1112-1123.

4. Fernandez-Moure, J.S., et al., Enhanced osteogenic potential of mesenchymal stem cells from cortical bone: a comparative analysis. Stem cell research & therapy, 2015. 6(1): p. 203.

5. Corradetti, B., et al., Hyaluronic acid coatings as a simple and efficient approach to improve MSC homing toward the site of inflammation. Scientific reports, 2017. 7(1): p. 7991.

6. Corradetti, B., et al., heparan sulfate: a Potential candidate for the Development of Biomimetic immunomodulatory Membranes. Frontiers in bioengineering and biotechnology, 2017. 5: p. 54.

7. Corradetti, B., et al., Chondroitin sulfate immobilized on a biomimetic scaffold modulates inflammation while driving chondrogenesis. Stem cells translational medicine, 2016. 5(5): p. 670-682.

8. Minardi, S., et al., Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation. Biomaterials, 2015. 62: p. 128-137.

9. Taraballi, F., et al., Biomimetic collagenous scaffold to tune inflammation by targeting macrophages. Journal of tissue engineering, 2016. 7: p. 2041731415624667.

10. Corradetti, B., et al., Immune tuning scaffold for the local induction of a pro-regenerative environment. Scientific reports, 2017. 7(1): p. 17030.

Acknowledgments

Authors would like to thank: Dr. D. Litner, D. Dong, H. Goble, Dr. B. Corradetti, Dr. S. Minardi, G. Bauza, A. Brozovich for their support and help to make our research great.

Introduction

Cartilage regeneration is one of surgeons most compelling challenges. In the last twenty years different surgical techniques have been developed to treat cartilage defects. When the size of the lesions becomes bigger, the treatment becomes more challenging.

- Donor site morbidity is one of the principal contraindications of autologous osteochondral grafting in large defects. Addtionally, fibrocartilage will form between the plugs when mosaicplasty with higher numbers of plugs is performed.

- The use of ACI is not cost-effective, requiring two surgical procedures. This procedure is almost completely abandoned, for example, in Italy.

- Fresh osteochondral allografts have been widely used to treat large osteochondral defects of the knee, but many questions are still open regarding cartilage viability and preservation and bone integration.

Tissue bio-engeneering has helped the orthopedic surgeons producing multiple scaffolds for the treatment of larger defects, aiming to create three-dimensional scaffolds which act as templates for tissue development. Lately the awareness of the involvement of the subchondral bone in these lesions, resulted in the need to develop cell-free treatment strategies focused on the entire osteochondral unit. The “cell-free” osteochondral grafts have been developed with the aim to give specific regenerative signals to mesenchymal cells coming from the bone marrow. An ideal graft would be an off-the-shelf product from both a surgical and commercial standpoint, so many biomaterials have been proposed in the last years to induce cartilage “regeneration” in situ, directly in the site of lesion.

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To address the subchondral bone, designated three dimensional scaffolds have been developed to treat more extended chondral and osteochondral defects. Maioregen® (Fin-Ceramica SpA, Faenza, Italy)is a nanostructured biomimetic scaffold with a porous 3-dimensional trilayer composite structure, mimicking the whole osteochondral anatomy. This scaffold was introduced into clinical practice because a cell-free approach after animal studies showed good results in terms of both cartilage and bone tissue formation. Clinical studies have showed that the implantation of this biomimetic scaffold to treat chondral and osteochondral knee defects proved to be effective in terms of clinical outcome at a short follow-up time in a large patient population, even though altered findings have been detected at MRI.

More recently various components processed with tissue engineering have been proposed as a valid alternative because they can participate actively to the process of tissue regeneration and are able to integrate with healthy tissues. Agili-C™ (CartiHeal, Israel) is a recently developed cell-free, resorbable, bi-phasic scaffold made of inorganic calcium carbonate (aragonite). Aragonite is a biological material similar to human bone in its three- dimensional structure, pore interconnections and crystalline form of calcium carbonate (CaCO 3), with osteoconductive ability which make it suitable for bone repair. The calcium carbonate structures are gradually resorbed and replaced by functional bone tissue. This implant has been used mostly in the knee joint, but also other joints as the ankle and the big toe have been treated. Results are nowadays promising, with improvement of all the clinical scores at short and medium follow-up and with an MRI and X-ray aspect that no other scaffolds have shown before with good cartilage formation and scaffold reabsorption. Moreover the uniqness of this implant is that you can treat wide range of patients, including arthritic and non-arthrititc joints, single and multiple lesions as well as both chondral and osteochondral defects

