Microfracture Versus Drilling of Articular Cartilage Defects: A Systematic Review of the Basic Science Evidence

Background: Microfracture (MFx) is one of the most common techniques used for the treatment of articular cartilage defects, although recently there has been a trend toward the use of drilling rather than MFx for the treatment of these defects. Purpose: To perform a systematic review of basic science studies to determine the effect of microfracture versus drilling for articular cartilage repair. Study Design: Systematic review. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and EMBASE to identify basic science studies comparing outcomes of MFx versus drilling. The search phrase used was microfracture AND (drilling OR microdrilling). Inclusion criteria were basic science studies that directly compared the effect of MFx versus drilling on subchondral bone, bone marrow stimulation, and cartilage regeneration. Results: A total of 7 studies met the inclusion criteria and were included in this systematic review. Of these, 4 studies were performed in rabbits, 1 study in sheep, and 2 studies in humans. All of the included studies investigated cartilage repair in the knee. In the animal studies, microfracture produced fractured and compacted bone and led to increased osteocyte necrosis compared with drilling. Deep drilling (6 mm) was superior to both shallow drilling (2 mm) and MFx in terms of increased subchondral hematoma with greater access to marrow stroma, improved cartilage repair, and increased mineralized bone. However, the overall quality of cartilage repair tissue was poor regardless of marrow stimulation technique. In 2 studies that investigated repair tissue after MFx and/or drilling in human patients with osteoarthritis and cartilage defects, the investigators found that cartilage repair tissue did not achieve the quality of normal hyaline articular cartilage. Conclusion: In the limited basic science studies that are available, deep drilling of cartilage defects in the knee resulted in improved biological features compared with MFx, including less damage to the subchondral bone and greater access to marrow stroma. Regardless of marrow stimulation technique, the overall quality of cartilage regeneration was poor and did not achieve the characteristics of native hyaline cartilage. Overall, there is a general lack of basic science literature comparing microfracture versus drilling for focal chondral defects.

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Stem Cells and Gene Therapy for Cartilage Repair

Stem Cells International ◽

10.1155/2012/168385 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 27

Author(s):

Umile Giuseppe Longo ◽

Stefano Petrillo ◽

Edoardo Franceschetti ◽

Alessandra Berton ◽

Nicola Maffulli ◽

...

Keyword(s):

Stem Cells ◽

Gene Therapy ◽

Articular Cartilage ◽

Cartilage Repair ◽

Treatment Strategies ◽

Cartilage Regeneration ◽

Biochemical Properties ◽

Cartilage Defects ◽

Type I ◽

Repair Tissue

Cartilage defects represent a common problem in orthopaedic practice. Predisposing factors include traumas, inflammatory conditions, and biomechanics alterations. Conservative management of cartilage defects often fails, and patients with this lesions may need surgical intervention. Several treatment strategies have been proposed, although only surgery has been proved to be predictably effective. Usually, in focal cartilage defects without a stable fibrocartilaginous repair tissue formed, surgeons try to promote a natural fibrocartilaginous response by using marrow stimulating techniques, such as microfracture, abrasion arthroplasty, and Pridie drilling, with the aim of reducing swelling and pain and improving joint function of the patients. These procedures have demonstrated to be clinically useful and are usually considered as first-line treatment for focal cartilage defects. However, fibrocartilage presents inferior mechanical and biochemical properties compared to normal hyaline articular cartilage, characterized by poor organization, significant amounts of collagen type I, and an increased susceptibility to injury, which ultimately leads to premature osteoarthritis (OA). Therefore, the aim of future therapeutic strategies for articular cartilage regeneration is to obtain a hyaline-like cartilage repair tissue by transplantation of tissues or cells. Further studies are required to clarify the role of gene therapy and mesenchimal stem cells for management of cartilage lesions.

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Magnetic Targeted Delivery of Induced Pluripotent Stem Cells Promotes Articular Cartilage Repair

Stem Cells International ◽

10.1155/2017/9514719 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Shinji Kotaka ◽

Shigeyuki Wakitani ◽

Akira Shimamoto ◽

Naosuke Kamei ◽

Mikiya Sawa ◽

...

