Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons

Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.     

Sustained Exposure of Substance P Causes Tendinopathy

Recently, neuromediators such as substance P (SP) have been found to be important factors in tendon homeostasis. Some studies have found SP to be the cause of inflammation and tendinopathy, whereas others have determined it to be a critical component of tendon healing. As demonstrated by these conflicting findings, the effects of SP on tendinopathy remain unclear. In this study, we hypothesized that the duration of SP exposure determines its effect on the tendons, with repetitive long-term exposure leading to the development of tendinopathy. First, we verified the changes in gene and protein expression using in vitro tenocytes with 10-day exposure to SP. SP and SP + Run groups were injected with SP in their Achilles tendon every other day for 14 days. Achilles tendons were then harvested for biomechanical testing and histological processing. Notably, tendinopathic changes with decreased tensile strength, as observed in the Positive Control, were observed in the Achilles in the SP group compared to the Negative Control. Subsequent histological analysis, including Alcian blue staining, also revealed alterations in the Achilles tendon, which were generally consistent with the findings of tendinopathy in SP and SP + Run groups. Immunohistochemical analysis revealed increased expression of SP in the SP group, similar to the Positive Control. In general, the SP + Run group showed worse tendinopathic changes. These results suggest that sustained exposure to SP may be involved in the development of tendinopathy. Future research on inhibiting SP is warranted to target SP in the treatment of tendinopathy and may be beneficial to patients with tendinopathy.     

A Tendon-Specific Double Reporter Transgenic Mouse Enables Tracking Cell Lineage and Functions Alteration In Vitro and In Vivo

We generated and characterized a transgenic mouse line with the tendon-specific expression of a double fluorescent reporter system, which will fulfill an unmet need for animal models to support real-time monitoring cell behaviors during tendon development, growth, and repair in vitro and in vivo. The mScarlet red fluorescent protein is driven by the Scleraxis (Scx) promoter to report the cell lineage alteration. The blue fluorescent protein reporter is expressed under the control of the 3.6kb Collagen Type I Alpha 1 Chain (Col1a1) proximal promoter. In this promoter, the existence of two promoter regions named tendon-specific cis-acting elements (TSE1, TSE2) ensure the specific expression of blue fluorescent protein (BFP) in tendon tissue. Collagen I is a crucial marker for tendon regeneration that is a major component of healthy tendons. Thus, the alteration of function during tendon repair can be estimated by BFP expression. After mechanical stimulation, the expression of mScarlet and BFP increased in adipose-derived mesenchymal stem cells (ADMSCs) from our transgenic mouse line, and there was a rising trend on tendon key markers. These results suggest that our tendon-specific double reporter system is a novel model used to study cell re-differentiation and extracellular matrix alteration in vitro and in vivo.     

Study on the improvement of compressive strength and fracture toughness of calcium phosphate cement

Calcium phosphate cement (CPC) has superior properties, such as excellent bioactivity, biocompatibility, osteoconductivity and degradability, since its hydration product is hydroxyapatite (HA). As a novel cement material, CPC also shows injectable and self-setting properties. However, the compressive strength (CS) and fracture toughness of most CPCs are far lower than that of human weight-bearing bones, which largely limit their applications in the repairment of weight-bearing bones. To improve the CS and fracture toughness of CPC, several methods, including in-situ reinforcement by Ca4(PO4)2O (TTCP) ceramic particles, suitable nanofibers are introduced in this study. The maximal CS of CPC prepared with TTCP (average particle size of 22.3 ± 0.4 μm) reached to 98.4 MPa, which is close to the strength of human long bones. The enhanced CS of CPC was attributed to the in-situ reinforcing effect of residual TTCP particles. Tendon collagen slices and HA nanofibers were used to improve the fracture toughness of CPC. The flexural strength (FS) and the work of facture (WOF) of CPC were slightly increased by adding HA nanofibers but was significantly increased by the addition of tendon collagen slices. With 1.000 wt% tendon collagen slices, the FS and WOF of CPC were increased by 61.3% and 22.6 times, respectively.     

Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide–polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.     

