Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.

Progressive knee joint degeneration occurs following removal of a torn meniscus. However, there is significant variability in the rate of development of post-meniscectomy osteoarthritis (OA). While there is no current consensus on the risk factors for development of knee OA in patients with meniscus tears, it is likely that both biological and biomechanical factors play critical roles. In this perspective paper, we review the mechanical and the biological predictors of the response of the knee to partial meniscectomy. We review the role of patient-based studies, in vivo animal models, cadaveric models, bioreactor systems, and statistically augmented computational models for the study of meniscus function and post-meniscectomy OA, providing insight into the important interplay between biomechanical and biologic factors. We then discuss the clinical translation of these concepts for "biologic augmentation" of meniscus healing and meniscus replacement. Ultimately, collaborative studies between engineers, biologists, and clinicians is the optimal way to improve our understanding of meniscus pathology and response to injury and/or disease, and to facilitate effective translation of laboratory findings to improved treatments for our patients.

Autologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

Purpose of Review The emergence of cell-based therapies has brought much excitement to the field of orthopedic sports medicine. However, the significant inconsistency of reporting has led to the poor understanding, misinformation, and false expectations for patients and clinicians alike. In this paper, we aim to clarify the available cell-therapy treatments and summarize some of the latest research. Recent Findings Although this technology is in early development, our understanding of cell biology has grown significantly over the last decade. Furthermore, it is becoming evident that tissue specificity may play a significant role in determining the effectiveness and overall clinical benefit attributed to cell therapy. Summary Cell therapy is an emerging field with tremendous potential for clinically significant benefit. However, in its current state, clinical application of these treatments is limited by federal regulations, variability in formulation, and limited understanding of the biologic activity of various cell formulations.