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Osteochondral defects pose a significant challenge in clinical practice, leading to increased medical care, diminished quality of life for patients, and elevated economic burden. The restoration of osteochondral defects, particularly in cartilage, is limited by its finite repair capacity and complex architecture. Treatment based on regenerative therapies acclaims the favorable alternative to contemporary procedures. Studies reveal that engineered biomaterials hold the significant importance in stimulating tissue repair with minimal cost and risks. In this study, a porous composite scaffold is developed, where host cells infiltrate and create the microenvironment for cellular adhesion and enhanced differentiation. Thus, a composite scaffold composed of natural glycosaminoglycan hyaluronic acid (HA), the protein component fibrin, bioceramic nanohydroxyapatite (nHAP), and graphene oxide (GO) is fabricated. Scanning electron microscopy observation and physiochemical characterization reveal an interconnected pore structure, optimum swelling potential, high porosity (80.14%), controlled biodegradation, high mechanical properties, and mineralization. Evaluation of scaffold's biocompatibility using osteoblast - like MG-63 cells - shows adequate viability, cell adhesion, and osteoinductive potential. The upregulated expressions of osteogenic and chondrogenic genes OCN, ALP, COL1A1, ACAN, SOX9, and COL2A1 promote mineralization and extracellular matrix formation. These findings suggest that the composite scaffold HA-GO-F-nHAP exhibits promising potential for osteochondral repair. [ABSTRACT FROM AUTHOR]

Hydrophilic bone morphogenetic protein 2 (BMP2) is easily degraded and difficult to load onto hydrophobic carrier materials, which limits the application of polyester materials in bone tissue engineering. Based on soybean-lecithin as an adjuvant biosurfactant, we designed a novel cell-free-scaffold of polymer of poly(ε-caprolactone) and poly(lactide-co-glycolide)-co-polyetherimide with abundant entrapped and continuously released BMP2 for in vivo stem cell-capture and in situ osteogenic induction, avoiding the use of exogenous cells. The optimized bioactive osteo-polyester scaffold (BOPSC), i.e. SBMP-10SC, had a high BMP2 entrapment efficiency of 95.35%. Due to its higher porosity of 83.42%, higher water uptake ratio of 850%, and sustained BMP2 release with polymer degradation, BOPSCs were demonstrated to support excellent in vitro capture, proliferation, migration and osteogenic differentiation of mouse adipose derived mesenchymal stem cells (mADSCs), and performed much better than traditional BMP-10SCs with unmodified BMP2 and single polyester scaffolds (10SCs). Furthermore, in vivo capture and migration of stem cells and differentiation into osteoblasts was observed in mice implanted with BOPSCs without exogenous cells, which enabled allogeneic bone formation with a high bone mineral density and ratios of new bone volume to existing tissue volume after 6 months. The BOPSC is an advanced 3D cell-free platform with sustained BMP2 supply for in situ stem cell capture and osteoinduction in bone tissue engineering with potential for clinical translation.

Background: The aim of this study was to evaluate the clinical and radiologic results of 2 different scaffolds with hyaluronan or chitosan-based structure used in the treatment of talus osteochondral lesions. Methods: Eighty-one patients who underwent chondral lesion repair with hyaluronan (n = 42) or chitosan-based (n = 39) scaffold were included. American Orthopaedic Foot & Ankle Society (AOFAS) and visual analog scale (VAS) scores were evaluated within and between groups preoperatively and at the 3rd, 12th, and 24th month postoperatively. In all patients, magnetic resonance imaging was performed between the 12 and 18th month postoperatively and compared with magnetic resonance observation of cartilage repair tissue (MOCART) scoring. Results: Within-group evaluations revealed significant improvements in AOFAS and VAS scores at postoperative 3 and 12 months. The postoperative 24th-month results of AOFAS scores in any group did not differ significantly from the 12th-month results. There was no significant difference between the groups in comparison of AOFAS, VAS, and MOCART scores at any time period. Conclusion: Both scaffolds were found to be effective in cartilage healing but had no clinical or radiologic superiority to each other. This is the first study to compare the use of different cell-free scaffold types in osteochondral defects of the talus. Level of Evidence: Level III, retrospective comparative study. [ABSTRACT FROM AUTHOR]

To promote bone healing, bone repair biomaterials are increasingly designed to incorporate growth factors. However, the impact of matrix mechanics of cell-free scaffold independent of microstructure on the osteogenic differentiation of endogenous osteoprogenitor cells orchestrating bone repair and regeneration remains not to be fully understood. In our recent study, three-dimensional (3D) scaffolds with different stiffness but same microstructure have been successfully fabricated by coating decellularized bone with collagen/hydroxyapatite (HA) mixture with different collagen rations. It has been demonstrated that the scaffold with optimal stiffness can induce the osteogenic differentiation of MSCs in vitro and in the subcutaneous tissue. The present in vivo study further investigated the repair efficiency of these scaffolds in a rabbit radius with a critical-sized segmental defect model and its potential mechanism. Micro-computed tomography (μ-CT), X-ray and histological analysis were carried out to evaluate the repair capacity of these scaffolds. The results demonstrated that the cell-free scaffold with optimal stiffness incorporation of endogenous osteoprogenitor cells significantly promoted the repair and reconstruction quality of mass bone defect. One of the crucial mechanisms was that hypoxia and stromal cell-derived factor-1α (SDF-1α) mediated mesenchymal stem cells (MSCs) migration by which matrix mechanics exerted influence on bone fracture healing. These findings suggested that only modulating the matrix stiffness of cell-free scaffold can be one of the most attractive strategies for promoting the progression of bone healing. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 833-841, 2016. [ABSTRACT FROM AUTHOR]

