Next-Generation Marrow Stimulation Technology for Cartilage Repair: Basic Science to Clinical Application

Given the relatively high prevalence of full-thickness articular cartilage lesions, including in patients who are <40 years of age, and an inability to detect some of these lesions until the time of arthroscopy, there is value in performing a single-stage cartilage procedure such as marrow stimulation (MS).

While the positive outcomes of first-generation MS (namely microfracture) have been observed to drop off after 24 months in several studies, improvements have been seen when compared with preoperative conditions for lesions that are 2 to 3 cm2 in size, and MS is considered to be a procedure with technical simplicity, fairly short surgical times, and relatively low morbidity. A recent study showed that autologous chondrocyte implantation (ACI) and osteochondral allograft (OCA) transplantation remain viable treatment options for chondral defects of the knee in the setting of failed MS.

Basic science principles that have been elucidated in recent years include (1) the creation of vertical walls during defect preparation, (2) an increased depth of subchondral penetration, (3) a smaller awl diameter, and (4) an increased number of subchondral perforations, which are all thought to help resolve issues of access to the mesenchymal stromal cells (MSCs) and the subchondral bone structure/overgrowth issues.

Pioneering and evolving basic science and clinical studies have led to next-generation clinical applications, such as a hyaluronic acid-based scaffold (ongoing randomized controlled trial [RCT]), an atelocollagen-based gel (as described in a recently published RCT), a micronized allogeneic cartilage scaffold (as described in a recently completed prospective cohort study), and a biosynthetic hydrogel that is composed of polyethylene glycol (PEG) diacrylate and denatured fibrinogen (as described in an ongoing prospective study).

This review summarizes important points for defect preparation and the recent advances in MS techniques and identifies specific scaffolding augmentation strategies (e.g., mesenchymal augmentation and scaffold stimulation [MASS]) that have the capacity to advance cartilage regeneration in light of recent laboratory and clinical studies.