Fabrication and characterization of 3-dimensional PLGA nanofiber/microfiber composite scaffolds

Novel three-dimensional (3-D) nano-/microfibrous poly(lactic-co-glycolic acid) (PLGA) scaffolds were fabricated by hybrid electrospinning, involving a combination of solution electrospinning and melt electrospinning. The scaffolds consisted of a randomly oriented structure of PLGA microfibers (average fiber diameter = 28 μm) and PLGA nanofibers (average fiber diameter = 530 nm). From mercury porosimetry, the PLGA nano-/microfiber (10/90) scaffolds were found to have similar pore parameters to the PLGA microfiber scaffolds. PLGA nano-/microfibrous scaffolds were examined and compared with the PLGA microfiber scaffolds in terms of the attachment, spreading and infiltration of normal human epidermal keratinocytes (NHEK) and fibroblasts (NHEF). The cell attachment and spreading of both cell types were several times higher in the nano-/microfiber composite scaffolds than in the microfibrous scaffolds without nanofibers. This shows that the presence of nanofibers enhanced the attachment and spreading of the cells on the nano-/microfiber composite scaffolds. Moreover, the nanofibers helped the cells infiltrate easily into the scaffolds. Overall, this novel nano-/microfiber structures has great potential for the 3-D organization and guidance of cells provided for tissue engineering.     

The Effect of Age and Intrinsic Aerobic Exercise Capacity on the Expression of Inflammation and Remodeling Markers in Rat Achilles Tendons

Old age, adiposity, and metabolic disorders are known as risk factors for chronic tendinopathy, which is a common problem in both athletes and the general population. However, the importance of these influencing factors has not yet been well understood. This study investigated alterations in gene expression and histology of Achilles tendons of young (10 weeks) and old (100 weeks) rats bred for low (low capacity runners, LCR) and high (high capacity runners, HCR) intrinsic aerobic exercise capacity. In this rat model, LCR displayed a phenotype of reduced exercise capacity, higher body weight, and metabolic dysfunctions compared to HCR. We hypothesized that the risk factors for tendinopathy in old LCR could lead to more pronounced impairments in Achilles tendon tissue. In quantitative real-time PCR (qPCR), age-related downregulation of tenocyte markers e.g., tenomodulin, genes related to matrix modeling and remodeling (e.g., collagens, elastin, biglycan, fibronectin, tenascin C) as well as transforming growth factor beta 3 (Tgfb3) have been detected. Inflammation marker cyclooxygenase 2 (Cox2) was downregulated in old rats, while microsomal prostaglandin E synthase 2 (Ptges2) was upregulated in old HCR and old LCR. In all groups, interleukin 6 (Il6), interleukin 1 beta (Il1b), and tumor necrosis factor alpha (Tnfa) showed no significant alteration. In histological evaluation, tendons of old rats had fewer and more elongated tenocyte nuclei than young rats. Even though a higher content of glycosaminoglycans, a sign of degeneration, was found in old HCR and LCR, no further signs of tendinopathy were detectable in tendons of old rats by histological evaluation. Low intrinsic aerobic exercise capacity and the associated phenotype did not show significant effects on gene expression and tendon histology. These findings indicate that aging seems to play a prominent role in molecular and structural alterations of Achilles tendon tissue and suggests that other risk factors associated with intrinsic aerobic exercise capacity are less influential in this rat model.     

Hemocompatibility of electrospun halloysite nanotube‐ and carbon nanotube‐doped composite poly(lactic‐co‐glycolic acid) nanofibers

One of the major problems of nanofiber scaffold or other devices like cardiovascular or blood‐contacting medical devices is their weak mechanical properties and the lack of hemocompatibility of their surfaces. In this study, halloysite nanotubes (HNTs) and carbon nanotubes (CNTs) were incorporated within poly(lactic‐co‐glycolic acid) (PLGA) nanofibers and the mechanical property and hemocompatibility of both types of composite nanofibers with different doping levels were thoroughly investigated. The morphology and internal distribution of the doped nanotubes within the nanofibers were characterized using scanning electron microscopy and transmission electron microscopy. Mechanical properties of the electrospun nanofibers were tested using a material testing machine. The hemocompatibility of the composite nanofibers was examined through hemolytic and anticoagulant assay, respectively. We show that the doped HNTs or CNTs are distributed in the nanofibers with a coaxial manner and the incorporation of HNTs or CNTs does not significantly change the morphology of the PLGA nanofibers. Importantly, the incorporation of HNTs or CNTs within PLGA nanofibers significantly improves the mechanical property of PLGA nanofibers, and PLGA nanofibers with or without doping of the HNTs and CNTs display good anticoagulant property and negligible hemolytic effect to human red blood cells. With the enhanced mechanical property, great hemocompatibility, and previously demonstrated biocompatibility of both HNTs‐ and CNTs‐doped composite PLGA nanofibers, these composite nanofibers may be used as therapeutic artificial tissue/organ substitutes for tissue engineering applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Retracted: A Photoclick Thiol-Ene Collagen-Based Hydrogel Platform for Skeletal Muscle Tissue Engineering

