Therapeutic Implants: Mechanobiologic Enhancement of Osteogenic, Angiogenic, and Myogenic Responses in Human Mesenchymal Stem Cells on 3D-Printed Titanium Truss.

This study investigates the effect of mechanotransduction on human mesenchymal stem cells (hMSCs) attached to structural elements of an implant, specifically a titanium truss element. It is found that surface features generated by 3D printing technology promote osteogenic activity, comparable to conventional treatments such as acid etching. Cell morphology and differentiation are evaluated using test coupons with either smooth or rough surface features.

Multi-Scale Analysis of Regional Pathology in the Human Trapezium During Osteoarthritis Progression.

Trapeziometacarpal (TMC) osteoarthritis (OA) is a prevalent condition that significantly impacts hand function and quality of life. In this study we sought to close gaps in knowledge related to the initiation and progression of TMC OA on the tissue scale by evaluating the morphology and gross appearance, wear patterns, mechanical properties, subchondral bone morphology, and histological characteristics of the tissue across a spectrum of disease severity and by correlating each of these properties to the clinically assessed radiographic grade. Thirty-two cadaveric hand specimens were first assigned a radiographic grade by three hand surgeons.

Evaluation of surgical fixation methods for the implantation of melt electrowriting-reinforced hyaluronic acid hydrogel composites in porcine cartilage defects.

The surgical repair of articular cartilage remains an ongoing challenge in orthopedics. Tissue engineering is a promising approach to treat cartilage defects; however, scaffolds must (i) possess the requisite material properties to support neocartilage formation, (ii) exhibit sufficient mechanical integrity for handling during implantation, and (iii) be reliably fixed within cartilage defects during surgery. In this study, we demonstrate the reinforcement of soft norbornene-modified hyaluronic acid (NorHA) hydrogels via the melt electrowriting (MEW) of polycaprolactone to fabricate composite scaffolds that support encapsulated porcine mesenchymal stromal cell (pMSC, three donors) chondrogenesis and cartilage formation and exhibit mechanical properties suitable for handling during implantation.

Linguistic Analysis Identifies Emergent Biomaterial Fabrication Trends for Orthopaedic Applications.

The expanse of publications in tissue engineering (TE) and orthopedic TE (OTE) over the past 20 years presents an opportunity to probe emergent trends in the field to better guide future technologies that can make an impact on musculoskeletal therapies. Leveraging this trove of knowledge, a hierarchical systematic search method and trend analysis using connected network mapping of key terms is developed. Within discrete time intervals, an accelerated publication rate for anatomic orthopedic tissue engineering (AOTE) of osteochondral defects, tendons, menisci, and entheses is identified.

Gravity-based patterning of osteogenic factors to preserve bone structure after osteochondral injury in a large animal model.

Chondral and osteochondral repair strategies are limited by adverse bony changes that occur after injury. Bone resorption can cause entire scaffolds, engineered tissues, or even endogenous repair tissues to subside below the cartilage surface. To address this translational issue, we fabricated thick-shelled poly(D,L-lactide-co-glycolide) microcapsules containing the pro-osteogenic agents triiodothyronine and-glycerophosphate, and delivered these microcapsules in a large animal model of osteochondral injury to preserve bone structure.

Six-Month Outcomes of Clinically Relevant Meniscal Injury in a Large-Animal Model.

Background: The corrective procedures for meniscal injury are dependent on tear type, severity, and location. Vertical longitudinal tears are common in young and active individuals, but their natural progression and impact on osteoarthritis (OA) development are not known. Root tears are challenging and they often indicate poor outcomes, although the timing and mechanisms of initiation of joint dysfunction are poorly understood, particularly in large-animal and human models.

Fabrication of MSC-laden composites of hyaluronic acid hydrogels reinforced with MEW scaffolds for cartilage repair.

Hydrogels are of interest in cartilage tissue engineering due to their ability to support the encapsulation and chondrogenesis of mesenchymal stromal cells (MSCs). However, features such as hydrogel crosslink density, which can influence nutrient transport, nascent matrix distribution, and the stability of constructs during and after implantation must be considered in hydrogel design. Here, we first demonstrate that more loosely crosslinked (i.