Keyword(s):

Magnetic Field ◽

Stem Cells ◽

Articular Cartilage ◽

Cartilage Repair ◽

Cartilage Regeneration ◽

Ips Cells ◽

Cartilage Defects ◽

Histologic Grading ◽

Nude Rats ◽

Induced Pluripotent

Cartilage regeneration treatments using stem cells are associated with problems due to the cell source and the difficulty of delivering the cells to the cartilage defect. We consider labeled induced pluripotent stem (iPS) cells to be an ideal source of cells for tissue regeneration, and if iPS cells could be delivered only into cartilage defects, it would be possible to repair articular cartilage. Consequently, we investigated the effect of magnetically labeled iPS (m-iPS) cells delivered into an osteochondral defect by magnetic field on the repair of articular cartilage. iPS cells were labeled magnetically and assessed for maintenance of pluripotency by their ability to form embryoid bodies in vitro and to form teratomas when injected subcutaneously into nude rats. These cells were delivered specifically into cartilage defects in nude rats using a magnetic field. The samples were graded according to the histologic grading score for cartilage regeneration. m-iPS cells differentiated into three embryonic germ layers and formed teratomas in the subcutaneous tissue. The histologic grading score was significantly better in the treatment group compared to the control group. m-iPS cells maintained pluripotency, and the magnetic delivery system proved useful and safe for cartilage repair using iPS cells.

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Morphologic Properties of Cartilage Lesions in the Knee Arthroscopically Prepared by the Standard Curette Technique Are Inferior to Lesions Prepared by Specialized Chondrectomy Instruments

The American Journal of Sports Medicine ◽

10.1177/0363546517745489 ◽

2017 ◽

Vol 46 (4) ◽

pp. 908-914 ◽

Cited By ~ 5

Author(s):

Adrian Blasiak ◽

Graeme P. Whyte ◽

Adrian Matlak ◽

Roman Brzóska ◽

Boguslaw Sadlik

Keyword(s):

Cartilage Repair ◽

Group Versus ◽

Cartilage Lesion ◽

Cartilage Defects ◽

Repair Tissue ◽

Treatment Groups ◽

Cartilage Lesions ◽

Morphologic Characteristics ◽

Wall Profile

Background: Cartilage lesion preparation is an important component to cartilage repair procedures, given the effect of prepared lesion morphology on the formation of durable and well-integrated repair tissue. Purpose: To compare the quality of arthroscopic cartilage lesion debridement performed by (1) the standard curette (SC) technique and (2) specialized chondrectomy (CM) instruments, to provide technical guidance for optimization of cartilage lesion preparation in the setting of arthroscopic cartilage repair. Study Design: Controlled laboratory study. Methods: Articular cartilage lesions of standardized size (8 × 15 mm) were demarcated within the trochlea and femoral condyles of 20 human cadaver knee specimens. Orthopaedic surgeons performed arthroscopic lesion preparation using 2 techniques that consisted of SC preparation and preparation by CM instruments. A histologic comparative analysis was performed within each treatment group and between treatment groups to evaluate the morphology of prepared cartilage defects. Results: The mean angle deviation from perpendicular of the cartilage wall at the front of the prepared cartilage lesions was significantly greater in the SC group versus the CM group (29.8° ± 21.4° vs 7.7° ± 7.6°, P < .001). In lesions prepared via the SC technique, the cartilage walls at the front of the prepared lesions were significantly less perpendicular than the cartilage walls at the rear of the lesions (29.8° ± 21.4° vs 11.0° ± 10.3°, P < .001), whereas lesions prepared by the CM technique demonstrated comparable verticality of surrounding cartilage walls at the front and rear aspects of the lesions (7.7° ± 7.6° vs 9.4° ± 12.3°, P = .827). Depth of lesion debridement was accomplished to the target level by the CM technique in 86% of prepared lesions, compared with 34% of lesions in the SC group. The prepared cartilage wall profile was characterized as the most ideal morphology in 55% of prepared lesions in the CM group, as opposed to 10% in the SC group. Conclusion: Arthroscopic cartilage lesion preparation with SC instruments results in superior perpendicularity of surrounding cartilage walls to subchondral bone and greater consistency of debrided lesion depth, as compared with the standard debridement technique with curettes. Clinical Relevance: Arthroscopic preparation using standard curette technique leads to suboptimal morphologic characteristics of prepared lesions that likely affect the quality of repair tissue, compared to preparation using specialized chondrectomy instruments.