References

Large fresh osteochondral allografts of the knee: a systematic clinical and basic science review of the literature. De Caro F, Bisicchia S, Amendola A, Ding L. Arthroscopy. 2015 Apr;31(4):757-65. doi: 10.1016/j.arthro.2014.11.025. Epub 2015 Feb 3. Review. PMID: 25660010

Treatment of Large Knee Osteochondral Lesions With a Biomimetic Scaffold: Results of a Multicenter Study of 49 Patients at 2-Year Follow-up. Berruto M, Delcogliano M, de Caro F, Carimati G, Uboldi F, Ferrua P, Ziveri G, De Biase CF. Am J Sports Med. 2014 Jul;42(7):1607-17. doi: 10.1177/0363546514530292. Epub 2014 Apr 28. PMID: 24778267

Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee. Delcogliano M, de Caro F, Scaravella E, Ziveri G, De Biase CF, Marotta D, Marenghi P, Delcogliano A. Knee Surg Sports Traumatol Arthrosc. 2014 Jun;22(6):1260-9. doi: 10.1007/s00167-013-2717-3. Epub 2013 Oct 22. PMID: 24146051

Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model.Kon E, Filardo G, Robinson D, Eisman JA, Levy A, Zaslav K, Shani J, Altschuler N. Knee Surg Sports Traumatol Arthrosc. 2014 Jun;22(6):1452-64. doi: 10.1007/s00167-013-2467-2. Epub 2013 Mar 12

Osteochondral regeneration with a novel aragonite-hyaluronate biphasic scaffold: up to 12-month follow-up study in a goat model. Kon E, Filardo G, Shani J, Altschuler N, Levy A, Zaslav K, Eisman JE, Robinson D. J Orthop Surg Res. 2015 May 28;10:81. doi: 10.1186/s13018-015-0211-y.

A novel aragonite-based scaffold for osteochondral regeneration: early experience on human implants and technical developments.Kon E, Robinson D, Verdonk P, Drobnic M, Patrascu JM, Dulic O, Gavrilovic G, Filardo G. Injury. 2016 Dec;47 Suppl 6:S27-S32. doi: 10.1016/S0020-1383(16)30836-1.

Agili-C implant promotes the regenerative capacity of articular cartilage defects in an ex vivo model. Chubinskaya S, Di Matteo B, Lovato L, Iacono F, Robinson D, Kon E. Knee Surg Sports Traumatol Arthrosc. 2018 Nov 1. doi: 10.1007/s00167-018-5263-1.

Autologous Matrix-Induced Chondrogenesis: A Systematic Review of the Clinical Evidence.Gao L, Orth P, Cucchiarini M, Madry H.Am J Sports Med. 2019 Jan;47(1):222-231. doi: 10.1177/0363546517740575. Epub 2017 Nov 21

Long-term follow-up evaluation of autologous chondrocyte implantation for symptomatic cartilage lesions of the knee: A single-centre prospective study.Berruto M, Ferrua P, Pasqualotto S, Uboldi F, Maione A, Tradati D, Usellini E. Injury. 2017 Oct;48(10):2230-2234. doi: 10.1016/j.injury.2017.08.005. Epub 2017 Aug 4.

Introduction

The subchondral bone plays and integral role in cartilage mechanics and health. Unfortunately, cartilage injury, defect creation during preclinical studies, or subchondral disruption from marrow stimulation can alter load transmission between the tissues and expose the subchondral bone to synovial and marrow factors [1], potentially leading to subchondral remodeling and degenerative changes. Thus, cartilage repair strategies must aim to either stabilize or reestablish the subchondral bone in order to maximize both the quality of the repair tissue and the clinical outcomes in patients.

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Introduction: The subchondral bone plays and integral role in cartilage mechanics and health. Unfortunately, cartilage injury, defect creation during preclinical studies, or subchondral disruption from marrow stimulation can alter load transmission between the tissues and expose the subchondral bone to synovial and marrow factors [1], potentially leading to subchondral remodeling and degenerative changes. Thus, cartilage repair strategies must aim to either stabilize or reestablish the subchondral bone in order to maximize both the quality of the repair tissue and the clinical outcomes in patients.

