Perspective: Challenges Presented for Regeneration of Heterogeneous Musculoskeletal Tissues that Normally Develop in Unique Biomechanical Environments

Abstract

Perspective: Musculoskeletal (MSK) tissues such as articular cartilage, menisci, tendons, and ligaments are often injured throughout life as a consequence of accidents. Joints can also become compromised due to the presence of inflammatory diseases such as rheumatoid arthritis. Thus, there is a need to develop regenerative approaches to address such injuries to heterogeneous tissues and ones that occur in heterogeneous environments. Such injuries can compromise both the biomechanical integrity and functional capability of these tissues. Thus, there are several challenges to overcome in order to enhance success of efforts to repair and regenerate damaged MSK tissues.Challenges: 1. MSK tissues arise during development in very different biological and biomechanical environments. These early tissues serve as a template to address the biomechanical requirements evolving during growth and maturation towards skeletal maturity. Many of these tissues are heterogeneous and have transition points in their matrix. The heterogeneity of environments thus presents a challenge to replicate with regard to both the cells and the ECM. 2. Growth and maturation of musculoskeletal tissues occurs in the presence of anabolic mediators such as growth hormone and the IGF-1 family of proteins which decline with age and are low when there is a greater need for the repair and regeneration of injured or damaged tissues with advancing age. Thus, there is the challenge of re-creating an anabolic environment to enhance incorporation of implanted constructs. 3. The environments associated with injury or chronic degeneration of tissues are often catabolic or inflammatory. Thus, there is the challenge of creating a more favorable in vivo environment to facilitate the successful implantation of in vitro engineered constructs to regenerate damaged tissues.Conclusions: The goal of regenerating MSK tissues has to be to meet not only the biological requirements (components and structure) but also the heterogeneity of function (biomechanics) in vivo. Furthermore, for many of these tissues, the regenerative approach has to overcome the site of injury being influenced by catabolism/inflammation. Attempts to date using both endogenous cells, exogenous cells and scaffolds of various types have been limited in achieving long term outcomes, but progress is being made.

Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System

“…It is clear that structure and function relationships are critical to the performance of functional activities. The prevailing wisdom is that engineering of artificial MSK tissues should lead to a construct that mimics the original that developed in utero and during growth and maturation, discussed in [ 75 ].…”

“…As these studies were focused on limited defects in the articular cartilage, there was likely sufficient residual cartilage present to serve as a template and/or provide local factors required to maintain cartilage which were active when provided the right cell/matrix construct. It remains to be determined in detail how a local mechanical environment contributes to the development of articular cartilage, menisci, or intravertebral discs in conjunction with biological cues, discussed in [ 75 ].…”

One of the Primary Functions of Tissue-Resident Pluripotent Pericytes Cells May Be to Regulate Normal Organ Growth and Maturation: Implications for Attempts to Repair Tissues Later in Life

“…Many of these issues have been reviewed recently by Hart [ 51 ]. Such approaches for the repair and regeneration of tissues/organs damaged by disease are complicated by the presence of an inflammation that can compromise the functionality of the cells [ 88 , 103 ] or the effectiveness of the effort [ 110 ]. However, some loss of these tissue-specific and more general pluripotent cells (i.e., in BM, SF, blood) occurs with aging, and no obvious disease association.…”

Preparation and Characterization of Tilapia Collagen-Thermoplastic Polyurethane Composite Nanofiber Membranes

“…Cell proliferation (%) = A s − A 0 /A c − A 0 × 100%, (1) where A c , A s , and A b were the absorbance at 450 nm of the control group, the experimental group, and the blank group, respectively.…”

“…As accidents and diseases lead to tissue damage, natural tissue repair materials are a popular area of research [ 1 ]. Collagen has good biocompatibility and can promote cell proliferation and differentiation [ 2 ].…”