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Repair of Osteochondral Defects With Predifferentiated Mesenchymal Stem Cells of Distinct Phenotypic Character Derived From a Nanotopographic Platform

The American Journal of Sports Medicine ◽

10.1177/0363546520907137 ◽

2020 ◽

Vol 48 (7) ◽

pp. 1735-1747

Author(s):

Yingnan Wu ◽

Zheng Yang ◽

Vinitha Denslin ◽

XiaFei Ren ◽

Chang Sheng Lee ◽

...

Keyword(s):

Mechanical Properties ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Articular Cartilage ◽

Cartilage Repair ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Cartilage Defects ◽

Defect Site

Background: Articular cartilage has a zonal architecture and biphasic mechanical properties. The recapitulation of surface lubrication properties with high compressibility of the deeper layers of articular cartilage during regeneration is essential in achieving long-term cartilage integrity. Current clinical approaches for cartilage repair, especially with the use of mesenchymal stem cells (MSCs), have yet to restore the hierarchically organized architecture of articular cartilage. Hypothesis: MSCs predifferentiated on surfaces with specific nanotopographic patterns can provide phenotypically stable and defined chondrogenic cells and, when delivered as a bilayered stratified construct at the cartilage defect site, will facilitate the formation of functionally superior cartilage tissue in vivo. Study Design: Controlled laboratory study. Methods: MSCs were subjected to chondrogenic differentiation on specific nanopatterned surfaces. The phenotype of the differentiated cells was assessed by the expression of cartilage markers. The ability of the 2-dimensional nanopattern-generated chondrogenic cells to retain their phenotypic characteristics after removal from the patterned surface was tested by subjecting the enzymatically harvested cells to 3-dimensional fibrin hydrogel culture. The in vivo efficacy in cartilage repair was demonstrated in an osteochondral rabbit defect model. Repair by bilayered construct with specific nanopattern predifferentiated cells was compared with implantation with cell-free fibrin hydrogel, undifferentiated MSCs, and mixed-phenotype nanopattern predifferentiated MSCs. Cartilage repair was evaluated at 12 weeks after implantation. Results: Three weeks of predifferentiation on 2-dimensional nanotopographic patterns was able to generate phenotypically stable chondrogenic cells. Implantation of nanopatterned differentiated MSCs as stratified bilayered hydrogel constructs improved the repair quality of cartilage defects, as indicated by histological scoring, mechanical properties, and polarized microscopy analysis. Conclusion: Our results indicate that with an appropriate period of differentiation, 2-dimensional nanotopographic patterns can be employed to generate phenotypically stable chondrogenic cells, which, when implanted as stratified bilayered hydrogel constructs, were able to form functionally superior cartilage tissue. Clinical Relevance: Our approach provides a relatively straightforward method of obtaining large quantities of zone-specific chondrocytes from MSCs to engineer a stratified cartilage construct that could recapitulate the zonal architecture of hyaline cartilage, and it represents a significant improvement in current MSC-based cartilage regeneration.

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A multicenter randomized controlled trial: matrix-augmented bone marrow stimulation with a polyglycolic acid membrane with hyaluronan vs. microfracture alone in local femoral cartilage defects of the femoral condyles

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967120s00289 ◽

2020 ◽

Vol 8 (5_suppl4) ◽

pp. 2325967120S0028

Author(s):

Johannes Glasbrenner ◽

Wolf Petersen ◽

Michael J. Raschke ◽

Matthias Steiger ◽

Claudio Castelli ◽

...