UV-cured collagen-based hydrogels hold promise in skeletal muscle regeneration due to their soft elastic properties and porous architecture. However, the complex triple helix conformation of collagen and environmental conditions, i.e., molecular oxygen, pose risks to reaction controllability, wet-state integrity, and reproducibility. To address this challenge, a photoclick hydrogel platform is presented through an oxygen-insensitive thiol-ene reaction between 2-iminothiolane (2IT)-functionalized type I collagen and multiarm, nonhomopolymerizable norbornene-terminated polyethylene glycol (PEG). UV-induced network formation is demonstrated by oscillatory time sweeps on the reacting thiol-ene mixture, so that significantly increased storage moduli are measured and adjusted depending on the photoinitiator concentration. Variations in PEG functionality (4-arm and 8-arm) and PEG content generate hydrogels with skeletal muscle native stiffness (E_c = 1.3 ± 0.2‒11.5 ± 0.9 kPa), diffusion-controlled swelling behavior and erosion-driven degradability. In vitro, no cytotoxic effect is detected on C2C12 murine myoblasts, while myogenic differentiation is successfully accomplished on hydrogel-seeded cells in then low serum culture medium. In vivo, 7 d subcutaneous implantation of selected thiol-ene hydrogel in rats reveal higher cell infiltration, blood vessel formation, and denser tissue interface compared to a clinical gold standard collagen matrix (Mucograft, a trademark of Geistlich Biomaterials). These results, therefore, support the applicability and further development of this hydrogel platform for skeletal muscle regeneration.     

Poly(lactide-co-glycolide) nanoparticles embedded in a micropatterned collagen scaffold for neuronal tissue regeneration

Micropatterned collagen scaffold with axially oriented pores embedded with poly(lactide-co-glycolide) nanoparticles (PLGA NPs) was synthesized and characterized. Two different concentrations of PLGA nanoparticles have been tested and the experimental results indicate that the concentration affects the release kinetic, whereas the stiffness, the crosslink density, and the degradation rate of the collagen matrix are comparable to bare scaffold. Further, the proposed crosslinking procedure provides a resistance to thermal and enzymatic degradation, thereby promoting the persistence of scaffold for a period of time compatible with nerve regeneration.     

Fabrication and characterization of aligned nanofibrous PLGA/Collagen blends as bone tissue scaffolds

Aligned nanofibrous blends of poly (d, l-lactide-co-glycolide) (PLGA) and collagen with various PLGA/collagen compositions (80/20, 65/35 and 50/50) were fabricated by electrospinning and characterized for bone tissue engineering. Morphological characterization showed that the addition of collagen to PLGA resulted in narrowing of the diameter distribution and a reduction in average diameter. Differential scanning calorimetric (DSC) studies showed that the triple helix structure of the native collagen was not destroyed during the fabrication process. However, the blending had a marked effect on the overall enthalpy of the blends, whereby the total enthalpy decreased as the collagen content decreased. Thermogravimetric analysis showed the addition of collagen increased the hydrophilicity of the scaffolds. The crosslinking of collagen to increase the biostability was done using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in ethanol and an overall ∼25% degree of crosslinking was achieved. The EDC crosslinking had little effect on the nanofibrous morphology of the 80/20 blend system; however, the nanofibrous features were compromised to some extent at higher collagen concentrations. The mechanical characterization under dry and wet conditions showed that increasing collagen content resulted in a tremendous decrease in the mechanical properties. However, crosslinking resulted in the increase in elastic modulus from 47 MPa to 83 MPa for the wet PLGA/Collagen 80/20 blend system, with little effect on the tensile strength. In conclusion, the aligned nanofibrous scaffold used in this study constitutes a promising material for bone tissue engineering.     

