Architectured materials offer tailored mechanical properties but are limited in engineering applications due to challenges in maintaining toughness across their attachments. The enthesis connects tendon and bone, two vastly different architectured materials, and exhibits toughness across a wide range of loadings. Understanding the mechanisms by which this is achieved could inform the development of engineered attachments. Integrating experiments, simulations, and previously unexplored imaging that enabled simultaneous observation of mineralized and unmineralized tissues, we identified putative mechanisms of enthesis toughening in a mouse model and then manipulated these mechanisms via in vivo control of mineralization and architecture. Imaging uncovered a fibrous architecture within the enthesis that controls trade-offs between strength and toughness. In vivo models of pathology revealed architectural adaptations that optimize these trade-offs through cross-scale mechanisms including nanoscale protein denaturation, milliscale load-sharing, and macroscale energy absorption. Results suggest strategies for optimizing architecture for tough bimaterial attachments in medicine and engineering.

The adaptive response of bones to mechanical loading is essential for musculoskeletal development. Despite the importance of collagen in bone mineralization, little is known about how cyclic strain influences physicochemical...

Mechanical loads from physiologic activities such as walking and running generate bioelectricity in bones. By mimicking bioelectricity, external electrical stimulations have also been used therapeutically to stimulate bone-forming cells and, thus, to promote bone regeneration. However, little is known about the physicochemical mechanism(s) by which electrical stimulations drives calcium phosphate mineralization of collagen. Here, we showed that, during in vitro collagen mineralization in the absence of cells, application of pulsed electrical stimulation significantly enhanced the transport of ionic body fluid components through a micrometer-scale channel (∼100–200 μm gap space between the inner surfaces of tube-like collagen scaffolds and a cathode placed inside the collagen scaffolds). The enhanced transport of ionic precursors increased diffusion of the charged precursors from the channel to the inner collagen surface, where bone mineralization was otherwise restricted. The results indicate that pulsed electrical signals can locally accelerate the nucleation of calcium phosphate nanocrystals in or on collagen, allowing us to better control the spatial distribution of the nanocrystals at the microscale. The findings from this study provide insights into the utilization of electrical stimulation for applications such as facilitating bone-fracture healing and designing better bone-specific biomaterials.

Architectured materials offer tailored mechanical properties but are limited in engineering applications due to challenges in maintaining toughness across their attachments. The enthesis connects tendon and bone, two vastly different architectured materials, and exhibits toughness across a wide range of loadings. Understanding the mechanisms by which this is achieved could inform the development of engineered attachments. Integrating experiments, simulations, and novel imaging that enabled simultaneous observation of mineralized and unmineralized tissues, we identified putative mechanisms of enthesis toughening in a mouse model and then manipulated these mechanisms via in vivo control of mineralization and architecture. Imaging uncovered a fibrous architecture within the enthesis that controls trade-offs between strength and toughness. In vivo models of pathology revealed architectural adaptations that optimize these trade-offs through cross-scale mechanisms including nanoscale protein denaturation, milliscale load-sharing, and macroscale energy absorption. Results suggest strategies for optimizing architecture for tough bimaterial attachments in medicine and engineering.

Clinical Burden of Rotator Cuff DiseaseThe rotator cuff comprises the set of tendons that stabilize the glenohumeral joint (Fig. 1). Rotator cuff degeneration is a common pathology that results in pain, disability, lost productivity, and limitations to recreational activities 1 . Rotator cuff pathology carries a large clinical burden: in the United States, >4.5 million individuals suffer from rotator cuff tendinopathy, and >17 million individuals have a rotator cuff injury 2 . The incidence of rotator cuff pathology is high, with approximately 50% of the population who are ‡65 years of age experiencing a rotator cuff tear [3][4][5] . These injuries result in >500,000 rotator cuff repairs annually in the U.S. 1,3,[6][7][8] . Despite being one of the most common orthopaedic shoulder procedures, outcomes after rotator cuff repair are unpredictable and depend on factors such as tendon length, bone quality, and muscle quality, with failure rates ranging from 20% to 94% [9][10][11][12] . Repairs are typically performed arthroscopically and rely on sutures that are passed through the torn cuff tendon(s) and fixed to the humerus via suture anchors 13 . This serves to reapproximate the tendon to its native footprint in order to promote healing of the tendon to the bone. When the tendon is deemed irreparable due to irreversible degeneration and/or retraction, reconstruction may be recommended 14 .Before completing either repair or reconstruction, subacromial decompression often is performed (Fig. 1). This includes broadening of the subacromial space by resecting the subacromial bursa (subsequently referred to as the "bursa"), the coracoacromial ligament, and the inferior side of the acromion to varying degrees depending on the diagnosis and clinician preference 15,16 . Decompression is indicated in shoulders with or without refractory subacromial bursitis or subacromial impingement because it also improves visualization of the rotator cuff repair site 15,17,18 . However, decompression that includes subacromial bursectomy with acromioplasty has recently been shown to have no benefit over bursectomy alone, calling into question the necessity of acromioplasty 19 . Similarly, a systematic review of subacromial impingement treatment strategies revealed that bursectomy without acromioplasty is sufficient for treating symptoms of impingement 20 . Interestingly, subacromial decompression has been shown to impart no clinically meaningful improvement in patient outcomes 21,22 . Bursectomy has even been shown to be less effective in patients with subacromial pain syndrome if they also had degeneration in the shoulder 23 . Despite the judicious use of bursectomy, the impact that this procedure has on tendon-healing has not been established. Hence, investigating the involvement of the bursa in the tendon-healing response is critical for defining best surgical repair practices. Historical PerspectiveThe bursa was first discussed in the literature in 1906 when Codman reported its involvement in "stiff and painful shoulders." 24 The bursa...