Keyword(s):

Bone Marrow ◽

Controlled Trial ◽

Polyglycolic Acid ◽

Cartilage Defects ◽

Bone Marrow Stimulation ◽

Repair Tissue ◽

Marrow Stimulation ◽

Randomized Controlled ◽

Defect Filling

Aims and Objectives: Microfracture is the gold standard for the treatment of small localized chondral defects of the knee joint. There is evidence from animal studies that the augmentation of bone marrow stimulation by a matrix improves the quality of the repair tissue (matrix-augmented bone marrow stimulation = m-BMS). Aim of this randomized controlled trial was to examine the outcome of a matrix made of polyglycolic acid and hyaluronan in comparison to a conventional microfracture technique. Materials and Methods: In a randomized controlled trail (RCT) patients between 18-60 years with an articular femoral cartilage defect of 1-4 cm2 in the weight bearing area of the femoral condyles with indication for MF were enrolled and randomized to MF or m-BMS using a polyglycolic acid membrane with hyaluronan. Defect filling in MRI assessment at 12 weeks postoperatively was defined as primary outcome measure. MRI scans and follow up examinations including patient reported clinical outcome scores (VAS pain, KOOS, IKDC and SF-36) were performed at 12, 54 and 108 weeks after surgery. Results: There was no statistically significant difference between both groups in terms of defect filling assessed by MRI at 12, 54 and 108 weeks postoperatively. At 12 weeks there was a tendency towards higher degree of defect filling in the MF group when compared to the m-BMS group, whereas no difference was found after 54 and 108 weeks. The m-BMS group revealed superiority in terms of improvement over time in the KOOS subscales pain, knee-related symptoms, activity of daily living, sports and recreation and quality of life at 54 weeks and 108 weeks after treatment. Conclusion: This is the first RCT comparing m-BMS using a polyglycolic acid membrane with hyaluronan to any different treatment strategy in localized cartilage defects of any human joint. The use of the Chondrotissue® membrane in m-BMS of cartilage defects has proven to be a safe procedure with side effects comparable to those of MF. There seems to be an accelerated formation of cartilage repair tissue after MF when compared to m-BMS at 12 weeks postoperatively, whereas at one and two years after treatment there was no difference concerning the quantity of repair tissue. The improvement in clinical outcome scores over time after m-BMS might be due to the formation of cartilage repair tissue of higher quality. Long term follow up studies including histological assessment are desirable for further investigation.

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Surgical Treatment of Articular Cartilage Defects in the Knee: Are We Winning?

Advances in Orthopedics ◽

10.1155/2012/528423 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

A. R. Memon ◽

J. F. Quinlan

Keyword(s):

Articular Cartilage ◽

Cartilage Regeneration ◽

Current Level ◽

Cartilage Defects ◽

Level Of Evidence ◽

Bone Marrow Stimulation ◽

Marrow Stimulation ◽

Ac Injury ◽

Articular Cartilage Defects ◽

And Cartilage

Articular cartilage (AC) injury is a common disorder. Numerous techniques have been employed to repair or regenerate the cartilage defects with varying degrees of success. Three commonly performed techniques include bone marrow stimulation, cartilage repair, and cartilage regeneration. This paper focuses on current level of evidence paying particular attention to cartilage regeneration techniques.

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Scientific Developments and Clinical Applications Utilizing Chondrons and Chondrocytes with Matrix for Cartilage Repair

Cartilage ◽

10.1177/1947603520968884 ◽

2020 ◽

pp. 194760352096888 ◽

Cited By ~ 1

Author(s):

Sarav S. Shah ◽

Kai Mithoefer

Keyword(s):

