Advanced age causes skeletal muscle to undergo deleterious changes including muscle atrophy, fast-to-slow muscle fiber transition, and an increase in collagenous material that culminates in the age-dependent muscle wasting disease known as sarcopenia. Advanced glycation end-products (AGEs) non-enzymatically accumulate on the muscular collagens in old age via the Maillard reaction, potentiating the accumulation of intramuscular collagen and stiffening the microenvironment through collagen cross-linking. This review contextualizes known aspects of skeletal muscle extracellular matrix (ECM) aging, especially the role of collagens and AGE cross-linking, and underpins the motor nerve’s role in this aging process. Specific directions for future research are also discussed, with the understudied role of AGEs in skeletal muscle aging highlighted. Despite more than a half century of research, the role that intramuscular collagen aggregation and cross-linking plays in sarcopenia is well accepted yet not well integrated with current knowledge of AGE’s effects on muscle physiology. Furthermore, the possible impact that motor nerve aging has on intramuscular cross-linking and muscular AGE levels is posited.

Current strategies to treat volumetric muscle loss use primarily pedicle or free muscle transfers, but these grafts fail to adequately regenerate functional tissue. Decellularized soft tissue grafts possess physical and chemical cues to promote muscle regeneration, suggesting their potential for use in large muscle defects. In this study, we developed a decellularized muscle matrix (DMM) graft using rat gastrocnemius. Anisotropy and chemical components of the extracellular matrix were retained, including laminin, fibronectin, and collagen. We compared the ability of DMM, autologous muscle grafts (clinical standard), and type I collagen plugs (negative control) to support muscle regeneration. DMM supported regeneration over a 56-day period in 1 × 1 cm and 1.5 × 1 cm gastrocnemius defects in rats. Muscle function tests demonstrated improved muscle recovery in rats with DMM grafts when compared to collagen. Histological sections were assessed using morphometrics and immunostaining. DMM supported muscle regeneration with less fibrosis and more de novo neuromuscular receptors than either autograft or collagen. Overall, our results indicate that DMM may be used as a muscle replacement graft based on its ability to improve muscle function recovery, promote muscle regeneration, and support new neuromuscular junctions.

The use of metallic and polymeric materials for implants has been increasing over the past decade. This trend can be attributed to a variety of factors including a significant increase in basic science research focused on implant material characteristics and how various surface modifications may stimulate osseointegration and, ultimately, fusion. There are many interbody fusion devices and dental implants commercially available; however, detailed information about their surface properties, and the effects that various materials and surface modifications may have on osteogenesis, is lacking in the literature. While the concept of bone-implant osseointegration is a relatively recent addition to the spine fusion literature, there is a comparatively large body of literature related to dental implants. The purpose of this article is to summarize the science of surface modified bone-facing implants, focusing on biomimetic material chemistry and topography of titanium implants, to promote a better understanding of how these characteristics may impact bone formation and osseointegration. This manuscript has the following aspects: highlights the role of titanium and its alloys as potent osteoconductive bioactive materials; explores the importance of biomimetic surface topography at the macro-, micro- and nano-scale; summarizes how material surface design can influence osteogenesis and immune responses in vitro; focuses on the kinds of surface modifications that play a role in the process. Biomimetic surface modifications can be varied across many clinically available biomaterials, and the literature supports the hypothesis that those biomaterial surfaces that exhibit physical properties of bone resorption pits, such as roughness and complex hierarchical structures at the submicron and nanoscale, are more effective in supporting osteoblast differentiation in vitro and osteogenesis in vivo.

Implant osseointegration is reduced in patients with systemic conditions that compromise bone quality, such as osteoporosis, disuse syndrome, and type 2 diabetes. Studies using rodent models designed to mimic these compromised conditions demonstrated reduced bone-to-implant contact (BIC) or a decline in bone mineral density. These adverse effects are a consequence of disrupted intercellular communication. A variety of approaches have been developed to compensate for the altered microenvironment inherent in compromised conditions, including the use of biologics and implant surface modification. Chemical and physical modification of surface properties at the microscale, mesoscale, and nanoscale levels to closely resemble the surface topography of osteoclast resorption pits found in bone has proven to be a highly effective strategy for improving implant osseointegration. The addition of hydrophilicity to the surface further enhances osteoblast response at the bone-implant interface. These surface modifications, applied either alone or in combination, improve osseointegration by increasing proliferation and osteoblastic differentiation of osteoprogenitor cells and enhancing angiogenesis while modulating osteoclast activity to achieve net new bone formation, although the specific effects vary with surface treatment. In addition to direct effects on surface-attached cells, the communication between bone marrow stromal cells and immunomodulatory cells is sensitive to these surface properties. This article reports on the advances in titanium surface modifications, alone and in combination with novel therapeutics in animal models of human disease affecting bone quality. It offers clinically translatable perspectives for clinicians to consider when using different surface modification strategies to improve long-term implant performance in compromised patients. This review supports the use of surface modifications, bioactive coatings, and localized therapeutics as pragmatic approaches to improve BIC and enhance osteogenic activity from both structural and molecular standpoints.