Cartilage repair strategies are heavily reliant upon the state of the subchondral bone. In fact, a review of recent cartilage repair clinical trials determined that >60% of studies excluded patients that had undergone previous repair, most likely due to the complicated status of the subchondral bone [2]. Our work shows that the creation of full thickness focal cartilage defects in a large animal model, followed by either microfracture or scaffold implantation, can have high variability with regards to subchondral bone response [Fig 1]. Furthermore, the status of the subchondral bone was extremely influential in the quality of cartilage repair tissue within the defect, motivating the need to maintain subchondral bone quality during cartilage repair and regeneration procedures. Recently, our group investigated the use of bisphosphonates (alendronate, 40mg daily), and determined that pre- and post-operative administration reduced the subchondral bone response in both defect and microfracture scenarios [Fig 2]. This effect is most likely related to the inhibition of osteoclast activity with alendronate [3], and thus cartilage regeneration techniques in the future may need to similarly administer treatments to prevent a significant subchondral bone response. Finally, in addition to these advances in drugs to treat subchondral bone during cartilage repair, cartilage tissue engineers have designed biphasic ostechondral constructs to regenerate a stiff bone layer that provides proper load support to the cartilage layer, enhancing the formation of hyaline-like cartilage. These advances may allow for treatment in patients with poor subchondral bone quality following prior cartilage repair procedures or microfracture. Overall, the treatment of the subchondral bone, whether by preservation or replacement, is integral to cartilage repair, and ultimately joint preservation.

Figure Legends:

Figure 1. Histological staining (Safranin O/Fast Green) of MFx and Scaffold treated defects determined that subchondral bone quality is influential in the quality of articular cartilage repair/regeneration, and is highly variable between animals/patients. Scale bar = 1mm.

Figure 2. µCT of subchondral bone from control, defect, and microfracture (MFX) conditions, untreated or treated with alendronate. Warmer colors indicate increased BMD.

References

[1] Fisher+ 2015, Tissue Eng Part A.

[2] Martin+ 2019, Nat Regen Med

[3] Orth+ 2013, ECM J

Introduction

Introduction

Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability in the adult population. Initially it was considered as a primary disorder of the articular cartilage, however studies have demonstrated that all joint structures are affected including the calcified cartilage, subchondral cortical and trabecular bone, joint capsular tissues, and the synovium. Recently, there have been significant advances in characterizing the structural and functional alterations in periarticular bone associated with OA, and several groups have demonstrated that the presence of bone marrow edema correlates with the severity of joint pain and progression of cartilage and bone lesions.

Lately, there has been an increasing interest and awareness of the importance of the subchondral bone and its role in the pathogenic processes, as well as the necessity to carefully consider this structure in the treatment of articular surface damage, in the evaluation of the results over time, and in the determination of the patients’ prognosis.

Bone marrow lesions (BMLs) are characterized by increased signal on T2-weighted sequences with fat suppression on magnetic resonance imaging (MRI), known as bone edema lesions, indicate a mechanically and histologically altered subchondral bone. Such lesions have been related to pain, joint surface deformation, and accelerated osteoarthritis progression. Histological evaluations of these lesions demonstrate that these are not edema areas per se, but rather a set of nonspecific changes involving fibrosis, medullary fat necrosis, microfractures of the trabecular bone, and poor mineralization, confirming the hypothesis of areas of excessive bone remodeling without the ability to form bone with normal characteristics.

Therefore, the treatment goal for BML, associated or not with large chondral or osteochondral defects, should be to try to restore the physiological properties of the osteochondral unit, aiming to achieve a more predictable repair tissue that closely resembles native articular surface and remains durable over time.

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Subchondroplasty

Subchondroplasty consists of the application of a synthetic bone substitute based on calcium phosphate in the BML for the treatment of lesions in which conservative treatment failed. The goal is to improve the structural quality of the affected subchondral bone and promote local bone remodeling, aiming to prevent bone collapse and the progression of arthritis. Previous reports in the literature have demonstrated the feasibility and applicability of the technique to reduce pain and improve function, with a small risk of complications. The procedure is effective in pain reduction in the short and mid-term, however there still no data regarding long term results.

Bone Autografts and Osteochondral Autografts

Bone autografts are commonly used in orthopedics to stimulate healing in surgical procedures and to address issues of bony deficiency. More recently, the use of bone autografts in the field of cartilage repair has increased to treat osteochondral defects associated or not with surface cartilage repair procedures. Historically, iliac crest bone graft has been utilized as a source for bone autograft; however, this harvest site is associated with substantial post-operative pain and morbidity. Therefore, the use of autograft bone from the proximal tibia or distal femur; or the use of allografts are options of a viable source of structural graft. In osteochondral defects, such as osteochondritis dissecans, affecting both the subchondral bone and cartilage surface, bone graft can be impacted into the defect, up to the level of the subchondral plate in order to restore the subchondral bone defect. For smaller defects, no additional fixation is required. In larger defects, a layer of fibrin glue can be added, with or without collagen membrane coverage, to secure the graft from displacement.