Flurbiprofen axetil loaded coaxial electrospun poly(vinyl pyrrolidone)–nanopoly(lactic‐co‐glycolic acid) core–shell composite nanofibers: Preparation,characterization, and anti‐adhesion activity

Flurbiprofen axetil (FA)‐loaded coaxial electrospun poly(vinyl pyrrolidone) (PVP)–nanopoly(lactic‐co‐glycolic acid) core–shell composite nanofibers were successfully fabricated by a facile coaxial electrospinning, and an electrospun drug‐loaded system was formed for anti‐adhesion applications. The FA, which is a kind of lipid microsphere nonsteroidal anti‐inflammatory drug, was shown to be successfully adsorbed in the PVP, and the formed poly(lactic‐co‐glycolic acid) (PLGA)/PVP/FA composite nanofibers exhibited a uniform and smooth morphology. The cell viability assay and cell morphology observation revealed that the formed PLGA/PVP/FA composite nanofibers were cytocompatible. Importantly, the loaded FA within the PLGA/PVP coaxial nanofibers showed a sustained‐release profile and anti‐adhesion activity to inhibit the growth of the IEC‐6 and NIH3T3 model cells. With the significantly reduced burst‐release profile, good cytocompatibility, and anti‐adhesion activity, the developed PLGA/PVP/FA composite nanofibers were proposed to be a promising material in the fields of tissue engineering and pharmaceutical science. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41982.     

Characterization of CS/PVA/GO electrospun nanofiber membrane with astaxanthin

Tissue engineering has been widely used in regenerative medicine and tissue engineering scaffolds have become a new research direction for periodontal regenerative repair. We aim to develop a biological scaffold material that can support host immunity and promote periodontal regeneration. In this paper, chitosan (CS)/polyvinyl alcohol (PVA)/graphene oxide (GO)/astaxanthin (ASTA) nanofibers membranes were prepared by electrospinning. The nanofibers were characterized by scanning electron microscopy, infrared spectroscopy, mechanical testing, antibacterial testing and cytotoxicity testing. The CS/PVA/GO/ASTA nanofiber membrane had favorable micro-morphology, good mechanical properties and no cytotoxicity. This preliminary study demonstrates that the CS/PVA/GO/ASTA nanofiber membrane can be used for in vivo and in vitro experiments related to periodontal regeneration. The related mechanism of periodontal regeneration will be evaluated in future studies.     

Effect of solution properties on nanofibrous structure of electrospun poly(lactic‐co‐glycolic acid)

Electrospinning of poly(lactic‐co‐glycolic acid) (PLGA) in chloroform or 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) was investigated, focusing on its solution parameters, to develop nonwoven biodegradable nanofibrous structures for tissue engineering. PLGA nanofibers were obtained by electrospinning of 15 wt % PLGA solution and the resulting average fiber diameters were varied with the range of 270–760 nm, depending on solution property. When small amounts of benzyl triethylammonium chloride (BTEAC) was added to the PLGA/chloroform solution, the average diameter was decreased from 760 to 450 nm and the fibers were densely amounted in a straight shape. In addition, the average fiber diameter (270 nm) of nanofibers electrospun from polar HFIP solvent was much smaller than that (760 nm) of nanofibers electrospun from nonpolar chloroform solvent. Therefore, it could be concluded that conductivity or dielectric constant of the PLGA solution was a major parameter affecting the morphology and diameter of the electrospun PLGA fibers. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 1214–1221, 2006     

Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.     

Characterization and cell response of electrospun Rana chensinensis skin collagen/poly(l‐lactide) scaffolds with different fiber orientations

Collagen was extracted from Rana chensinensis skin supplied from byproducts via an acid enzymatic extraction method. The R. chensinensis skin collagen (RCSC) and poly(l ‐lactide) (PLLA) were blended at a 3:7 ratio in 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP) at a concentration of 10% (g/mL) and electrospun to produce nanofibers in an aligned and random orientation. For comparison, pure PLLA nanofibrous membranes with aligned and random nanofiber orientations were also produced. The secondary structure of the RCSC nanofibers was investigated by circular dichroism to confirm that the extracted substance was collagen. The presence of collagen in the blend nanofiber was verified by LSCM. The blended nanofibers showed uniform, smooth, and bead‐free morphologies and presented a smaller fiber diameter (278 and and 259 nm) than the pure the ones of PLLA (559 and and 439 nm) nanofibers. It was found that the addition of RCSC and the modification of the nanofiber's orientation affected the fiber's diameter and the crystallization of PLLA. The cell viability studies with human fibroblast cells demonstrated that the RCSC/PLLA nanofibrous membranes formed by electrospinning exhibited good biocompatibility and that the aligned scaffolds could regulate the cell morphology by inducing cell orientation. The empirical results in this study indicated that the aligned RCSC/PLLA nanofibrous membrane is a potential wound dressing candidate for skin regeneration. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45109.     