Background: Chondral defects of the articular surface are a common condition that can lead to osteoarthritis if not treated. Therapy of this condition is a topic of constant debate and a variety of chondral repair strategies are currently used. One strategy involves implantation of a cell-free matrix of type I collagen (COL1), to provide a scaffold for chondrocyte migration and proliferation and extracellular matrix production. Although several studies have suggested that chondrocytes can move, to the best of our knowledge there is still no proof of chondrocyte occurrence in a former cell-free scaffold for articular cartilage repair in humans. Case presentation: An 18-year-old male patient underwent arthroscopic surgery of the knee for patellar instability and a chondral defect of the femoral condyle. Clinical outcome scores were recorded pre-operatively, after 6 weeks and after 6, 12, 24 and 36 months. MRI was recorded after 6 weeks and after 6, 12, 24 and 36 months postoperatively. At 42 months after implantation of a cell-free type I collagen matrix and reconstruction of the medial patellofemoral ligament, the patient was again treated arthroscopically for a tear of the medial meniscus of the same knee. A biopsy of the previous chondral defect was taken during arthroscopy for histological examination. Conclusion: In addition to good clinical and radiological results reported for cell-free scaffolds for cartilage repair in several other studies, transformation of the scaffold could be observed during re-arthroscopy for the meniscal tear. Histological examination of the specimen revealed articular cartilage with vital chondrocytes and a strong staining reaction for type II collagen (COL II), but no reaction for type I collagen staining. This might indicate a complete transformation of the scaffold and supports the theory that cell free scaffolds could support cell migration. Although the cell source remains unclear, migrating chondrocytes from the periphery remain a possibility [ABSTRACT FROM AUTHOR]

Purpose: To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide) scaffold. Methods: By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water-dioxane-PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT-PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O'Driscoll score. Results: In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells. Conclusion: The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide scaffold with cells. [ABSTRACT FROM AUTHOR]

Whereas the conventional tissue engineering strategy involves the use of scaffolds combined with appropriate cell types to restore normal functions, the concept of in situ tissue regeneration uses host responses to a target-specific scaffold to mobilize host cells to a site of injury without the need for cell seeding. For this purpose, local delivery of bioactive molecules from scaffolds has been generally used. However, this approach has limited stem cell recruitment into the implants. Thus, we developed a combination of systemic delivery of substance P (SP) and local release of stromal-derived factor-1 (SDF-1) from an implant. In this study, we examined whether this combined system would significantly enhance recruitment of host stem cells into the implants. Flow cytometry and immunohistochemistry for CD29/CD45, CD146/-smooth muscle actin, and c-kit demonstrated that this system significantly increased the number of stem cell-like cells within the implants when compared with other systems. In vitro culture of the cells that had infiltrated into the scaffolds from the combined system confirmed that host stem cells were recruited into these implants and indicated that they were capable of differentiation into multiple lineages. These results indicate that this combined system may lead to more efficient tissue regeneration. [ABSTRACT FROM AUTHOR]

Tendons are subjected to high strength dynamic mechanical forces in vivo. Mechanical strength is an essential requirement for tendon scaffold materials. A composite scaffold was used in this study to provide mechanical strength, which was composed of an inter part of nonwoven polyglycolic acid (PGA) fibers and an outer part of the net knitted with PGA and polylactic acid (PLA) fibers in a ratio of 4:2. This study compared three different approaches for in vivo tendon engineering, that is, cell-free scaffold and allogeneic and autologous cell seeded scaffolds, using a rabbit Achilles tendon repair model. Dermal fibroblasts were, respectively, isolated from the dermis of regular rabbits or green fluorescence protein transgenic rabbits as the autologous and the allogeneic cell sources, respectively. The cell scaffolds and cell-free scaffolds were implanted to bridge a partial segmental defect of rabbit Achilles tendon. The engineered tendons were harvested at 7 and 13 months postsurgery for various examinations. The results showed that all three groups could achieve in vivo tendon regeneration similarly with slightly better tissue formation in autologous group than in other two groups, including better scaffold degradation and relatively thicker collagen fibrils. There were no statistically significant differences in mechanical parameters among three groups. This work demonstrated that allogeneic fibroblasts and scaffold alone are likely to be used for tendon tissue engineering.