Pegylated insulin-like growth factor-1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model.

Tears in the rotator cuff are challenging to repair because of the complex, hypocellular, hypovascular, and movement-active nature of the tendon and its enthesis. Insulin-like Growth Factor-1 (IGF-1) is a promising therapeutic for this repair. However, its unstable nature, short half-life, and ability to disrupt homeostasis has limited its clinical translation. Pegylation has been shown to improve the stability and sustain IGF-1 levels in the systemic circulation without disrupting homeostasis. To provide localized delivery of IGF-1 in the repaired tendons, we encapsulated pegylated IGF-1 mimic and its controls (unpegylated IGF-1 mimic and recombinant human IGF-1) in polycaprolactone-based matrices and evaluated them in a pre-clinical rodent model of rotator cuff repair. Pegylated-IGF-1 mimic delivery reestablished the characteristic tendon-to-bone enthesis structure and improved tendon tensile properties within 8 weeks of repair compared to controls, signifying the importance of pegylation in this complex tissue regeneration. These results demonstrate a simple and scalable biologic delivery technology alternative to tissue-derived grafts for soft tissue repair.

Regenerative engineering: a review of recent advances and future directions.

Regenerative engineering is defined as the convergence of the disciplines of advanced material science, stem cell science, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems. It is an expansion of tissue engineering, which was first developed as a method of repair and restoration of human tissue. In the past three decades, advances in regenerative engineering have made it possible to treat a variety of clinical challenges by utilizing cutting-edge technology currently available to harness the body's healing and regenerative abilities. The emergence of new information in developmental biology, stem cell science, advanced material science and nanotechnology have provided promising concepts and approaches to regenerate complex tissues and structures.

The Mechanism of Metallosis After Total Hip Arthroplasty.

Metallosis is defined as the accumulation and deposition of metallic particles secondary to abnormal wear from prosthetic implants that may be visualized as abnormal macroscopic staining of periprosthetic soft tissues. This phenomenon occurs secondary to the release of metal ions and particles from metal-on-metal hip implants in patients with end-stage osteoarthritis. Ions and particles shed from implants can lead to local inflammation of surrounding tissue and less commonly, very rare systemic manifestations may occur in various organ systems. With the incidence of total hip arthroplasty increasing as well as rates of revisions due to prosthesis failure from previous metal-on-metal implants, metallosis has become an important area of research. Bodily fluids are electrochemically active and react with biomedical implants. Particles, especially cobalt and chromium, are released from implants as they abrade against one another into the surrounding tissues. The body's normal defense mechanism becomes activated, which can elicit a cascade of events, leading to inflammation of the immediate surrounding tissues and eventually implant failure. In this review, various mechanisms of metallosis are explored. Focus was placed on the atomic and molecular makeup of medical implants, the component/surgical associated factors, cellular responses, wear, tribocorrosion, joint loading, and fluid pressure associated with implantation. Current treatment guidelines for failed implants include revision surgery. An alternative treatment could be chelation therapy, which may drive future studies.

The Role of Body Mass Index in Perioperative Complications Among Patients Undergoing Total Knee Arthroplasty.

Obesity is a modifiable risk factor that causes mechanical forces to be exerted within the joints, further contributing to the debilitating effects of osteoarthritis. Total Knee Arthroplasty (TKA) can have a profound impact on patients with osteoarthritis, providing them with increased quality of life, improved function, reduction of pain, while simultaneously preventing the development of additional comorbidities. Although there is inconclusive evidence that increased body mass index (BMI) is linked to increased perioperative complications among TKA patients, recent studies suggest this association exists. The aim of this study is to provide conclusive data on the effects of BMI on perioperative complications in TKA using the national risk-adjusted database, ACS-NSQIP. Our study demonstrated that there was a correlation between increased BMI and perioperative outcomes, particularly with surgical site infections, renal, and respiratory complications. (Journal of Surgical Orthopaedic Advances 29(4):205-208, 2020).

Combined effects of troglitazone and muscle contraction on insulin sensitization in Balb-c mouse muscle.

Thiazolidinediones, represented by troglitazone, are insulin-sensitizing agents with proven efficacy for the treatment of type 2 diabetes. Exercise is also recommended for patients with type 2 diabetes because it both stimulates glucose uptake directly and it increases insulin sensitivity following exercise. The purpose of this study was to investigate the effects of troglitazone combined with exercise on 2-deoxyglucose (2DG) uptake in both the epitrochlearis and soleus muscle of Balb-c mice. Acute, 1-h treatment with troglitazone (10 or 20 microM), in the presence or absence of insulin, had no effect on 2DG uptake in either muscle. Chronic treatment with troglitazone by feeding enhanced the insulin sensitivity and responsiveness of 2DG uptake primarily in the epitrochlearis. Direct electrical stimulation of in situ muscle was used to model exercise while the contralateral muscle was used as the unexercised control. This model mimicked exercise in that glycogen was depleted, immediate 2DG uptake was enhanced, and there was a post-exercise increase in insulin sensitivity. Troglitazone feeding had no effect on 2DG uptake in the soleus when measured immediately after electrical stimultion. However, 2DG uptake in the unstimulated epitrochlearis from troglitazone-fed mice was elevated when measured immediately after removal such that no additional effects of the electrical stimulation were measured. We found that the insulin-sensitizing effect of troglitazone was not additive to the insulin-sensitizing effect of exercise, which suggests that troglitazone and exercise share similar pathways. A unique finding in this study was the differential response to troglitazone between the epitrochlearis (fast twitch) and the soleus (slow twitch) muscle types. Possible mechanisms are discussed.