Albumin is a constitutional plasma protein, with well-known biological functions, e.g., a nutrient for stem cells in culture. However, albumin is underutilized as a biomaterial in regenerative medicine. This review summarizes the advanced therapeutic uses of albumin, focusing on novel compositions that take advantage of the excellent regenerative potential of this protein. Albumin coating can be used for enhancing the biocompatibility of various types of implants, such as bone grafts or sutures. Albumin is mainly known as an anti-attachment protein; however, using it on implantable surfaces is just the opposite: it enhances stem cell adhesion and proliferation. The anticoagulant, antimicrobial and anti-inflammatory properties of albumin allow fine-tuning of the biological reaction to implantable tissue-engineering constructs. Another potential use is combining albumin with natural or synthetic materials that results in novel composites suitable for cardiac, neural, hard and soft tissue engineering. Recent advances in materials have made it possible to electrospin the globular albumin protein, opening up new possibilities for albumin-based scaffolds for cell therapy. Several described technologies have already entered the clinical phase, making good use of the excellent biological, but also regulatory, manufacturing and clinical features of serum albumin.

Fibrin, a homologous polymer, is the natural scaffold of wound healing and therefore a candidate as a carrier for cell transplantation. We explored a novel matrix-based implant cartilage repair composed of both fibrin and hyaluronan in a defined ratio that takes advantage of the biological and mechanical properties of these two elements. The matrix was seeded with autologous chondrocytes expanded in the presence of a proprietary growth factor variant designed to preserve their chondrogenic potential. We prospectively followed eight patients with symptomatic-chronic cartilage defects treated with this carrier. Patients had arthroscopy to harvest autologous chondrocytes then grown in autologous serum. Chondrocytes were cultured in the presence of the FGF variant and then seeded on the fibrin-hyaluronan matrix. About 4 weeks following biopsy, the patients underwent implantation of the constructs by miniarthrotomy. Three of the eight patients had transient effusion. Clinical performance was measured by Lysholm and IKDC scores, MRI, and the need for secondary surgery. The clinical outcome of a 1-year followup demonstrated increase of clinical scores. The MRI followup showed good filling of the defect with tissue having the imaging appearance of cartilage in all patients. Apart from the transient effusion in three patients we observed no other adverse events during the followup. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Platelet-rich fibrin (PRF) membrane is a three-dimensional biodegradable biopolymer, which consists of platelet derived growth factors enhancing cell adhesion and proliferation. It is widely used in soft and hard tissue regeneration, however, there are unresolved problems with its clinical application. Its preparation needs open handling of the membranes, it degrades easily, and it has a low tensile strength which does not hold a suture blocking wider clinical applications of PRF. Our aim was to produce a sterile, suturable, reproducible PRF membrane suitable for surgical intervention. We compared the biological and mechanical properties of PRF membranes created by the classical glass-tube and those that were created in a single-syringe closed system (hypACT Inject), which allowed aseptic preparation. HypACT Inject device produces a PRF membrane with better handling characteristics without compromising biological properties. Freeze-thawing resulted in significantly higher tensile strength and higher cell adhesion at a lower degradation rate of the membranes. Mesenchymal stem cells seeded onto PRF membranes readily proliferated on the surface of fresh, but even better on freeze/thawed or freeze-dried membranes. These data show that PRF membranes can be made sterile, more uniform and significantly stronger which makes it possible to use them as suturable surgical membranes.

Artificial intelligence (AI) in medicine is a rapidly growing field. In orthopedics, the clinical implementations of AI have not yet reached their full potential. Deep learning algorithms have shown promising results in computed radiographs for fracture detection, classification of OA, bone age, as well as automated measurements of the lower extremities. Studies investigating the performance of AI compared to trained human readers often show equal or better results, although human validation is indispensable at the current standards. The objective of this narrative review is to give an overview of AI in medicine and summarize the current applications of AI in orthopedic radiography imaging. Due to the different AI software and study design, it is difficult to find a clear structure in this field. To produce more homogeneous studies, open-source access to AI software codes and a consensus on study design should be aimed for.

Osteoarthritis (OA) is described by an imbalance between anabolic and catabolic processes in the affected joint. This dysregulation of metabolism affects not only chondrocytes within cartilage tissue but also the cells of the synovial membrane across the border of the joint. An important factor in OA is the low viscosity of the synovial fluid. High-molecular-weight hyaluronic acid (HA) can be used to increase the viscosity and also reduce inflammatory processes. The purpose was to establish an in vitro inflammation model and to evaluate the effects of high-molecular-weight HA in a co-cultivation inflammation model of osteoarthritic chondrocytes and M1 macrophages. For the establishment of the inflammation model THP-1 cells were, at first, differentiated to M0 macrophages and then activated to the M1 subtype after 5 days of resting period. Surface markers, cytokine release, and gene expression, were analyzed to examine the successful differentiation. In the inflammation model, the defined M1 macrophages were co-cultivated with osteoarthritic chondrocytes for 2 days, with and without the addition of 10 % HA and further analyzed for chondrogenic gene expression markers and the release of cytokines in the supernatant. The differentiation and activation process was successful as M1 macrophages expressed higher levels of pro-inflammatory cytokines and specific genes. Similarly, the surface marker CD14 was significantly decreased compared to M0 macrophages. For the co-culture system, the analysis of gene expression showed that HA increased the expression of cartilage-specific genes while catabolic-encoding genes exhibited lower expression levels than the control group. This positive effect of HA was also demonstrated by the measurement of pro-inflammatory cytokines, as their level decreased. Our study implies that high-molecular-weight HA has a chondroprotective effect in the present co-cultivation inflammation model, as it decreases pro-inflammatory cytokines and increases anabolic factors.

Objective. To assess the impact of a computerized system on physicians’ accuracy and agreement rate, as compared with unaided diagnosis. Methods. A set of 124 unilateral knee radiographs from the Osteoarthritis Initiative (OAI) study were analyzed by a computerized method with regard to Kellgren-Lawrence (KL) grade, as well as joint space narrowing, osteophytes, and sclerosis Osteoarthritis Research Society International (OARSI) grades. Physicians scored all images, with regard to osteophytes, sclerosis, joint space narrowing OARSI grades and KL grade, in 2 modalities: through a plain radiograph (unaided) and a radiograph presented together with the report from the computer assisted detection system (aided). Intraclass correlation between the physicians was calculated for both modalities. Furthermore, physicians’ performance was compared with the grading of the OAI study, and accuracy, sensitivity, and specificity were calculated in both modalities for each of the scored features. Results. Agreement rates for KL grade, sclerosis, and osteophyte OARSI grades, were statistically increased in the aided versus the unaided modality. Readings for joint space narrowing OARSI grade did not show a statistically difference between the 2 modalities. Readers’ accuracy and specificity for KL grade >0, KL >1, sclerosis OARSI grade >0, and osteophyte OARSI grade >0 was significantly increased in the aided modality. Reader sensitivity was high in both modalities. Conclusions. These results show that the use of an automated knee OA software increases consistency between physicians when grading radiographic features of OA. The use of the software also increased accuracy measures as compared with the OAI study, mostly through increases in specificity.