Autologous osteochondral transplantation (OAT) was developed to treat relatively small and medium-sized focal chondral and osteochondral defects of the weight bearing surfaces of the femoral condyles and is a surgical technique that provides hyaline cartilage to restore the osteochondral anatomy of the articular surface. Long-term results with OAT were reported by Hangody et al. with good or excellent outcome in 91% of femoral condyle resurfacing procedures. In this procedure, osteochondral plugs are harvest from the patient’s own knee, and donor site morbidity can become an issue, depending on the size of the lesion that is being treated.

Osteochondral Allograft

The fundamental concept governing fresh osteochondral allografting is the transplantation of architecturally-mature hyaline cartilage, with living chondrocytes that survive transplantation, and are thus capable of supporting the cartilage matrix. Fresh osteochondral allografts possess the ability to restore a wide spectrum of chondral and osteochondral pathology. In our experience, allografts can be considered as a primary treatment option for osteochondral lesions >2 cm², as a revision cartilage restoration procedure when other cartilage treatments have been unsuccessful and are also indicated for salvage reconstruction of post-traumatic defects of the tibial plateau, patella or the femoral condyle. In selected cases, allografts can be used to treat more severe disease situations such as unicompartimental arthritis. The two commonly used techniques for the preparation and implantation of osteochondral allografts include the press-fit plug technique and the shell-graft technique. Long-term results have been reported with this technique, with more than 80% survivorship in 10 years with good and excellent clinical outcome. Osteochondral allografts do present the surgeon with unique and important differences from other cartilage repair techniques, such as limited allograft tissue availability and the potential for transmission of infectious disease from the graft or immunologic response by the recipient.

Autologous Chondrocyte Transplantation and Scaffolds

Since it was first reported in 1994, autologous chondrocyte implantation technique was further developed and led to the matrix-induced autologous chondrocyte implantation (MACI), which simplified the surgical procedure and reduced the likelihood of adverse events such as adhesions, hypertrophy, and delamination. For osteochondral defects, the “sandwich” technique is usually utilized, using bone graft to restore the osseous portion of the defect a then two layers of scaffolds with cells for cartilage restoration. A few studies showed the presence of subchondral bone changes after autologous chondrocyte implantation. Considering regenerative procedures, short-term results reported by some authors showed that the status of the subchondral bone was significantly correlated with clinical outcomes. These findings demonstrate the importance of the subchondral bone and the need for further studies to better clarify its role in the pathologic processes, the importance of carefully considering this structure in the treatment of articular surface damage, in the evaluation of the results over time, and in the determination of the patients prognosis. Several authors have highlighted the need for biphasic scaffolds, in order to reproduce the different biological and functional requirements for guiding the growth of the two tissues (bone and cartilage), to result in a predictable and durable repair. New scaffolds with osteochondral regenerative potential have been developed and evaluated with promising preliminary results.

References

Goldring, S.R. 2009.Role of bone in osteoarthritis pathogenesis. Med. Clin. North Am. 93: 25–35, xv.

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Moyad TF, Minas T (2008) Opening wedge high tibial osteotomy: a novel technique for harvesting autograft bone. J Knee Surg 21:80–84

Hangody L, Vasarhelyi G, Hangody LR, et al. Autologous osteochondral grafting--technique and long-term results. Injury 2008; 39 Suppl 1: S32-39. 2008/05/28. DOI: 10.1016/j.injury.2008.01.041.

Görtz S and Bugbee WD. Allografts in articular cartilage repair. J Bone Joint Surg Am 2006; 88: 1374-1384. Lectures 2006/06/13.

Tírico LE, Demange MK, Santos LA, et al. Fresh osteochondral knee allografts in Brazil with a minimum two-year follow-up. Rev Bras Ortop 2017; 52: 75-81. 2017/02/15. DOI: 10.1016/j.rboe.2016.12.009.

Peterson L, Vasiliadis HS, Brittberg M, et al. Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med 2010; 38: 1117-1124. DOI: 10.1177/0363546509357915.

Minas T, Von Keudell A, Bryant T, et al. The John Insall Award: A minimum 10-year outcome study of autologous chondrocyte implantation. Clin Orthop Relat Res 2014; 472: 41-51. 2013/08/28. DOI: 10.1007/s11999-013-3146-9.

Gobbi A, Karnatzikos G and Sankineani SR. One-step surgery with multipotent stem cells for the treatment of large full-thickness chondral defects of the knee. Am J Sports Med 2014; 42: 648-657. DOI: 10.1177/0363546513518007.