A biomimetic mesoporous silica–polymer composite scaffold for bone tissue engineering

A biomimetic organic–inorganic composite system comprising of microspheres fabricated from combination of a biodegradable polymer poly(lactide-co-glycolide) (PLGA) and bioactive mesoporous silica (SBA-15) has been developed through sintering technique for bone regeneration applications. The morphological and structural properties of the SBA-15/PLGA composite scaffold were evaluated using electron microscopy and fourier transform infrared spectroscopy and the results showed spherical morphology and composite nature. The presence of mesopores in the silica was confirmed through nitrogen adsorption–desorption isotherms. The surface area and pore size of mesoporous silica were found to be 792 m² g^?1 and 3.7 nm, respectively. The thermal characteristics of the SBA-15/PLGA composites studied using thermogravimetry analysis shows a weight loss of around 80% with the degradation occurring at 324?°C. The prepared scaffold is also found to support the adhesion and proliferation of osteoblast cells. The expression of specific bone markers is significantly enhanced in the SBA-15/PLGA composite scaffold when compared with the pristine polymeric scaffold indicating the positive effect of mesoporous silica. Hence, these SBA-15/PLGA composite scaffolds can be explored further for bone regeneration applications.     

Hemocompatibility of polymers for use in vascular endoluminal implants

Implanted polymers for cardiovascular applications may function as structural supports, barriers, or provide a means for local drug delivery. Several thermoplastic biodegradable drug delivery polymers are potential candidates for blood-contacting implant applications. For intravascular applications specifically, a criterion for material selection is the intrinsic hemocompatibility of the baseline polymer. As an initial screening approach for selection of polymers for in vivo use, thin films of polyesters: poly(ɛ-caprolactone) (PCL), poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA); polyanhydrides: poly(fatty acid dimer-co-sebacic acid) (PFAD:SA) and poly(biscarboxyphenoxypropane-co-sebacic acid) (PCPP:SA); and poly(ethylene glycol) (PEG)-ylated polyesters: PLA:PEG, PCL:PEG and PCL:PLA:PEG polymers were spin-cast on glass cover slips and placed in an in vitro flow system exposing them at a controlled shear to overflowing human whole blood. Platelet adherence, aggregate formation, and thrombus formation, as well as leukocyte adherence were assessed following 5 min of flow. At 5 min of flow the rank order of materials, in terms of least to most thrombogenic was: PCL < PFAD:SA < PCPP:SA < PLGA < PLA. All PEGylated materials, in general, had less thrombus formation than baseline unmodified materials.     

In vitro degradation behavior of electrospun polyglycolide,polylactide, and poly(lactide‐co‐glycolide)

The electrospinning of polyglycolide (PGA), poly(L ‐lactide) (PLA), and poly(lactide‐co‐glycolide) (PLGA; L ‐lactide/glycolide = 50/50) was performed with chloroform or 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) as a spinning solvent to fabricate their nanofiber matrices. The morphology of the electrospun PGA, PLA, and PLGA nanofibers was investigated with scanning electron microscopy (SEM). The PLGA nanofibers, electrospun with a nonpolar chloroform solvent, had a relatively large average diameter (760 nm), and it had a relatively broad distribution in the range of 200–1800 nm. On the other hand, the PGA and PLA fibers, electrospun with a polar HFIP solvent, had a small average diameter (～300 nm) with a narrow distribution. This difference in the fiber diameters may be associated with the polarity of the solvent. Also, the in vitro degradation of PGA, PLA, and PLGA nanofiber matrices was examined in phosphate buffer solutions (pH 7.4) at 37°C. The degradation rates of the nanofiber matrices were fast, in the order of PGA > PLGA ? PLA. Structural and morphological changes during in vitro degradation were investigated with differential scanning calorimetry and wide‐angle X‐ray diffraction. For the PGA matrix, a significant increase in the crystallinity during the early stage was detected, as well as a gradual decrease during the later period, and this indicated that preferential hydrolytic degradation in the amorphous regions occurred with cleavage‐induced crystallization, followed by further degradation in the crystalline region. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 193–200, 2005