Extracellular Matrix ◽

Articular Cartilage ◽

Cartilage Repair ◽

Basic Science ◽

Matrix Theory ◽

Operative Management ◽

Clinical Applications ◽

Osteochondral Allograft ◽

Cartilage Defects ◽

Comprehensive Overview

Injuries to articular cartilage of the knee are increasingly common. The operative management of these focal chondral lesions continues to be problematic for the treating orthopedic surgeon secondary to the limited regenerative capacity of articular cartilage. The pericellular matrix (PCM) is a specialized, thin layer of the extracellular matrix that immediately surrounds chondrocytes forming a unit together called the chondron. The advancements in our knowledge base with regard to the PCM/chondrons as well as interterritorial matrix has permeated and led to advancements in product development in conjunction with minced cartilage, marrow stimulation, osteochondral allograft, and autologous chondrocyte implantation (ACI). This review intends to summarize recent progress in chondrocytes with matrix research, with an emphasis on the role the PCM/extracellular matrix (ECM) plays for favorable chondrogenic gene expression, as a barrier/filtration unit, and in osteoarthritis. The bulk of the review describes cutting-edge and evolving clinical developments and discuss these developments in light of underlying basic science applications. Clinical applications of chondrocytes with matrix science include Reveille Cartilage Processor, Cartiform, and ACI with Spherox (which was recently recommended for the treatment of grade III or IV articular cartilage defects over 2 cm2 by the National Institute of Health and Care Excellence [NICE] in the United Kingdom). The current article presents a comprehensive overview of both the basic science and clinical results of these next-generation cartilage repair techniques by focusing specifically on the scientific evolution in each category as it pertains with underlying chondrocytes with matrix theory.

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Formation of cartilage repair tissue in articular cartilage defects pretreated with microfracture and covered with cell-free polymer-based implants

Journal of Orthopaedic Research® ◽

10.1002/jor.20879 ◽

2009 ◽

Vol 27 (10) ◽

pp. 1353-1360 ◽

Cited By ~ 117

Author(s):

Christoph Erggelet ◽

Michaela Endres ◽

Katja Neumann ◽

Lars Morawietz ◽

Jochen Ringe ◽

...

Keyword(s):

Articular Cartilage ◽

Cartilage Repair ◽

Cartilage Defects ◽

Repair Tissue ◽

Articular Cartilage Defects

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Extracellular Matrix Cartilage Allograft and Particulate Cartilage Allograft for Osteochondral Lesions of the Knee and Ankle Joints: A Systematic Review

The American Journal of Sports Medicine ◽

10.1177/0363546517717494 ◽

2017 ◽

Vol 46 (7) ◽

pp. 1758-1766 ◽

Cited By ~ 14

Author(s):

Dexter Seow ◽

Youichi Yasui ◽

Eoghan T. Hurley ◽

Andrew W. Ross ◽

Christopher D. Murawski ◽

...

Keyword(s):

Systematic Review ◽

Clinical Studies ◽

Cartilage Regeneration ◽

Osteochondral Lesions ◽

Level Of Evidence ◽

Bone Marrow Stimulation ◽

Marrow Stimulation ◽

Ankle Joints

Background: Extracellular matrix cartilage allografts (EMCAs) and particulate cartilage allografts (PCAs) are relatively new biologics that may improve the quality of cartilage regeneration after bone marrow stimulation. The increasing popularity of these novel biologics in the treatment of osteochondral lesions (OCLs) of the knee and ankle joints prompts a systematic evaluation of their efficacies. Purpose: The purpose of this systematic review was to clarify the effectiveness of EMCAs and PCAs on cartilage regeneration. Study Design: Systematic review; Level of evidence, IV. Methods: Two reviewers searched MEDLINE and Embase in February 2016 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Predetermined variables from each study were extracted and analyzed. Results: For EMCAs, 1 in vitro study and 2 clinical studies for OCLs of the ankle joint were found. For PCAs, 3 in vitro studies, 5 clinical studies for OCLs of the knee joint, and 5 clinical studies for OCLs of the ankle joint were found. For all studies, in vitro chondrogenesis and clinical outcomes favored EMCAs and PCAs. However, the highest level of evidence was IV, and the methodological quality of evidence was indicated to be poor. Conclusion: Both EMCAs and PCAs have yielded favorable outcomes in both in vitro and clinical studies. However, the available studies were of limited data with significant confounding factors. Therefore, it is unclear whether the effectiveness of these novel biologics is any greater than that of bone marrow stimulation alone in the repair of knee and ankle cartilage.

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Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application

npj Regenerative Medicine ◽

10.1038/s41536-021-00122-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Kangkang Zha ◽

Xu Li ◽

Zhen Yang ◽

Guangzhao Tian ◽

Zhiqiang Sun ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Articular Cartilage ◽

Cartilage Repair ◽

Cartilage Damage ◽

Cartilage Regeneration ◽

Great Promise ◽

Traditional Treatment ◽

Different Types ◽

Selection Of

AbstractArticular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.

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