The porcine accessory carpal bone as a model for biologic joint replacement for trapeziometacarpal osteoarthritis.

Given its complex shape and relatively small size, the trapezium surface at the trapeziometacarpal (TMC) joint is a particularly attractive target for anatomic biologic joint resurfacing, especially given its propensity to develop osteoarthritis, and the limited and sub-optimal treatment options available. For this to advance to clinical translation, however, an appropriate large animal model is required. In this study, we explored the porcine accessory carpal bone (ACB) as a model for the human trapezium.

Fabrication and maturation of integrated biphasic anatomic mesenchymal stromal cell-laden composite scaffolds for osteochondral repair and joint resurfacing.

Articular cartilage injury can lead to joint-wide erosion and the early onset of osteoarthritis. To address this, we recently developed a rapid fabrication method to produce patient-specific engineered cartilage tissues to replace an entire articular surface. Here, we extended that work by coupling a mesenchymal stromal cell-laden hydrogel (methacrylated hyaluronic acid) with the porous polycaprolactone (PCL) bone integrating phase and assessed the composition and mechanical performance of these constructs over time.

Optimized Media Volumes Enable Homogeneous Growth of Mesenchymal Stem Cell-Based Engineered Cartilage Constructs.

Despite marked advances in the field of cartilage tissue engineering, it remains a challenge to engineer cartilage constructs with homogeneous properties. Moreover, for engineered cartilage to make it to the clinic, this homogeneous growth must occur in a time-efficient manner. In this study we investigated the potential of increased media volume to expedite the homogeneous maturation of mesenchymal stem cell (MSC) laden engineered constructs over time .

Transection of the medial meniscus anterior horn results in cartilage degeneration and meniscus remodeling in a large animal model.

The meniscus plays a central load-bearing role in the knee joint. Unfortunately, meniscus injury is common and can lead to joint degeneration and osteoarthritis (OA). In small animal models, progressive degenerative changes occur with the unloading of the meniscus via destabilization of the medial meniscus (DMM).

Measuring clinically relevant knee motion with a self-calibrated wearable sensor.

Low-cost sensors provide a unique opportunity to continuously monitor patient progress during rehabilitation; however, these sensors have yet to demonstrate the fidelity and lack the calibration paradigms necessary to be viable tools for clinical research. The purpose of this study was to validate a low-cost wearable sensor that accurately measured peak knee extension during clinical exercises and needed no additional equipment for calibration. Sagittal plane knee motion was quantified using a 9-axis motion sensor and directly compared to motion capture data.

A Wearable Magnet-Based System to Assess Activity and Joint Flexion in Humans and Large Animals.

Functional outcomes, such as joint flexion and gait, are important indicators of efficacy in musculoskeletal research. Current technologies that objectively assess these parameters, including visual tracking systems and force plates, are challenging to deploy in long-term translational and clinical studies. To that end, we developed a wearable device that measures both physical activity and joint flexion using a single integrated sensor and magnet system, and hypothesized that it could evaluate post-operative functional recovery in an unsupervised setting.

Biphasic Finite Element Modeling Reconciles Mechanical Properties of Tissue-Engineered Cartilage Constructs Across Testing Platforms.

Cartilage tissue engineering is emerging as a promising treatment for osteoarthritis, and the field has progressed toward utilizing large animal models for proof of concept and preclinical studies. Mechanical testing of the regenerative tissue is an essential outcome for functional evaluation. However, testing modalities and constitutive frameworks used to evaluate in vitro grown samples differ substantially from those used to evaluate in vivo derived samples.

Anatomic Mesenchymal Stem Cell-Based Engineered Cartilage Constructs for Biologic Total Joint Replacement.

Cartilage has a poor healing response, and few viable options exist for repair of extensive damage. Hyaluronic acid (HA) hydrogels seeded with mesenchymal stem cells (MSCs) polymerized through UV crosslinking can generate functional tissue, but this crosslinking is not compatible with indirect rapid prototyping utilizing opaque anatomic molds. Methacrylate-modified polymers can also be chemically crosslinked in a cytocompatible manner using ammonium persulfate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED).