# Is Microfracture Alone Enough?
## 5 Microfracture Plus Cell-Free Injectable Scaffolds  
There are three basic elements in tissue engineering: cells, biodegradable scaffolds, and growth factors, which together provide a new method for the repair of articular cartilage. Scaffolds can provide a 3D structure for cartilage cells and favor cell adhesion and proliferation. They also mediate the signals and interactions between cells. The available literature offers various cell-free injectable scaffolds for treating cartilage lesions, such as HA-based, collagen-based, and chitosan-based [31]. Hyaluronic acid is a lubricant designed to reduce the pain and inflammation of articular surfaces and completes the endogenous joint fluid. Intra-articular injections are utilized for cartilage lesions and joint degeneration. HA has a high-molecular-weight glycosaminoglycan component, which is the reason for its viscoelastic attributes. Moreover, in order to provide joint lubrication and shock absorption, HA represents the main way for proteoglycans of the extracellular matrix to create a hydrated pathway through which cells can migrate [32; 33]. As for the procedure itself, HA can be injected 3 weeks after the surgical procedure. Hyaluronic acid-based scaffolds can also be inserted to fill defects in dry conditions with a small arthotomy. This procedure can be done alone or in combination with other adjuvant therapies [34]. HA as a scaffolding material depends largely on its bulk surface. The parameters that are used to describe the network structure of hydrogels include the molecular weight of the polymer chains, the corresponding mesh size, and the effective network density. HA-based scaffolds can bind to proteins and cells through cell surface receptors, such as CD44, RHAMM, and ICAM-1. HA scaffolds can bind to chondrocytes via CD44. Multiple biological processes mediated by these scaffolds are important for the wound healing process. This, coupled with the capacity to offer an open, hydrated structure for the passage of nutrients, makes them candidates for tissue regeneration and repair techniques [35; 36]. Reports on HA as an adjuvant therapy with MFX are shown in Table 2. This table contains the studies published in the last 5 years, with the methodology and results explained. \begin{table}
\begin{tabular}{c c c} \hline
**Article/Reference** & **Number of Patients (N0)** & **Method** & **Results** \\ \hline [PERSON] et al. (2020) *[3] & 30 & Saline injection on 1, 8, 15, and 22 days after surgery (M group)/HA injection on 1, 8, 15, and 22 days after MKY (MR group)/ADSC injection on days 1 and 22 and HA injection on days 8 and 22 (MSR group). & Patients in MS and MSR groups showed meaningful response to therapy based on clinically evaluation with WOMAC and SF-36 scores. Both groups also showed significant improvement in quantitative evaluation of defect size and cartilage volume with MRI and arthroscopy. During the first 9 months after treatment, discrepancies between groups were non-significant; after 12 months, clinical improvement was significantly greater in the MSR group than the M and MS groups on most scales. M group maintained clinical improvement for 9 months. For MS and MSR patients, clinical benefits were still improved at 24 months follow-up compared with baseline. \\ \hline [PERSON] et al. (2017)[34] & 43 & HA-based cell-free scaffold used as adjuvant for MIX (group 1, \(n=19\))/MEX alone as surgical procedure (group 2, \(n=24\)). \\  & & Retrospective evaluation of 20 patients with MFX and HA and end-to-fire IA-based scaffold combination. American Orthopedic Foot and Ankle Society (AOFAS) Angle-Hindoor Scale score and VAS score used to assess postoperative outcomes. Patient satisfaction also questioned. \\ \hline [PERSON] et al. (2016)[38] & 50 & 25 patients treated with MFX alone and 25 with MFX + HA-based scaffold. \\ \hline \end{tabular}
\end{table} 
Table 2: HA as an adjuvant therapy for microfracture. Chitosan is a semi-crystalline polymer, and the amount of crystallinity represents the de-acetylation ability.