Bioactive Stratified Polymer Ceramic-Hydrogel Scaffold for Integrative Osteochondral Repair

Abstract

Due to the intrinsically poor repair potential of articular cartilage, injuries to this soft tissue do not heal and require clinical intervention. Tissue engineered osteochondral grafts offer a promising alternative for cartilage repair. The functionality and integration potential of these grafts can be further improved by the regeneration of a stable calcified cartilage interface. This study focuses on the design and optimization of a stratified osteochondral graft with biomimetic multi-tissue regions, including a pre-designed and pre-integrated interface region. Specifically, the scaffold based on agarose hydrogel and composite microspheres of polylactide-co-glycolide (PLGA) and 45S5 bioactive glass (BG) was fabricated and optimized for chondrocyte density and microsphere composition. It was observed that the stratified scaffold supported the region-specific co-culture of chondrocytes and osteoblasts which can lead to the production of three distinct yet continuous regions of cartilage, calcified cartilage and bone-like matrices. Moreover, higher cell density enhanced chondrogenesis and improved graft mechanical property over time. The PLGA-BG phase promoted chondrocyte mineralization potential and is required for the formation of a calcified interface and bone regions on the osteochondral graft. These results demonstrate the potential of the stratified scaffold for integrative cartilage repair and future studies will focus on scaffold optimization and in vivo evaluations.

Hydrogels for the Repair of Articular Cartilage Defects

“…In freeswelling culture, increases in the density of chondrocytes seeded in agarose, alginate, and peptide gels over a range from 4 to 64 million cells/ml resulted in increases in ECM production and mechanical properties. 103,190,214,215 However, in the presence of mechanical loading, there were no differences in ECM accumulation and mechanical properties between hydrogels seeded with 20 or 60 million cells/mL. 190 Chondrogenic gene expression of MSCs co-encapsulated with TGFb1 was greater for a seeding density of 10 million cells/ mL than 20 million cells/mL in OPF hydrogels, possibly because of a higher dose of TGFb1 per cell.…”

Controlled Release Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

“…184 An obvious interesting approach for a multiple delivery system is the regeneration of orthopedic interfaces, such as ligament-to-bone, 185,186 tendon-to-bone, 187 and cartilage-tobone. 188 Many approaches have been used to fabricate scaffolds for osteochondral application by changing material composition, mechanical properties, and architecture between the chondrogenic and osteogenic layers. [172][173][174][188][189][190][191][192][193] Hierarchical scaffolds loaded with inductive factors disposed in two phases or even in gradients, capable of stimulating each layer toward the maturation of the specific tissue, are being increasingly explored.…”

“…188 Many approaches have been used to fabricate scaffolds for osteochondral application by changing material composition, mechanical properties, and architecture between the chondrogenic and osteogenic layers. [172][173][174][188][189][190][191][192][193] Hierarchical scaffolds loaded with inductive factors disposed in two phases or even in gradients, capable of stimulating each layer toward the maturation of the specific tissue, are being increasingly explored. By using gradients of multiple bioactive factors, multiple tissue regeneration can be addressed via a single-cell source; that is, stem cells can differentiate along different lineages within the same constructs.…”

Delta-sleep inducing peptide entrapment and release from polymer hydrogels based on modified polyvinyl alcohol

“…Для получения полимерных матриц используются различные природные полимеры, например, коллаген [4], шёлк [5], полигидроксибутират [6] и синтетические полимеры, такие как полиэфиры молочной и гликолиевой кислот [7][8][9][10], полиаминокислоты [11], поливиниловый спирт [12,13], либо их композиты, например, ПВС-альгинат [14], ПВС-хитозан [15][16]. Полимерные матрицы изготавливают в виде макропористых губок [12,17], либо микро-и нановолокон [18][19], либо микроносителей [20].…”