Background: Autologous platelet-rich plasma (PRP) application appears to improve tendon healing in traumatic tendon injuries, but basic knowledge of how PRP promotes tendon repair is needed. Hypothesis: Platelet-rich plasma has a positive effect on cell proliferation and collagen production and induces the production of matrix-degrading enzymes and endogenous growth factors by human tenocytes. Study Design: Controlled laboratory study. Methods: Human tenocytes were cultured 14 days in 2% fetal calf serum medium complemented with 0%, 10%, or 20% vol/vol platelet-rich clot releasate ([PRCR] the active releasate of PRP) or platelet-poor clot releasate (PPCR). At day 4,7, and 14, cell amount, total collagen, and gene expression of collagen Iα1 (COL1) and Mod (COL3), matrix metalloproteinases ([MMPs] MMP1, MMP3, and MMP13), vascular endothelial-derived growth factor (VEGF)-A, and transforming growth factor (TGF)-β1 were analyzed. Results: Platelet numbers in PRP increased to 2.55 times baseline. Growth-factor concentrations of VEGF and platelet-derived growth factor (PDGF)-BB were higher in PRCR than PPCR. Both PRCR and PPCR increased cell number and total collagen, whereas they decreased gene expression of COL1 and COL3 without affecting the COL3/COL1 ratio. PRCR, but not PPCR, showed upregulation of MMP1 and MMP3 expression. Matrix metalloproteinase 13 expression was not altered by either treatment. PRCR increased VEGF-A expression at all time points and TGF-β1 expression at day 4. Conclusion: In human tenocyte cultures, PRCR, but also PPCR, stimulates cell proliferation and total collagen production. PRCR, but not PPCR, slightly increases the expression of matrix-degrading enzymes and endogenous growth factors. Clinical Relevance: In vivo use of PRP, but also of PPP to a certain extent, in tendon injuries might accelerate the catabolic demarcation of traumatically injured tendon matrices and promote angiogenesis and formation of a fibrovascular callus. Whether this will also be beneficial for degenerative tendinopathies remains to be elucidated.

Bone marrow–derived mesenchymal stem cells (MSCs) have demonstrated potential for regenerative medicine strategies. Knowledge of the way these cells respond to their environment in in vitro culture and after implantation in vivo is crucial for successful therapy. Oxygen tension plays a pivotal role in both situations. In vivo , a hypoxic environment can lead to apoptosis, but hypoxic preconditioning of MSCs and overexpression of prosurvival genes like Akt can reduce hypoxia-induced cell death. In cell culture, hypoxia can increase proliferation rates and enhance differentiation along the different mesenchymal lineages. Hypoxia also modulates the paracrine activity of MSCs, causing upregulation of various secretable factors, among which are important angiogenic factors such as vascular endothelial growth factor and interleukin-6 ( IL6 ). Finally, hypoxia plays an important role in mobilization and homing of MSCs, primarily by its ability to induce stromal cell–derived factor-1 expression along with its receptor CXCR4 . This article reviews the current literature on the effects of hypoxia on MSCs and aims to elucidate its potential role in regenerative medicine strategies.

Porous titanium scaffolds have good mechanical properties that make them an interesting bone substitute material for large bone defects. These scaffolds can be produced with selective laser melting, which has the advantage of tailoring the structure's architecture. Reducing the strut size reduces the stiffness of the structure and may have a positive effect on bone formation. Two scaffolds with struts of 120‐µm (titanium‐120) or 230‐µm (titanium‐230) were studied in a load‐bearing critical femoral bone defect in rats. The defect was stabilized with an internal plate and treated with titanium‐120, titanium‐230, or left empty. In vivo micro‐CT scans at 4, 8, and 12 weeks showed more bone in the defects treated with scaffolds. Finally, 18.4 ± 7.1 mm³ (titanium‐120, p = 0.015) and 18.7 ± 8.0 mm³ (titanium‐230, p = 0.012) of bone was formed in those defects, significantly more than in the empty defects (5.8 ± 5.1 mm³). Bending tests on the excised femurs after 12 weeks showed that the fusion strength reached 62% (titanium‐120) and 45% (titanium‐230) of the intact contralateral femurs, but there was no significant difference between the two scaffolds. This study showed that in addition to adequate mechanical support, porous titanium scaffolds facilitate bone formation, which results in high mechanical integrity of the treated large bone defects. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 792–799, 2013

Partially due to the unavailability of ideal bone substitutes, the treatment of large bony defects remains one of the most important challenges of orthopedic surgery. Additively manufactured (AM) biodegradable porous metals that have emerged since 2018 provide unprecedented opportunities for fulfilling the requirements of an ideal bone implant. First, the multi-scale geometry of these implants can be customized to mimic the human bone in terms of both micro-architecture and mechanical properties. Second, a porous structure with interconnected pores possesses a large surface area, which is favorable for the adhesion and proliferation of cells and, thus, bony ingrowth. Finally, the freeform geometrical design of such biomaterials could be exploited to adjust their biodegradation behavior so as to maintain the structural integrity of the implant during the healing process while ensuring that the implant disappears afterwards, paving the way for full bone regeneration. While the AM biodegradable porous metals that have been studied so far have shown many unique properties as compared to their solid counterparts, the unprecedented degree of flexibility in their geometrical design has not yet been fully exploited to optimize their properties and performance. In order to develop the ideal bone implants, it is important to take advantage of the full potential of AM biodegradable porous metals through detailed and systematic study on their biodegradation behavior, mechanical properties, biocompatibility, and bone regeneration performance. This review paper presents the state of the art in AM biodegradable porous metals and is focused on the effects of material type, processing, geometrical design, and post-AM treatments on the mechanical properties, biodegradation behavior, in vitro biocompatibility, and in vivo bone regeneration performance of AM porous Mg, Fe, and Zn as well as their alloys. We also identify a number of knowledge gaps and the challenges encountered in adopting AM biodegradable porous metals for orthopedic applications and suggest some promising areas for future research.